PHARMA, BIOTECH & LIFE SCIENCE WHAT’S INSIDE DISCOVERY6 RESEARCH & DEVELOPMENT 12 PRECLINICAL17 CLINICAL TRIALS 28 DIAGNOSTICS33 BUSINESS & GOVERNMENT POLICY 36 TOOLS & TECHNOLOGY Optibrium integrates NextMove algorithm.......................8 Catalent, Sanofi collaborate on SMARTag, ADCs.........14 Agilent tool enhances integrity of genomics experiments...................................................16 Optimizing trials through mobile health technology......32 On the cutting edge.............................................................38 FINANCE/MARKETS3 EDITORIAL/COMMENTARY10 LATE-BREAKING NEWS 42 AWARDS & HONORS 43 PRODUCTS & SERVICES 44 PEOPLE & PROMOTIONS 45 Q&A46 SHOW PREVIEW AACR Annual Meeting 2015 22 American Association for Cancer Research brings the world’s largest oncology research conference to Philadelphia MARCH 2015 : VOLUME 11 : NUMBER 3 PUBLISHED SINCE 2005 03.15 MMRF and Inflection collaborate on new cancer treatment Current focus is on preclinical testing of innovative dualmechanism PIM/PI3K inhibitor IBL-202 BY JEFFREY BOULEY DUBLIN & NORWALK, Conn.— Inflec- tion Biosciences Ltd., a private company developing what it calls “highly innovative” treatments for cancer, announced in February a collaboration with the Multiple Myeloma Research Foundation (MMRF) on preclinical testing of its dual-mechanism PIM/PI3K inhibitor IBL-202. PIM and PI3K are two key regulators in signaling pathways that have proved essential for the proliferation and survival of myeloma cells. The MMRF investigators will test the effectiveness of IBL-202 alone and in combination with other therapeutics in preclinical models of multiple myeloma. These models are recognized to be predictive of clinical efficacy in cancer patients with multiple myeloma. IBL-202’s dual-mechanism MMRF CONTINUED ON PAGE 21 Inflection Biosciences and the Multiple Myeloma Research Foundation are pursuing preclinical studies of a compound that targets two key regulators in signaling pathways that have proved essential for the proliferation and survival of myeloma cells. Roaring back…but more modestly Pfizer makes first M&A deal since failing to land AstraZeneca, committing to $17 billion for Hospira BY JEFFREY BOULEY & LLOYD DUNLAP least one thing that Pfizer shared in common with Valeant Pharmaceuticals last year: going all-in with a huge takeover offer for a major company ($117 billion offered by Pfizer for AstraZeneca and $54 billion offered by Valeant for Allergan), and ultimately failing in that bid. And, much like Valeant (see story on page 42 for more on that), Pfizer is confidently getting back on the saddle in recent weeks with a smaller but still multibillion merger and acquisition (M&A) agreement—in this case, a $17-billion dollar deal under which Pfizer will buy Hospira Inc. The two companies announced Feb. 5 that they have entered into a definitive merger agreement under which Pfizer will acquire Hospira, a leading provider of injectable drugs and infusion technologies CREDIT: BUSINESS WIRE NEW YORK & LAKE FOREST, Ill.—There’s at Pfizer hopes to boost its injectable drug pipeline and biosimilars pipeline with the recently announced acquisition of Hospira. Pictured here is a lab worker at Pfizer’s new Kendall Square R&D facility in Cambridge, Mass., which was established in June of last year and focuses on such therapeutic areas as inflammation and remodeling, immunoscience, rare diseases, cardiovascular and metabolic disease and neuroscience. and a global leader in biosimilars, for $90 per share in cash. “The proposed acquisition of Hospira demonstrates our commitment to prudently deploy capital to create shareholder value and deliver incremental revenue and EPS [earnings per share] growth in the near term,” said Ian Read, chairman and CEO of Pfizer. “In addition, Hospira’s business aligns well with our new commercial structure and is an excellent strategic fit for our Global Established Pharmaceutical (GEP) business, which will benefit from a significantly enhanced product portfolio in growing markets. Coupled with Pfizer’s global reach, Hospira is expected to drive greater sustainability for our GEP business over the long term.” This “strategically complementary” combination will add a growing revenue stream and a platform for building up Pfizer’s GEP business. The expanded portfolio of sterile injectable pharmaceuticals includes acute care and oncology injectables, with a number of differentiated presentations, as well as a biosimilars portfolio that is expected to reinforce GEP’s growth strategy to build a broad portfolio of biosimilars in Pfizer’s therapeutic areas of strength. “The addition of Hospira has the potential to fundamentally improve the growth trajectory of the Global Established Pharmaceutical business, vault it into a leadership position in the large and growing off-patent sterile injectables marketplace by combining the specialized talent and capabilities of both companies, including enhanced manufacturing, and advance its goal to be among the world’s most preeminent biosimilars providers,” said John Young, GEP group president. HOSPIRA CONTINUED ON PAGE 41 EVERY CANCER TELLS A STORY IF YOU HAVE THE TOOLS TO READ IT © 2015 PerkinElmer, Inc. 400311_05. All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners. Mantra Workstation CANCER IMMUNOLOGY RESEARCH SOLUTIONS Opal™ Multiplex Staining Vectra® and Mantra™ Multiplex Biomarker Imaging inForm® Image Analysis Software Visualize this: Our Mantra™ workstation with inForm® software enables you to quantify, phenotype, and detect spatial relationships among immune cells in FFPE tissue, in situ. It’s a hands-on, semi-automated solution that complements your research skills, using a workflow you can trust. Best of all, it’s an ideal entry point into our comprehensive Cancer Immunology Research Solutions – everything from multiplexed staining reagents and methodologies to advanced image acquisition, visualization, and analysis. Mantra: It’s quantitative pathology the way you knew it could be. For research use only. Not for use in diagnostic procedures. www.perkinelmer.com/Mantra FINANCE For more information, visit www.DDN-News.com MARCH 2015 | | DDNEWS 3 G1 Therapeutics raises $33 million in Series B round RESEARCH TRIANGLE PARK, N.C.— In early February, G1 Therapeutics Inc., a clinical-stage pharmaceutical company developing smallmolecule therapies to address significant unmet needs in oncology, announced the completion of a $33-million Series B financing round. Lead investors Eshelman Ventures and RA Capital Management were joined by new investors Lumira Capital and Boxer Capital of Tavistock Life Sciences, as well as the company’s existing investors Hatteras Venture Partners, MedImmune Ventures and Mountain Group Capital. As part of all this, Dr. Fred Eshelman, founder of Eshelman Ventures, and Dr. Peter Kolchinsky, managing Vaxxas raises $20 million to accelerate vaccine platform general partner of RA Capital, have joined G1’s board of directors. G1 plans to use the proceeds to advance its lead program, G1T28, a highly potent and selective CDK4/6 inhibitor, through proof of concept as an antineoplastic agent and as a bone marrow chemoprotectant. G1T28 is currently being evaluated in Phase 1a clinical trials to assess safety, pharmacokinetics and pharmacodynamics in healthy volunteers. Data collected from this study will inform the dose and schedule for multiple Phase 1a/b clinical trials in cancer patients, which are expected to begin in 2015. “This financing from new and existing investors is a testament to G1T28’s potential in multiple oncology indications,” said Dr. Mark Velleca, CEO of G1. “We’re especially fortunate to have Fred and Peter on our board, as their business acumen and scientific expertise will be invaluable as we advance G1T28 through the clinic.” “Rarely does an entirely novel, orthogonal mechanism emerge in oncology that has the ability to combine with other approaches,” noted Kolchinsky. “There are many inhibitors of angiogenesis, immune evasion, DNA replication and growth signaling. Shutting down the G1/S cell cycle transition via precise CDK4/6 inhibition is now emerging as a category unto itself, and G1 Therapeutics is the only small company with a selective agent in the clinic. While three pharmas are ahead and have done much to validate this class, we expect significant interest from the many others that already appreciate—or soon will—that they have a gap in their toolkit.” n Break free from qPCR Find gene targets faster BRISBANE, Australia—Vaxxas, a bio- technology company commercializing a novel vaccination platform, announced recently that it has secured equity funding of A$25 million (approximately $20 million in U.S. dollars) from new and existing investors. The company’s corporate offices are in Australia, but its global partnering and licensing operations are in Cambridge, Mass. These funds represent the first closing of a Series B venture financing round, the proceeds from which will be used to advance a series of clinical programs and develop a pipeline of new vaccine products for major diseases using Vaxxas’ patented Nanopatch platform. This new round of financing brings the total capital raised by Vaxxas to A$40 million (about $33 million). “As we have advanced the development of our Nanopatch needlefree vaccination technology, we have seen tremendous opportunities to create our own proprietary pipeline of Nanopatch-based vaccine products, as well as those with partners,” said David L. Hoey, president and CEO of Vaxxas. “This funding creates an important inﬂection point for Vaxxas, as we are now poised to create significantly increased value through our first clinical studies.” Vaxxas’ proprietary Nanopatch platform induces robust immune system activation by targeting a vaccine to the abundant immunological cells immediately below the surface of the skin. Vaxxas’ plans call for applying its patented needle-free vaccination technology against major diseases such as influenza, polio, bacterial infections and cancer. n Validating gene targets with qPCR is often slow and costly due to lengthy primer design, experimental assay optimization, and sample processing time. QuantiGene® Plex Assays validate gene targets faster: No RNA purification or reverse transcription is required Multiplex panels of up to 80 genes are functionally validated One QuantiGene Plex® plate provides as much information as 20 qPCR plates Download “The 7 best reasons to break free from qPCR” at www.ebioscience.com/breakfree-ddn Biology for a better world. NORTH AMERICA: 888-999-1371 EUROPE: +43 1 796 40 40-305 JAPAN: +81 (0)3 6430 4020 INQUIRIES: [email protected] ©2015 Affymetrix, Inc. All rights reserved. For Research Use Only. Not for use in diagnostic or therapeutic procedures. QG05255-Ad-QGPlex-DDNews-March_2015_0215.indd 1 3/2/15 11:33 AM MARKETS 4 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Pharmaceutical and biotech market indices O Biotechnology Index n feb. 24, 2015, the S&P 500 Health Care Sector Index ended the day at 835.99, down 0.06 percent but having advanced by 5.44 percent in the previous three months. Overall that day, the NASDAQ Composite ended up 0.14 percent, the Dow Jones Industrial Average rose by 0.51 percent and the S&P 500 closed with a gain of 0.28 percent. Advances were broad-based, with nine out of 10 sectors ending the session in the positive. 2736 2374 14/Mar 11/Apr 2505 09/May 2707 13/Jun 2794 11/Jul 2911 15/Aug 3082 3018 12/Sep 17/Oct 3254 3421 14/Nov 12/Dec 535 532 14/Nov 12/Dec 3523 3715 16/Jan 13/Feb 553 557 16/Jan 13/Feb SOURCE: NYSE ARCA Mini-pharma and Mini-biotech Indices 127 99 14/Mar 146 154 151 135 140 101 103 105 101 106 99 09/May 13/Jun 11/Jul 15/Aug 12/Sep 17/Oct 119 125 96 11/Apr MINI-BIOTECH 171 163 Pharmaceutical Index 186 181 495 107 106 111 14/Nov 12/Dec 16/Jan 505 512 522 09/May 13/Jun 11/Jul 481 506 530 497 111 13/Feb 14/Mar M I NI-PHAR MA SOURCE: NYSE ARCA 11/Apr 15/Aug 12/Sep 17/Oct SOURCE: NYSE ARCA THREE THERAPEUTIC MARKETS POISED TO GROW BY JEFFREY BOULEY NEW YORK & LONDON—For GBI Research and GlobalData, as they gaze into their financial crystal balls, colorectal cancer (CRC), irritable bowel syndrome (IBS) and Cushing’s syndrome (CS) all show up as markets to watch for gains—though not all of them hold spellbinding potential. From GBI comes a prognostication that the CRC therapeutics market will increase moderately, from $8.3 billion in 2013 to $9.4 billion by 2020, representing a compound annual growth rate (CAGR) of just 1.8 percent. The company’s latest report states that this growth, which will occur across eight major developed countries—the United States, United Kingdom, France, Germany, Spain, Italy, Japan and Canada—will be limited by the patent expirations of Avastin and Erbitux during the forecast period, which will prompt the uptake of lower-priced biosimilar versions of these drugs. However, Saurabh Sharma, senior analyst for New York-based GBI Research, says that despite its patent expiration, Avastin is expected to retain its market-leading position in the global CRC space through to 2020, explaining, “Avastin is heavily prescribed in both first- and second-line settings, regardless of the patient’s KRAS status. Its dominance is consistent across both the metastatic KRAS wild-type and mutation-positive settings, despite the availability of epidermal growth factor receptor inhibitors for the treatment of KRAS wild-type disease. Additionally, Stivarga is expected to be one of the biggest drivers of growth in the CRC market, due primarily to its anticipated line extension as a maintenance treatment in the first-line metastatic setting for patients with resected liver metastases.” The predictions are more dramatic for IBS and CS from the market-watchers for GlobalData in London. According to the firm, the global therapeutics market for IBS is set to rise in value from $589.6 million in 2013 to $1.5 billion by 2023, representing a CAGR of almost 9.9 percent. This expansion will be driven primarily by rising IBS prevalence, GlobalData says, along with the increasing uptake of Linzess in the United States, United Kingdom, France, Germany, Italy and Spain. Linzess’ anticipated launch in P U B L I C C O M BioCryst announces Q4 and full year RESEARCH TRIANGLE PARK, N.C.—BioCryst Pharmaceuticals Inc. recently announced financial results for the fourth quarter and full year ended Dec. 31, 2014, with President and CEO Jon P. Stonehouse saying, “We are proud of our 2014 achievements, most notably our successful completion of the BCX4161 OPuS-1 trial and the initiation of OPuS-2 for the treatment of hereditary angioedema (HAE), as well as our first U.S. regulatory approval of a BioCryst-discovered drug, Rapivab for the treatment of acute uncomplicated influenza in patients 18 years and older. We have also made substantial progress in our second-generation kallikrein inhibitor program and are now preparing BCX7353 to enter Phase 1 testing as a potential once-daily oral treatment to prevent HAE attacks.” In the fourth quarter, total revenues decreased to $5.4 million from $10.6 million in the fourth quarter of 2013, and research and development expenses increased to $18.5 million from $15.5 million. Fluidigm reports financials SOUTH SAN FRANCISCO, Calif.—Fluidigm major driver behind the significant growth in the CS therapeutics arena, along with the arrivals of Novartis’ Signifor LAR in the six major markets (United States, France, Germany, Italy, Spain and the United Kingdom) in 2018 and HRA Pharma’s Ketoconazole HRA (ketoconazole) in Europe in 2015. Shaan Thakerar, GlobalData’s analyst covering cardiovascular and metabolic disorders, says, “Additionally, the U.S. launch of secondgeneration steroidogenesis inhibitors, such as Cortendo AB’s NormoCort (COR-003) and Novartis’ LCI699, will also boost the market over the forecast period.” n Japan in 2017 will further boost the market. Linzess faces competition from Amitiza and the potential introduction of two additional IBS-C products, plecanatide and tenapanor, acknowledges Dr. Toli Koutsokeras, GlobalData’s senior analyst covering immunology, but GlobalData still expect the drug’s uptake to rise by 2023. Meanwhile, the global CS treatment market will expand rapidly in value from approximately $179 million in 2013 to $499 million by 2018, representing an impressive CAGR of 22.74 percent, predicts GlobalData. Increasing disease prevalence will be a Corp. announced its financial results for the fourth quarter and full year ended Dec. 31, 2014, noting that total revenue for the fourth quarter of 2014 was $33.5 million, an increase of 60 P A N Y N E W S percent from $20.9 million in the fourth quarter of 2013. Organic revenue for the fourth quarter of 2014 (excluding revenue attributable to the DVS Sciences acquisition, comprised of the CyTOF 2 system and proteomics analytical consumables) was $25.2 million, an increase of 21 percent from $20.9 million in the fourth quarter of 2013. Total revenue for the full year of 2014 was $116.5 million, an increase of 64 percent from $71.2 million in 2013. Organic revenue for the full year of 2014 was $95.9 million, an increase of 35 percent from $71.2 million in 2013. Net sales down for Genmab’s Arzerra COPENHAGEN, Denmark—On Feb. 4, Genmab A/S announced that net sales of Arzerra (ofatumumab) during the fourth quarter of 2014 were about $17.6 million. Under the terms of its collaboration with GlaxoSmithKline, Genmab expects to receive a royalty payment of approximately $3.5 million. Full-year 2014 net sales of Arzerra totaled about $84.4 million worldwide, compared to about $116 million in 2013. The total royalty income to Genmab for 2014 is approximately $15.4 million. During the second half of 2014, sales of Arzerra were impacted by sales related to the supply of Arzerra for clinical trials run by other companies. Sales were not impacted by clinical trial material sales during the first half. 58xx centrifuges with new rotor generation Reliable Performance Eppendorf Multipurpose Centrifuge 5804/R and 5810/R Eppendorf centrifuges go beyond speed and capacity offering you unparalleled ergonomic operation, advanced temperature management and eco-friendly features for energysavings. With their renowned quality and reliability, Eppendorf centrifuge 5804/R and 5810/R are the cost efficient solution for your lab. > Outstanding rotor versatility > Low access height > Quiet operation > Space-saving design > Ergonomic Eppendorf QuickLock® caps and lids www.eppendorf.com • 800-645-3050 012.A1.0114.B © 2015 Eppendorf AG. 012.A1.0114.B.US-DDN.indd 1 Full page tabloid ad Drug Discovery News – DDN 2/6/15 4:00 PM 6 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com DISCOVERY ‘Wake-up’ pills for cancer immunotherapy BR IEFS CGEN-15049 results presented at Keystone Symposia Curis and Aurigene stretch hands across the sea to jointly discover, develop and eventually commercialize pills to fight cancer TEL AVIV—The head of Compugen Ltd.’s immunol- ogy group, Dr. Arthur Machlenkin, recently presented new experimental results for CGEN-15049, a novel immune checkpoint protein discovered by Compugen as a potential cancer immunotherapy target. The data demonstrate expression of this protein on tumors isolated from ovarian cancer patients, both on the cancer cells themselves and on immune cells in the tumor, as well as expression of CGEN-15049 on a population of tumor-infiltrating immune cells in mouse models. The data also support the ability of this protein to affect key components of the immune system known to play a role in anti-tumor immune responses. The studies that provided those data examined the protein’s expression on cells isolated from primary tumors of ovarian cancer patients. CGEN-15049 has been shown to be expressed on a number of cancers, including ovarian, lung, breast, colorectal, gastric, prostate and liver cancers. BY LORI LESKO LEXINGTON, Mass.—Imagine a day when cancer patients no longer suffer through bouts of chemotherapy and radiation, a day when cancer is treated—and cured—with pills purchased at the local pharmacy. That day is not far off, according to Dr. Ali F. Fattaey, president and CEO of Curis Inc., a biotech focused on the development and commercialization of new targets to treat cancer. Curis has teamed up with Bangalore, India-based Aurigene Discovery Technologies Ltd., a specialized, discovery-stage biotech developing novel therapies to treat cancer and inflammatory diseases, entering into an exclusive collaboration agreement focused on immuno-oncology. Together, the two biotechs have ratified a two-year agreement worth an initial $190 million to take two small-molecule targets through development and into the market. HemoShear, Pfizer ink DIVI collaboration IN THIS SECTION Compound optimization Optibrium integrates NextMove algorithm................................. 8 Oncology CGEN-15049 results presented at Keystone Symposia............................... 6 Investigating immunocytokines................. 6 ‘Wake-up’ pills for cancer immunotherapy.......................................... 6 Parkinson’s disease Trash pickup problem................................ 6 Vascular injury HemoShear, Pfizer ink DIVI collaboration... 6 “We are thrilled to partner with Aurigene in seeking to discover, develop and commercialize small-molecule drug candidates generated from Aurigene’s novel technology, and we believe that this collaboration represents a true transformation for Curis that positions the company for continued growth in the development and eventual commercialization of cancer drugs,” Fattaey stated in a news release. “The multiyear nature of our collaboration means that the parties have the potential to generate a steady pipeline of novel drug candidates in the coming years,” he said. The concept of using the body’s own immune system to fight off disease is not new, Fattaey tells DDNews. “But what we have done for the first time is bring the use of small-molecule oral drugs to wake up each cancer immunotherapy,” he explains. Dr. Mark Hannink and colleagues at the University of Missouri (pictured here) believe that a drug based on the PGAM5 pathway could be useful in restoring mitochondrial recycling in certain cells, like neurons affected in Parkinson’s, while blocking this recycling pathway in other cells, like cancer cells. CREDIT: UNIVERSITY OF MISSOURI CHARLOTTESVILLE, Va.—A multiyear platform collabo- ration is now underway between HemoShear and Pfizer Inc., under which the former will apply its proprietary discovery platform in pursuit of developing a predictive model for preclinical drug-induced vascular injury (DIVI). No financial terms were disclosed. The initial phase will allow the partners to recreate the drivers of DIVI biology in the lab with HemoShear Translational Tissue Systems. Currently, no generally accepted, specific diagnostic or predictive biomarkers exist to determine when or why DIVI occurs, nor are there models to choose the safest compound prior to animal testing. “The overall goal of the collaboration is to develop robust biological criteria and associated computational tools to reliably identify and predict DIVI in animals and, ultimately, to elucidate potential drug effects in humans,” said Dr. Brett Blackman, co-founder and chief scientific officer of HemoShear. “What we have done for the first time is bring the use of smallmolecule oral drugs to wake up each cancer immunotherapy,” says Dr. Ali F. Fattaey, president and CEO of Curis. “Technologically, it allows us to go out and get an oral drug to treat cancer rather than let patients and their families go through the effects of chemotherapy and radiation.” cells are functioning normally, mitochondria—the “powerhouses” of cells—generate the necessary energy to keep cells alive. When they become damaged and unable to make energy, mitochon- Investigating immunocytokines Kymab partners with industry expert for more efficacious, tolerable therapies BY KELSEY KAUSTINEN dria are sent to a portion of the cell called a lysosome to be repaired. In the brains of Parkinson’s disease patients, mitochondria fail to move to the lysosomes, causing accumulations of damaged mitochondria that kill brain cells. PEPTIDE CONTINUED ON PAGE 9 IMMUNO CONTINUED ON PAGE 8 Peptide could repair damaged mitochondria to regulate Parkinson’s disease COLUMBIA, Mo.—When brain CURIS CONTINUED ON PAGE 7 CAMBRIDGE, U.K.—In the hopes of using its proprietary platform to develop new cancer therapeutic options, Kymab has announced a collaboration with Dr. Stephen Gillies, a leader in cancer immunotherapy who has invented promising immunocytokine platforms. Gillies is the founder and CEO of Provenance Biopharmaceuticals Corp. and is also on the board of directors for Cambridge, Mass.-based Galenea Corp. “I’m delighted to work with Kymab on development of novel treatments, work that promises to produce improved products for drug development in cancer. The program hits the ‘sweet spot’ of our joint expertise and will be used to develop new and transformational drugs in this fast-moving field,” said Gillies. Kymab and Gillies will work together to develop new immunocytokine-based drugs that could exploit the synergistic potential of combining antibodies directed against immuno-oncology drug targets with the antitumor activity of certain cytokine molecules. Steve Arkinstall, chief scientific officer of Kymab, says the company has licensed Gillies’ immunocytokine intellectual property “as it relates to specific oncological drug targets.” Kymab will be responsible for all experimental work while Gillies will act in an advisory role for the project’s scientific and strategic direction. The collaboration will focus on targets that could have potential Trash pickup problem BY ILENE SCHNEIDER “Technologically, it allows us to go out and get an oral drug to treat cancer rather than let patients and their families go through the effects of chemotherapy and radiation.” The collaboration with Aurigene “is very exciting,” Fattaey says. “First, oral medication is efficient, less costly than chemo and biologics, and you can still combine drugs to design the medicine to treat each individual cancer patient.” Investigational New Drug (IND) application filings for both initial collaboration programs are expected this year, and the first trials will begin with human patients this year, he said. The Curis-Aurigene collaboration provides for the inclusion of multiple programs, with Curis having the option to exclusively license compounds once a development DISCOVERY For more information, visit www.DDN-News.com CONTINUED FROM PAGE 6 candidate is nominated within each respective program, according to the companies. The partnership draws from each company’s respective areas of expertise, with Aurigene responsible for conducting all discovery and preclinical activities, including IND-enabling studies and providing Phase 1 clinical trial supply, and Curis in charge of all clinical development, regulatory and commercialization efforts worldwide, excluding India and Russia, for each program for which it exercises an option to obtain a license. The first two programs under the biotech collaboration are an orally available small-molecule antagonist of programmed death ligand-1 (PD-L1) in the immunooncology field and an orally available small-molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4) in the precision oncology field. Although several global Big Pharma and biotech start-ups have immunotherapy molecules, Aurigene has a completely different class of them—peptides and peptidomimetics (molecules that mimic peptides)—and says it is the only company in the world developing peptides against immune checkpoints, natural mechanisms that cancers hijack to evade the immune system. Addressing immune checkpoint pathways is now a well-validated strategy to treat human cancers, and the ability to target PD-1/PD-L1 and other immune checkpoints with orally available small-molecule drugs has the potential to be a major advancement for patients. Recent studies have also shown that alterations of the MYD88 gene lead to dysregulation of its downstream target IRAK4 in a number of hematologic malignancies, including Waldenström’s Macroglobulinemia and a subset of diffuse large B-cell lymphomas, making IRAK4 an attractive target for the treatment of these cancers. CSN Murthy, CEO of Aurigene, stated, “We are excited to enter into this exclusive collaboration with Curis under which we intend to discover and develop a number of drug candidates from our chemistry innovations in the most exciting fields of cancer therapy. We have established a large panel of preclinical tumor models in immunocompetent mice and can show significant in-vivo antitumor activity using our smallmolecule PD-L1 antagonists. We are also in the late stages of selecting a candidate that is a potent and selective inhibitor of the IRAK4 kinase, demonstrating excellent in-vivo activity in preclinical tumor models.” Aurigene, with its own internal pipeline, works with established pharmaceutical and biotechnology companies in early-stage collaborations, bringing drug candidates from hit generation through IND filing. Aurigene has worked on more than 40 partner targets over the last nine years and has delivered eight clinical candidates which are in development by partners. In connection with the transaction, Curis has issued to Aurigene approximately 17.1 million shares of its common stock, or 19.9 percent of its outstanding common stock immediately prior to the transaction, in partial consideration for the rights granted to Curis under Copyright Cisbio Bioassays. All rights reserved. All trademarks are property of Cisbio Bioassays. CURIS MARCH 2015 | | DDNEWS 7 the collaboration agreement. The shares issued to Aurigene are subject to a lock-up agreement until Jan. 18, 2017, with a portion of the shares being released from the lockup in four equal biannual installments between now and that date. The agreement provides that the parties will collaborate exclusively in immuno-oncology for an initial period of approximately two years, with the option for Curis to extend the broad immuno-oncology exclusivity. DISCOVER AN EPIGENETICS ASSAY PORTFOLIO YOU’LL NEVER OUTGROW Curis has agreed to pay Aurigene up to $52.5 million per program for the first two programs, including $42.5 million per program for approval and commercial milestones, totaling $190 million. For the third and fourth programs, the figures are up to $50 million per program, including $42.5 million per program for approval and commercial milestones, and for any programs thereafter, up to $140.5 million per program, including $87.5 million per program in approval and commercial milestones. For all programs, there would also be specified approval milestone payments for additional indications, if any. Curis has agreed to pay Aurigene royalties on any net sales ranging from high single-digits to 10 percent in territories where it successfully commercializes products, and will also share in amounts that it receives from sublicensees depending upon the stage of development of the respective molecules. n EDITCONNECT: E031504 EPIgEnEous™ EPIgEnEtIcs AssAys. From universal to specific assays, biochemical to cell-based, no one gives you a broader range of tools to research enzymatic targets in epigenetics than Cisbio. 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For more information on our complete line or to discuss your specific custom requirements, please email us at [email protected] or visit www.htrf.com/epigenetic-screening www.cisbio.com DISCOVERY 8 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Optibrium integrates NextMove algorithm IMMUNO CONTINUED FROM PAGE 6 StarDrop software suite will incorporate Matsy algorithm, which generates and searches databases of matched molecular series BY ZACK ANCHORS technologies are widely used in drug discovery have announced a collaboration that could make it easier for scientists to quickly identify novel, active compounds based on matched molecular series analysis. Software developer Optibrium has announced that the latest version of its StarDrop software suite will feature an integration with NextMove Software’s Matsy algorithm, which generates and searches databases of matched molecular series to identify chemical substitutions that are most likely to improve target activity. “Both Optibrium and NextMove realized that Matsy and StarDrop were highly complementary and that a collaboration could bring additional benefits to our users,” Roger Sayle, NextMove CEO and founder, tells DDNews. StarDrop is a software platform used in the drug discovery process that was first launched in 2005, when it was a product of Inpharmatica. The core research group behind the technology has worked together since 2001 and founded Optibrium as a management buyout in 2009 to focus on its development. The primary function of the software is to facilitate multiparameter optimization, which involves guiding the identification of effective leads and assisting their transformation into candidate drugs with a high probability of success. The software features a highly visual and interactive interface designed to make it easy for all members of a project team to make decisions regarding CREDIT: OPTIBRIUM CAMBRIDGE, U.K.—Two companies whose Optibrium’s StarDrop is a software platform used in the drug discovery process that was first launched in 2005, when it was a product of Inpharmatica. It will now incorporate NextMove Software’s Matsy algorithm. compound selection and design. NextMove’s Matsy algorithm grew out of a collaboration last year with computational chemists at AstraZeneca that was designed to help researchers make more informed decisions during the lead optimization process. The goal of the project was to create a tool that would help medicinal chemists to identify which compounds to prioritize after they develop molecules and measure their biological activities. “Typically this decision is based on the medicinal chemist’s experience with related projects or based on their chemical intuition,” Sayle tells DDNews. “In contrast, TOOLS & TECHNOLOGY Matsy makes suggestions using a knowledge base of experimental data.” The data used by Matsy’s algorithm can include either a company’s own in-house database or a database such as ChEMBL that contains experimental data on molecules with drug-like properties extracted from published literature. “The advantage of this approach is that all predictions are backed by experimental results which can be viewed and assessed by the medicinal chemist when considering the predictions,” says Sayle. NextMove Software and Optibrium predict that integrating the Matsy technology with StarDrop will provide researchers more STARDROP CONTINUED ON PAGE 9 Versatility that goes with your flow Introducing the new Thermo Scientific™ Varioskan™ LUX Multimode Microplate Reader. Designed to provide optimal flexibility, reduce human error and deliver reproducible, trustworthy results. Varioskan LUX is equipped with a user-friendly interface, automatic dynamic range selection and smart safety controls that notify you of potential problems before they happen. So you can concentrate on your research, not your reader. The way it should be. We are on the same wavelength • Experience simplified versatility at thermoscientific.com/varioskanlux Varioskan LUX Multimode Microplate Reader © 2015 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries. against several types of cancer. “This new collaboration with one of the leading figures in immunocytokine research offers an exciting opportunity to develop new anticancer drug candidates,” Arkinstall commented. “Our world-beating antibody discovery technology will enable us to develop novel immunooncology drug candidates through leveraging the synergy of antibodies targeting cancer cells fused to selected cytokines localizing them to the tumor microenvironment. This in essence will give a ‘double-hit’ on cancer cells.” Some cytokines demonstrate antitumor activity, but as is the case with a number of chemotherapeutic drugs, their therapeutic potential is hampered by their toxicity. As explained on Provenance’s website, Gillies’ approach uses a whole antibody format, in which a cytokine is genetically fused to the end of an antibody-heavy chain. The effect this has depends on both the cytokine that is used and the type of immune cell, because “In some cases, the effect is similar to a bi-specific antibody when the cytokine acts as a trigger for an immune effector cell leading to direct tumor lysis, while in other cases it results in immune cell activation and proliferation of tumor-specific T cells that indirectly kill the tumor cells through their own recognition molecules (T cell receptors).” “The benefits of immunocytokine drugs is that they are able to leverage the well-known anticancer therapeutic activity of some cytokines (e.g. IL-2, IL-12) while at the same time, minimizing the toxic side effects of these cytokines through targeting their activity specifically to the tumor micro-environment,” Arkinstall explains. “It is believed that high therapeutic benefit may be achieved at significantly lower doses than is achieved with approved cytokine treatment regimens.” For its part, Kymab’s Kymouse technology can rapidly generate a range of fully human antibodies, offering highaffinity, candidate-quality molecules that require no further lead optimization since the molecules “are already optimized in vivo for affinity and biophysical properties,” the company website asserts. “Our search for new treatments drives us to seek the best opportunities to move research forward towards drug development,” Dr. Christian Grøndahl, outgoing CEO of Kymab, said in a press release. “This is a biology-based, genome-driven, rational program that will use the power of our understanding of the immune system’s ability to combat cancer and will feed new and exciting products into our pipeline.” “We are convinced that immunocytokine drugs, such as those emerging from our collaboration with Dr. Gillies, have the potential to be an important part of a new and varied armory of immuno-oncology-based treatments for cancer,” Arkinstall adds. n EDITCONNECT: E031506 For more information, visit www.DDN-News.com DISCOVERY MARCH 2015 | | DDNEWS 9 PEPTIDE peptide did in the experiments. “We don’t know if this will reverse or stop Parkinson’s,” Hannink adds. “That will need to be tested in animal models, as the next step. But the idea is that by switching from the PINK1/PARKIN pathway, which is defective in some forms of familial Parkinson’s, to the FUNDC1 pathway, it might be possible to bypass the defective pathway and activate a compensatory pathway.” Early-stage results of this research look promising, accord- CONTINUED FROM PAGE 6 STARDROP CONTINUED FROM PAGE 8 powerful capabilities as they search for the most promising chemical substitutions. Unlike the conventional approach of relying on matched molecular pair analysis, the Matsy algorithm uses data from longer series of matched compounds, rather than just pairs, to make more relevant predictions for a particular chemical series of interest. Matsy will be integrated into StarDrop through the software platform’s Nova module, which automatically generates new compound structures to stimulate the search for optimization strategies related to initial hit or lead compounds. The options that result from this process can then be analyzed using StarDrop’s capabilities for multiparameter optimization and predictive modeling so that highquality compounds with the best EDITCONNECT: E031505 3292R DSC XP2_3.375x10_Layout 1 5/2/14 9:34 AM Page 1 CREDIT: RANDY MERTENS, CAFNR The situation is what University of Missouri (MU) researcher Dr. Mark Hannink calls a “trash pickup problem,” as waste continues to be generated and not recycled or removed. Hannink, a professor in the MU Department of Biochemistry and an investigator at the university’s Bond Life Sciences Center, has discovered a molecule that could aid mitochondrial recycling and keep brain cells alive. This could help to develop drugs to keep brain cells healthy in individuals with Parkinson’s disease, as he reported in “A conserved motif mediates both multimer formulation and allosteric activation of phosphoglycerate mutase 5,” recently published in the Journal of Biological Chemistry. Peter Tipton, MU professor of biochemistry, and graduate students Jordan M. Wilkins and Cyrus McConnell contributed to the research. As Hannink explains, “Mitochondria eventually become damaged and no longer function properly, so the cell has a mechanism to recycle them, keeping them strong. If that recycling pathway doesn’t work, the defective mitochondria will build up and will disrupt cell physiology, ultimately causing that cell to die.” Parkinson’s disease is the clearest example of this recycling failure. “In early-onset Parkinson’s, mutated proteins ‘forget’ to recycle mitochondria, resulting in a buildup of toxic waste and early onset of the disease,” he says. “In our study, we found a peptide, or molecule, responsible for an alternative pathway that bypasses the mutant Parkinson’s proteins and allows mitochondrial recycling. We feel that this peptide could prove useful in fighting diseases in the brain.” He adds, “The process that I am ing to Hannink. If additional studies are successful within the next few years, MU officials will request authority from the federal government to begin human drug development. After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for Parkinson’s and other diseases. “Commercial potential is sheer speculation at this point,” Hannink concludes. n Pipet-Aid XP2 Dr. Mark Hannink and Kim Jasmer (pictured here in a University of Missouri photo from October 2014) worked to discover a molecule that treats oxidative stress and could lead to therapies for cancer, Alzheimer’s and Parkinson’s disease. In a more recent development, Hannink and colleagues have discovered a molecule that could aid mitochondrial recycling and keep brain cells alive in Parkinson’s patients. looking at is not repair of damaged mitochondria, but the removal/ disposal/degradation of damaged mitochondria. This alternative pathway for mitochondrial recycling uses a protein called phosphoglycerate mutase family member 5 (PGAM5). A peptide acts as a ‘switch’ to cause the protein to create an alternate pathway.” By regulating the protein with the peptide that Hannink discovered, it may be possible to restore mitochondrial recycling in neurons of patients with Parkinson’s, lessening the severity of the disease. He thinks that development of a drug based on the PGAM5 pathway could be useful in restoring mitochondrial recycling in certain cells, like neurons affected in Parkinson’s. while blocking this recycling pathchance of success are identified. Sayle tells DDNews that the integration of Matsy and Stardrop, which the companies began working on late last year, is progressing quickly. He expects a initial version of the technology to be available for demonstration at the American Chemical Society Spring National Meeting in March, followed by a release for users of StarDrop this year. The Matsy technology will initially be integrated into an updated version of StarDrop’s optional Nova module, providing all current users of the Nova module with access to the extended capabilities. Sayle says the partnership between his company and Optibrium could lead to further collaboration. “This is our first collaboration, and based on its success, we hope to identify further areas in which we can work together going forward,” Sayle says. NextMove, which was founded in 2010, offers a range of other chemoinformatics solutions for way in other cells, like cancer cells. “The PGAM5 protein would be regulated by an allosteric mechanism, in which its biological function would switch from activation of the PINK1/PARKIN pathway for removal of damaged mitochondria to the FUNDC1 pathway for removal of damaged mitochondria,” according to Hannink. “Peptides behave like drug molecules; any time you can identify a biological process that is regulated by a peptide, that peptide becomes a leading candidate in the search for small, drug-like molecules that will act the same way.” For Parkinson’s disease, the goal is to find ways to repair the mitochondria recycling process. The next step of the research is to produce a drug molecule that can regulate the PGAM5 protein in cells, just as the pharmaceutical and chemicals industries besides Matsy. The firm’s product portfolio includes LeadMine, a program used for extracting chemical names and terms from text such as patents; HazELNut, a suite of tools used to extract, normalize and analyze information in electronic lab notebooks; and Sugar & Splice, a technology used for perceiving, naming and depicting biopolymer structures. “We are delighted to announce our collaboration with NextMove Software, which has a proven track record of developing innovative informatics solutions for pharma companies worldwide,” said Matthew Segall, Optibrium’s CEO. “We remain committed to working with NextMove and our other partners to provide access to the leading compound optimization technologies through StarDrop’s unique environment that guides efficient discovery of novel, high-quality drugs.” n EDITCONNECT: E031507 ® Advanced Ergonomics for Working on a Bench Comfort The most comfortable pipettor you ever laid a hand on Convenience Uninterrupted extended operation Control Quiet precision pump responds instantly to the touch of the button Drummond Pipet-Aids have set the standard for making pipetting in the laboratory safer, easier, and more convenient. 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From the Developers of the Original Pipet-Aid® MADE IN USA 500 Parkway, Box 700 Broomall, PA 19008 10 DDNEWS | | MARCH 2015 EDITORIAL For more information, visit www.DDN-News.com Out with the broad and in with the rare A In what BIO says is a first-of-its-kind study on venture financing broken down by disease area DDNews’ managing editor, Lloyd and novelty of research over a 10-year period Dunlap, for his first editorial in from 2004 to 2013, encompassing $38 billion these pages, I decided to run a of venture capital into more than 1,200 U.S. drug companies that received more piece on a new report, than 2,000 rounds of funding, “The “Transforming Rare Disease Patients’ aim was to identify funding trends Lives Through Innovation” (both can for emerging drug developers within be found right next door on page 11) specific therapeutic areas and across to fill the remaining space, since varying levels of innovation,” said Dr. reports from industry organizations Cartier Esham, BIO’s executive vice are, in my mind, certainly a form of president of emerging companies. commentary themselves. Two findings that struck me were As I pondered what to write for that disease areas affecting large my own editorial this issue, I didn’t populations—diabetes, psychiatry, expect to be addressing a counter- Jeffrey Bouley, DDNews Chief Editor gastrointestinal, respiratory and point to what one would think would be only good news—after all, who doesn’t want cardiovascular—all have experienced a decline to see rare diseases get attention? And, besides, in novel drug R&D venture funding, while rare such treatments can be good business for phar- disease funding has seen a large increase over mas and biotechs because while the patient the past decade in terms of both dollars raised populations might be small, the price points for and number of companies funded. In an article about the report, San Francisrare disease therapeutics can be quite attractive. But a sort of counterpoint I did get, when by co Business Times reporter Ron Leuty quoted chance I stumbled upon the very recent “Ven- OncoMed Pharmaceuticals Inc. President and ture Funding of Therapeutic Innovation” report CEO Paul Hastings as saying venture capitalists from the Biotechnology Industry Organization are more likely to invest in companies develop(BIO) that talks about venture funding and ing orphan disease treatments or cancer treatwhere it is—and isn’t—going these days. Appar- ments because those disease areas have wellently, rare diseases are getting the shine right tested pathways and are relative easy targets now, and diseases that affect large populations compared to more general ailments that require very large clinical trials and longitudinal studies. are not. BY JEFFREY BOULEY H, SERENDIPITY. As we bring out It would be easy to look at Hastings’ statement and say, “Of course; makes sense.” But he’s not simply talking about a longstanding venture capital preference. Because what BIO has tracked is a trend toward the niche and away from the broad. This is certainly not alarming to me by any means. While venture capital is important in any market, and perhaps pharma and biotech more than many, there are plenty of established companies working on plenty of treatments and vaccines for common diseases. And even with flat funding and cuts over the years in government support and financial challenges for foundations, academic institutions get many grants for innovative life-sciences research. But at the same time, one of the other things we’ve seen over recent years is a tightening of the belts even in Big Pharma, and a resulting constriction of R&D spending. So, increasingly, some of the most interesting innovation we see in big companies comes by way of smaller companies they’ve partnered with or acquired— companies that might not have existed at all without venture funding. No, I’m not worried about a significant decline in therapeutics for large-population disease areas. But I do feel a twinge of regret that for the “attractive” needs of the few, the more “banal” needs of the many may miss out on some innovative treatment solutions in the coming years. n www.DDN-News.com PUBLISHER Bruce Poorman [email protected] ASSOCIATE PUBLISHER Laurence Doyle [email protected] EDITORIAL Jeffrey Bouley, Chief Editor [email protected] Lloyd Dunlap, Managing Editor [email protected] Kelsey Kaustinen, Senior Editor [email protected] FEATURES EDITOR Randall C Willis CONTRIBUTING EDITORS Zack Anchors, Jim Cirigliano, Lori Lesko, Ilene Schneider, Mel J. Yeates ADVERTISING NORTHEAST Michael Stack 1127 Kristin Drive, Suite 100 Libertyville, IL 60048 847.922.1799 TEL [email protected] MIDWEST/MIDATLANTIC Ryan King 1900 N. Hudson, #D Chicago, IL 60614 773.414.9292 TEL [email protected] NORTHWEST/SOUTHWEST OUT OF ORDER: THE VACCINE DE-BAIT C BY RANDALL C WILLIS AN WE PLEASE STOP CALLING THE vaccine controversy a debate? This is not a debate. This is two groups of people standing atop their personal mountains throwing unpleasant epithets and “evidence” at each other. On one mountain, you have scientists and healthcare specialists throwing out statistics and medical jargon and epidemiology. On the other mountain, you have vaccine-cautioners showing photographs of sick vaccinated children (and correlating the two adjectives) and demands for individual freedoms and the defense of their child from potential harm. Both sides are adamant about the absolute truth of their positions, and therefore, there is Unfortunately, the Western world has become incredibly risk-adverse and benefit-demanding, and this is where the statistical nature of science and healthcare runs up against the individual nature of health. no point in discussion. The other side is either willfully stupid or lying to push forward an agenda, so there is no point in discussion. Unfortunately, I think if an actual debate was held and, say, televised, science and healthcare might come out with the short end of the stick. Please note, before you read on, that I am provaccination (although please do not ask me the last hear all the statistics they want, time I was vaccinated for anything, but show them a single photo of a including the flu). harmed child, and I can guarantee It’s not that the facts aren’t what direction they will lean. Having there. It is rather that the facts are worked in medical marketing, I have largely indirect and require certain seen it time and again. assumptions. “National measles vaccination proUnlike pretty much every other grams effectively eradicated measles category of therapeutic, patients do in Canada and the United States,” a not get better (e.g., an existing dishealth policy advocate may argue, but ease condition relapses or is cured) what does that really mean to a young when they are vaccinated, but rather, Randall C Willis parent with no exposure (apologies) they do not get sick. Or at least, we assume they did not get the disease because they to measles. I’m 51 years old and I have never seen were vaccinated. All we can truly measure is that anyone with measles who was more than itchy they produced antibodies against the infectious and miserable. In a recent commentary in The Toronto Star, organism. True placebo-controlled experiments would be unethical and might take decades to University of Toronto respirologist Sami Gupta discussed the current vaccination challenge. show statistical advantage. “Studies show that didactic repetition of facts Ah, but what about population statistics that show how the introduction of widespread vac- just doesn’t change behavior, and that our topcination led to large-scale reductions in the inci- down and adversarial approach further polarizes dence of the disease? I am woefully ignorant of communities and actually alienates parents.” My marketing experiences suggest his comstatistics (really should be better at them, but alas), but I don’t know that we can prove causa- ment is correct, but I also don’t think it goes tion here, only be overwhelmed by the correla- far enough. We talked about the idea of disease prevention (please correct me, if I am wrong). And leaving aside any conversation about tion, but tended to gloss over the low-but-notautism (which I believe is baseless), the fact is zero risks of adverse events. Then, when the very that all vaccines (as with all therapeutics) are rare adverse event does occur, usually with a associated with experienced adverse events photo of a forlorn child, we are caught in a sin (actual events, not just the risk of the event). of omission. We talked about the power of herd immunity While the rates of most of these events are incredibly low, they are not zero. That is the and are now seeing that used as ammunition nature of the risk-benefit analysis for any thera- against the vaccination of individuals. “If everyone else’s child is immunized, why should mine peutic decision. Unfortunately, the Western world has become have to be?” Unfortunately, because of the unique format of incredibly risk-adverse and benefit-demanding, and this is where the statistical nature of sci- vaccines, I think we have to “stoop” to the level of ence and healthcare runs up against the indi- the other side and focus on the risks of not vacvidual nature of health. A mother or father can ORDER CONTINUED ON PAGE 11 Kayte Miller 8124 Cantershire Way Granite Bay, CA 95746 510.759.7529 TEL [email protected] EUROPE, AFRICA, ASIA Stephanie Painter Painter-Lowe Communications [email protected] www.painter-lowe.com +44 1634 829386 TEL +44 1622 690302 FAX MARKETING Laurence Doyle 610.619.3568 TEL 610.450.4906 FAX [email protected] PRODUCTION John O’Brien [email protected] 207.865.9908 TEL OPERATIONS Margaret Gorsline, Manager [email protected] 440.331.6600 TEL 440.331.7563 FAX REPRINTS Chris West [email protected] READER SERVICES ICN, Inc. 2900 New Rodgers Road, Bristol, PA 19007 215.785.5196 TEL 19035 Old Detroit Road #203 Rocky River, OH 44116 440.331.6600 TEL 440.331.7563 FAX PRESIDENT Bruce Poorman EXECUTIVE VICE PRESIDENT Laurence Doyle Bio-Ohio Membership Application to Mail at Periodicals Postage Rates is at Cleveland, OH 44101-9603 For more information, visit www.DDN-News.com EDITORIAL MARCH 2015 | | DDNEWS 11 COMMENTARY: Candy Land, opioid addiction and help that’s on its way R BY LLOYD DUNLAP ECENTLY, I discovered that a Veteran’s Administration hospital (can’t they do anything right?) in Wisconsin has experienced a fourfold increase in opioid use between 2005 and 2012 and earned the nickname Candy Land as a result. Since I had just been assigned the task of writing this, my first editorial for DDNews, and had covered the subject of opioid addiction for our Feb. Q&A feature, I thought I would look into the issue further. As Mark Sirgo, president and CEO of BioDelivery Sciences Inc. told our readers in the Q&A, there are more than two million people in the United States who were dependent on opioids as of 2012, according to the National Institute on Drug Abuse. There are five different classes: 1) heroin, which has no medical value; 2) morphine, oxycodon and hydrocodone; 3) buprenorphine, which is both an agonist and antagonist and exhibits a low propensity to develop a “high” or craving; 4) antianxities such as diazepam and alprazolam; and finally, 5) cough syrup ties. The low abuse with codeine. Sirgo’s potential of the new company has developed molecule may open new a buccal patch that avenues for the treatallows buprenorphine ment of neuropathic to be easily and quickly pain, a chronic pain absorbed to enhance condition that can affect bioavailability and people after a stroke or patient compliance. with multiple sclerosis, Dr. Eliseo Salinas HIV infection, diabetes notes that Relmada Lloyd Dunlap, DDNews and other conditions. Managing Editor Therapeutics, where LevoCap ER: The he is president and chief sci- Relmada research team is working entific officer, has four pain meds to develop an extended-release, in the pipeline—one of which is tamper-resistant form of levorpbuprenorphin—that collectively hanol for the treatment of chronic reflect a diverse range of reformu- pain when an opioid is needed. lation and repositioning strategies. Stronger than morphine, it was Their efforts are targeting impro- created as its alternative more than ved efficacy as well as reduced risk 40 years ago. There is great demand of abuse and new drug delivery for extended-release formulations technologies. Here’s an “executive for pain due to limited availability summary” as Salinas describes it: in the market today. d-Methadone: Researchers at MepiGel: Here they are working Relmada have identified a process on a reformulation of the local anewhere they can separate out the “d” sthetic mepivacaine for the treatfrom the “l” isomer in methadone, ment of neuropathic pain (postheran NMDA (N-methyl D-aspartate) petic neuralgia and HIV-associated agonist, to create a new molecule neuropathy). MepiGel is a topical with the benefits of methadone that formulation that has U.S. Food and may not have the addictive proper- Drug Administration Orphan Drug designation. As a topical formulation, it may provide greater ease of use and efficacy (skin penetration) for those with neuropathic pain. There are no other topical gel dosage forms for a local anesthetic for the treatment of neuropathic pain available today. BuTab ER: Here the team is working to develop an oral dosage form of the opioid analgesic buprenorphine with modified release and improved oral bioavailability. All other forms of buprenorphine are either injected, use a patch or are sublingual, so a successful repositioning of this compound may make this the first tablet available. Timothy Lepak is president and cofounder of the National Alliance of Advocates for Buprenorphine (NAABT), which is responsible for www.treatmentmatch.org that claims to have matched a total of more than 82,000 patients with 28,000 doctors nationwide, only about 10,000 of whom actually prescribe, he tells DDNews. The NAABT Patient/Physician Matching System is a centralized list of patients from which certified physicians can draw A decade of notable progress against rare diseases WASHINGTON, D.C.—The Phar- maceutical Research and Manufacturers of America (PhRMA) released on Feb. 25 a new report, “A Decade of Innovation in Rare Diseases,” to document the significant progress made in the last 10 years in understanding a broad range of rare diseases and translating this knowledge into groundbreaking therapies for a variety of patient populations. The report illustrates that more than 230 new medicines to treat rare, or orphan, diseases were approved by the U.S. Food and Drug Administration in the last decade, and there are currently more than 450 orphan drugs in development. It also explores significant treatment advances seen over the past decade in five rare diseases which have led to improvements in patient survival and quality of life: chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), pulmonary arterial hypertension (PAH), hereditary angioedema (HAE) and cystic fibrosis (CF). Furthermore, the report spotlights additional rare conditions where major milestones transformed treatment—including several in which first-ever treatment options have become available to patients. Key findings include: Targeted therapies can now effectively treat many of the recently identified mutated forms of CML and allow for treatment plans tailored to each patient’s particular genetic profile. Novel targeted therapies treat the root cause of CLL, resulting in lasting remissions and new treatment options for even the sickest patients. New treatments go beyond symptom management to treat the underlying cause of PAH, allowing patients to maintain active lifestyles with reduced risk of serious heart events. New discoveries in the underlying cause of HAE have led to breakthroughs in both preventative and acute treatment options for patients, including those targeting the root cause of the disease. CF patients now have new treatment options allowing for better management of symptoms, as well as a new option which allows many to target the ■■ ■■ ■■ ■■ ■■ underlying cause of their disease. If mortality rates continue to decline, patients may now hope to live into their 50s. “Rare diseases are one of the most scientifically complex health challenges we face,” said PhRMA President and CEO John J. Castellani. “Over the last 10 years, biopharmaceutical researchers have leveraged cutting-edge technologies and dramatically expanded our understanding of rare diseases to develop new therapies for chronic myelogenous leukemia, cystic fibrosis and other diseases which often impact very small patient populations. We continue to work toward options for rare disease patients, where there may currently be few or no treatments available.” The new report was released ahead of Rare Disease Day, which was celebrated Feb. 28, 2015. The day is an opportunity for the international rare disease community—including academia, patient advocacy groups, pharmaceutical and biotechnology companies, research and regulatory government agencies—to collectively educate and raise awareness about rare diseases and their impact on the lives of patients and their families. Thirty million Americans, about one in 10, and an estimated 350 million people worldwide are currently living with a rare disease, which is defined as a condition that affects fewer than 200,000 people. There are currently 7,000 known rare diseases, and approximately 80 percent are caused by genetic abnormalities. However, despite incredible progress made against rare disease in recent years, only 5 percent have available treatment options. While there remains a significant need to develop new medicines for patients, this is a challenging endeavor, PhRMA notes. Rare diseases are often complex, and the underlying biological mechanisms that cause them are not always well understood. Nevertheless, researchers continue to build on recent breakthroughs and are dedicated to bringing new medicines to patients. With more than 450 medicines in development to treat rare disease, the promise has never been greater for patients. n when they have an opening. Ideally, when a patient decides he or she needs treatment, a phone call is made to a physician on the “Find a Certified Physician” list, and the patient gets an immediate appointment and is treated the next day. However, there is a limit on how many patients a doctor can treat, which began at 30 per year in year one and is now 100. The law specifies that there must be three societies who train physicians, but Lepak points out that the training is a mere eight hours. The transition to buprenorphine goes quickly, Lepak notes and can be accomplished in only a few days. “We’re not switching one addiction for another,” he states. “It allows people to get their lives back.” As with many mental health issues, there is help for those who have the pluck to reach out for it. And the research reported on here indicates more help is on its way. But if you persist, figuratively speaking, in squeezing the trigger on your morphine drip too often, you may wind up like many of the patients in Candy Land. n ORDER CONTINUED FROM PAGE 10 cinating, at a personal level. No more statistics, no more history lessons, but rather anecdotes and photos of people with the infectious diseases. Yes, it is fear-mongering, but if we are honest about our own limitations, then it is at least balanced fear-mongering and is a starting point for a conversation rather than a shouting match. Later tonight (as I write this column), the Canadian television news program The National is convening a panel to discuss the current vaccine conversation. I will be intrigued to see if they actually include a so-called “anti-vaxxer” on the panel to make this a true debate, or if it will be a panel of like-minded healthcare specialists espousing the official line—the “didactic repetition of facts” about which Gupta warned. [Added note: The only place I have seen an actual debate on this topic was on The Nightly Show with Larry Wilmore on Comedy Central, which included a vaccine-cautioner on its panel. Read into that what you will.] n The opinions expressed in guest commentaries do not necessarily represent those of DDNews and/or its owners, editors or other staff. 12 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com RESEARCH & DEVELOPMENT STEVENAGE, U.K.—Plasticell got a boost in early February with a grant of approximately £1.3 million (roughly $1.5 million) from Innovate UK. The grant is for a research consortium—one led by Plasticell that also includes the University of Oxford and the Cell Therapy Catapult—for a project titled “Exvivo expansion of cord blood and bone marrow stem cells.” Plasticell’s CombiCult has been tested with millions of combinations of cell culture components to develop cord blood expansion media that can amplify stem cells up to a hundredfold, and the grant will enable the development of a clinically compliant process to expand cord blood stem cells ex vivo via Plasticell’s media. Cornell researchers create new computational method ITHACA, N.Y.—Scientists from Cornell University have developed a computational method that can identify positions in the human genome that play a role in the proper functioning of cells, and that work was published in Nature Genetics Jan. 19. The new method utilizes two existing techniques to identify selective pressure: one that looks for divergences between human and chimpanzee genomes, and another that looks for polymorphisms between individual humans. The new method clusters functionally similar genome markers into groups, then estimates the probability of that group contributing to the fitness of the species based on associated patterns of divergence and genomic polymorphisms. This generates a “fitness consequence” (fitCons) score that predicts the genetic material that may be under selective pressure and biologically significant. Reportedly, fitCons scores have a much greater power to predict genetic material that regulates gene expression compared to existing methods. IN THIS SECTION Antibody-drug conjugates Catalent, Sanofi collaborate on SMARTag, ADCs...................................... 14 Antibiotic resistance New ammo in arms race against antibiotic resistance................... 12 Genomics Agilent tool enhances integrity of genomics experiments........................ 16 Cornell researchers create new computational method.................... 12 Oncology Taming the tsunami................................. 12 Stem cells Plasticell awarded £1.3M from Innovate UK..................................... 12 Tissue culturing Onward and upward with organoids....... 12 Taming the tsunami Onward and upward with organoids UCSD, UCSF launch Cancer Cell Mapping Initiative BY ILENE SCHNEIDER SAN FRANCISCO & SAN DIEGO—The Univer- sity of California, San Diego (UCSD) School of Medicine and University of California, San Francisco (UCSF), with support from a diverse team of collaborators, have launched an ambitious new project that may last 20 years and could make personalized medicine a practical reality. The Cancer Cell Map Initiative (CCMI) has been created to determine how all of the components of a cancer cell interact. It was motivated by the “tsunami of genomic information available” in recent years, but the inability to make sense of it, according to Dr. Nevan Krogan, director of the UCSF division of life-sciences research institute and accelerator QB3 and an investigator at Gladstone Institutes. Krogan is also co-director of the CCMI with Dr. Trey Ideker, chief of medical genetics in UCSD’s Department of Medicine and founder of the UC San Diego Center for Computational Biology & Bioinformatics. CCMI CONTINUED ON PAGE 13 Culturing techniques for liver and pancreas organoids can mirror disease, cancerous states BY KELSEY KAUSTINEN Institutes of Health (NIH) that will assist the researchers in developing new and improved tools for studying the formation and structure of cell walls in bacteria, a line of resea- UTRECHT, The Netherlands— The promise of lab-grown tissues, especially organs, has captivated scientists to a large degree over the years. Model organs, also known as organoids, could offer a variety of potential uses: they can enable researchers to more accurately Prof. Hans Clevers, test the toxic- professor of ity of compounds molecular genetics before risking at the Hubrecht participants in Institute/UMC human trials, Utrecht, and colleagues recently allow closer study announced the of disease pro- development of a gression and pos- culturing system sibly represent a for liver stem cells new solution to and stem cells the great need for from pancreatic transplant organs. cancer. And a pair of papers featuring research out of the Hubrecht Institute and University Medical Center Utrecht (UMC Utrecht) could offer a new avenue for exploring that potential. This research began several years ago when, in 2009, a research group led by Prof. Hans Clevers, professor of molecular genetics at the Hubrecht Institute/UMC Utrecht and president of the Royal Dutch Academy of Arts and Sciences, detailed a revolutionary culturing method that enabled the culturing of mini-guts from single mouse intestine stem cells. The organoids are functional miniature organs that can be grown in tissue culture. That same group of researchers has now announced the development of a culturing system for liver stem cells and stem cells from pancreatic cancer. Both sets of research appeared recently in Cell. The culturing system for liver INDIANA CONTINUED ON PAGE 14 HUBRECHT CONTINUED ON PAGE 15 CREDIT: DANIELLE SWANEY Plasticell awarded £1.3M from Innovate UK Induced pluripotent stem cells from the Krogan lab are pictured here. One goal of the CCMI is to make cancer-related mutations in iPS cells and see how the protein interaction networks change as the cells differentiate. CREDIT: INDIANA UNIVERSITY BRIEFS Indiana University researchers will use $3.3 million from the National Institutes of Health to embark on a four-year effort to develop improved tools for studying the formation and structure of cell walls in bacteria and combat antibiotic resistance. New ammo in the arms race against antibiotic resistance NIH provides grant to Indiana University to build knowledge base about key bacterial cell processes BY JIM CIRIGLIANO BLOOMINGTON, Ind.—A team of chemists and microbiologists at Indiana University (IU) announced earlier this year that it will receive a $3.3-million grant from the National RESEARCH & DEVELOPMENT For more information, visit www.DDN-News.com CCMI CONTINUED FROM PAGE 12 “We’re going to draw the complete wiring diagram of a cancer cell,” Krogan explains. “We’re going to use network biology to make sense of genomic data, make physical maps of proteins and genes and introduce mutations to see how functions are perturbed.” While progress in genome sequencing enables researchers to decipher hundreds of mutations found in a patient’s tumor, scientists rarely understand how these mutations cause cancer or indicate treatment plans. Mutations in each patient are usually different, but they can lead to the same type of cancer. Inasmuch as these mutations are unique to individuals, they attack the same cancer pathways or genetic circuits. The complete wiring diagram of the cell will establish all of the connections between normal and mutated genes and proteins. “We have the genomic information already. The bottleneck is how to interpret the cancer genomes,” says Ideker. A comprehensive map of cancer cells would help—and accelerate the development of personalized therapy, the central aim of what has come to be called precision medicine. This process, according to Ideker, “will enable applications to start with the genome, identify the genes, determine their interactions and use the information for personalized treatment.” Krogan adds, “The key to understanding genomic information is being able to place it into biological context. Mutations in tumor DNA that at first appear to be unrelated may in fact be clustered in specific pathways or multiprotein machines in the cell. The information, in context, will point to areas that we can target with specific therapies.” The CCMI is a multimillion-dollar collaboration between the UC San Diego Moores Cancer Center and the UCSF Helen Diller Family Comprehensive Cancer Center, funded by QB3 at UCSF, UC San Diego Health Sciences and support from Fred Luddy, founder of ServiceNow, a provider of enterprise service management software. Thermo Fisher Scientific is providing mass spectrometers to characterize protein-protein interactions. The project combines UCSD’s expertise in extracting knowledge from big biomedical data sets with advances developed at UCSF for experimentally interrogating the structure and function of cells. Both schools have two comprehensive cancer centers with samples that constitute a library of mutations associated with the disease. Actual patients with cancer and the stories contained within their DNA will drive the project, according to the researchers. UCSD’s primary mission will be to provide tools for network generation and integrate them into the project to visualize the effects of mutations on cells. UCSF will contribute its ability to generate pluripotent stem cells and its expertise in genetic engineering. Additionally, the CCMI will provide key infrastructure for the recently announced alliance between UC San Diego Health Sciences and San Diego-based Human Longevity Inc., which plans to generate thousands of tumor genomes from UC San Diego cancer patients. It will also leverage resources and information from the National Cancer Institute (NCI), including large databases of cancer genomes and pathways that are being developed in collaboration with the San Diego Supercomputer Center and UC Santa Cruz. David Haussler, director of QB3 at UC Santa Cruz and creator of the NCI Cancer Genomics Browser, said, “This is an exciting opportunity to utilize the unique NCI MARCH 2015 | | DDNEWS 13 repository of 1.5 petabytes of cancer genomics data, combined with proteomic and functional data, to dive deeper into the molecular processes of cancer.” For the near term, CCMI will compare healthy cells to tumor cells to see how treatments work on various mutations. Researchers will simplify the procedure to find three or four pathways to tailor a particular treatment, not treat patients with a drug that has an effect on everything. Initially, CCMI will focus on breast and HPV cancer, including head and neck and cervical cancers, and then address subcategories. Eventually, the researchers hope to use genomics to look at other diseases. “Eventually, patients will be able to go to their doctors and get genome sequences that will interpret the diagnosis of diseases and suggest a path to the cure,” Krogan concluded. “The specific goal is personalized medicine.” n EDITCONNECT: E031508 Introducing HIGHEST QUALITY PRODUCT PORTFOLIO Proteins Small Molecules Stem Cell Products Antibodies Proteome Profiler Arrays ™ ELISAs Luminex ® TRUSTED GLOBAL BRANDS [email protected] [email protected] North America Europe ● Middle East ● Africa TEL 800 343 7475 TEL +44 (0)1235 529449 China [email protected] TEL +86 (21) 52380373 Rest of World bio-techne.com/find-us/distributors TEL +1 612 379 2956 Bio-Techne is a trading name for R&D Systems BT_Ad_bubbles_DDN 9/18/2014 RESEARCH & DEVELOPMENT 14 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com BY LORI LESKO SOMERSET, N.J.—Catal- president of Advanced Delivery Technologies, stated in a news release. “Through invivo toxicology studies, we have demonstrated that ADCs generated using Catalent’s SMARTag platform have a better toxicity profile than a conventional ADC, while efficacy studies also point to an improved therapeutic index. We look forward to partnering with Sanofi to support the development of their next generation of ADC products.” “Catalent has been in discussions with a number of potential partners on the SMARTag platform, and partner interest has continued to grow based on continued strong data,” Michael Riley, vice president and general manager of Catalent Biologics, tells DDNews. “Sanofi will now have the ability to leverage SMARTag to optimize their ADCs in development.” “Our goal with the SMARTag technology is to partner with leading ADC developers to help them commercialize their next generation of products,” Riley continues. “This agreement provides the opportunity to leverage our technology with a leader in the industry, with the ultimate goal of helping Sanofi to get TOOLS & TECHNOLOGY ent Pharma Solutions and Paris-based pharma giant Sanofi have launched a joint venture to develop Sanofi’s proprietary antibodies using Catalent’s SMARTag antibody drug conjugate (ADC) platform. Catalent’s precision protein-chemical engineering technology will enable Sanofi to evaluate site-selective payload conjugation to enhance ADC pharmacokinetics, efficacy and safety. The financial terms were not disclosed. Sanofi teams will be carrying out the joint research at Catalent’s facility in Emeryville, Calif., formerly headquarters to Redwood Bioscience Inc., according to Catalent. In October 2014, Catalent announced the purchase of the remaining stake in Redwood Bioscience after invivo and in-vitro proof-of-concept milestones were achieved and an improved toxicity profile was demonstrated with SMARTag ADCs compared with conventional ADCs. “We are pleased to enter this agreement with Sanofi as we jointly work toward the goal of creating better drugs to meet patient needs,” Barry Littlejohns, Catalent’s INDIANA CONTINUED FROM PAGE 12 rch with the potential to uncover a multitude of targets for new compounds to combat strains of bacteria that have become resistant to existing antibiotics. IU’s Clyde Culbertson Professor of Biology Dr. Yves Brun and associate professor of chemistry Dr. Michael VanNieuwenhze, two of the co-authors of the grant proposal, also led an IU team in 2012 that discovered a nanoscale, fluorescent chemical probe that pinpoints where bacterial cells build a compound called peptidoglycan (PG), which is a mesh-like polymer that gives shape and structure to cell walls. The grant will allow principal investigators Brun, VanNieuwenhze and IU professor of biology Dr. Malcolm Winkler to undertake a four-year project to improve upon previously discovered methods of investigating the peptidoglycan building process. Co-investigators for the research will be associate professor of biology Daniel Kearns, chemistry professor Stephen Jacobson and associate professor of biology Sidney Shaw. The grant will also allow the team to hire eight to 10 additional research personnel and purchase the necessary reagents and lab supplies for the proposed research. The research will consist of three main facets: creating a second-generation probe that will improve upon the probe discovered in 2012, testing two long-standing hypotheses about PG synthesis in ovoid bacteria (Streptococcus pneumoniae), and systematically screening for genes responsible for key functions of PG dynamics and coordination in model species Escherichia coli and Bacillus subtilis. The improved probes will be designed to observe PG synthesis in action, capturing imaging of PG construction in E. coli and B. subtilis in greater resolution than previously possible, and in real time. The probes are called FDAAs for the fluorescent D-amino acids that are used. “We will synthesize probes with a variety of properties (e.g. sizes, colors) with the emphasis on improved brightness and photostability,” says Brun. “These improved properties will enhance the utility of these probes in microscopy applications to analyze the dynamics of PG synthesis.” Using the newly optimized probes in concert with the existing ones, the team will analyze the mechanisms of PG dynamics in bacterial model systems for two better ADCs to market.” The SMARTag platform “provides precise payload positioning and defined stoichiometry of payload-protein ratios,” he adds. “The control afforded by the technology enables identification of superior drugs from libraries of differentially designed conjugates. While many in the industry have recognized the benefits of ‘site-specific’ technologies to create homogeneous ADCs, a key differentiator of the SMARTag system vs. most other available ADC technologies is the ability to specifically select the site [or sites] of conjugation on the antibody.” “Our studies have shown that varying this site of payload conjugation can have measurable impact on ADC performance,” he explains. “By offering partners the ability to test multiple conjugation sites on a given antibody, the SMARTag system allows for ADC optimization that is analogous to a structureactivity relationship study traditionally used in small-molecule development.” According to Amy Ba of Sanofi’s global R&D communications, “Sanofi has been evaluating the site-specific conjugation field, and the SMARTag platform is one of several that we have been evaluating.” “Sanofi has a strong commitment to the field of oncology and evaluADC CONTINUED ON PAGE 16 Sanofi maintains that it has a strong commitment to the field of oncology and that it sees antibody-drug conjugates as a potential solution to improve the lives of cancer patients. MICHAEL BOERSMA—INDIANA UNIVERSITY Catalent’s tech will help Sanofi evaluate site-selective payload conjugation to enhance ADC PK, efficacy and safety CREDIT: SANOFI Catalent, Sanofi collaborate on SMARTag, ADCs Regions of active cell wall synthesis shown by high-resolution imaging of the bacterial pathogen Streptococcus pneumoniae. Long-term labeling is revealed with blue FDAA and short-time labeling with red FDAA. different cell shapes and two cell envelope architectures. “We will test two major longstanding hypotheses about the spatiotemporal coordination of the elongation and the division PG synthesis machineries and about the coordination between PG hydrolysis and synthesis in the major model for ovoid-shaped cells, the pathogen S. pneumonia,” says Brun. “We will also analyze PG spatiotemporal dynamics at super-resolution for the major model species for rodshaped gram-negative bacteria with a thin layer of PG (E. coli) and for rod-shaped gram-positive bacteria with a thick layer of PG (B. subtilis).” Finally, the team will take advantage of high-throughput screening technology and extensive genetic data relating to these model bacteria species to randomly and systematically screen for genes that may be involved in PG dynamics and coordination in bacterial cell walls. “We will further take advantage of our recent development of a high-throughput microscopy screening platform, the availability of a comprehensive strain collection in which each gene has been separately deleted and the powerful genetics of both species,” says Brun. The goal of this multifaceted approach is to identify the core principles of PG dynamics and how they can be modified to yield different outcomes in dynamics, cell shape, and cell envelope architecture. Understanding PG synthesis can lead to new treatments and targets for new antibiotics active across diverse bacterial groups, including antibiotic-resistant strains. “At the end of the funding period, we expect that we will have generated a powerful and unprecedented pipeline for the high-throughput isolation of loss-of-function mutants and conditional alleles defective in PG synthesis, and for the single-cell quantitative analysis of their effect on PG spatiotemporal dynamics,” says Brun. “Not only will we gain insight onto the molecular mechanism of PG synthesis and dynamics in well-established model organisms, but the pipeline can be applied to any bacterial species, including pathogens, limited only by the ability to be grown in the laboratory.” Widely considered an emerging and urgent health threat worldwide, antibiotic-resistant bacteria affect more than 2 million Americans each year. n EDITCONNECT: E031509 For more information, visit www.DDN-News.com HUBRECHT CONTINUED FROM PAGE 12 stem cells is detailed in the paper “Long-Term Culture of GenomeStable Bipotent Stem Cells from Adult Human Liver,” specifically the conditions that allow “longterm expansion of adult bile ductderived bipotent progenitor cells from human liver.” The paper notes that the expanded cells are highly stable at both the chromosome and structural levels, and the cells “can readily be converted into functional hepatocytes in vitro and, upon transplantation, in vivo.” The resulting organoids grown from cells from patients with α1-antitrypsin deficiency and Alagille syndrome— an inherited disorder that can lead to liver disease and/or cirrhosis and a genetic disorder characterized by liver damage due to abnormalities in the bile ducts, respectively— accurately represent the in-vivo pathology of the disorders. This approach, which enables long-term replication of harvested liver tissue, makes it possible to culture the equivalent of a full-grown liver from a single liver cell over the course of four months, and the cultured tissue is genetically similar to healthy liver tissue and very stable. Human “mini-livers” cultured in the lab have been successfully transplanted into mouse models with liver damage. The second paper, “Organoid Models of Human and Mouse Ductal Pancreatic Cancer,” details the team’s development of a technology enabling long-term laboratory culturing of healthy and diseased pancreatic stem cells. The work was co-led by Clevers and Dr. David Tuveson, professor at Cold Spring Harbor Laboratory (CSHL) and director of research for The Lustgarten Foundation. Culturing either healthy or cancerous pancreatic cells in the lab has failed in the past, in part due to the fact that the normal ductal cells that can become cancerous represent about 10 percent of the cells in the pancreas. The organoids generated from this culturing method consist entirely of ductal cells, excluding the other cell types that can contaminate pancreas samples. The organoids are grown as hollow spheres in a gel-like substance full of growth-inducing factors and connecting fibers, and once grown, they can be transplanted back into mice, where they accurately duplicate pancreatic cancer. As noted in the paper, these organoids “can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease-stagespecific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas.” RESEARCH & DEVELOPMENT “We can now rapidly generate organoids from any patient, which offers us the potential to study the disease in a much wider population.” Dr. Dannielle Engle of Cold Spring Harbor Laboratory “We now have a model for each stage in the progression of the disease,” said Dr. Chang-Il Hwang, one of the lead authors of the second paper working in The Lustgarten Foundation’s Pancreatic Cancer Research Lab at CSHL directed by Tuveson. Dr. Dannielle Engle of CSHL, another lead author of the “Organoid Models” paper, added that while biopsies are the current standard for cancer diagnosis, “We can now rapidly generate organoids from any patient, which offers us the potential to study the disease in a much wider population.” The researchers found that thanks to this method, the tumor tissue samples from individual patients can be tested to determine MARCH 2015 | | DDNEWS 15 their sensitivity or resistance to different cancer drugs. The technology was also used to create a ‘Living Biobank’ of cultured pancreatic tumors from a large group of patients with pancreatic tumors, which was established with support from the Dutch Cancer Society/Stand up to Cancer. The biobank is open to cancer researchers and companies worldwide to aid in the development of new drugs and therapies for cancer. n EDITCONNECT: E031510 Reach your full potential… …with ATCC® iPSCs • Diverseethnic,gender,anddiseasestates • Pre-configuredall-in-onestartupkit • Modelsfordrugdiscovery,tissuerepair,anddiseasepathogenesis ProducethecellsyouneedusingATCC®iPSCresearchtools www.atcc.org/ipsc MeetATCCscientistsatBooth#2207duringAACRAnnualMeeting2015. ©2015AmericanTypeCultureCollection.TheATCCtrademarkandtradename,andanyothertrademarkslistedinthispublicationaretrademarksownedbytheAmerican TypeCultureCollectionunlessindicatedotherwise.ATCCproductsareintendedforlaboratoryresearchonly.Theyarenotintendedforuseinhumans,animals,ordiagnostics. RESEARCH & DEVELOPMENT 16 DDNEWS | | MARCH 2015 Agilent tool enhances integrity of genomics experiments SANTA CLARA, Calif.—This winter saw the announcement by Agilent Technologies Inc. that it would aid those conducting genomics experiments to “enhance integrity” by helping ensure quality of tissue samples. That aid comes by way of the addition of a new feature to Agilent’s Genomic DNA ScreenTape assay—the DNA Integrity Number (DIN). The feature is designed to ensure the quality of genomics experiments generally, but especially next-generation sequencing (NGS). It reportedly builds on Agilent’s technology for assessing the integrity of RNA—the RNA Integrity Number, which Agilent describes as having “become a market-leading standard.” With the new software feature, the Agil- A new feature of Agilent’s Genomic DNA ScreenTape assay—the DNA Integrity Number—is designed to ensure the integrity of genomic DNA. CREDIT: AGILENT TECHNOLOGIES According to Agilent, the ability to accurately assess the quality of DNA samples is becoming more important as researchers engage in ever-larger NGS studies. Kite Pharma announces expanded agreement with Tel Aviv Sourasky Medical Center on chimeric antigen receptor approaches for cancer immunotherapy CREDIT: AGILENT TECHNOLOGIES TOOLS & TECHNOLOGY ent Genomic DNA ScreenTape assay is now said to provide an objective measure of DNA integrity for a wide range of samples. This includes not just intact samples from fresh tissue, but even the highly degraded samples often obtained from formalin-fixed, paraffinembedded tissues. Agilent expects the DIN to play a key role in determining the quality of samples as they enter the NGS workflow, allowing researchers to better define their genomic DNA samples, standardize their integrity assessment and potentially streamline their sequencing workflow. Agilent notes that the ability to accurately assess the quality of DNA samples is becoming more important as researchers engage in ever-larger NGS studies. The company also theorizes that DIN could prove invaluable at biobanks, as a tool for measuring archival quality. Agilent is making DIN freely available as a software upgrade. n SANTA MONICA, Calif.— Kite Pharma Inc., a clinical-stage biopharmaceutical company focused on developing engineered autologous T cell therapy (eACT) products for the treatment of cancer, today announced that the company has expanded its agreement with Tel Aviv Sourasky Medical Center in Israel to research and develop novel approaches to chimeric antigen receptor (CAR) T cell therapy, the technology underlying Kite’s most advanced programs in cancer immunotherapy. Under the agreement, Kite will collaborate with Dr. Zelig Eshhar, a leading pioneer in CAR T cell research and chair of immunology research within the Tel Aviv SouraskyMedical Center’s Division of Research and Development. “Zelig’s award-winning research has been at the center of CAR T cell programs currently advancing in clinical studies. We are pleased to have an expanded agreement with Zelig and the Tel Aviv Sourasky Medical Center. We believe this collaboration will facilitate continued development and advancement of novel, efficacious and more selective CAR T cell products for various tumor types,” said Dr. Arie Belldegrun, Kite Pharma’s president and CEO. Eshhar himself stated, “I have dedicated my career to the advancement of this transformative area of medicine, and I am excited about the opportunities before us.” “Originally,” Eshhar continued, “my research had addressed the question of whether T cells can be programmed to effectively recognize and eliminate cancerous cells and to solve the central problem of how and ADC CONTINUED FROM PAGE 14 Host Cell Protein Reagents & Services Call Us for a Free HCP Consultation! For more information, visit www.DDN-News.com ates antibody-drug conjugates as a potential solution to improve the lives of cancer patients,” Ba tells DDNews. “Sanofi has the great opportunity to launch six new medicines in 2015, with one new launch every six months for a total of 18 new medicines by 2020. As part of our research program, Sanofi has a strong commitment to oncology. Our goal is to invest more in projects and emerging fields.” Catalent’s proprietary SMARTag site-specific protein modification and cytotoxin-linker technologies developed by Redwood enable the generation of homogenous bioconjugates engineered why cancer cells escape the immune system. Now, we believe that we can further enhance this platform technology to develop a whole new generation of CAR T cell products for many tumor types. I look forward to the progress of this program.” Eshhar recently was named one of the recipients of the prestigious Massry Prize, along with Kite collaborator Dr. Steven Rosenberg, chief of Surgery Branch at the U.S. National Cancer Institute (NCI), “We believe this collaboration will facilitate continued development and advancement of novel, efficacious and more selective CAR T cell products for various tumor types.” Dr. Arie Belldegrun, president and CEO of Kite Pharma not only for his pioneering efforts in immunotherapy, but also for his adoptive T cell approaches to cancer treatment. In partnership with the NCI Surgery Branch through a Cooperative Research and Development Agreement, Kite is advancing a pipeline of proprietary eACT peripheral blood product candidates, both CAR and TCR (T cell receptor) products, directed to a wide range of cancer indications. n to enhance potency, safety and stability. The technology employs natural posttranslational modifications found in human cells to create one or more aldehyde tags at designated sites on protein molecules, the company states. These chemical handles are then stably conjugated to cytotoxic payloads to prevent their systemic release. The SMARTag platform provides precise payload positioning and defined stoichiometry of payload–protein ratios. The control afforded by the technology enables identification of superior drugs from libraries of differentially designed conjugates, according to the company. n EDITCONNECT: E031511 E.coli HCP Antibody 2D Stain of E.coli HCP www.Rockland-Inc.com/HCP 1-800-656-7625 Representatives of Catalent bringing in the close of the New York Stock Exchange on Sept. 8, 2014. Catalent and Sanofi recently launched a joint venture to develop Sanofi’s proprietary antibodies using Catalent’s SMARTag antibody-drug conjugate platform. For more information, visit www.DDN-News.com MARCH 2015 | | DDNEWS 17 PRECLINICAL BRIEFS Covance announces new drug development offering PRINCETON, N.J.— Covance Inc. has launched Early Phase Development Solutions, a multidiscipline approach to early drug development that will provide sponsors with access to a molecule solution team of experts from nonclinical, clinical and regulatory disciplines with experience in early drug discovery and development. The ongoing support from a single point of contact makes the process more efficient, allowing Covance to ensure accelerated program timelines can be met. “Our market research showed that the two greatest challenges our biopharma clients face today are continuity of a drug development program—both scientific and operational—and the need for stronger outsourcing partnerships,” said Dr. Steve Street, vice president and global general manager, Covance Early Development. “We created Early Phase Development Solutions to help our clients overcome those challenges—something that Covance is uniquely positioned to do given the depth and breadth of our services and expertise from the CRO industry as well as global pharma.” FluCide candidate boasts promising safety profile BOVINE EPIPHANY Cows inspire TSRI researchers to create therapy that fuses hormones and antibodies BY ZACK ANCHORS LA JOLLA, Calif.—Scientists at The Scripps Research Institute (TSRI) have made progress toward a new therapy that could be used to treat a range of conditions involving hormone deficiencies—and they have cows to thank for it. A new study from TSRI suggests that the therapeutic approach has the potential to significantly improve quality of life for people who currently take daily injections of human growth hormone to treat their conditions. TSRI research associate Tao Liu, a coauthor of the study, tells DDNews that researchers were inspired by the bovine immune system to develop a compound that fuses hormones with antibodies. “We’ve previously found that immune molecules in cows have a structure that is quite different from humans,” says Liu. “We were inspired by this unique structure to assemble an antibody with the potential to treat a range of conditions in humans.” Current treatments for conditions that feature hormone deficiencies often involve injections of human growth hormone (HGH). While this course of treatment can be highly effective, it is usually necessary for patients to receive injections with great frequency due to the quickness with which the body breaks down HGH. In some cases, the body degrades HGH within 30 minutes. “A major disadvantage of hormones as a treatment is the need for frequent injections,” says Liu. “Children with growth hormone deficiency, for example, have to receive injections of growth hormone every day, and Researchers at The Scripps Research Institute took their lead from the immune systems of cows when they set out to fuse hormones with antibodies for therapeutic purposes in humans. that can be very painful for a little kid.” TSRI’s study suggests it may be possible to develop hormonebased treatments that remain active in the human body long enough to be administered much less frequently—perhaps weekly or monthly. This could be accomplished by fusing hormones with antibodies, which can survive for weeks in the body. An older TSRI study from COWS CONTINUED ON PAGE 19 WEST HAVEN, Conn.—NanoViricides Inc. has report- ed that an optimized FluCide drug candidate has demonstrated a good safety profile in a toxicology study in rats. The candidate was administered intravenously at doses of up to 300 mg/kg per day for 14 days, and no direct adverse clinical effects were seen upon administration or in gross organ-level histological examination. This study was conducted at BASi in a cGLP-like fashion. The next phase of toxicology package studies will involve larger animals and will be performed in a cGLP-compliant manner to provide the safety and toxicology data required for an Investigational New Drug submission to regulatory authorities. IN THIS SECTION INdiscovery THISand SECTION Drug development services Head Covance announces new drug Text����������������������������������������������������������� development offering.............................. 170 Text............................................................ 0 Hormone therapies Head Bovine epiphany...................................... 17 Text����������������������������������������������������������� 0 Influenza Text............................................................ 0 FluCide candidate boasts promising safety profile........................... 17 Neurology/Gene therapy Industry-academia attack on GM1-gangliosidosis........................... 18 Oncology An answer for glioblastoma?.................. 17 MMRF and Inflection collaborate on new cancer treatment (MMRF from cover)...... 21 The guiding light...................................... 17 The guiding light Oregon State’s ‘glowing’ nanotechnology guides cancer surgery, zaps remaining malignant cells BY LORI LESKO Corp., a specialty biopharmaceutical company focused on developing therapeutic products to treat ophthalmologic, oncologic and dermatologic diseases, thinks it may have an answer. CORVALLIS, Ore.—Targeted toward improving the outcome of cancer surgery, researchers at Oregon State University (OSU) have developed and launched a new tumor-seeking weapon to theoretically extinguish all malignant cancer cells by selectively inserting compounds into the cancer cells, thus allowing surgeons to identify malignant tissues. Then, in combination with phototherapy, the tumor will not only be removed, but the innovative method will kill any remaining cancer cells, both through mild heating and generating reactive oxygen species. This procedure may one day answer, at least for some, the age-old lingering question: Doc, did you get it all? “It’s about as simple as, ‘If it glows, cut it out,’ David Stauth, science writer at OSU, stated in a recent news release. “And if a few malignant cells remain, they’ll soon die.” The findings, published in the journal Nanoscale, have shown remarkable success in laboratory animals, Stauth said. The concept should allow more accurate surgical removal of solid tumors at the same time as it eradicates any remaining cancer cells. In laboratory tests, it completely prevented cancer recurrence in mice after phototherapy. “This is kind of a double attack that could significantly improve the success of cancer surgeries,” says Oleh Taratula, an assistant professor in OSU’s College of Pharmacy. “With this approach, cancerous cells and tumors will literally glow and fluoresce RES-529 CONTINUED ON PAGE 18 GLOW CONTINUED ON PAGE 20 Pictured above: Dr. David Sherris (currently chief scientific officer of RestorGenex) when he was president of Paloma Pharmaceuticals Inc., talking at the 16th Mars Society Convention about an agent that showed both anticancer properties and radiologic protective benefits. An answer for glioblastoma? RES-529 targets TORC1 and TORC2 protein complexes in dissociative manner BY ILENE SCHNEIDER BUFFALO GROVE, Ill.—Gliobla- stoma, also known as glioblastoma multiforme (GBM), is the most common and most aggressive type of primary brain tumor in adults. RestorGenex 18 DDNEWS | | MARCH 2015 PRECLINICAL For more information, visit www.DDN-News.com Trio of Lysogene, UMass Medical School and Auburn University announce collaboration in CNS disease BY LLOYD DUNLAP PARIS—Lysogene, a clinical-stage gene ther- apy biotechnology company in France, has entered into a strategic collaboration with the University of Massachusetts Medical School (UMMS) in Worcester and Auburn University (AU) in Alabama. Through the collaboration, the three organizations will develop IND-supporting preclinical studies in GM1-gangliosidosis, a rare inherited disorder characterized by severe neurological impairment, using adeno-associated virus (AAV) gene therapy technology. The collaboration will combine Lysogene’s translational and clinical expertise in gene therapy for central nervous system (CNS) disorders with the unique preclinical expertise and infrastructure of UMMS and AU to design and test innovative AAV-based gene therapy RES-529 CONTINUED FROM PAGE 17 RestorGenex presented scientific data on a potential treatment for GBM at the Keystone Symposia Series on PI 3-Kinase (PI3K) Signaling Pathways in Vancouver, British Columbia, in January. “GBM is a disease with a very poor prognosis,” said Stephen M. Simes, CEO of RestorGenex. GBM is challenging to treat because the cells within the tumor are very resistant to most treatments. In addition, these rapidly growing tumors tend to have a tentacle-like structure, so it can be difficult to fully remove the tumor surgically. Titled “Validation of RES-529, a novel TORC1/TORC2 allosteric dissociative PI3K inhibitor in glioblastoma multiforme,” the RestorGenex presentation showed how the approaches to treat GM1-gangliosidosis. The development of a potential treatment for GM1-gangliosidosis using AAV gene therapy was initiated in 2005 by Dr. Miguel SenaEsteves, associate professor in the neurology department and the Gene Therapy Center at UMMS, and Dr. Douglas R. Martin, associate professor in the Scott-Ritchey Research Center and department of anatomy, physiology and pharmacology at AU. The approach developed by the investigators uses AAV vectors to treat the entire brain and spinal cord after injection at only a few intracranial sites. Lysogene and the two U.S academic institutions forged their collaboration on their shared interest for AAV-based gene therapies in CNS disorders, Karen Aiach, founding president and CEO of Lysogene, tells DDNews. “More specifically,” she adds, “in lysosomal storage disorders (LSDs). Based on in-depth due diligence performed by the company to identify a new, robust and commercially viable target for its pipeline, the two U.S. institutions attracted TRIO CONTINUED ON PAGE 20 proprietary first-in-class PI3K/Akt/mTOR pathway inhibitor is capable of dissociating both TORC1 and TORC2. “This, and other work, supports the rationale for RestorGenex’s plans to advance RES-529 into clinical trials in GBM,” said Dr. David Sherris, chief scientific officer of RestorGenex. Sherris explained that RES529 is an “allosteric, dissociative, first-inclass inhibitor of the PI3K/Akt/mTOR pathway.” It inhibits both TORC1 and TORC2 and is mechanistically differentiated from other PI3K inhibitors in development. “Signaling components of the PI3K pathway are central regulators of cell proliferation, growth, differentiation, survival and angiogenesis,” Sherris added. The poster presentation discussed invitro and in-vivo data from preclinical stud- CREDIT: UNIVERSITY OF MASSACHUSETTS Industry-academia attack on GM1-gangliosidosis The University of Massachusetts Medical School, the Aaron Lazare Medical Research Building of which is pictured here, is engaged in a collaboration with Paris-based Lysogen and fellow U.S. academic and research institution Auburn University to develop IND-supporting preclinical studies in GM1-gangliosidosis. ies evaluating RES-529 in GBM, a disease often characterized by elevated expression of PI3K. In the first study, RES-529 demonstrated an ability to inhibit signal transducers of the PI3K pathway controlled by TORC1 and TORC2 in a variety of tumor cells, including cells that have lost tumor suppressor PTEN. A second study compared RES-529 with two catalytic inhibitors of the PI3K pathway now in the clinic: a combination PI3K/ mTOR agent and a combination PI3K/Akt agent. RES-529 showed a twentyfold to more than hundredfold increase in activity above other inhibitors and the ability to inhibit tumor cell survival up to two orders of magnitude over that of a rapamycin analog PI3K inhibitor in a tumor model known to show resistance to TORC1 inhibition. A third study showed RES-529 penetrates the blood-brain barrier. This was supported by efficacy data of RES-529 in an orthotopic GBM xenograft model where RES529 showed an improvement in survival vs. control, similar to radiation treatment. When combined with radiation, RES-529 showed synergy extending survival above that of either RES-529 or radiation alone. Sherris concluded, “The data both as monotherapy and in combination therapy with radiation suggest that RES-529 should be evaluated in glioblastoma where standard of care has at best resulted in approximate survival of 12 months—fewer than 25 percent of patients survive two years, and fewer than 10 percent of patients survive five years.” ■ EDITCONNECT: E031513 AACR Booth #2365 New Dimensions in Cancer Diagnostics and Services™ 3 Dimensional (3D) Tumor Spheroids Perfusion Co-Culture Primary Tumors In Vitro Drug Response Phenotypic Profiling More Clinically Relevant Can your 3D model do this? KIYATEC INC. | 900-B West Faris Rd. • Greenville, SC 29605 | 864.502.2013 | [email protected] Stromal Fibroblasts K I YAT E C . C O M CONTINUED FROM PAGE 17 2013 showed that compounds providing a potential model for fusing hormones and antibodies exist in the immune system of cows. The 2013 study of the bovine antibody revealed an unusual structure that features a round base with a long amino-acid stalk extending outwards. On the top of the stalk is a “knob region” that was believed to bind to pathogens. Researchers designed the new TSRI study to test whether it is possible to switch the knob region of the bovine antibody with DNA from a human hormone, such as HGH. They first pursued this theory by using recombinant DNA technology to fuse HGH to a coiled version of the bovine antibody’s stalks. The results were promising: the fusion proved stable and did not prevent HGH from retaining its normal function. The next step of the study involved an attempt to create a fully humanized version of the antibody to test whether it was possible for “We’ve previously found that immune molecules in cows have a structure that is quite different from humans.” Tao Liu, a TSRI research associate the molecules to be applied in human therapy. Researchers used the humanized anticancer drug Herceptin as the antibody base to develop an antibody-hormone molecule without any cow DNA. “We used Herceptin because it has already been used as a drug to treat cancer and it has a well-established profile,” says Liu. “We modified it so it didn’t have anything to do with treating cancer and its only function was to help the growth hormone grow correctly and to improve the half life of the compound.” The researchers then tested their antibody-HGH molecule in rat models. They found that HGHdeficient rats that received the treatment grew normally. In fact, the treated rats only needed injections two times a week to grow, compared with daily injections for rats given HGH without the antibody base. “It acts just like the normal growth hormone,” according to Liu. “This means the treatment might only need to be injected once a week or even once a month in humans. It would be so much easier for patients.” The study ultimately demonstrated that human hormones and antibodies can be fused together in a way that mimics the long, stalk-like cow antibodies. The senior authors of the new study, which was published in the journal Proceedings of the National Academy of Sciences, were Peter Schultz of TSRI and Feng Wang of the California Institute for Biomedical Research. The researchers are continuing to explore how this new therapeutic approach could provide longerlasting doses of HGH that would improve treatments for people with conditions ranging from Turner Syndrome, which causes short stature in females, to low birth weight. Liu believes the therapy could eventually improve treatments for an even wider spectrum of individuals, including those who require insulin to treat type 2 diabetes. Reducing the frequency of injections for all these conditions, he says, has the potential to improve patient compliance and quality of life. ■ EDITCONNECT: E031502 MARCH 2015 | | DDNEWS 19 CREDIT: TSRI COWS Copyright © 2015 PerkinElmer, Inc. 400285_09 All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners. th PRECLINICAL For more information, visit www.DDN-News.com Researchers at The Scripps Research Institute designed a new study recently to test whether it is possible to switch the “knob region” of a bovine antibody with DNA from a human hormone, such as human growth hormone. SPEED OR SENSITIVITY? THE ANSWER IS YES When analyzing complex cell models, you don’t want to compromise on your imaging technologies. And that’s what the Opera Phenix™ High Content Screening System is all about. Building on over a decade of experience with confocal high-throughput HCS, the system's new confocal Synchrony™ Optics deliver the speed to image millions of cells per hour in up to four colors – simultaneously – without compromising sensitivity. So you can obtain more accurate phenotypic information. Opera Phenix: More physiological relevance. No compromise. www.perkinelmer.com/YES 20 DDNEWS | | MARCH 2015 PRECLINICAL TRIO neurodegenerative disorder characterized by severe cognitive and motor developmental Lysogene’s interest because of particularly delays resulting in death of most patients at a compelling preclinical proof-of-concept data very young age. It is caused by mutations in the in GM1-gangliosidosis, a model disease for neu- GLB1 gene, which encodes an enzyme called beta-galactosidase necessary for recycling of rological disorders with motor impairment.” Lysogene’s ultimate mission is to transl- a molecule (GM1-ganglioside) in neurons. ate the initial proof of concept into a viable This brain lipid is indispensable for normal drug development program to the benefit of function, but its overabundance causes neupatients in urgent need. The parties are colla- rodegeneration, resulting in the severe neuborating on IND-supporting preclinical stu- rological symptoms of GM1-gangliosidosis. LSDs are attractive candidates for gene dies. Under the agreements, Lysogene-sponsored efficacy studies will be performed at replacement therapy because they are monoboth UMMS and AU. The company will also genetic conditions, and genetic correction design and execute translational activities, of a small subset of neural cells may be sufi.e. GMP vector manufacturing, toxicity and ficient to target large regions of the CNS, biodistribution studies, regulatory affairs, as secreted lysosomal enzymes can diffuse and be captured by adjacent and distal cells IND procedure and clinical development. Preclinical studies demonstrated a remark- (cross-correction mechanism). Moreover, able extension in lifespan from eight months tight regulation of produced enzyme levels in untreated GM1 cats to greater than 4.5 years is not required because a low level of enzyme in AAV-treated cats, with dramatic improve- activity (around 10 percent) may be sufficient ments in quality of life. Results were published to have therapeutic effects and conversely supraphysiological levels of many of the in Science Translational Medicine in 2014. “We are thrilled by our collaboration with acidic hydrolases have no deleterious effect. In the past decade, recombinant adenoUMMS and AU, which constitutes a significant step towards the development of a treat- associated virus (rAAV) approaches have ment for patients affected with GM1-ganglio- rapidly advanced to the forefront of gene sidosis. For each of these patients and their therapy, with hundreds of subjects injectfamilies, there is currently no option and an ed and with no serious adverse events yet urgent need for a safe and effective therapy,” reported. According to Lysogene, rAAV vecaccording to Aiach. “AAV-based therapies are tors are excellent tools in gene therapy for particularly suitable for inherited disorders treatment of neurological diseases as they of the CNS. In this new program, Lysogene transduce post-mitotic cells that mediate will leverage its unique capacity to develop the sustained, long-term gene expression these therapies and bring them to patients that is required to treat chronic diseases. with unmet needs. We will also reinforce our Injected in the CNS, AAVs can be transscientific and technology base through our ported along neuronal connections to distal sites and secreted enzymes can be collaboration with leaders in the field.” “Collaborating with Lysogene will allow transported antero and retrograde to crossus to leverage their clinical and translational correct cells distal from the injection site. Other AAV serotypes with different expertise and advance the development of a gene transfer therapy for treating patients expression cassette constructs will be tested affected with GM1-gangliosidosis,” said Sena- in GM1 murine and feline models, as well Esteves. “In our minds, what ultimately mat- as new injections routes to determine the approach to be translated to human ters is the ability to deliver a treatment to the4:58optimal Indigo Bio Ad March 2015.pdf 1 2/17/15 PM children suffering from this horrible disease.” patients. ■ GM1-gangliosidosis is a rare, inherited EDITCONNECT: E031515 For more information, visit www.DDN-News.com GLOW CONTINUED FROM PAGE 18 CONTINUED FROM PAGE 17 when exposed to near-infrared light, giving the surgeon a precise guide about what to remove. That same light will activate compounds in the cancer cells that will kill any malignant cells that remain. It’s an exciting new approach to help surgery succeed.” This research was done with ovarian cancer cells. Ovarian cancer is the deadliest of all cancers affecting the female reproductive system, with very few effective treatments available, according to the National Institutes of Health (NIH). The work is based on the use of a known compound called naphthalocyanine, which, when exposed to near-infrared light, can make a cell glow to guide the surgeon, OSU researchers stated. However, naphthalocyanine isn’t watersoluble, and also tends to clump up, or aggregate, inside the body during the process, thus losing its ability to make cells glow and generate reactive oxygen species. This also makes it difficult or impossible for it to find its way through the circulatory system and take up residence only in cancer cells. OSU experts overcame these problems by use of a special water-soluble polymer, called a dendrimer, which allows the napthalocyanine to hide within a molecule that will attach specifically to cancer cells, Stauth said. The dendrimer, an extremely tiny nanoparticle, takes advantage of certain physical characteristics that blood vessels leading to cancer cells have, but healthy ones do not. It will slip easily into a tumor, but largely spare any healthy tissue. This “one-two punch of surgery and a nontoxic, combinatorial phototherapy holds significant promise,” Taratula says. “It’s quite different from existing chemotherapies and radiotherapies.” He adds that this process “could someday eliminate— or at least reduce—the need for chemotherapy and radiation. For many cancers, surgery is a first choice of treatment. In coming years, we may have a tool to make that surgery more precise, effective and thorough than it’s been before.” “Our findings highlight substantial progress in employing a single-agent-based nanomedicine platform capable of both NIR fluorescence imaging and anticancer therapy (combinatorial phototherapy in this case) with the near future prospective to detect and eradicate unresected cancer cells intraoperatively,” Taratula continues. “What we have learned from these studies is that it is possible to visualize and destroy cancer cells with a single agent, minimizing the cost, time and toxicity of intraoperative anticancer therapy.” In order to get FDA approval for clinical trials with humans, the convincing therapeutical and safety results in animals have to be obtained, Taratula notes. “At the moment, we are continuing complete evaluation of this modality in mice. However, we are getting ready to test this system on dogs in collaboration with the Oregon State College of Veterinary Medicine.” Systems with technology similar to this are also being tested by other researchers, but some of them require several imaging and therapeutic agents, repeated irradiation and two lasers, OSU researchers stated. This increases cost and may lessen effectiveness and increase the risk of side effects. This nanotechnology work was initially supported by OSU College of Pharmacy. “Recently, we received $120,861 from Venture Funds OSU to optimize the developed nanomedicine platform and complete critical animal studies, including detailed efficacy and toxicity, to advance this technology,” Taratula said. “Earlier, in 2013, $40,000 from the Medical Research Foundation of Oregon also supported initial work for this project.” With cuts in grant funding, though, the future is uncertain. ■ EDITCONNECT: E031514 INDIGO now offers PXR kits and service assays for Human and Rat Get to KNOW INDIGO ADVERSE DRUG INTERACTION We create innovative products and services that help you to minimize risk in drug discovery while improving speed and lowering cost. PXR ACTIVATION ENVIRONMENTAL POLLUTANTS We are your nuclear receptor solution! Smart assays know INDIGO! BOOTH 1006 AT For the full portfolio of our products and services, please visit: indigobiosciences.com DRUG METABOLISM VISIT US SOT FOOD CONTAMINANTS M S PRECLINICAL For more information, visit www.DDN-News.com MMRF CONTINUED FROM PAGE 1 kinase inhibition is said to selectively inhibit PIM and PI3K without affecting the activity of other kinases. “Initial preclinical data we have generated for IBL-202 holds promise for those patients suffering with multiple myeloma,” according to Darren Cunningham, CEO of Inflection Biosciences. “MMRF support will greatly assist us in further evaluating the potential of IBL-202 for patients with multiple myeloma, one of the many indications we hope to consider.” The MMRF is working with Inflection Biosciences through its Translational Network of Excellence program, which supports critical research at leading academic medical centers focused on promising investigational therapies for multiple myeloma. “Inflection Biosciences, and its innovative PIM/PI3K program, is precisely the type of visionary biotech/pharma partnership the MMRF is committed to, in our relentless pursuit of promising treatment options for multiple myeloma,” according to Walter M. Capone, president and CEO of the MMRF. “The MMRF launched its Translational Network of Excellence last year to advance the most promising research for novel targets and drug validation, immune biology, myeloma-related diseases and minimal residual disease. We are tremendously excited to partner with Inflection Biosciences in the development of this novel and potentially promising therapy.” Dr. Michael O’Neill, director of research and development at Inflection Biosciences, added, “This collaboration with a leading cancer research foundation is a tremendous validation for our compound and our work so far. We look forward to working with the MMRF and its network of researchers to establish the effectiveness of our compound in multiple myeloma.” In other recent MMRF news, but on the discovery-oriented front in this case, MMRF announced that it has partnered with Cambridge, Mass.-based GNS Healthcare, a provider of analytics solutions for driving personalized interventions that improve population health, in a collaboration to speed the discovery of innovative treatments for patients with multiple myeloma. The effort is said to “combine the unprecedented genomic and clinical data from the MMRF’s landmark CoMMpass Study with revolutionary GNS machine learning platforms and rapid computer simulations. The work supports the development of computer models of myeloma disease that may uncover novel molecular pathways that can prevent progression of disease and address the unmet treatment needs of patients with multiple myeloma.” CoMMpass is a longitudinal study of 1,000 newly diagnosed patients with active multiple myeloma. Its objective is to map each of these patients’ genomic profiles to clinical outcomes to develop a more complete understanding of patient responses to treatments. “Through creative, dynamic partnerships, we continually build new research models to accelerate development of the most promising treatments for patients with multiple myeloma,” said the MMRF’s Capone. “This collaboration with GNS to apply leading-edge computer models and analytics to uncover disease pathways in the diverse CoMMpass data set exemplifies this strategy.” GNS will use an in-silico process, applying its MAX architecture and patented REFS inference engine and simulation platforms to the CoMMpass data. REFS will identify causal drivers and underly- MARCH 2015 | | DDNEWS 21 ing molecular processes of disease progression. REFS will also discover the most likely targets for therapeutics to treat, and perhaps to predict and prevent, relapses and refractory disease. REFS will also discover predictive diagnostic biomarkers that determine which treatments will work and for which patients. “This work embodies the transformative role for Big Data analytics to uncover specific treatment protocols that have a much better chance of success for individual patients,” says Colin Hill, CEO and co-founder of GNS. “REFS turns large datasets into computer models that reveal new molecular pathways and targets that, up until now, could not be easily identified. It ultimately accelerates many of the traditional steps in the drug discovery and development process, bypassing obstacles that often delay or prevent promising, new treatments from reaching patients.” ■ EDITCONNECT: E031512 AA CR bo oth 20 19 In vivo grade isotype control antibodies formulated specifically for preclinical screening and in vivo assays • Suitable for in vivo studies and standard immunoassays WB, IHC, FC, IP, ELISA, etc. • Very low endotoxin levels (< 0.5 EU/mg) • Supplied at high concentration (2-5 mg/ml) • Supplied in PBS only; no carriers or additives • > 95% purity as analyzed by SDS-PAGE and HPLC Human IgG Isotype Controls Mouse IgG Isotype Controls Human IgG1, kappa Mouse IgG1, kappa Human IgG1 (non-glycosylated), kappa Mouse IgG2a, kappa Human IgG1 (D265A), kappa Mouse IgG2a (non-glycosylated), kappa Human IgG2, kappa Mouse IgG2b, kappa Human IgG3, kappa Mouse IgG3, kappa Human IgG4, kappa Quantities up to 10 grams are available. Representative data: SEC-HPLC (0.5 ml/min; 30 min; UV280) analysis of Human IgG1, kappa Isotype Control, catalog # C0001. Representative data: SDS-PAGE analysis of Human IgG1, kappa Isotype Control, catalog # C0001, under reducing and non-reducing conditions. Contact us at (855) 827-6968 or [email protected] for specialized pricing. Please visit us at AACR - booth 2019 www.crownbio.com 3375 Scott Blvd., Suite 108, Santa Clara, CA 95054 Contact: Tel. 855.827.6968 / Fax. 408.884.2339 [email protected] 22 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Pennsylvania Convention Center Philadelphia April 18-22, 2015 n Dr. Kenneth C. Anderson, director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at the Dana-Farber Cancer Institute in Boston ■■ Dr. Carlos L. Arteaga, director of the Center for Cancer Targeted Therapies, director of the Breast Cancer Program and associate director for clinical research at Vanderbilt-Ingram Cancer Center of Vanderbilt University in Nashville, Tenn. ■■ Dr. Anton J.M. Berns, senior group leader of the Division of Molecular Genetics at the Netherlands Cancer Institute in Amsterdam and director of the Skoltech Center for Stem Cell Research in Moscow ■■ Dr. Bruce A. Chabner, director of clinical research at Massachusetts General Hospital in Boston ■■ Dr. Ronald A. DePinho, president of the University of Texas MD Anderson Cancer Center in Houston ■■ Dr. Susan D. Desmond-Hellmann, CEO of the Bill & Melinda Gates Foundation in Seattle ■■ Dr. Robert N. Eisenman, a member of the Division of Basic Sciences at Fred Hutchinson Cancer Research Center in Seattle ■■ Dr. Douglas R. Lowy, deputy director of the Center for Cancer Research, chief of the Laboratory of Cellular Oncology and head of the Signaling and Oncogenesis Section at the National Cancer Institute in Bethesda, Md. ■■ Dr. Carol L. Prives, Da Costa Professor at Columbia University in New York City ■■ Dr. Steven A. Rosenberg, chief of surgery at the National Cancer Institute ■■ Dr. Craig B. Thompson, president and CEO of Memorial Sloan Kettering Cancer Center in New York City ■■ Bringing cancer discoveries to the patients AACR brings the world’s largest cancer research conference to Philadelphia T BY LLOYD DUNLAP HE AMERICAN ASSOCIATION for Cancer Research (AACR) Annual Meeting 2015, which AACR President Dr. Carlos Arteaga reminds us is the largest cancer research conference in the world, will highlight the “latest, most exciting” discoveries in every area of cancer research and is designed to provide a unique opportunity for investigators from all over the world to meet, interact and share their insights. This year’s meeting theme, “Bringing Cancer Discoveries to Patients,” underscores the vital and inextricable link between discovery and treatment, Arteaga says, and it reinforces the fact that research underpins all the progress being made in the field toward cancer cures. CREDIT: © 2014 AACR/TODD BUCHANAN Research will formally induct its 2015 class of elected fellows of the AACR Academy at the AACR Annual Meeting 2015 to be held in Philadelphia from April 18-22. The academy serves to recognize and honor distinguished scientists whose major scientific contributions have propelled significant innovation and progress against cancer. All fellows are nominated and elected through a peer-review process conducted by existing fellows of the AACR Academy and ratified by the AACR Executive Committee. This process involves an assessment of each candidate on the basis of his or her scientific achievements in cancer research and cancer-related biomedical science. “Our 2015 class of fellows includes 11 luminaries in the field of cancer research, in honor of the 11 founders of the AACR in 1907. We are delighted to recognize the incredible scientific accomplishments of these illustrious researchers and celebrate how their dedicated efforts have helped accelerate the pace of progress against many of the hundreds of diseases we collectively call cancer,” said Dr. Margaret Foti, CEO of the AACR. This brain trust of global leaders in cancer research offers invaluable insight into the future of cancer research and patient care and continues to work with the AACR in its mission to prevent and cure all cancers. Members of the 2015 class of fellows of the AACR Academy are: A view from the AACR Annual Meeting 2014. This year’s event will be held in Philadelphia. Looking to the present “This year is very exciting,” states Dr. Lewis C. Cantley of the Sandra and Edward Meyer Cancer Center at Weill CREDIT: © 2014 AACR/TODD BUCHANAN AACR Academy inducts 11 PHILADELPHIA—The American Association for Cancer n Attendees of last year’s meeting are pictured here. This year’s attendees will enjoy a large roster of speakers, hundreds of invited talks and more than 6,000 proffered papers from researchers all over the world. Cornell Medical College, the AACR 2015 program committee chairperson. “A lot of progress has been made over the past year, particularly in immune therapy, targeted therapies and molecular medicine. There will be several major sessions in these areas and also on clinical trials, which will be emphasized more than in previous years. New drugs hitting new targets will be featured as part of this year’s emphasis on patients. Novel targets—the P13K gene, for example, that is often mutated in breast cancer—will be discussed.” There will also, he says, be lectures discussing the biochemistry behind trials. “Notably, the Obama administration provided additional funding in the area of precision medicine during the past year,” Cantley notes, “and we’ll have sessions focused on molecular therapy in this area.” In the area of immune therapy, new targets have been discovered in melanoma, lung and pancreatic cancer. “Some patients are cured, others don’t respond at all,” Cantley observes. There will be a session exploring why this is AACR 2015 CONTINUED ON PAGE 23 AACR 2015 For more information, visit www.DDN-News.com AACR 2015 Vanderbilt-Ingram Cancer Center’s associate director for Clinical Research, leader of the Breast Cancer Research Program, director of the Center for Cancer Targeted Therapies and Donna S. Hall Chair in Breast Cancer. A summary of the “Vision for the Future” session will be provided by Jose Baselga of the Memorial Sloan Kettering Cancer Center in New York City. Cantley’s focus is targets and preclinical work, Nelson is an expert CONTINUED FROM PAGE 22 and discussing new targets and new approaches. “Early-stage trials will focus on mechanisms of resistance,” adds Arteaga, who works at Vanderbilt-Ingram Cancer Center. Prevention will also be a topic of considerable attention. A recent article in Science suggested that up to one-third of all cancers could be prevented if smoking, obesity and diabetes were avoided. How lifestyles figure into prevention will be discussed. Arteaga also noted the presumptive links between obesity and diabetes and their links to cancer which will be the subject of two sessions. Insulin resistance, he observes, may be linked to cancer. “There are signals of hope,” he states, “and we are the window to the rest of the world.” in prevention and epidemiology and Arteaga’s focus is clinical trials. “Themes of the session are likely to include precision medicine and what it’s telling us, immune combination therapies and exciting clinical trials,” Cantley opines. For everyone—presenters, early-career and established researchers, clinicians and advocates—AACR’s annual meeting is a must-attend event, according to Cantley, who says, “We are developing a comprehensive and APRIL 18-22, 2015 PENNSYLVANIA CONVENTION CENTER PHILADELPHIA, PA MARCH 2015 | | DDNEWS 23 multidisciplinary program, with an outstanding roster of speakers, hundreds of invited talks and more than 6,000 proffered papers from researchers all over the world. We want to thank the Program Committee co-chairpersons and Education Committee members for their incredible guidance in shaping an innovative program that will be both enjoyable and educational to all attendees and attract major media attention from around the world.” “Together we are making astounding progress in the fight against cancer,” Cantley continues. “It is taking less time than ever for our research to be translated into improved prevention, diagnosis and treatment strategies for patients. This is an exciting time for cancer research. By attending the AACR Annual Meeting, you will find ideas, people and moments that provide you with renewed energy, inspiration and focus in your work.” n EDITCONNECT: E031529 B7 FAMILY ANTIBODIES Vision for the Future New this year will be a wrap-up session on the final day of the conference, chaired by M. Celeste Simon of the Abramson Family Cancer Research Institute in Philadelphia. The session will distill “what’s new and important down to the hour-and-a-half session, collect and present the key information with supporting slides,” Cantley notes, with a rueful aside that admits to the enormity of the task. “I’ll have a lot of help,” he adds, with colleagues and staff working throughout the duration of the conference to aid in the process. The presenters will be Cantley, the Margaret and Herman Sokol Professor and director of the Meyer Cancer Center at Weill Cornell Medical College; Dr. William G. Nelson, the Marion I. Knott Director and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University; and Arteaga, CST development scientist optimizing IHC protocols PIVOTAL TARGETS CANCER IMMUNOLOGY Proven specificity. Results you can count on. Antibodies for PD-L1, B7-H3, and B7-H4 from CST that detect endogenous CREDIT: © 2014 AACR/TODD BUCHANAN protein in human tissue and do not cross react with other B7 family members. A poster presenter explains her research to an attendee of the AACR Annual Meeting 2014. PD-L1 (E1L3N®) XP® Rabbit mAb #13684: IHC analysis of paraffinembedded human lung carcinoma using #13684. B7-H3 (D9M2L) XP® Rabbit mAb #14058: IHC analysis of paraffinembedded ovarian carcinoma using #14058. www.cellsignal.com/B7DDN Visit our website to request our Tumor Immunology Poster and for additional validation and competitor comparison data. For Research Use Only. Not For Use In Diagnostic Procedures. © 2015 Cell Signaling Technology, Inc. Cell Signaling Technology, CST, E1L3N and XP are trademarks of Cell Signaling Technology, Inc. 14PADCANRIMMU0257ENG_00 AACR 2015 24 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Plenary and educational sessions at the annual meeting Opening Plenary: The Genome and Beyond Sunday, April 19, 9 a.m. to 12:15 p.m. Chairperson: Lewis C. Cantley, Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, New York ■■ “Insights from cancer genomes into the mutational processes underlying cancer development” by Michael R. Stratton, Wellcome Trust Sanger Institute, Cambridge, U.K. ■■ “Above the genome: The epigenome and its biology and translational potential” by Stephen B. Bayline, Johns Hopkins University School of Medicine, Baltimore, Md. ■■ “Engineering the cancer genome” by Tyler Jacks, David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, Mass. ■■ “Using genomics to personalize cancer immunotherapy” by Robert D. Schreiber, Washington University School of Medicine, St. Louis Precision Medicine Comes to Cancer Prevention and Screening Monday, April 20, 8:15 a.m. to 10:15 a.m. This session will include four presentations that highlight recent advances in cancer prevention. The first presentation will focus on the use of multitarget stool DNA testing to enhance colorectal cancer screening. The second presentation will provide an update of our understanding of the chemopreventive properties of aspirin. The identification of molecular endpoints and pathways that help to identify individuals most likely to benefit from aspirin will be reviewed. The third presentation will focus on liver cancer, which remains among the top causes of cancer mortality in the world. Evidence will be presented that liver injury is carcinogenic because it stimulates regenerative responses that relax forces which normally constrain the inherent multipotency of adult liver cells. The final presentation will focus on HPV-related cancers. The latest advances in reducing the burden of HPV-related cancers through primary and secondary prevention will be reviewed. Chairperson: Andrew J. Dannenberg. Weill Medical College of Cornell University, New York ■■ “Stool DNA detection of colorectal neoplasia: A new high bar for noninvasive screening” by David A. Ahlquist, Mayo Clinic, Rochester, Minn. ■■ “Molecular risk stratification for aspirin chemoprevention” by Andrew T. Chan, Massachusetts General Hospital, Boston ■■ “Early Detection and Prevention of Liver Cancer: Leveraging Lessons Learned from Liver Repair” by Anna Mae E. Diehl, Duke University School of Medicine, Durham, N.C. ■■ “Drastically reducing HPV-associated cancers through etiologically based primary and secondary prevention” by Douglas R. Lowy, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Md. ■■ Drug Resistance Tuesday, April 21, 8:15 a.m. to 10:15 a.m. Drug resistance is the primary challenge faced by all practicing oncologists. The advent of targeted therapies has provided exciting opportunities not only to understand the mechanisms through which resistance occurs, but also to design approaches that overcome this resistance. The presentations in this session will describe the latest developments in this area of research, from the perspectives of genetics, drug development, clinical application and cell biology. Chairperson: Bert Vogelstein, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Md. ■■ “Drug resistance: A genetic perspective” by Bert Vogelstein ■■ “Genetic screens to understand drug resistance” by Alan Ashworth, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco ■■ “Drug resistance: Translating discoveries into the clinic” by Alice T. Shaw, Massachusetts General Hospital Cancer Center, Boston ■■ “Drug resistance: A cell biologist’s perspective” by Joan S. Brugge, Harvard Medical School, Boston ■■ Oncology Meets Immunology: Not Just Another “Hallmark” Wednesday, April 22, 8 a.m. to 10 a.m. It is now well appreciated that a fundamental aspect of cancer biology involves interactions of neoplastic cells with the immune system, which can either promote or inhibit tumor growth, depending on complex networks in the tumor microenvironment. Mechanistic insights from basic studies in cancer immunology have resulted in novel, rational therapeutics for patients with advanced cancer that have produced unprecedented clinical results, even in tumors not previously regarded as amenable to such approaches. The consensus in the field—to be illustrated in this plenary session—is that we have only seen the tip of the iceberg for cancer immunotherapy, posing a challenge to investigators, advocates, government, industry and others to capture this opportunity quickly and fully for the benefit of our patients. Chairperson: Robert H. Vonderheide, Abramson Cancer Center of University of Pennsylvania, Philadelphia ■■ “Engineering improved cancer vaccines” by Glenn Dranoff, Dana-Farber Cancer Institute, Boston ■■ CREDIT: B. KRIST FOR VISIT PHILADELPHIA B ECAUSE IT IS NOT possible to attend every session at AACR’s annual meeting, a new plenary session will provide meeting highlights spanning basic, translational and clinical science, as well as prevention and early detection. Four plenary sessions featuring leading experts in their field have been developed to cover topics of broad importance and areas of growth. Built in 1926, the Benjamin Franklin Bridge, which traverses the Delaware River, connects Philadelphia, the nation’s fifth-largest city, and New Jersey. “Leukocytes as targets for therapy in solid tumors” by Lisa M. Coussens, OHSU Knight Cancer Institute, Portland, Ore. ■■ “Fatal Attraction: A new story featuring the immune system and pancreatic cancer” by Elizabeth M. Jaffee, Johns Hopkins University, Baltimore, Md. ■■ “The mechanistic basis of cancer immunotherapy” by Ira Mellman, Genentech Inc., South San Francisco, Calif. ■■ Educational Sessions In addition to these Plenary Sessions, there are a number of additional Educational Sessions that are expected to be of major interest to AACR attendees. Tumor Immunology and Immunotherapy for the Non-Immunologist Saturday, April 18, 8 a.m. to 10 a.m. This session is intended to familiarize non-immunologists with fundamental immune responses to cancer and highlight innovative strategies for immunotherapy of cancer. It will also be informative to tumor immunologists as they will learn of the latest research efforts of the speakers. Immediately following the session, the Cancer Immunology Working Group has set up one-on-one round table tutorials with experts in the field. This session will be held from 10 a.m. to noon in the Liberty Ballroom (Level 3) of the Philadelphia Marriott Downtown for participants who are interested in learning more. The immune system is a powerful deterrent to cancer development and progression, and its evasion is a key hallmark of cancer. Innate immunity serves as the first line of defense which, when breached, allows the establishment of a tumor that can create an environment conducive to suppression of adaptive immunity against cancer. With loss of innate and adaptive immunity, the growth potential of tumors goes unchecked. Ironically, inflammation may positively or negatively impact cancer immunity and tumor growth. Recent work on inflammation and cancer points to the gut microbiome as an important component in balancing immune responses to cancer. Better understanding of the underlying mechanisms of immune modulation in cancer is needed to develop new therapeutic strategies that can effectively recover immunity against cancer and result in a durable clinical outcome and better patient survival. The presentations in this session will touch upon all these areas, beginning with the microbiota, followed by deliberation on the role of various types of innate lymphoid cells and T cells and bringing to the clinic practical approaches to treat cancer from lessons learned. What antigens T cells must recognize to tame the cancer is also a critical issue, as well as how neoantigens created by mutant genes in the cancer cell can be identified and put to use. There will be a brief discussion after each presentation. Chairperson: Julie Y. Djeu, Moffitt Cancer Center and Research Institute, Tampa, Fla. ■■ “Microbiome, inflammation and cancer” by Giorgio Trinchieri, NCI-Frederick, Frederick, Md. ■■ “Innate immunity and cancer” by Todd A. Fehniger, Washington University School of Medicine, St. Louis ■■ “Neoantigens and immunotherapy of cancer” by Ton Schumacher, Netherlands Cancer Institute, Amsterdam ■■ “Checkpoint inhibitors and clinical application in melanoma” by Jeffrey S. Weber, Moffitt Cancer Center and Research Institute ■■ Computation and Functional Modeling of Hot Big Data Saturday, April 18, 10:15 a.m. to 12:15 p.m. In recent years, we have experienced a spectacular increase in the power and versatility of both analytical and modeling platforms. This ranges from new technologies to decipher nucleic acid sequences and identify proteins at great depth and decreas- ing cost, to effective methods to functionally mine the genome in vitro and in animal models. The typical output of such approaches is so-called Big Data, which comes with several challenges. The topic that the speakers in this session will cover is the functional annotation of Big Data. For example, you will get insight into data-driven identification of synthetic lethality networks to identify cancer-specific vulnerabilities on a genome-wide scale. Speakers will discuss high-throughput shRNA and CRISPR-Cas9 genetic perturbation screens in vitro and in vivo, aiming to uncover novel cancer genes as well as targets amenable to therapeutic intervention. Finally, large-scale mouse knockout programs will be presented that allow for identification of tumor modifiers. There will be a brief discussion after each presentation. Chairperson: Daniel S. Peeper, Netherlands Cancer Institute, Amsterdam ■■ “Analyzing large genomic, phenotypic and clinical data identifies novel syntheticlethal cancer drug targets” by Eytan Ruppin, Center for Bioinformatics and Computational Biology, College Park, Md. ■■ “Large-scale genetic screens in mice: Pathways, drivers and drug resistance” by David J. Adams. Wellcome Trust Sanger Institute, Cambridge, Mass. ■■ “Genome-scale CRISPR/Cas9 screening: Technology and applications” by Neville Sanjana, Broad Institure of MIT and Harvard, Cambridge, Mass. ■■ Pan-Cancer Analysis of Whole Genomes Sunday, Apr 19, 1 p.m. to 3 p.m. The Pan-Cancer Analysis of Whole Genomes (PCAWG) project of the International Cancer Genome Consortium and The Cancer Genome Atlas is coordinating analysis of more than 2,000 whole cancer genomes. Each genome is characterized through a suite of centralized algorithms, including alignPLENARY CONTINUED ON PAGE 25 SHOW For more information, visit www.DDN-News.com PLENARY CONTINUED FROM PAGE 24 ment to the reference genome, standardized quality assessment and calling of all classes of somatic mutation. Scientists participating in the research projects of PCAWG are addressing a series of fundamental questions about cancer biology and evolution based on these data, a sample of which will be presented at this session. Key areas of study include discovery of driver mutations outside of the protein-coding regions of the genome; integrating mutational signatures across tumor types and mutation categories; characterizing subclonal structures and patterns of genome evolution across cancers; investigating relationships between germline and somatic mutations; and investigating biological pathways targeted by driver mutations. There will be a brief discussion after each presentation. Chairperson: Peter J. Campbell, Wellcome Trust Sanger Institure, Cambridge, U.K. n■ “Cancer genome analysis in the cloud: Technical, ethical and legal challenges” by Lincoln Stein, Ontario Institute for Cancer Research, Toronto n■ “Investigation of germline genetic variation in 2,500 whole cancer genomes” by Jan Korbel, European Molecular Biology Laboratory, Heidelberg, Germany n■ “Pathways and Drivers in 2,000 cancer genomes” by Joshua M. Stuart, University of California, Santa Cruz n■ “Structural variation in 2,000 cancer genomes” by Peter J. Campbell, Wellcome Trust Sanger Institute n■ Chairperson: Giorgio Trinchieri. NCIFrederick, Frederick, Md. n■ “The microbiota in carcinogenesis and cancer therapy” by Giorgio Trinchieri n■ “Microbial-driven cytokine expression fuels colorectal cancer progression” by Sergei I. Grivennikov, Fox Chase Cancer Center, Philadelphia n■ “Microbial activities promote development of CRC” by Christian Jobin, University of Florida, Gainesville n■ “Ipilimumab and gut microbiota: Novel aspects of immunotherapy” by Laurence Zitvogel, Institute Gustave-Roussy, Villejuif, France n■ Liquid Biopsy Approaches for Detecting, Monitoring and Characterizing Human Cancer Tuesday, Apr 21, 1 p.m to 3 p.m. Analyses of cancer genomes have revealed mechanisms underlying tumorigenesis and new avenues for personalized therapeutic intervention. Nevertheless, there is great complexity in the alterations of individual tumors and a realization that these can change during disease progression. This session MARCH 2015 | | DDNEWS 25 will focus on new technologies that have emerged to analyze molecular alterations in the circulation of cancer patients, including as circulating tumor cells, cell-free tumor DNA and exosomal nucleic acids. These approaches have important implications for noninvasive detection and monitoring of human cancer, therapeutic stratification and identification of mechanisms of resistance to targeted therapies. n■ Chairperson: Victor E. Velculescu, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Md. “Characterization of circulating tumor cells” by Daniel A. Haber, Massachusetts General Hospital, Charlestown n■ “SY37-02: Monitoring tumor evolution by whole-genome plasma sequencing” by Michael R. Speicher, Ellen Heitzer, Peter Ulz and Jochen B. Geigl, Medical University of Graz, Austria n■ “Exosomes: Next generation diagnostics” by Johan Skog, Exosome Diagnostics Inc., New York n■ “Liquid biopsy approaches for characterizing cancer genomes” by Victor E. Velculescu n n■ “ cancer metabolism research WE’RE BRINGING A NEW PERSPECTIVE TO XF technology provides the easiest and most comprehensive assessment of cancer cell metabolism, measuring glucose and glutamine metabolism, and fatty acid oxidation of cancer cells in a microplate, in real time! ” — Kacey Caradonna PhD, Applications Scientist Seahorse Bioscience Microbiome and Tumor Immunity Monday, Apr 20, 1 p.m. to 3 p.m. Commensal microorganisms colonize barrier surfaces of all multicellular organisms. For more than 500 million years, commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and non-immune functions of its host, and de facto, the two together comprise one metaorganism. Microbial imbalance may play a critical role in the development of multiple diseases. The commensal microbiota affects the development, progression and immune evasion of cancer, but it has also important effects on the response to cancer immune therapy and chemotherapy. Tumor-associated myeloid cells play a dual role inducing antitumor immune responses but mostly promoting immune evasion, tumor progression and metastases formation. Myeloid cells respond to signals derived from commensal microbes that modulate their function and reactivity in inflammation and their ability to act as antigen presenting cells controlling adaptive immunity, thus affecting the tumor environment and the response to cancer therapy. Background Well The Seahorse XFp Extracellular Flux Analyzer Measurements of cellular glycolysis are essential to understanding cancer. The XFp Analyzer and XFp Glycolysis Stress Test Kit make it easy to measure the three key parameters of cellular glycolysis in a microplate: glycolysis, glycolytic capacity, and glycolytic reserve, revealing critical information not evident in mitochondrial respiration measurements alone. See what’s possible. Scan this QR code to view videos and see what the XF technology can achieve. Visit www.seahorsebio.com/ddn for more information! Experimental Group Control Group Background Well AACR 2015 26 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Technology at the annual meeting CREDIT: © 2014 AACR/TODD BUCHANAN T HE AACR IS dedicated to bringing attendees the latest innovations in mobile technology to enhance and facilitate their annual meeting experience, offering the following technology products and services: Free wireless internet access will be available to meeting attendees in the convention center. Online Proceedings/Itinerary Planner: Search all annual meeting presentations (including all proffered abstracts) by author/ speaker, title word and keyword, and create a personal itinerary for the meeting. Mobile Itineraries: Personal itineraries created in the Itinerary Planner can be exported as an iCalendar file into users’ personal Outlook, Google Calendar or Apple iCal applications. Itineraries are also available as an HTML page that can be e-mailed to users’ smartphones (iPhone, Palm Pre/Centro, HTC Touch Pro and Blackberry Curve/Storm/Pearl). Mobile Proceedings: The digital edition of the Proceedings will contain abstracts of all proffered papers accepted for presentation as well as the extended abstracts submitted A view of the entrance to the AACR Annual Meeting 2014’s exhibits. Exhibitors this year will include a wide array of companies with the latest in products and services in laboratory and clinical research. The exhibits will be located adjacent to the poster sessions, and special areas of interest include the AACRcentral, Non-Profit section and Publishers’ Row. by invited speakers. The abstracts will be available in mobi and e-pub file formats for download to devices such as the Amazon Kindle, iPad, iPhone, iPod Touch, Sony Reader and the Barnes & Noble Nook. Proceedings CD-ROM: Search and browse all annual meeting abstract presentations by author/ speaker, title word, keyword and session type. The annual meeting CD-ROM will only be available for purchase. To receive a copy of the CD-ROM at the meeting, you must check the appropriate box on the registration form. The cost will be $10. Annual Meeting 2015 Program Guide App: Carry the annual meeting with you wherever you go—with or without a network connection. The Program Guide App is available in native versions to serve users of iPhone, iPad and Android devices, and also in a browser-based version for use on most web-enabled smartphones and tablets. The Program Guide App offers the following features: Native Storage. Once downloaded, all app content and functionality is stored natively on your Apple or Android device and can be accessed without an Internet connection. (Note: The browser-based version of the app is a mobile-optimized website and requires an Internet connection. The performance of the mobile web version will depend on the speed and strength of the user’s internet connection.) Meeting Abstracts. The full text of more than 5,800 abstracts is stored natively in the Apple and Android Apps, so you can access the poster session and minisymposium presentations wherever you are. Personal Itinerary. Sessions can be bookmarked and saved to your schedule folder to create a personal itinerary for the meeting. Search/Browse. You can browse annual meeting sessions by type and title. You can also search the complete list of invited and proffered presentations, including the full text of abstract presentations, by keyword or presenter. Annual meeting exhibitors can also be searched for or browsed by company name. Maps. Detailed floor plans of all annual meeting venues— including the complete exhibit hall and poster area map as well as the hotel map—are stored natively in the app for easy browsing. Attendee Information. Look up the locations and hours of critical annual meeting services, including the Internet Café, the coat and bag check and the child care/nursing mothers room. Save, Share, Make Notes. You can add notes to sessions, presentations or exhibitors and also mark them as favorites. Notes can be emailed for later retrieval. AACR Video App: Recordings of all AACR press conferences and relevant AACR videos are available at no charge through the AACR Video App, downloadable for the iPhone, iPad and Android devices. Learn more at www. AACR.org/videoapp. n ■■ ■■ ■■ ■■ ■■ ■■ ■■ ■■ Continuing Medical Education (CME) Credit Designation Statement The AACR has designated this live activity for a maximum of 45.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. Credit certification for individual sessions may vary, dependent upon compliance with the ACCME accreditation criteria. The final number of credits may vary from the maximum number indicated above. Claiming (CME) Credit Physicians and other health care professionals seeking AMA PRA Category 1 Credit(s) for this live continuing medical education activity must complete the CME Request for Credit Survey by Wednesday, June 3, 2015. Certificates will only be issued to those who complete the survey. Your CME certificate will be sent to you via email after the completion of the activity. Statement of Educational Need, Target Audience and Learning Objectives New technologies, scientific advances and exponential developments in the field of translational cancer medicine have led to changes in oncology practice and significant patient benefit. By bridging the gap between what physicians understand about cancer biology and the clinical applications, this meeting aids basic researchers, physicians and clinician-scientists in obtaining, synthesizing and integrating the most cutting-edge research. This exposure is essential for the implementation of best practices, such as the most current molecular-based tests to aid in the diagnosis, treatment and prevention of cancer. Through the active participation of clinical investigators and physicians in the meeting, laboratory researchers will obtain a better understanding of the wider context of their research in the “bench-to-bedside” continuum. After participating in this CME activity, physicians should be able to: Identify technological advances and tools to accelerate progress in cancer research, improve early detection and early intervention, with the ultimate goal of extending patients’ lives and improving their ■■ cal research efforts towards the prevention and early detection of cancer. Develop collaborations amongst physicians, researchers and clinician-scientists to advance the cause of treating and preventing cancer. ■■ CREDIT: B. KRIST FOR VISIT PHILADELPHIA Accreditation Statement The American Association for Cancer Research is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education activities for physicians. Opened in June 1993, the Pennsylvania Convention Center in Philadelphia boasts famed landmarks within short walks of the facility, including Independence Hall, Chinatown and Rittenhouse Square. Outside of the western entrance is the Museum Mile, which stretches along Benjamin Franklin Parkway. quality of life. Explain the integration of information from basic and translational sciences to drug development, clinical research and application of new findings. Integrate the use of biomarkers and other indicators to improve patient selection (or stratification) ■■ ■■ for clinical trials. Incorporate the latest research findings regarding therapies and treatment options including immunotherapy in a variety of cancer types in order to improve patient outcomes. Formulate new strategies that will further scientific and clini■■ ■■ Disclosure Statement It is the policy of the AACR that the information presented at AACR CME activities will be unbiased and based on scientific evidence. To help participants make judgments about the presence of bias, the AACR will provide information that Program Committee members and speakers have disclosed about financial relationships they have with commercial entities that produce or market products or services related to the content of this CME activity. This disclosure information will be made available in the program/proceedings of this conference. Acknowledgement of Financial or Other Support This activity is supported by grants and will be disclosed at the activity. Questions about CME? Please contact the Office of CME at (215) 440-9300 or [email protected] n AACR 2015 CREDIT: B. KRIST FOR VISIT PHILADELPHIA AACR 2015 Cancer and Biomedical Research Career Fair SATURDAY, APRIL 18, 9 A.M. TO 3 P.M. Scientists at all levels are invited to attend the AACR Career Fair during the annual meeting. The fair will enable job seekers to connect with EARLY EXPOSURE E ARLY-CAREER SCIENTISTS were invited to apply to give a talk in a Major Symposium or Recent Advances Session at the AACR Annual Meeting 2015. Speaking slots are limited and available to all AACR associate members and any AACR active members who are at the junior faculty level (not higher than assistant professor or equivalent). This program debuted in 2014 with five AACR NextGen Stars giving short talks in major sessions. The NextGen Stars program provides an opportunity to increase the visibility of early-career scientists at the AACR Annual Meeting and to support the professional development and advancement of those selected to speak. NextGen Stars for 2015 will receive travel support and complimentary registration for the meeting. n Exhibit Show Hours SUNDAY, APRIL 19 1 p.m. to 5 p.m. MONDAY, APRIL 20 9 a.m. to 5 p.m. TUESDAY, APRIL 21 9 a.m. to 5 p.m. employers from government, industry and academia. Representatives from prospective employers will be available to interview job seekers. n MARCH 2015 | | DDNEWS 27 Robert Indiana’s iconic Love sculpture is located in the JFK Plaza across from City Hall. It was installed in 1976, and its location, JFK Plaza, is now better known as Love Park. CREDIT: © 2014 AACR/TODD BUCHANAN For more information, visit www.DDN-News.com The poster presentation area at the AACR Annual Meeting 2014 is pictured here. Poster sessions at the 2015 meeting will be located adjacent to the exhibitor area. OncoSignature HTS Platform Screen Your Compounds Against 300 Cancer Cell Lines Reveal the antiproliferative signature of your compounds as single agents or in combination across 300 cancer cell lines. Our OncoSignature HT Screening Platform allows you to profile your compounds of interest as mono or combination therapy across a comprehensive panel of 300 cancer cell lines. Study drug response, compare activity against 200 oncology reference compounds, identify combination interactions and aid in identifying the best patient population for your drug candidate or drug combination. Other Lung Brain Throat Endometrium Head & Neck Liver Up to 300 cell lines including Gastric Colorectal Pancreas Skin Powering Genomic Research and Translational Medicine, from Sequence to Treatment Lymphoma Ovary Breast WEDNESDAY, APRIL 22 9 a.m. to noon Future Annual Meetings APRIL 16-20, 2016 New Orleans APRIL 1-5, 2017 Washington, D.C. APRIL 14-18, 2018 Chicago To learn more about OncoSignature visit: info.horizondiscovery.com/oncosignature MARCH 30-APRIL 3, 2019 Philadelphia HD 17022015 DDN_Portrait.indd 1 2/19/2015 9:37:53 AM 28 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com CLINICAL TRIALS WALTHAM, Mass.—Biopharmaceutical company Minerva Neurosciences Inc. recently released preliminary results from a Phase 1 clinical study that demonstrated that treatment with MIN-202, a selective orexin-2 antagonist, produced significant improvements in sleep onset and sleep duration in patients with comorbid insomnia related to major depressive disorder. The company also shared preliminary results from two other Phase 1 studies that suggest the compound is well tolerated, with positive pharmacokinetic and pharmacodynamic features. Janssen Research and Development LLC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, conducted the studies as part of a collaboration to develop MIN-202. Sleep disturbances have been linked to a suboptimal response to antidepressants in patients with mood disorders, which leads to an increased risk for relapse and prodromal depression. Myriad RBM, Institut Pasteur set sights on TB SALT LAKE CITY—Myriad RBM, a wholly owned subsidiary of Myriad Genetics Inc., has teamed up with the Institut Pasteur in a public-private research collaboration taking aim at tuberculosis. The partners will conduct a proof-of-concept study to evaluate patients with latent and active tuberculosis infections who are affiliated with the South African Tuberculosis Vaccine Initiative clinical study sites. The aims of the study will be to field-test Myriad RBM’s TruCulture system as a point-of-care blood collection and immune response monitoring method and to stratify patients with active and latent tuberculosis. Matthew Albert, co-coordinator of Milieu Interieur and director of the Immunology Department at Institut Pasteur, noted that, “Prior studies support the use of the TruCulture system in settings with limited resources, and may help us improve the diagnosis of TB and accelerate the development of new drugs and vaccines to treat the disease.” IN IN THIS THIS SECTION SECTION Alzheimer’s disease Head Treatment to target tangles.................... 28 Text����������������������������������������������������������� 0 Fabry disease Text............................................................ A fine showing for migalastat in Fabry... 280 Head Insomnia Text����������������������������������������������������������� 0 Orexin-2 antagonist Text............................................................ yields positive Phase 1 data.................... 280 Oncology ‘Catapulting’ forward with MultiStem.... 30 Double, double; myeloma in trouble?..... 28 Respiratory Myriad RBM, Institut Pasteur set sights on TB.......................... 28 Trial optimization Optimizing trials through mobile health technology........................ 32 A fine showing for migalastat in Fabry Amicus reports positive Phase 3 data from a pair of studies BY KELSEY KAUSTINEN CRANBURY, N.J.—Biopharmaceutical com- pany Amicus Therapeutics has released positive data on prespecified patient-reported outcomes from both of its Phase 3 studies of migalastat HCl, an oral small-molecule pharmacological chaperone for Fabry disease. The company presented the data at WORLDSymposium 2015 in Orlando, Fla. The first study, Study 011 (FACETS), was a Phase 3 study measuring the reduction of disease substrate (globotriaosylceramide, or GL-3) in Fabry patients with amenable mutations after treatment with migalastat. The study also evaluated clinical outcomes such as renal function and left ventricular mass index (LVMi) as secondary endpoints. Patients enrolled in this study were treatment-naïve or had not received enzyme replacement therapy for at least six months prior to joining the study. In Study 011, the recent data reported improvements in gastrointestinal symptoms, including a significant decrease CREDIT: NASDAQ Orexin-2 antagonist yields positive Phase 1 data Representatives of Amicus gather for the closing bell of NASDAQ on Feb. 28, 2014. The company recently reported positive patient-reported outcomes on gastrointestinal symptoms, pain and quality of life from two Phase 3 studies of migalastat in Fabry disease. in diarrhea in patients receiving migalastat vs. placebo, and after 18 to 24 months of treatment with migalastat, significant improvements in diarrhea and indigestion were seen, as well as promising trends in reflex and constipation. Study 012 (ATTRACT) was a Phase 3, open-label study comparing oral migalastat to standard-of-care enzyme replacement therapies for Fabry disease (Fabrazyme and Replagal). Patients in this study had Fabry AMICUS CONTINUED ON PAGE 29 Double, double; myeloma in trouble? Genmab announces preliminary results in Phase 2 study of daratumumab in double refractory multiple myeloma BY LLOYD DUNLAP COPENHAGEN, Denmark— er’s disease (AD), but nobody has an approved treatment to target the tangles at the moment, according to Dr. Claude Wischik, Genmab A/S has announced preliminary results from the Phase 2 study of daratumumab in double refractory multiple myeloma conducted by its collaboration partner Janssen Biotech Inc. The overall “We are very pleased with response rate (ORR) in the these positive results in this study was 29.2 percent in study of daratumumab as a for the the 16 mg/kg dosing group, monotherapy treatment of double refractory and the median duration of multiple myeloma,” says Dr. response was 7.4 months as Jan van de Winkel, CEO of determined by an indepen- Genmab. “We look forward to presenting additional data of dent review committee. The study evaluated mul- this trial at a key upcoming tiple myeloma patients who medical conference this year.” have received at least three different lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent (IMiD), or who are double refractory to a proteasome inhibitor and an IMiD. (Examples of proteasome inhibitors TAURX CONTINUED ON PAGE 30 GENMAB CONTINUED ON PAGE 31 Alzheimer’s disease is a major and growing problem worldwide, and tau-based vaccines may offer a new and more effective way to treat the disease in its early stages. Research and consulting firm GlobalData estimates the market for such a vaccine could be upwards of $10 billion. Treatment to target tangles TauRx demonstrates potential efficacy of tau aggregation inhibitor therapy in Alzheimer’s disease BY ILENE SCHNEIDER S I N G A P O R E — Ta n g l e s of neuronal fibers are correlated with abnormalities in brain scans of patients with Alzheim- CREDIT: GENMAB BRIEFS CLINICAL TRIALS For more information, visit www.DDN-News.com AMICUS CONTINUED FROM PAGE 28 disease with amenable mutations in a clinical trial assay and had been treated with enzyme replacement therapy for a minimum of 12 months prior to joining the study. Co-primary outcome measures were mean annualized changes in estimated glomerular filtration rate (GFR) and measured (iohexol) GFR assessed by descriptive comparisons of migalastat and enzyme replacement therapy over 18 months. Secondary outcome measures featured LVMi and a composite of Fabry-associated clinical events (e.g. renal, cardiac or cerebrovascular). For the new Study 012 data, patient-reported outcome measures of pain and quality of life were reported, with measures of both remaining stable when patients switched from enzyme replacement therapy to migalastat. “We are pleased to present compelling new data at WORLDSymposium on patient-reported outcomes on gastrointestinal symptoms, pain and quality of life from our Phase 3 studies. In addition to the previously reported migalastat Phase 3 data, it was also important to assess the impact of migalastat on some of the most commonly reported symptoms which can severely impact quality of life for people living with Fabry disease,” John F. Crowley, chairman and CEO of Amicus Therapeutics, said in a press release. “These positive results, shown for the first time today in both naïve and ERT switch patients, add to the totality of the data that suggest migalastat could be an important new therapy in the treatment of Fabry disease. These data also continue to show the positive effects for patients, owing, we believe, to migalastat’s novel mechanism of action in all key organs and tissues of disease. We continue to move forward rapidly to seek regulatory approval.” Previously reported Phase 3 data from both trials showed that migalastat treatment led to reductions in disease substrate, stability of kidney function and improvement in a key cardiac parameter in patients with amenable mutations. Amicus defines amenable mutations as having “an absolute increase of 3 percent of wild-type alphaGal A enzyme activity and a relative increase of 20 percent when exposed to migalastat in a cellbased in-vitro assay.” All patients in Study 011 and 012 presented with amenable mutations in the clinical trial HEK assay. After enrollment, Amicus developed a GLP HEK assay with a third party to measure the criteria for amenability with more quality control and rigor, and overall, based on results from mutations tested in that assay, the company believes approximately 30 to 50 percent of patients with Fabry disease have mutations MARCH 2015 | | DDNEWS 29 “These positive results, shown for the first time today in both naïve and ERT switch patients, add to the totality of the data that suggest migalastat could be an important new therapy in the treatment of Fabry disease. These data also continue to show the positive effects for patients, owing, we believe, to migalastat’s novel mechanism of action in all key organs and tissues of disease.” John F. Crowley, chairman and CEO of Amicus Therapeutics amenable to migalastat. Fabry disease, as defined by the Genetics Home Reference, a ser- vice of the U.S. National Library of Medicine, is “an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body’s cells.” The disease is caused by mutations in the GLA gene, which provides genetic instructions for the production of alpha-galactosidase A, an enzyme that normally breaks down globotriaosylceramide. The mutations alter the structure and function of alpha-galactosidase A, preventing it from breaking down globotriaosylceramide, which then builds up in cells—particularly those lining blood vessels in the skin and cells in the kidneys, heart and nervous system—and damages them. n EDITCONNECT: E031516 Discover actionable biomarkers from solid tumor samples Unmatched genome-wide copy number analysis with a single assay OncoScan® FFPE Assay Kit delivers Whole-genome copy number from only 80 ng of FFPE-derived DNA Copy-neutral loss of heterozygosity (cnLOH) and somatic mutation analysis Dynamic detection range of 50+ copies; high confidence in detecting low-level amplifications (<8 copies) Free analysis software, including a visual overlay of functional genomic data with DNA copy number variations Visit www.affymetrix.com/oncoscan OncoScan® FFPE Assay Kit ©2015 Affymetrix, Inc. All rights reserved. For Research Use Only. Not for use in diagnostic procedures. Genome-wide copy number in 48 hours Affy_OncoScan_FFPE_Assay_Kit_Ad_DDN_3-2015_v2.indd 1 3/2/2015 4:58:13 PM CLINICAL High Quality Screening Libraries ‘Catapulting’ forward with MultiStem Cell Therapy Catapult and £2 million from Innovate UK give some lift to Athersys BY LORI LESKO 1,000,000 Compounds to Support Your Research ►CORE Library - More than 530,000 compounds based on novel, sp3-enriched designs ►EXPRESS-Pick - More than 500,000 druglike compounds DIVERSITY LIBRARIES TM DIVERSet Libraries - Diverse chemical structures with broad pharmacophore coverage PremiumSet - Diverse compounds with high-scoring chemical features CombiSet - Selection of CORE Library compounds with built-in SAR MicroFormat - Representative selection of EXPRESS-Pick Collection compounds TARGETED LIBRARIES CNS-Set - Selected for increased probability of oral bioavailability and blood-brain barrier penetration ION Channel / IONCore - For ligandgated and voltage-dependent ion channel targets KINASet / KINACore - Compounds scoring highly against pharmacophores derived from known kinase actives or from ATP GPCR - Druglike compounds based on scaffolds representing ß-turn mimetics NHRCore - Nuclear hormone receptor-directed compounds Fragment Library - Rules of 3 biased compounds San Diego, CA, USA +1-858-451-7400 [email protected] LONDON— Aimed in part at situa- ting the United Kingdom as a gateway for regenerative medicine in Europe, Edinburgh, Scotland-based Athersys Ltd. and Cell Therapy Catapult, a not-forprofit located at Guy’s Hospital in London, announced recently that Athersys was awarded an Innovate UK grant. The grant—expected to provide up to £2 million ($3 million) in support over the course of three years—will support a Phase 2a clinical study evaluating MultiStem cell therapy on acute respiratory distress syndrome (ARDS) patients. The study will be conducted by Athersys at leading clinical sites in the United Kingdom in conjunction with Cell Therapy Catapult. “We are pleased to receive this award from Innovate UK and to work with the Cell Therapy Catapult to conduct this important study,” stated Dr. Gil Van Bokkelen, chairman and CEO of Athersys, in a news release announcing the award and collaboration. “Both organizations reflect a commitment to be a driving force in healthcare innovation and to establish the UK as the leading gateway for the regenera- TAURX CONTINUED FROM PAGE 28 co-founder of TauRx Therapeutics Ltd. Part of the reason for that, he believes, is that a huge investment of money and people’s careers has gone into approaching AD with amyloid therapy. Clearly, that approach is not working. While current treatments for AD are only able to ease symptoms temporarily, tau-based vaccines may offer a new and more effective way to treat AD in the early course of the disease, says an analyst with research and consulting firm GlobalData. The market could be worth upwards of $10 billion. “It takes an upstart biotech company like us to break the mold and show that a different approach is viable,” Wischik says. TauRx Therapeutics is a spin-out company from the University of Aberdeen in Scotland, established in Singapore in 2002 to develop new treatments and diagnostics for a range of neurodegenerative diseases. The company’s tau aggregation inhibitor, LMTX, which is currently in global Phase 3 clinical trials for Alzheimer’s and frontotemporal dementia, targets aggregates of abnormal fibers of tau protein that form inside nerve cells in the brain, giving rise to tau tangles. Recently, The Journal of Alzheimer’s Disease published the results of the first clinical trial of a Tau Aggregation Inhibitor (TAI) in AD. This Phase 2 clinical trial, conducted by TauRx, provided the basis and rationale for subsequent Phase 3 clinical trials of a Athersys will conduct, along with Cell Therapy Catapult, a Phase 2a clinical study at leading clinical sites in the United Kingdom to evaluate MultiStem cell therapy for acute respiratory distress syndrome. tive medicine field in Europe.” “ARDS is a serious condition that is ineffectively treated by current standards of care, resulting in substantial patient and healthcare system impact,” Van Bokkelen added. “We believe that MultiStem cell therapy may provide an important new option for treatment and has the potential to meaningfully improve clinical outcomes for patients that are extremely ill.” William (B.J.) Lehmann, president and chief operating officer of Athersys, tells DDNews that ARDS “is a serious condition, requiring ICU/ventilator treatment, and occurs from a variety of causes that catalyze a substantial inflammatory response that greatly affects the lungs.” The Phase 2a clinical study “will exp- TAI in AD currently in progress. “We believe that we can arrest disease progression, hit the pause button and possibly even use the treatment preventatively,” explains Wischik. “It’s a completely different kind of treatment that acts on neurodegeneration.” Tangles were originally discovered by Alois Alzheimer in 1906, and this discovery gave the disease its name. Tangles were found to be composed of abnormal filaments largely made up of a short fragment of the protein tau in 1988 by Wischik and his colleagues. Using Heiko Braak’s system for staging tangle pathology, the TauRx team has seen that the process of developing tangles begins in a person’s fifties or earlier, and spreads from one region of the brain to another. The progression of the disease goes through six stages with a decline in mental function. The double-blind dose-finding Phase 2 clinical trial with the TAI, which involved 321 patients in 16 clinical research centers in the United Kingdom and one center in Singapore, tested three doses of the drug. The study met its predefined primary efficacy endpoint at 24 weeks on the standard scale most commonly used to measure cognitive decline in clinical trials (ADAScog) at the 138 mg/day dose. The primary result was also supported by benefit on two other clinical scales. The effect sizes seen were statistically significant and clinically lore the safety and efficacy of MultiStem treatment in the ARDS patient population,” Lehmann says. “We have not yet disclosed the details of the study plan, but this will come soon.” “Based on our prior work, we hypothesize that the treatment will help bring the inflammation under control rapidly and assist in the healing of damaged lung tissue,” he continues. “This should result in better overall recoveries and reduce time on the ventilator and in the ICU setting. Our working in this area has been limited to large animal models of the condition, where we have seen good benefit. Our work in other clinical areas [such as graft-versus-host disease] suggests that we can have an impact in this patient population.” If the Phase 2a clinical study is successful, “most likely we would proceed with advanced clinical studies, designed to advance us to filing for registration,” Lehmann says. Keith Thompson, CEO of Cell Therapy Catapult, stated in a news release, “Bringing advanced therapeutic clinical trials to the UK is a key part of our strategy to accelerate the growth of the cell therapy industry to generate health and wealth. We are delighted to collaborate with Athersys on this important trial.” MultiStem cell therapy may provide an important new option to treatment, according to Thompson, who notes, ATHERSYS CONTINUED ON PAGE 32 meaningful in moderate subjects at 24 weeks. The clinical results were also supported by brain scan evidence of arrest of decline over the same period in mild subjects at the same dose. The beneficial effect was sustained to 50 weeks in both mild and moderate subjects at this dose, with 90-percent reduction in the rate of cognitive decline overall. However, the surprising observation that the top dose of 228 mg/day had reduced efficacy has taken TauRx scientists four more years to unravel. They discovered that the original formulation suffers from dose-dependent impairment in absorption when taken with food and developed an entirely new form of the molecule that enables direct absorption without need for active conversion in the gut. It is better absorbed, better tolerated and has fewer side effects, according to Wischik, thus enabling Phase 3 trials to test whether an even higher level of efficacy can be achieved without significant loss of tolerability and safety. The ongoing trials are testing LMTX in the dosage range of 150 to 250 mg/day. First results from the clinical trials are expected in the first half of 2016. If the Phase 3 clinical trials confirm a level of efficacy and safety similar to that seen in the Phase 2 trial reported in the Journal of Alzheimer’s Disease, a treatment targeting the Tau aggregation pathology of AD could be on the market as early as 2017. n EDITCONNECT: E031517 CLINICAL TRIALS For more information, visit www.DDN-News.com GENMAB ly, Genmab has a clinical pipeline with both late- and early-stage programs and an innovative preclinical pipeline. Genmab’s technology base consists of validated and proprietary next-generation antibody technologies—the DuoBody platform for generation of bispecific antibodies and the HexaBody platform that creates effector function-enhanced antibodies. The HexaBody platform strengthens the killing ability of antibodies while retaining regular CONTINUED FROM PAGE 28 are bortezomib or carfilzomib, and examples of IMiD agents are pomalidomide or lenalidomide.) This is the indication for which daratumumab was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) in May 2013. In August 2012, Genmab granted Janssen Biotech an exclusive worldwide license to develop and commercialize daratumumab. “We are very pleased with these positive results in this study of daratumumab as a monotherapy for the treatment of double refractory multiple myeloma,” said Dr. Jan van de Winkel, CEO of Genmab. “We look forward to presenting additional data of this trial at a key upcoming medical conference this year.” This two-part study enrolled 124 patients. Part one of the study defined an optimal daratumumab regimen going forward, while part two was an expansion, based on the optimal regimen determined in the first part. The primary objective of structure and specificity. The technology has the potential to enhance antibody therapeutics for a broad range of applications in cancer and infectious diseases. The DuoBody platform is a platform for the discovery and development of bispecific antibodies that may improve antibody therapy of cancer, autoimmune, infectious and central nervous system disease. Bispecific antibodies bind to two different epitopes either on the same or on different targets MARCH 2015 | | DDNEWS 31 (also known as dual-targeting), which may improve the antibodies’ specificity and efficacy in inactivating the disease target cells. DuoBody molecules are reportedly unique in combining the benefits of bispecificity with the strengths of conventional antibodies, which allows DuoBody molecules to be administered and dosed as other antibody therapeutics. The Genmab UniBody technology creates a stable, smaller antibody format. UniBody molecules will inhibit or silence cells, but not kill them, which could be an advantage in the treatment of certain diseases such as asthma or allergies. Genmab’s deep antibody expertise is expected to provide a stream of future product candidates. Partnering of selected innovative product candidates and technologies is a key focus of Genmab’s strategy, and the company has alliances with top tier pharmaceutical and biotechnology companies. n EDITCONNECT: 031518 CREDIT: GENMAB Redefining Microplate Washing...Again. Genmab’s technology base consists of the DuoBody platform for generation of bispecific antibodies and the HexaBody platform for creating effector function-enhanced antibodies. the study was to define the optimal dose and dosing schedule, to determine the efficacy of two treatment regimens of daratumumab as measured by ORR and to further characterize the safety of daratumumab as a single agent. Daratumumab is a human CD38 monoclonal antibody with broadspectrum killing activity, which is in clinical development for multiple myeloma. Daratumumab targets the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated human antibody therapeutics for the treatment of cancer. Founded in 1999, the company currently has one marketed antibody, Arzerra (ofatumumab), for the treatment of certain chronic lymphocytic leukemia indications. Additional- 405 Touch ™ Enhanced, high-resolution touch screen Simple protocol creation and execution USB ports for multi-user functionality NOW WITH VERIFY V ERIF RIFY Y ™ TECHNOLOGY Decades of proven expertise Enhance your microplate washing experience at www.405touch.com www.biotek.com 405 Touch Ad with Verify-DDN.indd 1 2/2/15 2:59 PM CLINICAL TRIALS 32 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Optimizing trials through mobile health technology NEW YORK— Medidata Solutions Inc. a global provider of cloud-based solutions for clinical research in life sciences, recently announced a strategic collaboration with Garmin International Inc., a unit of Garmin Ltd., aimed at making clinical trials better. By integrating Garmin’s vívofit activity tracker with the Medidata Clinical Cloud, Medidata says it is enabling its life-sciences customers to make use of mobile health (mHealth) devices with the potential to enhance patient engagement, data quality and operational efficiencies in clinical trials. Designed to be worn on a person’s wrist round-the-clock, Garmin’s vívofit measures steps taken, distance traveled, calories burned and hours slept. The water-resistant device—which displays fitness data through its always-on LCD display—is being used by Medidata to capture patient data in clinical trials. According to Medidata, the vívofit was chosen because of the ease of use provided by its year-long battery life, which can improve the convenience and speed associated with capturing direct-from-patient data and, as such, has the potential to increase compliance among study participants in a clinical trial setting. “We’re thrilled to be working with Garmin, a company that shares our passion for innovation and our commitment to enhancing people’s health and well-being,” said Glen de Vries, Medidata’s president. “Integrating the vívofit with the Medidata platform is part of our ongoing efforts to unify mHealth devices with cloud-based technologies in a clinical trial setting. We believe these efforts will result in better data, enhanced patient experiences and more efficient trials.” TOOLS & TECHNOLOGY The vívofit—with its year-long battery life and ability to record such data as steps taken, distance traveled, calories burned and hours slept—could play a key role in enhancing the capture of direct-from-patient data during clinical trials. Medidata has built cloud-based infrastructure that enables life-sciences companies to explore the use of mHealth technologies in clinical research. This infrastructure gathers data from devices worn by patients and integrates it with other traditional clinical data, “Integrating the vívofit with the Medidata platform is part of our ongoing efforts to unify mHealth devices with cloud-based technologies in a clinical trial setting. We believe these efforts will result in better data, enhanced patient experiences and more efficient trials.” Glen de Vries, president of Medidata ATHERSYS CONTINUED FROM PAGE 30 “Preclinical data suggests that MultiStem cells may have a protective effect by shifting the physiological response from pro-inflammatory to anti-inflammatory. In animal models, MultiStem cells have demonstrated an ability to reduce the severity of pulmonary distress, reduce alveolar edema and return lung endothelial permeability to normal.” Intravenous MultiStem treatment early on, following the onset of the condition, may ameliorate the initial hyperinflammation and reduce the fibrotic activity that follows, thereby speeding the return to and improving the likelihood of more normal lung function and helping patient recovery, he explains, adding that up to 45 patients will be recruited at six to eight sites for the study. “As part of our strategy, we are collaborating with a number of companies and institutions, not all grant-funded,” Thompson said. ”We were successful partners in three other projects in the same Innovate UK program this year.” Furthermore, the UK remains supportive of stem cell therapy. including labs, vital signs, medical history and adverse events. Medidata is currently working with top life-sciences organizations to explore the feasibility of using the vívofit in clinical trials. The data is pulled from the Garmin activity tracker in 15-minute increments and then analyzed to evaluate its connection with traditional clinical measures and determine whether it can provide better insight into patient health status or response to therapy. “At Garmin, our mission is to develop innovative technology that promotes healthy and active lifestyles,” said Allison Swelin, strategic partnership development manager at Garmin International. “We’re excited to see Medidata use the vívofit in their pursuit to help the global life-sciences industry find better, easier ways to collect data directly from patients.” n “ARDS is a serious condition that is ineffectively treated by current standards of care, resulting in substantial patient and healthcare system impact. We believe that MultiStem cell therapy may provide an important new option for treatment, and has the potential to meaningfully improve clinical outcomes for patients that are extremely ill.” Dr. Gil Van Bokkelen, chairman and CEO of Athersys “The government continues to remain squarely behind regenerative medicine as one of the eight great technologies of the UK,” Thompson said. “The Cell Therapy Catapult aims to develop a portfolio of clinical activities that covers the range of the sector, generating strong clinical data and building supportive structures for routes to market that will drive investment and value into the UK.” Characterized by widespread inflammation in the lungs, ARDS can be triggered by pneumonia, sepsis or other trauma and represents a major cause of morbidity and mortality in the critical care setting. ARDS has significant implications, as it prolongs intensive care unit and hospital stays and requires convalescence in the hospital and rehabilitation. There are limited interventions and no effective drug treatments for ARDS, making it an area of high unmet clinical need with high treatment costs. The medical need for a safe and effective treatment of ARDS is also significant due to its high mortality rate. Annually, it affects some 33,000 patients in the United Kingdom and 400,000 to 500,000 patients in Europe, the United States and Japan. n EDITCONNECT: E031519 For more information, visit www.DDN-News.com MARCH 2015 | | DDNEWS 33 DIAGNOSTICS oncgnostics licenses MDxHealth tech IRVINE, Calif. & HERSTAL, Belgium—Recently, oncgnostics GmbH announced that it had received a limited worldwide license to MDxHealth SA’s methylation specific PCR (MSP) technology. Per the license agreement, MDxHealth has granted oncgnostics a limited, non-transferable, nonexclusive, worldwide license to its patented MSP technology for diagnostic applications in cervical cancer, for which it will receive upfront and milestone payments in return, as well as royalties on net sales. “oncgnostics is pleased to obtain a license to MDxHealth’s proprietary epigenetic technology for use in our cervical cancer diagnostics programs. This technology allows for the accurate and sensitive assessment of DNA methylation markers included in our first test GynTect, which is intended for the early detection of cervical neoplasias that may progress to cancer,” said Dr. Alfred Hansel, CEO of oncgnostics. BJI InoPlex test gains CE marking PARIS— Diaxonhit recently announced the completion of the CE marking of its BJI InoPlex diagnostic test, reportedly the first blood test to aid in the diagnosis of prosthetic bone and joint infections. The marking was completed on schedule in late 2014, and the test is now ready for commercialization, with a planned launch date in the first quarter of this year directly through InGen, Diaxonhit Group’s commercial affiliate. BJI InoPlex demonstrated 82.2-percent specificity and 75.9-percent sensitivity compared to microbiological results from intraoperative samples, which includes all types of targeted staphylococci (the most common culprit in such infections). Approximately 10 to 20 percent of patients receiving joint replacements experience pain or functional impairment, and it is imperative to discern whether the cause is due to infection or mechanical malfunction in order to properly treat the issue. IN THIS SECTION Alzheimer’s disease Amarantus: Positive Alzheimer’s data.... 33 Infection BJI InoPlex test gains CE marking........... 33 Oncology A boost for NGS diagnostics................... 33 Advancing NSCLC diagnosis and treatment.......................................... 33 oncgnostics licenses MDxHealth tech...................................... 33 Prediabetes New study support for Metabolon.......... 34 Advancing NSCLC diagnosis and treatment Biocept, Insight to evaluate expression and mutation in ALK therapeutic target BY LLOYD DUNLAP SAN DIEGO— Biocept Inc., a molecular oncology diagnostics company specializing in biomarker analysis of cell-free circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), and Nashville, Tenn.-based Insight Genetics, a molecular diagnostic assay developer, are collaborating on an enhanced diagnostic for the expression and mutation of ALK, a major therapeutic target in treating non-small cell lung cancer (NSCLC). Biocept and Insight Genetics will evaluate the combination of both companies’ platform technologies to enhance detection of ALK status in NSCLC patients. Biocept’s proprietary technology will be used to capture and analyze CTCs and ctDNA. Insight Genetics will then utilize its technical expertise and proprietary evaluation methods to determine ALK expression and whether the gene has mutated over the course of cancer treatment. The initial aim is to better identify and monitor patients who may benefit from exist- ing ALK-based therapies as well as those that may benefit from second-generation therapies based on inhibitor resistance mechanisms. “ALK is incorporated into the testing guidelines for oncologists making treatment decisions in NSCLC patients,” notes Biocept’s Raaj Trivedi, vice president of commercial operations. “ALK-positive patients now have targeted treatment options with FDA-approved drugs: Pfizer’s Xalkori (crizotinib) and Novartis’s Zykadia (ceritinib). We are finding that many patients are still not being tested to determine their ALK status due to a lack of biopsy tissue. This lack of information makes personalized treatment decisions—either to use FDA-approved ALK target drugs or to include an ALK-positive patient in a trial for second- and third-generation therapies—much more difficult.” Part of Biocept’s business model is to help identify more patients for new and existing therapies using a simple, blood-based liquid biopsy when tissue biopsy is not available. Biocept currently offers an ALK rearrangement test using circulating tumor DNA found in a patient’s blood. “However, we are always looking for other technologies ALK CONTINUED ON PAGE 35 Biocept Inc. and Insight Genetics are working together to create an enhanced diagnostic for the expression and mutation of ALK, a therapeutic target in the treatment of nonsmall cell lung cancer. Amarantus: Positive Alzheimer’s data BY MEL J. YEATES to bolster Roche’s sequencing unit and accelerate its development of targeted next-generation sequencing (NGS)-based diagnostics. “Roche believes focused and high-quality next-generation sequencing assays using blood SAN FRANCISCO—Amarantus BioScience Holdings Inc. has announced positive top-line results of its LP-002 study of the Lymphocyte Proliferation Test (LymPro Test) blood diagnostic for Alzheimer’s disease (AD). The 140-subject study successfully demonstrated that multiple individual biomarkers achieved statistically significant results in correctly distinguishing patients with AD from healthy controls. “Not only is LymPro a consistent and reliable tool in diagnosing Alzheimer’s disease, having completed ‘fit-for-purpose’ assay validation at Icon [which provides lab testing and biomarker services], it may now be used to enrich inclusion criteria in pharmaceutical clinical studies,” said Colin Bier, chief development officer of Amarantus Diagnostics. Biomarker services using LymPro data will be available for investigational use only in pharmaceutical therapeutic clinical development programs. “LymPro represents an innovative approach to improving the diagnosis of Alzheimer’s disease by measuring a fundamental aspect of disease biology,” said Gerald E. Commissiong, president and CEO of Amarantus. “The fact that LymPro has the ability to distinguish patients with early-stage AD from control subjects will be important to the pharmaceutical industry engaged in Alzheimer’s research.” LymPro has shown itself able to differentiate Alzheimer’s disease from Parkinson’s and vascular dementias with a sensitivity of 94 percent and specificity of 65 percent. This finding ROCHE CONTINUED ON PAGE 34 LYMPRO CONTINUED ON PAGE 35 CREDIT: ROCHE BRIEFS For the Roche Sequencing Unit (pictured here), Signature’s most valuable asset may be its large tumor tissue and plasma biobanks that cover multiple cancers, including colorectal and lung cancer. A boost for NGS diagnostics Roche expands sequencing unit with acquisition of Signature Diagnostics BY ZACK ANCHORS PLEASANTON, Calif.— Roche has extended its recent run of acquisitions with the purchase of Signature Diagnostics AG, a privately held German translational oncology and genomics company. The move is intended DIAGNOSTICS 34 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com New study support for Metabolon Recent study results reinforce the clinical validity of the company’s IGT test BY KELSEY KAUSTINEN Metabolon’s Quantose IGT test recently appeared in the Journal of Diabetes Science and Technology, supporting the clinical validity of the test for assessing impaired glucose tolerance (IGT), a state of prediabetes. Quantose IGT is a laboratory-developed test that reflects the degree of impaired glucose tolerance, a core metabolic defect in dysglycemia and a known risk factor for developing diabetes and cardiovascular disease. “This study verified that the Quantose IGT test accurately reflects IGT, which may provide the opportunity for earlier clinical intervention that could help curb the epidemic of type 2 diabetes,” Eric Button, senior vice president of diagnostics at Metabolon, noted in a press release. “We look forward to bringing this new test to the market in the coming months.” The test is designed to enable physicians to easily identify IGT using a single, fasted blood draw, a simpler, less unpleasant approach than the oral glucose tolerance test (OGTT), the current clinical practice standard for measuring IGT. The OGTT is a somewhat involved process, requiring patients to fast prior to the test, undergo a blood draw to determine a fasting glucose level and then drink a glucose-rich beverage and undergo multiple blood draws over the course of ROCHE CONTINUED FROM PAGE 33 samples have the capacity to become cost-effective diagnostic tools for monitoring patients with cancer,” Dan Zabrowski, head of Roche Tissue Diagnostics and the Roche Sequencing Unit, tells DDNews. “We plan to leverage Signature’s unique expertise in both biobanks and cfDNA (cell-free DNA) tests to develop targeted diagnostics in the future.” Signature’s most valuable asset for Roche may be its large tumor tissue and plasma biobanks that cover multiple cancers, including colorectal and lung cancer. The company has created these biobanks within the framework of large multicenter prospective clinical studies. Among its key products are longitudinal plasma samples from cancer patients. Zabrowski explains that Roche sees high-quality, comprehensive CREDIT: METABOLON RESEARCH TRIANGLE PARK, N.C.— Results from a study of Metabolon recently announced additional results supporting the clinical validity of its Quantose IGT test, which could offer a more convenient alternative to the current standard oral glucose tolerance test. roughly two hours. Button explains that the OGTT currently stands as the standard for checking the blood glucose levels of pregnant women, specifically if a glucose screening test result is higher than normal and there is a concern about gestational diabetes. However, while there are approximately three million births in the United States each year, he says, fewer than a million tests are performed for OGTT due to its inconvenience. “From the patients’ perspective, it goes beyond just a level of inconvenience,” adds Doreen Bates, senior director of marketing at Metabolon. “Many people who’ve had to take this test end up with nausea, upset stomach, that kind of thing, because they go in fasted, and then they take blood draws. They do the test, you have to sit in the doctor’s office for those two or three hours, so there’s a physical and an inconvenient element to it as well.” Button tells DDNews that while OGTT is also the current standard when it comes to diagnosing diabetes, that is another instance in which physicians pass over the test given how time-intensive and taxing it is. “If one had a simple blood test that could replace OGTT, it would be used frequently as the convenient, gold-standard diabetes test,” he notes. Using its metabolomic profiling technology, Metabolon identified several metabolites whose fasting levels are associated with both dysglycemia and type 2 diabetes, which form the basis of its Quantose IGT test. The test was developed using fasting plasma samples taken just cancer biobanks as holding great potential when matched tumor tissue and plasma samples are combined with extensive clinical annotation. The company believes that such a resource could lead to the development of assays that identify the causes and mechanisms of resistance to treatment and disease recurrence. “Having access to such unique biobanks is a key component in the development of novel NGS diagnostics,” says Zabrowski. In addition to its biobanks, Signature has already developed several next-generation sequencing assays using targeted gene panels that are used for research purposes. The company has built expertise in developing ultra-deep sequencing tests that utilize cfDNA. Roche hopes that its effort to develop effective NGS diagnostics will benefit from Signature’s expertise in both biobanks and cfDNA testing. “Biobanks play an impor- tant role in uncovering the cause or origin of disease such as cancer, which is important in translational research and the development of personalized therapies for patients,” said Roland Diggelmann, chief operating officer of Roche Diagnostics, in an official statement. “Signature represents a unique bridge between high-value cancer biobanks and NGS assay development.” Signature was founded in 2004 and is currently based in Potsdam, Germany. It appears that the firm will continue to operate much as it has previously under the corporate umbrella of Roche. Signature will be integrated into the Roche Sequencing Unit and will continue to focus on expanding its genomic signature portfolio. “Signature is a strong company with excellent management,” says Zabrowski. “We plan to engage in a limited integration and expect Signature will act as a standalone enter- prise.” Neither company has disclosed the financial terms of the acquisition. “We are very pleased Roche recognizes the importance of high-quality longitudinal cancer biobanks for the development of novel NGS-based diagnostics,” said Andre Rosenthal, CEO of Signature, in the news release about the deal. “Joining forces with Roche is very exciting, as it will allow us to further develop our NGS assays for sequencing tests using cfDNA, which may advance the development of non-invasive treatment response monitoring for cancer patients.” The purchase of Signature is just one of several recent acquisitions by Roche. Within the last year it has also purchased Intermune, Genia Technologies, Santaris, Seragon Pharmacueticals and Bina Technologies. The Swiss firm recently posted a 16-percent drop in annual profits for 2014 but pre- prior to an OGTT from 1,623 nondiabetic subjects from two different cohorts: 955 from the Relationship between Insulin Sensitivity and Cardiovascular Disease Study (RISC Study; 11.7 percent IGT) and 668 subjects from the Diabetes Mellitus and Vascular Health Initiative cohort from the DEXLIFE project (11.8 percent IGT). Button says that the Quantose IGT test offers a more accurate approach, because the sugar solution that has to be drunk with the OGTT “adds a lot of unknown variables,” an issue Bates echoes. “We’re measuring what’s going on within a person’s body as it’s actually occurring, without, as Eric said, that artificial adjustment from the sugar drink that you have to take when you do the oral glucose tolerance test; that’s artificially adjusting your body to stress it in some ways, and we’re not doing that. We’re just measuring what’s happening in your body as it’s occurring currently,” she explains. As the company advances the Quantose IGT test, Button says they will be conducting additional studies to support its clinical utility, in addition to seeking reference laboratory partners to aid in the nationwide distribution of the test. In the third quarter of 2014, Metabolon announced a partnership with Metadia Biotech S.L. to commercialize its Quantose IR and Quantose IGT prediabetes tests in Europe (for more information, check out “Metabolon taps Metdia for European marketing of prediabetes test” in the Diagnostics section of our November 2014 issue). n EDITCONNECT: E031523 dicted profits and sales to increase significantly in 2015. While Roche’s recent acquisitions may fit into a broader strategy for the company, the merger with Signature also serves the more specific goals of the company’s sequencing unit. “The strategy for Roche Sequencing is to advance NGS through an integrated genomics portfolio that provides our customers with a complete, endto-end testing solution,” Zabrowski tells DDNews. “To this end, we are focused on developing an NGS workflow solution encompassing four key areas: sample preparation, platforms and technology, informatics and diagnostic testing menu.” Zabrowski says the sequencing unit is making significant internal investments in potential breakthrough technologies as well as seeking innovative technologies that are being developed by other companies. EDITCONNECT: E031521 DIAGNOSTICS For more information, visit www.DDN-News.com LYMPRO CONTINUED FROM PAGE 33 is important, as it could assist pharmaceutical companies in distinguishing dementia of the Alzheimer’s type from dementia of a disparate etiology. Amarantus has also identified a new, undisclosed biomarker that correlates with AD diagnosis in the LP-002 study. This new marker could become a component of a multivariate algorithm (LymPro Score) which will create a simplified assessment of a person’s probability of having Alzheimer’s disease. Commissiong tells DDNews, “The newly identified biomarker will impact the sensitivity of the assay and possibly improve the specificity of the test’s diagnostic capabilities.” Amarantus has also announced its first Alzheimer’s biomarker services collaboration with Anavex Life Sciences Corp. The investigational Alzheimer’s drug candidate ANAVEX 2-73 and drug combination ANAVEX PLUS will be used to evaluate the pharmacodynamic effect on biomarker CD69 in specific subpopulations of peripheral blood lymphocytes, using the LymPro diagnostic. LymPro is not the only test for Alzheimer’s currently in development, but Commissiong believes it has an advantage in that it does not only identify people with Alzheimer’s. Lympro is a dynamic assay, which may potentially assist in the development of therapeutic drugs for Alzheimer’s patients. “This is the type of collaboration that becomes possible with new diagnostic tools to help therapeutic interventions in AD. The mechanisms involved may begin to validate emerging targets in the field of AD, and I am excited to help bring this collaboration forward,” commented Dr. Robert A. Stern, director of the Clinical Core of the Boston University Alzheimer’s Disease Center. ANAVEX 2-73 is an orally available small molecule being investigated for AD treatment. ANAVEX 2-73 has preclinical data indicating potential for the drug to be able to prevent, halt and/or reverse the course of Alzheimer’s. The combined therapeutic ANAVEX 2-73 and donepezil (Aricept), called ANAVEX PLUS, has a promising synergistic effect: ANAVEX PLUS produced up to 80 percent greater reversal of memory loss in Alzheimer’s than individual usage of donepezil or ANAVEX 2-73. n ALK CONTINUED FROM PAGE 33 that will identify the full spectrum of patients who might qualify for existing therapies or therapeutic candidates,” Trivedi states. “Our hope is that by expanding our menu to include different methods of evaluating ALK status (such as ALK expression) we will be able to identify such patients.” “We established this research collaboration with Insight Genetics to identify and validate these additional methods of determining ALK status—specifically, the ALK kinase domain by mRNA expression. Qiagen already offers this Insight Genetics mRNA test for tissue biopsies, so the logical next step was for our companies to work together to bring Insight’s tissue-based offering to a less invasive, blood-based platform using Biocept’s proprietary blood-based detection technology.” “As the field of ALK-based therapies continues to grow with MARCH 2015 | | DDNEWS 35 second- and third-generation molecules, the concept of looking at both DNA and RNA from CTCs is a diagnostic approach Insight has been interested in exploring for some time. Biocept, as a leader in CTC and ctDNA capture and analysis, is well positioned to help us pursue this diagnostic innovation,” said Dr. Stephan Morris, chief scientific officer of Insight Genetics. “The ability to obtain information about a tumor through a simple, blood-based test is appealing in that it can not only qualify patients for targeted therapies, but also aid in the monitoring of these patients for changes in a tumor as disease progresses,” Morris continued. “By combining our existing expertise in ALK testing with Biocept’s liquid biopsy technologies, we are poised to expand our mutual efforts in profiling and monitoring ALK positive patients and mechanisms of resistance identified with this patient cohort.” n EDITCONNECT: E031520 INTEGRATED TOOL S FO R TRANSL ATIONAL RESEARCH · HUMAN BIOSPECIMENS · MOLECULAR SERVICES · STEM AND PRIMARY CELL REAGENTS · 3D CELL CULTURE SCAFFOLDS · DIFFERENTIATED IPS CELLS · CONTRACT SERVICES ReproCELL is an expanding global leader in providing researchers with integrated tools for translational research. ReproCELL, with its BioServe, Reinnervate and Stemgent brands offers a comprehensive suite of products and services from human biospecimen procurement to 3D cell culture, through cellular reprogramming and differentiation to readily-available differentiated cells. LE ARN MORE AT AAC R, B OOT H # 950! EDITCONNECT: E031522 www.reprocell.com · www.bioserve.com · www.stemgent.com · www.reinnervate.com 36 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com BUSINESS & GOVERNMENT POLICY BR IEFS Ontario Brain Institute receives $56M investment TORONTO—In hopes of supporting promising research into diagnosing and treating brain disorders such as autism, depression, Alzheimer’s disease and Parkinson’s disease, Ontario has made an investment of $56 million as part of its five-year, $100-million commitment to the not-for-profit Ontario Brain Institute. The investment will be broken down as follows: $25 million in renewal funding to support work in the diagnosis and treatment of cerebral palsy, epilepsy and neurodevelopmental disorders such as autism; $12 million in new funding to support work focused on the diagnosis and treatment of depression; and $19 million in new funding for research into the diagnosis and treatment of Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurodegenerative diseases. Galapagos gains grant for MRSA antibiotic MECHELEN, Belgium—Galapagos NV recently received a €2.5-million (approximately $2.8 million) grant from the Flemish Agency for Innovation through Science and Technology to support Galapagos’ novel antibiotics in a collaboration with Prof. Herman Goossens, head of the microbiology laboratory at the University of Antwerp (UA). The grant was for the project “Partnering tiered clinical Phase 2 anti-MRSA antibiotic with rapid diagnostic test development,” in which Galapagos will collaborate with the Laboratory of Medical Microbiology of UA. Among Galapagos’ candidates is GLPG1492, a narrow-spectrum antibiotic with a novel mode of action against all Staphylococcus aureas strains, including MRSA. The antibiotic has shown excellent antibacterial efficacy and broad coverage of all known MRSA strains. Valeant nabs Dendreon for $400M by Kevin Noonan Supreme Court revises patent claim construction review standards Valeant will gain rights to Provenge and certain other assets BY LLOYD DUNLAP LAVAL, Quebec—Valeant Pharmaceuticals International Inc. announced recently that it had been advised by Dendreon Corp. that no additional qualified bids have been received by the bid deadline provided by the courtapproved bidding procedures for the sale of substantially all of Dendreon’s assets. A hearing at which Dendreon and Valeant were to seek the required court approval of the sale was scheduled for Feb. 20, with Valeant expected to close the transaction very soon thereafter. Pursuant to the terms of the agreement, Valeant will acquire the worldwide rights to Dendreon’s Provenge (sipuleucel-T) product and certain other Dendreon assets. Provenge is an immunotherapy designed to treat men with advanced prostate cancer by taking the body’s own immune cells and reprograming them to attack advanced prostate cancer. The product was approved by the U.S. Food and DENDREON CONTINUED ON PAGE 37 “We believe that oncology has similar characteristics to our current therapeutic portfolios, such as strong growth, high durability, strong patient and physician loyalty and a terrific reimbursement regime.” J. Michael Pearson, chairman and CEO of Valeant T deal, GSK will acquire a small number of early-stage vaccines being developed against bacterial infections such as pneumonia, Pseudomonas, Staphylococcus aureus and Shigella. GlycoVaxyn was incorporated in 2004 as a spin-off from ETH Zurich and specializes in developing next-generation bioconjugate vaccines against bacterial infection. The company has an E. coli vaccine candidate in Phase 1 clinical trials, and expects to begin a Phase 1 trial for a shigellosis vaccine in the United States in the first quarter of this year, with financial support from the WellGSK CONTINUED ON PAGE 38 PATENT CONTINUED ON PAGE 40 CREDIT: GSK GSK has bulked up its early-stage vaccine pipeline with the recent acquisition of Swiss biopharma company GlycoVaxyn AG. Boosting vaccine vitality GSK bolsters vaccine division with GlycoVaxyn acquisition BY KELSEY KAUSTINEN LONDON—In a move that enhances its ear- ly-stage vaccine pipeline, GlaxoSmithKline plc (GSK) has acquired Zürich-Schlieren, Switzerland-based GlycoVaxyn AG, a specialist vaccine biopharmaceutical company. GSK has paid $190 million to purchase the remaining stake in GlycoVaxyn, which is valued at $212 million. Per the terms of the HE U.S. SUPREME COURT handed down an important patent decision recently in Teva v. Sandoz, changing the standards used by the Court of Appeals for the Federal Circuit that have been applied for over a decade. By way of background, a patent is comprised of two interrelated parts: the specification, which describes the invention in sufficient detail that the skilled worker will be able to practice it after the patent expires, and the claims, which Kevin Noonan, partner, define the paten- McDonnell tee’s legal right to Boehnen exclude others from Hulbert & making, using, sell- Berghoff LLP ing, offering to sell or importing the invention during the patent term. The scope and meaning of patent claims in litigation are determined by the trial court as a matter of law, according to an earlier Supreme Court decision (Markman v. Westview Instruments). The Federal Circuit, in deciding the standard of its review of those trial court decisions in Cybor v. FAS Technologies, adopted a completely de-novo standard, wherein neither the legal nor the factual determinations by the trial court were given any deference. The Teva case involved the meaning of the term “molecular weight” as used in the claims. The trial court had considered expert testimony regarding three meanings for the term used in the art; these are the “peak average molecular weight” (Mp, defined as the weight of the molecule that is most prevalent in a mixture); the “number average molecular weight” (Mn, defined as the average weight of all the different-sized molecules in the mixture); or the “weight average molecular weight” (Mw, determined by calculating the average weight of IN THIS SECTION Antibiotics Galapagos gains grant for MRSA antibiotic................................. 36 Brain disorders Ontario Brain Institute receives $56M investment...................... 36 Patent claim review Supreme Court revises patent claim construction review standards...... 36 FDA approval/Orphan drug Two orphans for OncoMed...................... 39 Genomics Deciphering the language of gene regulation................................... 40 M&A activity Boosting vaccine vitality......................... 36 Roaring back…but more modestly (HOSPIRA from cover).............................. 41 Valeant nabs Dendreon for $400M......... 36 Tools and technology On the cutting edge................................. 38 Patent Docs For more information, visit www.DDN-News.com BUSINESS & GOVERNMENT POLICY MARCH 2015 | | DDNEWS 37 DENDREON CONTINUED FROM PAGE 36 Drug Administration (FDA) in April 2010 and realized revenues of approximately $300 million in 2014. Provenge was approved by the European Medicines Agency in 2013. Dendreon has been a debtor under chapter 11 of the U.S. Bankruptcy Code since November 2014. The asset purchase agreement constitutes a “stalking horse bid” in a sale process being conducted under Section 363 of the U.S. Bankruptcy Code. As the “stalking horse bidder,” Valeant would have been entitled to a break-up fee and expense reimbursement if it ultimately did not prevail as the successful bidder at a subsequent auction for Dendreon’s assets. Valeant’s role as a stalking horse bidder, and the sale itself, are subject to approval by the Bankruptcy Court. “We believe that oncology has similar characteristics to our current therapeutic portfolios, such as strong growth, high durability, strong patient and physician loyalty and a terrific reimbursement regime,” stated J. Michael Pearson, Valeant’s chairman and CEO. “We have not previously found an economic way to enter this market, but with the unique dynamics of this situation, we believe that this transaction will create significant shareholder value.” Earlier, Valeant entered into an amended and restated stalking horse asset purchase agreement to acquire the worldwide rights to Dendreon’s Provenge product and certain other assets of Dendreon. At one point, Valeant raised its offer to $400 million in cash for the assets, which realized combined revenues of approximately $300 million in 2014. As it happened, there was no auction, as Valeant made the only bid for the Seattle company. It was in late January that Valeant bid $296 million to set the baseline for a potential auction. Indications were that one would indeed likely come, with Dendreon’s lawyers noting in court papers that “several bidders” wanted more time to put together potential offers. Shortly thereafter, Valeant kicked up its offer to $400 million. Whether that cooled off any potential counter-bids or whether the interest among other potential buyers wasn’t what the lawyers thought, no one emerged to challenge Valeant’s bid. Acquiring Dendreon’s assets after the company went into bankruptcy adds Provenge for prostate cancer to Valeant’s portfolio. For a while, Dendreon was a potential jewel in Seattle’s biotech community, with the company getting the first FDA approval for a cell-based cancer immunotherapy in 2010. Provenge required extracting cells from a patient, shipping them to a processing center, genetically engineering them and shipping them back to be reinfused into the patient—a logistical challenge, to be sure, but one the company seemed to have a handle on. Then things went wrong, with marketing woes and concerns over the $93,000 price tag and how that might be reimbursed. So Provenge’s launch had an albatross around its neck early on. Dendreon’s debt grew, and other new prostate cancer drugs happily took their place in the market at Dendreon’s expense, among them Zytiga and Xtandi. Provenge generated $300 million in sales last year. Abiraterone, by comparison, gener- PLAS ■ LABS, INC. Although Valeant is known for its aggressive strategy of inorganic growth through acquisitions, this deal took some by surprise as it was not a high-quality prospect with lucrative assets such as Allergan, which Valeant failed to take over last year. www.PLAS-LABS.com 517-372-7177 [email protected] ated $1.07 billion in the first half of 2014 alone. Valeant’s business model has long been to buy other drug companies to grow its portfolio rather than spend a lot developing its own pipeline. But the Dendreon purchase surprised some market watchers, partially because Valeant is taking a totally different tack than it did with its attempt to acquire Allergan. While Allergan was considered a high-quality pharmaceutical firm with lucrative products, Dendreon is quite the opposite. But analysts’ opinions weren’t all negative. Jefferies analyst David Steinberg raised estimates and his price target on Buy-rated Valeant to $179 (from $149) following updated fiscal 2015 guidance from the company. Steinberg commented on positive fiscal year 2015 forecasts with regard to revenue and earnings per share (EPS), and despite “substantial headwinds” that are expected to reduce rev- enues and EPS by about $300 million, relative to prior views after the third quarter of fiscal 2014, “New product launches, spearheaded by Jublia, are taking center stage.” Analyst Louise Chen at Guggenheim noted several positives from a recent Valeant conference call: CEO compensation is more aligned with shareholder value now and the CEO signed a five-year contract, plus the company is said to be well positioned for strong organic growth in 2016, with seven or eight launches and “best products” that include Vesneo, Brimonidine, Ultra platform and Emerade. She added that Jublia peak sales could be over $750 million, though Valeant’s expectation is $300 million to $400 million for now. Valeant made a much bigger deal after this one, as DDNews was going to press. Read more on that on page 42. n EDITCONNECT: E031524 BUSINESS & GOVERNMENT POLICY 38 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com ON THE CUTTING EDGE A roundup of instrumentation, software and other tools and technology news HIS MONTH, we take a look at remote access for life-sciences and diagnostic products, a commitment to sequencing technology to help push genomics forward in Scotland, a lung cancer monitoring collaboration and a cloud-based system for patient-centered translational research. TOOLS & TECHNOLOGY RealVNC licenses remote access technology to Beckman Coulter BREA, Calif.— This winter saw Beckman Coulter, a world leader in in-vitro diagnostics, and Cambridge, U.K.-based RealVNC, a global provider of VNC remote access technology, announce that Beckman Coulter will be licensing RealVNC’s technology. VNC enables a computer user to remotely access another computer or device in a secure and reliable manner, and Beckman Coulter will be deploying RealVNC’s top-end solution, VNC, with an enterprise license to its lifesciences and diagnostics products to enable it to efficiently support these systems. In addition, Beckman Coulter will also use RealVNC’s VNC Viewer SDK to create its own viewer for iOS, which will enable its technical support representatives to take control of their systems remotely from an iPad or iPhone, enabling reps the flexibility to use the technology in the field and onsite. “RealVNC’s technology and expertise will allow us to enhance our products and the way we serve our laboratory customers,” said John Hetzler, software engineering senior manager for workflow and IT solutions at Beckman CREDIT: COOLCAESAR T BY JEFFREY BOULEY Coulter Diagnostics. “The collaboration with RealVNC will enable us to develop customized technology that will enhance our IT solutions.” “This is yet another great example of a large organization leveraging the power of VNC as part of a range of commercially available devices worldwide,” said Richard Pickul, strategic alliances manager for RealVNC. “We are delighted to be working with Beckman Coulter to deliver remote access capabilities to their life-sciences and diagnostics products and continue to look forward to expanding the relationship in the future.” Illumina seeks to help put Scotland at forefront of gene-led healthcare Beckman Coulter will be licensing RealVNC’s technology for support systems related to lifesciences and diagnostics products. EDINBURGH & GLASGOW, Scotland—San ship will initially focus on very rapid screening of cancer patients, diagnosing childhood illnesses, disorders of the central nervous system and population studies. Prof. Jonathan Seckl, vice principal of research at the University of Edinburgh, said, “Scotland is uniquely placed to make a significant contribution to the field of genomics medicine. It has well-established and approved methods of linking electronic health records to medical research programs, governed by NHS and academic regulations. Edinburgh is also home to the U.K.’s national supercomputer facility, which will provide the high-performance data processing ability needed to analyze the vast volume of information that will be generated from this research. This affords an exceptional opportunity for Scotland’s outstanding researchers and clinicians to transform the way medicine is practiced in the coming years.” “Scotland has an ideal ecosystem to lead the world in precision medicine,” added Prof. Anna Dominiczak, vice principal and head of the College of Medical, Veterinary and Life Sciences at the University of Glasgow. “With a population of 5.3 million, cohesive and collaborative Diego-based sequencing and genomics company Illumina Inc. is partnering with the University of Edinburgh and University of Glasgow in a £15-million (about $23 million) project with a goal to “secure Scotland’s place as a world leader in a genomics revolution that is set to transform healthcare.” The initiative reportedly will enable scientists and clinicians to access equipment that can decode the entire genetic makeup of a person for less than £750 and study the genomes of both healthy and sick people on a large scale and faster than they have before. The investment will establish the Scottish Genomes Partnership, which will install 15 state-of-the-art Illumina HiSeq X sequencing instruments divided between two hubs within the universities. Linking genetic data with clinical information will enable more precise, molecular diagnoses for patients in the Scottish National Health Service (NHS), leading to more personalized treatment and safer selection of drug therapies, the partners say, and will bring new understanding of the causes of both rare and common diseases, opening the door to the development of new treatments. The partner- GSK come Trust. GlycoVaxyn brings with it 50 employees. “This is an exciting opportunity to expand our research efforts to develop a new generation of vaccines for common and severe bacterial infections, for many of which there are currently no effective vaccines,” Dr. Moncef Slaoui, chairman of vaccines at GSK, commented on the transaction. “It reinforces our commitment to seek out and invest in great science and complements our proposed transaction with Novartis, which will strengthen our leading position in vaccines.” (That transaction was completed March 2 as this issue was going to press, and with it GSK has, among other things, acquired Novartis’s global vaccines business, excluding influenza vaccines.) This GlycoVaxyn deal builds off of an existing relationship with GSK that began in 2012. GlycoVaxyn announced Dec. 19, 2012, that it had begun a collaboration with GSK Biologicals for the development of new bacterial vaccines using GlycoVaxyn’s bioconjugation technology. The CREDIT: GSK CONTINUED FROM PAGE 36 “This is an exciting opportunity to expand our research efforts to develop a new generation of vaccines for common and severe bacterial infections, for many of which there are currently no effective vaccines,” says Dr. Moncef Slaoui, chairman of vaccines at GSK. agreement included an undisclosed set of pathogen targets within the field of bacterial vaccines, and GSK had an option to obtain an exclusive license on the targets during the three years of the collaboration’s duration and to extend both the length and scope of the deal. In addition, GSK made an upfront payment to GlycoVaxyn as well as an equity investment in the company. GlycoVaxyn was eligible to receive milestone payments and royalties on any licensed vaccine candidates. “Since the spinoff from ETH Zurich, we have successfully advanced our biological conjugation technology and developed a strong pipeline of vaccine candidates. We are delighted to now work even closer with one of the leading vaccine companies in the world on the development of much-needed vaccines,” said Michael Wacker, co-founder and chief scientific officer of GlycoVaxyn. GlycoVaxyn’s bioconjugation platform enables the development and production of immunogenic glycoprotein conjugates via a biological process that bypasses many of the challenges faced with current chemical methods. The company notes that its platform “has broad potential applications in the field of bacterial vaccines, but also in viral and cancer vaccines and human therapeutic proteins.” The platform offers versa- NHS, academia and industry, we have developed unique capability to screen DNA from patients with cancer, rheumatoid arthritis and other inflammatory and infectious diseases.” “By unlocking the power of the genome, we can better understand cancer and rare diseases and ultimately transform how they are diagnosed and treated,” said Jay Flatley, CEO of Illumina. Monitoring EGFR mutational status in lung cancer patients SAN DIEGO—Trovagene Inc. announced recently that it has entered into a clinical collaboration with California-based City of Hope to conduct studies to determine the clinical utility of detecting and monitoring EGFR mutations in lung cancer patients using Trovagene’s Precision Cancer Monitoring platform. “Tracking various alterations in the EGFR oncogene, particularly emergence of the T790M mutation, has potential to improve therapeutic strategies for treating patients with non-small cell lung cancer,” said Dr. Mihaela Cristea, lead investigator and assoEDGE CONTINUED ON PAGE 41 tility across many pathogens and conjugates because it “enables the combination of any polysaccharide antigen with any protein antigen,” and also offers batch-to-batch consistency. GlycoVaxyn’s vaccines are highly immunogenic, the company explains on its website, because they “[express] polysaccharide epitopes in their most native (natural) conformation and [combine] them with the most immunogenic protein carriers also in a well-defined and preserved natural conformation.” This is the latest move in GSK’s efforts to boost its vaccines portfolio. Back in June 2014, GSK announced its three-part asset swap with Novartis. Under that agreement, GSK acquired Novartis’ global vaccines business, aside from influenza vaccines, for an initial cash consideration of $5.25 billion, with the potential for milestone payments of up to $1.8 billion and ongoing royalties. In conjunction with the acquisition, GSK agreed to sell Nimenrix and Mencevax, its meningitis vaccines, on a global basis, as well as divesting two small Novartis bivalent vaccines for protection against diphtheria and tetanus in Italy and Germany. n EDITCONNECT: E031525 BUSINESS & GOVERNMENT POLICY For more information, visit www.DDN-News.com MARCH 2015 | | DDNEWS 39 Two orphans for OncoMed CREDIT: ONCOMED Abraxane (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. The PINNACLE study is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive-stage small cell lung cancer patients. “Tumor Notch3 gene expression is estimated to be elevated in approximately 70 percent of pancreatic cancer patients, and BY LLOYD DUNLAP REDWOOD CITY, Calif.—OncoMed Phar- it is thought to be an indicator of poor progmaceuticals Inc., a clinical-stage company nosis and chemotherapy resistance,” noted developing novel therapeutics that target Dr. Jakob Dupont, OncoMed’s chief medicancer stem cells (CSCs), or tumor-ini- cal officer. “The data suggesting that the biotiating cells, has announced that the U.S. marker-positive patients may have improved response rates and survival with tarFood and Drug Administraextumab treatment are supportive tion’s Office of Orphan Prodof the Phase 2 design of the ALPINE ucts Development has granted study, where tarextumab’s impact Orphan Drug designation to on efficacy of all patients enrolled tarextumab (anti-Notch 2/3, as well as the biomarker posiOMP-59R5) for the treatment tive patients will be assessed. The of both pancreatic cancer and Notch3 predictive biomarker may small cell lung cancer. enable us to identify those patients “We are excited to receive that would gain the greatest benefit The U.S. Food and Drug Administration’s Office of Orphan Products Development has granted two separate orphan drug des- “Tumor Notch3 Orphan Drug designation to tarextumab (anti-Notch 2/3, OMP-59R5) for the treatment of both ignations for tarextumab for gene expression is from tarextumab treatment.” pancreatic cancer and small cell lung cancer. “Pancreatic cancer remains the treatment of pancreatic estimated to be elevated in among the most challenging can- pancreas cancer population and in specific newly diagnosed lung cancer cases and the and small cell lung cancer,” said 159,260 deaths estimated to occur in the cers in spite of recent treatment biomarker-selected subsets.” Paul J. Hastings, OncoMed’s approximately 70 According to the American Cancer Society, United States in 2014. It tends to grow and advances. The Phase 1b tarextumab chairman and CEO. “OncoMed percent of pancreatic cancer data confirm safety and early signals there are approximately 46,000 new cases spread quickly and is typically not discovis enrolling patients in two ran- patients, and it is of efficacy observed in earlier-stage of pancreatic cancer each year in the United ered until it has metastasized to other parts domized Phase 2 clinical trials thought to be an studies,” said Dr. Eileen O’Reilly, States. The majority of patients with pancre- of the body. In spite of a high sensitivity to of tarextumab in pancreatic and indicator of poor associate director of clinical atic cancer are diagnosed after their cancer chemotherapy and remission rates of up to small cell lung cancer, and we prognosis and research for Memorial Sloan Ketter- has spread locally and/or metastasized to dis- 80 percent following initial treatment, the recently reported promising chemotherapy ing Cancer Center and a principal tant organs. Rates of pancreatic cancer have median overall survival is less than one year safety and early efficacy data resistance,” says Dr. Jakob Dupont, investigator of ALPINE. “Further been increasing over the past 10 years, and for patients with extensive stage disease. from our Phase 1b studies in OncoMed’s chief Tarextumab is part of OncoMed’s collaboexploration of tarextumab’s poten- it is now the fourth-leading cause of cancerthese indications.” medical officer. tial as a new treatment option for related deaths. The average life expectancy ration with GlaxoSmithKline, which has an Tarextumab is a fully human monoclonal antibody that targets the Notch2 pancreatic cancer patients is warranted and after the diagnosis of metastatic pancreatic option to obtain an exclusive license to tarextumab through completion of the proofand Notch3 receptors. Preclinical studies ongoing in the randomized Phase 2 portion cancer is less than one year. Small cell lung cancer was estimated to of-concept Phase 2 trials. n have suggested that tarextumab exhibits of the study. The trial will evaluate the additwo mechanisms of action: (1) by down- tion of tarextumab in a frontline untreated make up about 10 to 15 percent of the 224,210 EDITCONNECT: E031527 regulating Notch pathway signaling, tarextumab has anticancer stem cell activity and (2) tarextumab affects pericytes, impacting the stromal and tumor microenvironment. Tarextumab is currently being studied in two randomized Phase 2 clinical trials. The Connect with the international network of ALPINE study is assessing tarextumab with “We are excited to receive two separate orphan drug designations for tarextumab for the treatment of pancreatic and small cell lung cancer. OncoMed is enrolling patients in two randomized Phase 2 clinical trials of tarextumab in pancreatic and small cell lung cancer, and we recently reported promising safety and early efficacy data from our Phase 1b studies in these indications.” Paul J. Hastings, chairman and CEO of OncoMed All of the luminaries of the stem cell field in one conference. Register now for ISSCR 2015. Co-Sponsored By: WWW.ISSCR2015.ORG CREDIT: U.S FOOD AND DRUG ADMINISTRATION FDA grants Orphan Drug designations to OncoMed’s tarextumab for pancreatic and small cell lung cancer 40 DDNEWS | | MARCH 2015 BUSINESS & GOVERNMENT POLICY For more information, visit www.DDN-News.com BETHSEDA, Md.—The U.S. National Institutes of Health (NIH) have awarded grants of more than $28 million total aimed at deciphering the language of how and when genes are turned on and off. These awards emanate from the recently launched Genomics of Gene Regulation (GGR) program of the NIH’s National Human Genome Research Institute (NHGRI). “There is a growing realization that the ways genes are regulated to work together can be important for understanding disease,” said Dr. Mike Pazin, a program director in the Functional Analysis Program in NHGRI’s Division of Genome Sciences. “The GGR program aims to develop new ways for understanding how the genes and switches in the genome fit together as networks. Such knowledge is important for defining the role of genomic differences in human health and disease.” With these new grants, researchers will study gene networks and pathways in different systems in the body, such as skin, immune cells and lungs. The resulting insights into the mechanisms controlling gene expression may ultimately lead to new avenues for developing treatments for diseases affected by faulty gene regulation, such as cancer, diabetes and Parkinson’s disease. Over the past decade, numerous studies have suggested that genomic regions outside of protein-coding regions harbor variants that play a role in disease. Such regions likely contain gene-control elements that are altered by these variants, which increase the risk for a disease. “Knowing the interconnections of these regulatory elements is critical for understanding the genomic basis of disease,” Pazin said. “We do not have a good way to predict whether particular regulatory elements are turning genes off or activating them, or whether these elements make genes responsive to a condition, such as infection. We expect these new projects will develop better methods to answer these types of questions using genomic data.” Recipients of the new GGR three-year grants (pending available funds) are: Memorial Sloan Kettering Cancer Center, Duke University, the University of Massachusetts Medical School, Stanford University and University of California, Los Angeles. n Regulatory roundup H ERE ARE just a few highlights of recent regulatory activities worldwide, from patents approved to designations granted to drugs given the green light for one indication or another. MediciNova gain U.S., Japanese patents LA JOLLA, Calif.— Biopharmaceutical company MediciNova Inc. got word in early February that it had received a Notice of Allowance from the U.S. Patent and Trademark Office for a pending patent application that covers MN-001 (tipelukast) and MN-002 (a major metabolite of MN-001) for the treatment of nonalcoholic steatohepatitis. The patent maturing from this allowed patent application is expected to expire no earlier than December 2032. A few days earlier, the company also noted that it had received a new patent from the Japanese Patent Office covering MN-029 (denibulin) di-hydrochloride that will expire no earlier than July 2032. FDA grants Breakthrough Therapy designation to Roche’s MPDL3280A BASEL, Switzerland—Following a Breakthrough Therapy designation for MPDL3280A from the U.S. Food and Drug Administration (FDA) in bladder cancer in 2014, Roche has gotten a second such designation for the investigational anti-programmed deathligand 1 (anti-PDL1) cancer immunotherapy for treatment of people with PD-L1-positive non-small cell lung cancer whose disease has progressed during or after platinum-based chemotherapy (and appropriate targeted therapy for those with an EGFR mutationpositive or ALK-positive tumor). Symplmed announces FDA approval of Prestalia for hypertension CINCINNATI & BEND, Ore.— Jan. 26 saw Symplmed Pharmaceuticals announce that the FDA had approved Prestalia (perindopril arginine and amlodipine) tablets, licensed from French pharma Servier, for the treatment of hypertension. Prestalia, the first fixed-dose combination of these two medications, may be used in patients whose blood pressure is not adequately controlled on monotherapy. Prestalia may be used as initial therapy if a patient is likely to need multiple drugs to achieve their blood pressure goals. ApoCell gains EU Orphan Drug designation for graft-versus-host disease JERUSALEM— Enlivex Therapeutics announced recently that the European Medicines Agency had granted Orphan Drug status to the company’s lead product candidate, ApoCell, for the prevention of graft-versus-host disease (GvHD). Previously, ApoCell received the same designation from the FDA. The company plans to initiate a Phase 2b/3 trial of ApoCell in GvHD in 2015. FDA approves Triferic for iron replacement and maintenance of hemoglobin in hemodialysis patients WIXOM, Mich.—In January, Rockwell Medical Inc., a biopharmaceutical company targeting end-stage renal disease and chronic kidney disease, noted that the FDA had approved its drug Triferic for commercial sale as an iron replacement product to maintain hemoglobin in adult patients with hemodialysis dependent chronic kidney disease. “We are extremely pleased with the FDA approval of Triferic. It is the first drug approved to replace ongoing iron losses and to maintain hemoglobin levels in hemodialysis patients,” stated Robert L. Chioini, founder, chairman and CEO of Rockwell. “Triferic’s unique ability to be delivered via dialysate and to deliver iron without increasing iron stores strengthens its potential to become the market-leading iron therapy treatment for hemodialysis patients.” n CREDIT: U.S. NATIONAL INSTITUTES OF HEALTH Deciphering the language of gene regulation Five research institutions stand to get a combined $28 million-plus in grants as part of the Genomics of Gene Regulation program of the National Human Genome Research Institute, which is part of the National Institutes of Health (the clinical center of which is pictured here). PATENT CONTINUED FROM PAGE 36 all the different-sized molecules in the mixture while giving heavier molecules a weight-related bonus when doing so). The trial court decided that the term meant the peak average molecular weight, and thus that the claim was sufficiently definite that it was not invalid. The Federal Circuit construed the claim without regard to the trial court’s determination and found the claim invalid for indefiniteness. The Supreme Court reversed, holding that the Federal Circuit must give deference to trial court decisions related to “subsidiary” facts upon which the court bases its legal construction of patent claims. No such deference is required when the trial court restricts it consideration to the “intrinsic” evidence (the claim language, the specification and the written record before the Patent Office), but any factual determinations by the trial court based on evidence outside that record (e.g., treatises, dictionaries, expert testimony) must be given deference by the appellate court and reversed only if the reviewing court finds clear error (i.e., actual mistake) in the factual findings. The Court’s asserted rationale was that standards for review of patent claim construction practice should be consistent with how other appellate courts review mixed questions of law and fact like claim construction (specifically, construing deeds and contracts). This standard of review was based on a trial court’s “greater opportunity to engage its capabilities of assessing the credibility of the witnesses and its capacity to immerse itself in the technical minutiae attendant upon construing claims in the first place.” The decision settled a question in the law that has bedeviled the Federal Circuit since the Cybor decision, being criticized by the patent bar, academics and even members of that court; much of this dissent related to the practice’s encouragement of every patent decision (because they all involve claim construction by the trial court) and the relatively high frequency of reversal because the Federal Circuit came to a different conclusion on the facts. However, applying the Supreme Court’s mandated standard raises the risk that U.S. patent practice will lose some of the harmonizing effect that was the principal motivation for and the primary benefit of having a specialized appellate court for patents. This is because matters of claim construction are often very dependent on the types of “factual” evidence for which the Federal Circuit must now give deference. Parties in patent litigation can be expected to try to make as much of the claim construction process before the trial court as possible dependent on expert testimony and other “subsidiary” fact-finding, to reduce the likelihood of having the trial court decision overturned on appeal. It is also possible that patentees (at least for patent applications filed after Teva) will try to limit the opportunity for such fact-finding by providing explicit definitions in their specifications. For highly complex technologies including biotechnology and pharmaceutical patents, it is likely that trial court judges will need expert or other testimony to understand the language of the claims even in the face of such express definitions. Thus, the Teva decision is likely to shift the center of patent claim construction towards the trial courts and away from the Federal Circuit. This can be expected to influence both how patents for pharmaceuticals are drafted, prosecuted and litigated in ways that are in some ways predictable and in others are beyond prediction. n EDITCONNECT: E031526 Kevin Noonan is a partner with the law firm McDonnell Boehnen Hulbert & Berghoff LLP and represents biotechnology and pharmaceutical companies on a myriad of issues. A former molecular biologist, he is also the founding author of the Patent Docs weblog, http://patentdocs.typepad.com/. For more information, visit www.DDN-News.com HOSPIRA CONTINUED FROM PAGE 1 According to Pfizer, the global marketplace value for generic sterile injectables is estimated to be $70 billion in 2020, and the marketplace for biosimilars is estimated to be approximately $20 billion in 2020. “The Pfizer-Hospira combination is an excellent strategic fit, presenting a unique opportunity to leverage the complementary strengths of our robust portfolios and rich pipelines,” said F. Michael Ball, CEO of Hospira. Despite having helped engineer the offer from Pfizer, which is valued at nearly 40 percent more per share for Hospira’s stock than it was worth just a day before the deal was announced, early speculation from analysts say Ball is not likely to stick around. “I would be really shocked to see him stay on at Hospira,” Michael Waterhouse, an analyst at Chicagobased Morningstar, told Crain’s Chicago Business. And he may be very far from the only one leaving, too, once the deal is done. Pfizer anticipates the transaction will deliver $800 million in annual cost savings by 2018. Market-watchers seem to think that can only come with layoffs, among them Ronny Gal, a senior research analyst at Sanford Bernstein, who told Crain’s, “I don’t see how they do that without firing [people]…Some of it will come from their business, presumably, but I don’t see how they would do that without taking out a lot of the cost structure of Hospira.” Kevin Kedra, an analyst at Gabelli & Co., agreed that “there will obviously be some degree of layoffs.” Pfizer dodged the question of the potential scale of layoffs at Hospira, which has around 19,000 employees globally, when it conducted its conference call with investors after announcing the M&A deal. But Pfizer’s Ian Read did say during the call, “We are very well aware that Hospira has a lot of talented individuals and have been very successful, as our organization has been successful, so we look to create a combined organization that has the best talent from both organizations,” which certainly seems to suggest a significant number of pink slips are on the way. “It remains to be seen what Pfizer will do with its GEP business after the integration of Hospira. The Hospira deal will add significant value to Pfizer’s GEP segment, a vertical which has been rumored to be sold or spun-off as a separate entity,” according to Adam Dion, GlobalData’s healthcare industry analyst. “This somewhat mirrors Pfizer’s strategic objective to focus on core growth platforms in the branded drug market while divesting its ancillary operations, similar to when it carved out its Animal Health business (Zoetis) and brought it public. The Zoetis initial public offering was preceded by Pfizer selling its Nutrition business and Capsugel pill unit, mobilizing significant capital for investment in its core growth areas. However, given Pfizer’s desire to retain its pharma leadership and move into biosimilars, it may decide against a split in favor of maintaining a level of operational independence between its innovative and mature portfolios.” Dion also notes that while Hospira’s generic specialty injectables product line will be seamlessly integrated into Pfizer’s GEP business, the newly acquired company’s biosimilar activities will also be of key importance to Pfizer’s strategic objective. “Hospira currently markets three biosimilars in Europe—Retacrit (erythropoietin zeta), Nivestim (filgrastim) and Inflectra (infliximab), the first biosimilar monoclonal antibody to be approved in Europe. Meanwhile, Hospira BUSINESS & GOVERNMENT POLICY “Hospira’s business aligns well with our new commercial structure and is an excellent strategic fit for our Global Established Pharmaceutical (GEP) business, which will benefit from a significantly enhanced product portfolio in growing markets.” Ian Read, chairman and CEO of Pfizer also has a number of biosimilars in its latestage pipeline, including trastuzumab, currently in Phase 3, which is being evaluated for breast cancer. This is hugely complementary to Pfizer’s own ongoing activities in biosimilar development, with biosimilars of Herceptin, Rituxan and Remicade currently in the pipeline,” Dion says. Right after the announcement of the M&A deal, Seamus Fernandez and Aneesh Kapur of Leerink Partners wrote that “Compared to recent pro-formas we have evaluated (among them Pfizer/AstraZeneca, Pfizer/ Shire and Pfizer/Bristol-Myers Squibb), Hospira is more accretive in the near term and ought to drive a higher valuation on a DCF [discounted cash flow] basis.” Just a day before that, the two Leerink analysts had also written positively about Pfizer and hinted at M&A possibilities, noting, “Ibrance’s early approval and disclosed $9,850/month pricing supports our expectations of a $3-billion to $5-billion market opportunity for CDK4/6 inhibitors in firstline advanced ER+/HER2- breast cancer. We expect brisk uptake with the potential for Ibrance (palbo) to exceed our $150 million 2015 estimate … We continue to expect Ibrance’s expansion into the recurrent disease and early breast cancer setting, building up to our $4 billion-plus forecasts in 2020. Despite an important Ibrance readout in recurrent breast cancer in 2015, we are more intrigued by building strength across Pfizer’s mid-stage vaccines, immunology and immuno-oncology pipeline and/or accretive M&A.” n EDITCONNECT: E031501 MARCH 2015 | | DDNEWS 41 EDGE practice genomically enhanced medicine, launched in late January a cloud-based system for conducting patient-centered translational research. Appistry CloudDx Translational is said to meet a critical need in clinical research centers: centralizing and coordinating data, processes and communication to leverage institutional expertise and deliver high-quality results to patients and the research community. CloudDx Translational enables clinical research centers engaged in the study of human disease to build a personalized medicine framework for organizing research activities. All project information is tied to individual patients—including clinical observations, research activities, reporting of results and deposition of appropriate findings into the public domain. CloudDx Translational integrates the various tasks needed to perform translational research, provides expert systems to facilitate the work of project team members and ensures that valuable data and insights are searchable and shareable to inform hypothesis generation and decision-making, while holding patient identifiable information secure in accordance with ethical practices of human-subject research. “CloudDx solutions have at their core a keen understanding of the complex workflows that must be managed and facilitated to put patients at the center of care, whether it be a research project or a genomic test,” said Kevin Haar, CEO of Appistry. “CloudDx Translational and CloudDx Clinical are very different products, because they are designed to meet the needs of different users. Yet they share a connection to using the cloud to minimize overhead and help institutions gain the capabilities they need to deliver value-added services based on genomics—what we call genomically enhanced medicine.” n CONTINUED FROM PAGE 38 ciate professor for the City of Hope Lung Cancer and Thoracic Oncology Program. “We look forward to evaluating Trovagene’s molecular diagnostics for the monitoring of circulating tumor DNA found in both urine and blood, with the goal of delivering highly personalized cancer treatment to improve patient outcomes.” The clinical study is expected to enroll 75 patients with lung cancer. Primary objectives of the study include evaluating concordance between urinary circulating tumor DNA (ctDNA), blood ctDNA and tumor tissue for determining EGFR mutational status. Additionally, the study investigators will evaluate the quantitative and qualitative performance of longitudinal EGFR mutation monitoring using both urine and blood specimens, as they relate to response to therapy over time. Exploratory objectives include evaluating the feasibility of identifying the TKI-resistant mutation, T790M, in urinary and blood ctDNA at the time of progression. “Enabling physicians to detect the emergence of problematic mutations in real-time is a key benefit of our Precision Cancer Monitoring platform, and one such mutation is EGFR T790M, which drives treatment resistance in non-small cell lung cancer patients,” said Dr. Mark Erlander, chief scientific officer of Trovagene. “This is an important part of our strategy to realize the full potential of our platform, as we partner with major cancer treatment centers in the U.S. to obtain clinical utility data and to integrate our technology into clinical practice.” Appistry launches cloud-based system for patient-centered translational research MOUNTAIN VIEW, Calif.—Appistry Inc., a provider of tools, software and services that enable healthcare institutions to EDITCONNECT: E031528 APRIL 18-22, 2015 PENNSYLVANIA CONVENTION CENTER PHILADELPHIA, PA Join us in Philadelphia for the most comprehensive cancer research meeting in the world... the AACR Annual Meeting 2015! Connect with the international cancer research community to foster new collaborations, learn about cutting-edge advances, and obtain feedback on your research. This must-attend meeting covers every aspect of cancer – from epidemiology, molecular biology, and clinical studies to prevention, survivorship, and patient advocacy. Register Today! 1409109J_15AM_ad_DDNews_7x4.875_1.indd 1 We look forward to welcoming you to our hometown of Philadelphia, PA! WWW.AACR.ORG 12/22/14 10:41 AM 42 DDNEWS | | MARCH 2015 LATE-BREAKING NEWS For more information, visit www.DDN-News.com Late-Breaking News Three M&A deals combine for about $16 billion in dealmaking in February HREE PARTICULARLY NOTABLE merger and acquisition (M&A) deals came together during the late stages of producing this issue. We’ve covered them in more detail online at our www.ddn-news.com website in the Daily News section, but here are some highlights for you. Valeant to acquire Salix Pharmaceuticals in $14.5 billion deal LAVAL, Quebec—While it isn’t anywhere near what Valeant Pharmaceuticals International Inc. tried to buy Allergan Inc. for last year ($54 billion in an unsolicited and ultimately failed takeover bid), Valeant just made its biggest acquisition deal ever this month, announcing a $158-per-share offer for Salix Pharmaceuticals, a major player in the growing U.S. gastrointestinal (GI) market, that has been accepted by the boards of both companies. That’s an all-cash deal for $10.1 billion, plus the assumption of more than $4 billion in debt, for a total enterprise value of $14.5 billion, the two companies announced Feb. 22. That clearly trumps Valeant’s acquisition of eyecare company Bausch & Lomb in 2013 for $8.7 billion. Salix is best known for its irritable bowel syndrome drug Xifaxan. However, the company’s portfolio of 22 total products also includes such prescription brands as Uceris, Relistor and Apriso, “as well as a strong near-term pipeline of innovative, new assets,” according to Valeant. “Salix’s market-leading gastrointestinal franchise is an ideal strategic fit for Valeant’s diversified portfolio of specialty products,” according to J. Michael Pearson, Valeant’s chairman and CEO. “The growing GI market has attractive fundamentals, and Salix has a portfolio of terrific products that are outpacing the market in terms of volume growth and a promising near-term pipeline of innovative products. With strong brand recognition among specialist GI prescribers, a highly rated specialty sales force and a significant product and commercial presence across the undertreated and underserved gastrointestinal market, this acquisition offers a compelling opportunity for Valeant to create a strong platform for growth and business development.” The combination is expected to yield more than $500 million in annual cost savings from the cost base of the combined company. Synergies are expected to be achieved within six months of close, primarily from reductions in corporate overhead and research and development rationalization, with the cost to achieve these synergies said to be approximately 65 percent. “We are pleased to have reached an agreement with Valeant, which is a logical partner and, importantly, creates immediate value for our shareholders. Combining Salix’s leading market position in gastroenterology with Valeant’s scale and resources will create a stronger and more diverse business committed to providing better health solutions to healthcare providers and their patients,” said Thomas W. D’Alonzo, chairman and acting CEO of Salix. On Nov. 6, 2014, Salix reported five- to nine-month wholesaler inventory levels for its top four products. Valeant says it has conducted extensive due diligence on Salix’s standalone wholesaler inven- tory levels, standalone inventory work-down plan and associated potential litigation and regulatory exposure. Valeant expects to work down wholesale inventory and plans to target two months or less of wholesale inventory by the end of this year. The net impact of the excess inventory on 2015 revenues is expected to be greater than $500 million. The all-cash offer for all of the outstanding shares of Salix common stock will be financed through a combination of bank debt and bonds. As a result of the need to draw down inventories, Valeant says that earnings before interest, taxes, depreciation and amortization will be artificially low in 2014 and 2015, resulting in the initial net leverage ratio of approximately 5.6. Valeant says it is committed to reducing its net leverage ratio to be below 4.0 by the second half of 2016. As a result of the plan to reduce wholesaler inventory levels in 2015, the transaction is expected to be modestly accretive to 2015 cash earnings per share, but more than 20-percent accretive to 2016 cash earnings per share. For the full version of this story online, search for Editconnect code E02251502 on our website. Also, we will have additional coverage of this deal in our April issue of DDNews, examining some of the implications of the acquisition and its market impact. Immediately following a deal to acquire NPS Pharma for $5.2 billion, announced January of this year, Shire has now acquired Meritage Pharma, a developer of drugs for gastrointestinal and rare diseases, for $70 million up front and as much as $175 million in milestone fees. Bristol-Myers Squibb to pay up to $1.25 billion for Flexus CREDIT: NYSE T BY JEFFREY BOULEY & KELSEY KAUSTINEN NEW YORK & SAN CARLOS, Calif.—Bristol-Myers Squibb Co. and Flexus Biosciences Inc. have struck a definitive agreement by which Bristol-Myers Squibb will acquire all of Flexus’ outstanding capital stock in a deal with a potential total consideration of $1.25 billion, which includes $800 million up front and up to $450 million in development milestone payments. Both companies’ boards of directors have approved the transaction, as have Flexus’ stockholders, and the deal was expected to close in the first quarter of this year. “Bristol-Myers Squibb is a recognized leader in the cancer immunotherapy field, and we are delighted with the opportunity to have their organization advance the development of our potentially best-inclass IDO/TDO inhibitors and to bring more innovative cancer immunotherapies to patients,” said Dr. Terry Rosen, CEO of Flexus. “With the consummation of this acquisition, we will continue to advance our oncology and immuno-oncology pipeline of Agents for Reversal of Tumor Immunosuppression in the newly created spin-off, with the strong support of our committed group of investors.” IDO and TDO are enzymes expressed by a number of tumor cells and cells in the tumor microenvironment, and these enzymes suppress T cell function through the production of kynurenine, a potent immunosuppressive factor that prevents the immune system from identifying and destroying the tumors. IDO/TDO inhibitors reduce the production of kynurenine, freeing up the immune system to better attack tumors. With this acquisition, Bristol-Myers Squibb gains full rights to F001287, Flexus’ lead preclinical small-molecule IDO1-inhibitor, which is aiming for Investigational New Drug filing in the second half of this year. Bristol-Myers Squibb also gets Flexus’ IDO/TDO discovery program, which Representatives of Valeant ring in the closing bell for the New York Stock Exchange on Oct. 10, 2013, on World Sight Day. In May of that year, Valeant’s acquisition of Bausch and Lomb at nearly $8.6 billion was the company’s largest acquisition to date. That has been eclipsed now by the $14.5-billion deal to acquire Salix. includes the company’s IDO-selective, IDO/TDO dual and TDO-selective compound libraries. Per the terms of the agreement, a newly formed entity established by Flexus’ current shareholders will retain all non-IDO/TDO Flexus assets, including those related to Flexus’ Phase 1 FLT3 and CDK4/6 inhibitor, its earlier-stage small-molecule Treg cancer immunotherapy programs and its current personnel and facilities. “Bristol-Myers Squibb is committed to leading scientific advances in immuno-oncology, and our acquisition of Flexus will expand our innovative pipeline with an important approach to enhancing immune responses in cancer,” said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer at Bristol-Myers Squibb. “With the addition of a potentially best-in-class IDO1 inhibitor and the broad IDO/TDO programs, Bristol-Myers Squibb will accelerate its ability to explore numerous immunotherapeutic approaches across tumor types, including combinations with our biologic checkpoint and co-stimulatory agents that target different and complementary pathways.” For the full version of this story, which also addresses a collaboration made at the same time as the M&A deal, search for Editconnect code E02241501 on our website. Shire to pay up to $245 million in Meritage acquisition LEXINGTON, Mass. & SAN DIEGO—Shire plc has announced the acquisition of privately held Meritage Pharma Inc., which specializes in developing prescription products for the treatment of gastrointestinal and atopic diseases, for $70 million up front and as much as $175 million in milestone fees. With this deal, Shire gains the global rights to Oral Budesonide Suspension (OBS), Meritage’s Phase 3-ready compound for the treatment of adolescents and adults with eosinophilic esophagitis (EoE), a rare, chronic inflammatory gastrointestinal disease. OBS has received Orphan Drug designation from the U.S. Food and Drug Administration for the treatment of patients with EoE. Shire obtained the rights to acquire Meritage last year, in connection with its acquisition of ViroPharma. Shire closed the deal with ViroPharma in early 2014, announcing on Jan. 24 that it had successfully completed its tender offer for all outstanding shares of ViroPharma stock. Shire does not expect the Meritage transaction to affect its previously published earnings guidance for the year. “Shire’s pipeline and strategic focus on rare diseases is further strengthened with the acquisition of Meritage, which also complements our strong GI capabilities. Adding this Phase 3-ready compound to our late-stage portfolio will allow us to leverage our expertise to further develop this important therapy that, if approved, will give hope to patients living with eosinophilic esophagitis,” Dr. Philip J. Vickers, head of research and development at Shire, commented in a statement. For the full version of this story, search for Editconnect code E02261501 on our website. n For more information, visit www.DDN-News.com AWARDS & HONORS MARCH 2015 | | DDNEWS 43 Awards & Honors WITec’s RISE microscope wins Prism Award 2015 SAN FRANCISCO—WITec and Tescan have been recognized with a 2015 Photonics Prism Award for their RISE microscope. The award is given for top innovations in the field of photonics, granted by Photonics Media and sponsored by the international Society for Optics and Photonics (SPIE). The winners were chosen from more than 130 applicants and were announced during SPIE Photonics West on Feb. 11. RISE microscopy is a novel correlative microscopy technique that combines confocal Raman imaging and scanning electron (hence the acronym RISE) microscopy within one integrated microscope system. This combination is said to enable the most comprehensive sample characterization, as electron microscopy is an excellent technique for visualizing sample surface structures in the nanometer range and confocal Raman imaging is an established spectroscopic method used for the detection of the chemical and molecular components of a sample. It can also generate 2D- and 3D-images and depth profiles to visualize the distribution of the molecular compounds within a sample. “The RISE Microscope is another striking example of WITec’s enormous innovative strength. We are proud to once again receive a Prism Award, the second after being recognized in 2011 for WITec’s TrueSurface microscopy technology,” said Dr. Olaf Hollricher, WITec’s managing director of research and development. The microscope’s development was a joint effort of WITec and Tescan within the UNIVSem project, funded by the European Union. n Dr. Klaus Weishaupt (left), WITec managing director of marketing and sales, and the WITec/ Tescan team accept the Prism Award 2015. From left to right of Weishaupt are Jeff Streger of Tescan USA Inc., Radomír Koprˇiva of Tescan Orsay Holding and Steve Rapp of WITec. EMD Millipore, the Life Science division of Merck KGaA (pictured here), recently announced NGM Biopharmaceuticals Inc. as the recipient of its 2014 Emerging Biotech Grant Program. From left to right are Drs. Yutaka Takahasi, Alain Fischer and Theodore Friedmann, winners of the 2015 Japan Prize. EMD Millipore announces Emerging Biotech Grant Program winner Horizon Discovery CEO wins Entrepreneur of the Year award BILLERICA, Mass.—EMD Millipore, the life-sciences division of Merck KGaA in Darmstadt, Germany, announced in January that NGM Biopharmaceuticals Inc. is the recipient of its 2014 Emerging Biotech Grant Program. Committed to helping advance lifesaving drugs to market, EMD Millipore hosted its first emerging biotech grant program, in which the winner receives products and services from EMD Millipore to help develop their molecule. More than 300 entries were accepted from Sept. 3 through Nov. 30, 2014. The winning entry was selected based on objective criteria of equal weight: the scientific and societal merit of the therapy being developed and the process challenges and expertise gaps associated with the development of the therapy. NGM Biopharmaceuticals is an innovative drug discovery company located in San Francisco that is engaged in identifying and developing biologics for the treatment of cardiometabolic conditions, bile acid-related disease and potentially other diseases resulting from manifestations of cardiometabolic abnormalities and metabolic-related cancers. 2015 Japan Prize honors pair of gene therapy pioneers TOKYO—The Japan Prize Foundation recently announced that it has selected three distinguished scientists as winners of the Japan Prize, now in its 31st year, which is awarded annually to scientists and researchers in two categories who, regard- less of nationality, made substantial contributions to their fields and advancement of science and technology as well as serving the cause of peace and prosperity of mankind. This year’s winners were Drs. Theodore Friedmann, Alain Fischer and Yutaka Takahasi. Friedmann and Fischer were honored in the field of Medical Science and Medicinal Science as the world’s first researchers to propose and clinically prove a gene therapy concept. Friedmann, currently professor of pediatrics at the medical school of the University of California, San Diego, proposed the concept of gene therapy in the 1970s and pioneered the early phase of basic research in the field. Regarded internationally as the “father of gene therapy,” he has also been at the vanguard of ethical issues surrounding this field as an opinion leader for the past 40 years. For his part, Fischer used hematopoietic stem cell gene therapy to treat children with a fatal genetic disorder called X-linked severe combined immunodeficiency and clinically demonstrated efficacy of gene therapy with dramatic effectiveness for the first time. Fischer has been director of Institut Imagine in Paris, a leading research institute on genetic diseases, since 2007 and a professor at Collège de France since 2014. Takahasi, a professor emeritus of the University of Tokyo, won in the field of Resources, Energy and Social Infrastructure for his contribution to development of an innovative concept on river basin management and reduction of water-related disasters. CAMBRIDGE, U.K.—Horizon Discovery Group plc an international life-sciences company supplying research tools and services to organizations engaged in genomics research and the development of personalized medicines, announced in January that the company’s CEO, Dr. Darrin Disley, had been awarded Entrepreneur of the Year at the Quoted Company Awards 2015 in London. Disley has overseen a transformational year for Horizon, during which the company transitioned from a private life-sciences business employing 85 staff on a single 18,000-square-foot site in Cambridge to a publicly listed international life-sciences group employing 200 staff across over 85,000 square feet of facilities located in the United Kingdom, Austria and the United States. Under his leadership, Horizon listed on AIM market of the London Stock Exchange in March 2014, when the company was able to raise £68.6 million, nearly three times the initial target for its initial public offering. Since then, Disley has driven Horizon’s growth through a series of targeted acquisitions into high-value areas of the personalized medicines space: CombinatoRx based in Cambridge, Mass.; SAGE Labs based in St. Louis and Boyertown, Penn.; and most recently, Haplogen Genomics located in Vienna, Austria. He has also expanded the suite of products and services available to Horizon’s customers, bolstered the company’s intellectual property position and delivered high-value contracts with leading life-sciences companies. “To be recognized as an innovator and leader by my peers is a tremendous honor,” said Disley. “This has been an incredibly dynamic and exciting year for me and my colleagues at Horizon, and it is a testament to them that we have been able to be as successful as we have and to be as well positioned as we are for the future.” Prosensa wins Scrip Biotech Company of the Year award LEIDEN, The Netherlands—Late last year, Prosensa Holding N.V., a biopharmaceutical company focusing on RNA-modulating therapeutics for rare diseases with a high unmet medical need, won the Scrip Biotech Company of the Year award for 2014, announced in London. The Scrip Awards provide an opportunity to acknowledge and applaud the highest achievers across the biotechnology and pharmaceutical industry, recognizing both corporate and individual accomplishments. The award for Biotech Company of the Year is given to the company which has demonstrated the greatest achievements for the year. Hans Schikan, CEO of Prosensa, said, “Winning Scrip’s Biotech Company of the Year award is a great honor and a testament to the dedication and hard work of the Prosensa team. Our drive to succeed is fueled by patients and their families, who continue to inspire us to make innovative therapies available as quickly and efficiently as possible.” The other five finalists were Ablynx, Horizon Discovery, Isis Pharmaceuticals, Mesoblast and Silence Therapeutics. n PRODUCTS & SERVICES 44 DDNEWS | | MARCH 2015 Thermo Scientific Q Exactive Focus hybrid ouadrupole-Orbitrap mass spectrometer. Sensitivity, selectivity and flexibility. 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BioTek http://www.biotek.com/products/imaging/ cytation3_cell_imaging_multi_mode_ reader.html SEE US AT AACR BOOTH 1463 ValuMix qPCR assay Fluorescent TrueBlot Biosearch Technologies Inc. Rockland Immunochemicals Inc. Custom probes and primers for real-time PCR combined together within a single tube for your convenience. Spend more time on your research and less time prepping your assays. This formulation reduces waste, minimizes pipetting errors and simplifies your protocol. All probes are quenched by Black Hole Quencher (BHQ) dyes and are available with a variety of fluorophore options. BioSearch www.biosearchtech.com SEE US AT AACR BOOTH 1550 Fluorescent TrueBlot, a new format of Rockland’s popular TrueBlot product line, combines the power and specificity of the original products with the versatility of fluorescent and near-infrared dyes. Conjugating highly optimized TrueBlot reagents to a full spectrum of fluorescent labels results in multipurpose reporter molecules that can be used in a variety of immunoassays. Highly optimized Fluorescent TrueBlot provides pinpoint specificity while limiting background interference from non-specific binding. Rockland Immunochemicals Inc. www.rockland-inc.com SEE US AT AACR BOOTH 2412 The XFp Extracellular Flux Analyzer is an affordable extension to the XF product platform. This new, lowercost instrument will enable many more labs’ access to Seahorse’s unique technology. Seahorse Extracellular Flux (XF) Analyzers perform real time “stress tests” of the two major energy-producing pathways of the cell—mitochondrial respiration and glycolysis—detecting important changes in metabolism as reported in more than 1,000 peer-reviewed publications. Seahorse Bioscience www.seahorsebio.com SEE US AT AACR BOOTH 425 Visit Bio-Techne at Booth 2135 at the AACR Annual Meeting Bio-Techne Bio-Techne brings together the worldclass brands of R&D Systems, Novus Biologicals, Tocris and ProteinSimple to better serve our customers and help scientists reach their research goals. We are adding innovative instruments to our portfolio in a way that allows us to leverage our gold-standard reagents into complete solutions for both lifesciences and diagnostic markets. Bio-Techne www.bio-techne.com SEE US AT AACR BOOTH 2135 PRODUCTS & SERVICES For more information, visit www.DDN-News.com MARCH 2015 | | DDNEWS 45 ADVERTISER ’S INDEX The Simplicity-888 Controlled Atmosphere Chamber OncoSignature high-throughput screening platform PLAS-LABS Inc. Horizon Discovery Our OncoSignature HT Screening Platform allows you to profile your compounds of interest as mono or combination therapy across a comprehensive panel of 300 cancer cell lines, including isogenic cell lines. Study drug response, compare activity against 200 oncology reference compounds, identify combination interactions and aid in identifying the best patient population for your drug candidate or drug combination. Horizon Discovery www.horizondiscovery.com/GENASSIST SEE US AT AACR BOOTH 1055 The Simplicity-888 Controlled Atmosphere Chamber is a completely automatic anaerobic chamber designed for life-science and chemistry applications. The Simplicity-888 includes a programmable catalyst heater unit, factory-installed drying train system, internal outlet strip, transfer chamber and Plas-Labs’ standard twoyear warranty. The glove box comes ready to use; no installation required. The optically clear top provides completely visibility and light into the glove box. Customization is available, along with our 70-plus accessories. Clearly your best choice! PLAS-LABS Inc. www.plas-labs.com Eppendorf announces new BioFlo 320 bench-scale bioprocess control station Eppendorf Suitable for microbial and cell culture, scale up to scale down, batch, fedbatch and continuous processes, the new Eppendorf BioFlo 320 can meet the ever-changing needs of all segments of the biotech and pharmaceutical industries. New features—including autoclavable and single-use vessel flexibility, intelligent sensors and IP network communication for multiunit control—set it apart as the new premium choice in the bench-scale bioprocess market. Eppendorf www.eppendorf.com AACR Conference.......................................................41 Affymetrix.....................................................................29 ATCC..............................................................................15 Bio-Rad Laboratories, Inc.........................................48 Biosearch Technologies, Inc...................................47 BioTek Instruments, Inc............................................31 Cell Signaling Technology, Inc................................23 ChemBridge Corporation..........................................30 Cisbio US, Inc................................................................ 7 Crown Bioscience, Inc..............................................21 Drummond Scientific Company................................. 9 eBioscience .................................................................. 3 Eppendorf North America........................................... 5 Horizon Discovery Ltd................................................27 INDIGO Biosciences..................................................20 ISSCR Conference......................................................39 Kiyatec, Inc..................................................................18 Kuraray Co. Ltd............................................................32 OriGene Technologies, Inc................................ Cover PerkinElmer.............................................................2, 19 Plas-Labs,Inc...............................................................37 R&D Systems, Inc. .....................................................13 Rockland Immunochemicals, Inc...........................16 Seahorse Bioscience................................................25 Stemgent, Inc...............................................................35 Thermo Fisher Scientific............................................. 8 www.aacr.org www.affymetrix.com www.atcc.org www.bio-rad.com www.biosearchtech.com www.biotek.com www.cellsignal.com www.chembridge.com www.htrf.com www.crownbio.com www.drummondsci.com www.ebioscience.com www.eppendorf.com www.horizondiscovery.com www.indigobiosciences.com www.isscr.org www.kiyatec.com www.kuraray.us.com www.origene.com www.perkinelmer.com www.plas-labs.com www.RnDSystems.com www.rockland-inc.com www.seahorsebio.com www.stemgent.com www.thermoscientific.com People & Promotions Vaccinogen makes significant moves in early 2015 FREDERICK, Md.—A trio of news items marked the early part of this year for Vaccinogen Inc., a cancer vaccine company that is clinically testing OncoVAX, a treatment designed to prevent the recurrence of colon cancer and potentially other solid tumors—two of them related to people being placed in important positions and one of them arguably attributable to all of the people involved with the company. On Jan. 12 came the news that Dr. Peter Morsing, a 20-year pharmaceutical industry veteran whose most recent jobs were roles of increasing responsibility with AstraZeneca, had joined the company as head of business development. Morsing says of his new job, “I am eager to apply my decades of experience in licensing and pharmaceutical development to help the Vaccinogen team establish a first-in-class monoclonal antibody library using immune cells collected during the upcoming OncoVAX clinical study. This will be a significant milestone for advancing personalized medicine, and we hope to bring more optimal cancer therapies to the broader patient population by partnering with leading pharmaceutical and genomics companies.” Just under a month later, the company announced that Håkan Edström, a healthcare industry veteran with more than 40 years of experience, had been elected to the company’s board of directors and would chair the company’s Compensation Committee as well as serve on the Audit Committee. Edstrom was recently named CEO of MannKind Corp., following his 14-year tenure as president and chief operating officer of the company. He previously held leadership roles Sanofi SNBL USA Ltd. Olivier Brandicourt, M.D. Tina Rogers, Ph.D. Chief Executive Officer Director of Safety Assessment Mark Page PARIS—On Feb. 19, Sanofi appointed Dr. Olivier Brandicourt as CEO, with the plan for him to begin his duties officially on April 2. He has 28 years of global experience in the pharmaceutical industry, most recently as chairman of the board of management of Bayer HealthCare AG and member of the executive council of Bayer AG. Previously, Brandicourt held numerous positions of increasing responsibility within major global pharmaceutical groups, such as ParkeDavis/Warner-Lambert and Pfizer. Notably, Brandicourt served as a member of Pfizer’s global executive leadership team from 2010 to 2013. As the head of various key healthcare divisions, he has a broad range of expertise and knowledge of the pharmaceutical industry and has led the launch of numerous new medicines and the completion of strategic acquisitions and integrations. E V E R E T T, Wash.—On Feb. 12, SNBL USA announced the appointment of Dr. Tina Rogers as the director of safety assessment. In this position, she will manage dayto-day operations of the department to ensure continued operational and scientific excellence and help direct strategic plans, objectives and policies to support sponsors with the highest level of compliance and efficiency. Over her 20 years of industry experience, Rogers has provided preclinical drug development services to biopharma, the U.S. National Institutes of Health and the U.S. Department of Defense. SNBL USA offers programs ranging from regulatory toxicology to customized study designs in multiple drug classes (biologics, small molecules, oligonucleotides and vaccines). Chief Financial Officer PETACH TIKVA, Israel—Macrocure, a clinicalstage biopharmaceutical company focused on developing a novel therapeutic platform to address chronic and hard-to-heal wounds, announced recently that Mark Page would join the company as chief financial officer, effective Feb 10, 2015. Page joins Macrocure from Credit Suisse’s Global Healthcare Investment Banking Group, where he led the firm’s medical device franchise since 2010, adding to his healthcare-dedicated corporate finance and strategic background that spans 20 years of experience. Macrocure Ltd. SCYNEXIS Inc. Marco Taglietti, M.D. Chief Executive Officer RESEARCH TRIANGLE PARK, N.C.— In February, drug discovery and development company SCYNEXIS named Dr. Marco Taglietti as CEO, effective April 1. Taglietti, a member of the SCYNEXIS board of directors, will succeed Dr. Yves Ribeill, who will remain the company’s president and continue to serve on the SCYNEXIS board. Taglietti was appointed to the SCYNEXIS board in December 2014. He previously served as executive vice with Bausch & Lomb, serving as vice president and president of the Global Surgical Division and senior corporate vice president of the Americas Region. In between those two pieces of news came word from Vaccinogen on the closing of the second $10-million tranche of a $80-million financing announced August 2014. This second tranche brings the total amount closed to $20 million of the $80 million committed at $5.50 per share or unit. The capital will be used to fund further company expansion and ACTIVE, a confirmatory Phase 3b study of OncoVAX. president of research and development and chief medical officer of Forest Laboratories Inc. and also as president of the Forest Research Institute until the company was acquired by Actavis plc. Prior to joining Forest Labs, Taglietti was senior vice president and head of global research and development at Stiefel Laboratories Inc. In an unrelated matter, Dr. Carole Sable, the chief medical officer at SCYNEXIS, stepped down, effective Feb. 20. Rexahn Pharmaceuticals Inc. Ely Benaim, M.D. Chief Medical Officer ROCKVILLE, Md.—Rexahn Pharmaceuticals, a clinical-stage biopharmaceutical company focused on therapeutics for the treatment of cancer, recently announced the appointment of Dr. Ely Benaim, as chief medical officer. In this role, Benaim will be responsible for leading Rexahn’s clinical development programs and providing strategic and clinical guidance for the company. Benaim has more than 25 years of experience in healthcare, including 15 years of clinical research experience in academia, government and pharmaceutical industry, as well as extensive experience in global regulatory affairs. Q&A: Nissim Mashiach Q&A of Macrocure 46 DDNEWS | | MARCH 2015 For more information, visit www.DDN-News.com Macrocure and the wound-care market C BY LLOYD DUNLAP HRONIC AND HARD-TO-HEAL wounds are a serious and growing $5.3-billion problem affecting more than 2 million people in the United States, European Union and Japan. Common results of chronic wounds include comorbidities and mortality, lengthened hospital stays and a significant increase in the cost of care, all of which have a negative impact on the quality of life of both the patients and caregivers. DDNews recently explored possible remedies with Nissim Mashiach, president and CEO of the Israeli company Macrocure Ltd. DDNews: Nissim, could you explain to our readers your company’s track record in regenerative medicine, wound care and the development and commercialization of biologics? Nissim Mashiach: Founded in 2008, Macro- cure is focused on developing a novel therapeutic platform to address chronic and hardto-heal wounds, such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). My company’s lead product candidate, CureXcell, is a monthly injectable of living, human, activated white blood cells. More than 5,000 patients have been treated in Israel to date, where it has been approved for commercialization for the past 17 years. We are currently in two pivotal double-blind Phase 3 clinical trials in the U.S., with data expected in the second half of 2015. My management team has a wide range of experience in developing and commercializing biologics. For example, I have worked at Ethicon (Johnson & Johnson) and Omrix Biopharmaceuticals. DDNews: How does your product’s contact with the injured person’s wound bed trigger a body’s endogenous healing process? The healing process can be triggered by the injection of a mixture of activated white blood cells obtained from young healthy donor blood into the wound bed. The mixture can replenish the imbalanced inflammatory environment in the nonhealing wound with functionally active immune cells that release the necessary growth factors and are capable of phagocytosis of bacteria and dead cells in the wound bed. Recent findings from our mechanism of action study confirmed that CureXcell has over 55 growth factors and cytokines that participate in all stages of wound healing. The amplification of the cytokines and growth factors found in CureXcell assures a very high concentration of these activated Mashiach: growth factors, which can explain the high closure rate our product has demonstrated versus standard of care in our previous clinical studies. By recreating the natural environment for wound healing, the appropriate cell activities and factor secretions are maintained as required during wound healing. DDNews: Will CureXcell have applications beyond chronic and hard-to-heal wounds such as DFUs and VLUs? Mashiach: Yes, CureXcell has potential mar- ket applications in a wider range of regenerative medicine applications, including aesthetic surgery, orthopedic surgery and reconstructive surgery. One of the reasons why we are doing robust clinical studies is that we see CureXcell as a platform technology that may be applicable in many indications beyond wound healing. DDNews: Would you explain to our readers the important commercial potential of your company and its products? Chronic, hard-to-heal wounds represent one of the largest, fastest-growing segments of the wound-care market. The worldwide advanced wound-care market has existing sales of approximately $5.3 billion; there are approximately 800,000 new DFU patients and approximately 1,300,000 new VLU patients each year in the U.S., EU and Japan. Twenty-five percent of diabetes patients will develop a foot ulcer; currently, 15 percent of hard-to-heal wounds result in amputations. In fact, 80 percent of all amputations in the U.S. are the result of nonhealing DFUs. Overall, the problem places a $25-billion burden on the U.S. healthcare system, which we believe we can help alleviate. In addition to this high unmet medical need, there is an existing desire on the part of physicians for alternate treatment options Mashiach: The amplification of the cytokines and growth factors found in CureXcell assures a very high concentration of these activated growth factors, which can explain the high closure rate our product has demonstrated versus standard of care in our previous clinical studies. By recreating the natural environment for wound healing, the appropriate cell activities and factor secretions are maintained as required during wound healing. Macrocure’s lead product is CureXcell, a cell-based therapy for hard-to-heal wounds that is designed to restore the wound-healing process. It is currently only available for sale in Israel. that are backed by strong clinical data and favorable reimbursement. We believe that CureXcell can address these unmet medical needs and become an attractive solution for physicians and patients. data in the second half of 2015, file our BLA in the second half of 2016 and obtain approval in late 2017). We are seeking a broad-label indication for CureXcell for all wounds below the knee. DDNews: Please explain the Macrocure process, i.e., how it functions to heal wounds. DDNews: What have been the results of clinical studies thus far? Mashiach: CureXcell is an injectable suspension of living white blood cells, including macrophages, neutrophils and lymphocytes, which are crucial to initiating, promoting and completing the process of cellular regeneration and wound healing. Macrocure activates the white blood cells via its proprietary hypoosmotic shock cell activation technology, a process that changes the concentration and pH of the suspension surrounding the cells. Once activated, these cells undergo a change in gene expression that results in an increase in the cells’ secretion of numerous growth factors and other biochemical factors. A physician draws CureXcell from its sterile package using a standard syringe for injection into a patient’s wound. A direct application into the wound bed is a major advantage, in that it allows the treatment to bypass the biofilm and contaminated environment and promote healing from the inside out. And as a major boon to patients, the therapy involves only one injection per month. Mashiach: An Israeli clinical trial harnessing DDNews: What are the regulatory hurdles you may still face in the U.S. to obtain FDA approval for this unique product? Mashiach: FDA approval is contingent upon meeting the DFU and VLU clinical trial endpoints (we expect to report full and interim CureXcell has shown that after only approximately three injections directly into the wound bed, there was a 64-percent closure rate in DFU and over 80 percent in VLU. The current clinical trials in the U.S. are designed similarly to the Israeli trial in terms of inclusion/exclusion criteria. The trial is enrolling the worst of the worst and includes patients with low ABI and infection, and can include patients post-amputation. n EDITCONNECT: E031530 Nissim Mashiach has served as president and CEO of Macrocure Ltd. since June 2012. Before joining Macrocure, he served as general manager at Ethicon, a Johnson & Johnson company, from 2009 to 2012. Prior to that, he served as president and CEO at Omrix Biopharmaceuticals Inc., a company acquired by Johnson & Johnson in 2008. Prior to Omrix, Mashiach held various leadership positions at several pharmaceutical companies. He holds an MBA from the University of Manchester in England, a master of pharmaceutical science degree from the Hebrew University in Jerusalem and a bachelor’s degree in chemical engineering from the Technion-Israel Institute of Technology in Haifa, Israel. DDNEWS (USPS 024-504) is published monthly by Old River Publications LLC, 19035 Old Detroit Road, Suite 203, Rocky River, OH 44116; 440-331-6600. Periodical postage paid at Cleveland, Ohio and additional mailing offices. Publisher assumes no responsibility for unsolicited material or prices quoted in the magazine. Contributors are responsible for proprietary classified information. ©2015 by Old River Publications. All rights reserved. Reproduction, in whole or in part, without written permission of the publisher is expressly prohibited. 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