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BIOWORLD TODAY TM THE DAILY BIOPHARMACEUTICAL NEWS SOURCE JANUARY 11 , 2016 BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS ANTI-BOOKMARK DRUG PUT TO TEXT BIOPHARMA OPTIMISTIC, FLUSH WITH CASH Despite ‘choppy’ markets, fundamentals strong as health care world heads to JPM By Marie Powers, News Editor SAN FRANCISCO — As investors in biopharma, medtech and affiliated industries descend on San Francisco for the start of the 34th Annual J.P. Morgan Healthcare Conference (JPM), invited guests and throngs of hangers-on could be forgiven for glancing nervously over their shoulders at the global capital markets. In the wake of geopolitical and macroeconomic uncertainties – currency and stock roiling in China, oil-fueled power brokering in the Middle East, election year politicking in the U.S. and saber-rattling in North Korea – the first trading days of 2016 took investors on $535M Roche cancer BET more than ‘Tensha’ relief; key to TNBC in NUTshell? By Randy Osborne, Staff Writer With a phase II trial in stubborn triplenegative breast cancer (TNBC) set to begin soon and results already disclosed against nuclear protein in testis (NUT) midline carcinoma, bromodomain See JPM, page 3 FINANCINGS DEALS AND M&A PRESENTING AT J.P. MORGAN Zai’s series B brings $100M-plus for R&D in China, global markets By Shannon Ellis, Staff Writer SHANGHAI – Zai Labs Ltd., of Shanghai, has done it again, this time raising more than $100 million from seasoned health care venture firms led by Advantech By Michael Fitzhugh, Staff Writer Mylan NV and Momenta Pharmaceuticals Inc. agreed to work together to develop, manufacture and commercialize six of Momenta’s current biosimilar candidates under an exclusive new deal. The arrangement provides Mylan with a maturing biosimilars platform that could Read this week’s edition Nice slice of ‘mud’ pie as Accelerator launches Lodo with $17M series A By Marie Powers, News Editor The New York arm of Accelerator Corp. launched its second biopharma in less than a week as Lodo Therapeutics Corp. set out with a $17 million series A financing. The round included the same See Lodo, page 7 See Momenta, page 6 THE BIOWORLD BIOME BioWorld Science Editor Anette Breindl takes a closer look at translational medicine See Tensha, page 4 NEWCO NEWS Mylan, Momenta strike $245M biosimilars deal See Zai, page 5 BENCH PRESS VOLUME 27, NO. 6 IN THE CLINIC THE YEAR FOR NANOMEDICINE? CALL ME MAYBE Cardiac variants fail to predict risk in prospective study By Anette Breindl, Senior Science Editor In findings that illustrate the gap between risk variants and clinical disease, scientists from Vanderbilt See Risk, page 8 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. Nanobiotix launches U.S. trial, enters hot immuno-oncology field By John Brosky, Contributing Writer PARIS – At the start of what promises to be a big year for nanomedicine developer Nanobiotix SA, of Paris, the company reported approval for its first clinical See Nanobiotix, page 9 MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY FINANCINGS Aequus Pharmaceuticals Inc., of Vancouver, British Columbia, said it intends to complete a nonbrokered private placement in the U.S. of up to 2 million shares and a nonbrokered public offering in Canada up to 3.5 million shares at a price of C50 cents (US35 cents) each, for aggregate gross proceeds of up to C$2.75 million. Aequus intends to use funds for research and development and general working capital purposes. The deal is expected to close Jan. 12. Ardelyx Inc., of Fremont, Calif., priced a public offering of 7.5 million shares of its common stock at a public offering price of $10 each for gross proceeds of $75 million. The firm granted the underwriters the right to purchase up to about 1.12 more million shares of common stock at the public offering price. Ardelyx intends to use its existing cash and cash equivalents and the net proceeds of the offering to support the tenapanor and RDX022 phase III programs, including manufacturing of clinical trial materials, as well as to support the investigational new drug application filing for RDX009 and to fund additional research and development for its earlier-stage programs. Citigroup and Leerink Partners LLC are acting as joint bookrunning managers. Wedbush Pacgrow is acting as lead manager, and JMP Securities LLC, Cantor Fitzgerald & Co. and Ladenburg Thalmann are serving as co-managers. Shares of Ardelyx (NASDAQ:ARDX) closed Friday at $10.72, up 63 cents. Collegium Pharmaceutical Inc., of Canton, Mass., priced a public offering of about 2.8 million shares of its common stock at $20 per share. Gross proceeds are expected to be $55 million. In addition, Collegium granted the underwriters a 30-day option to purchase up to an additional 412,500 shares of common stock. The offering is expected to close Jan. 13. Jefferies and Piper Jaffray are acting as joint book-running managers. William Blair and Needham are acting as co-lead managers, while Janney Montgomery Scott is acting as a comanager. Shares of Collegium (NASDAQ:COLL) closed Friday at $19.72, down $1.41. (See BioWorld Today, Sept. 14, 2015.) Zymeworks Inc., of Vancouver, British Columbia, closed a BIOWORLD TODAY BioWorld™ Today (ISSN# 1541-0595) is published every business day by Thomson Reuters, 115 Perimeter Center Place, Suite 1100, Atlanta, GA 30346 U.S.A. Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. All Rights Reserved. No part of this publication may be reproduced without the written c onsent of Thomson Reuters (GST Registration Number R128870672). OUR NEWSROOM Atlanta - Lynn Yoffee (News Director), Jennifer Boggs & Amanda Lanier (Managing Editors), Peter Winter (BioWorld Insight Editor), Karen Pihl-Carey (Database Editor), Ann Duncan (Senior Production Editor), Marie Powers (News Editor), Randy Osborne (Staff Writer) // East Coast Anette Breindl (Senior Science Editor), Mari Serebrov (Regulatory Editor) // West Coast - Michael Fitzhugh (Staff Writer) // Europe - Nuala Moran & Cormac Sheridan (Staff Writers) // Asia: John Fox, Shannon Ellis, Catherine Makino, Alfred Romann, Dave Silver, Cornelia Zou (Staff Writers) PAGE 2 OF 15 $61.5 million series A mezzanine financing to support the advancement of its Azymetric therapeutics pipeline. The financing was supported by a syndicate of U.S. and Canadian institutional investors. It was co-led by new investors BDC Capital and Lumira Capital and joined by existing Zymeworks investors Indianapolis-based Eli Lilly and Co., Summit, N.J.based Celgene Corp., CTI Life Sciences Fund and the Fonds de solidarité FTQ. New investors in the financing include Perceptive Advisors, Teralys Capital, Northleaf Venture Catalyst Fund, Brace Pharma Capital, Merlin Nexus and others. Proceeds of the financing will support clinical development of Zymeworks’ lead candidates, the potential cancer therapies ZW25 and ZW33, which the company plans to move into clinical development later this year. In separate news, Zymeworks inked a deal making an undisclosed equity investment in Kairos Therapeutics Inc., also of Vancouver, which specializes in the discovery and development of antibody-drug conjugates. Under the terms, Zymeworks and Kairos also have the option to merge to further integrate their respective platforms, resources and pipelines to accelerate the development of cancer biotherapeutics. (See BioWorld Today, Jan. 22, 2015.) OTHER NEWS TO NOTE Ampliphi Biosciences Corp., of San Diego, said it acquired key assets from U.K.-based Novolytics Ltd., including bacteriophage-related intellectual property, bacteriophage libraries, formulation and regulatory know-how as well as GLP toxicology data. Terms were not disclosed. Ariad Pharmaceuticals Inc., of Cambridge, Mass., said its partner, Otsuka Pharmaceutical Co. Ltd., of Tokyo, submitted a new drug application to the Japanese Pharmaceuticals and Medical Devices Agency seeking approval for Iclusig (ponatinib) for the treatment of resistant or intolerant chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Ariad expects Otsuka to receive a decision on the new drug application in Japan in the second half of 2016. PRACTICAL INFORMATION For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_ Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-3364474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. For ad rates & information, contact Tyler Beatty toll free at (855) 260-5607 or, outside the U.S. and Canada, at (646) 223-7585, email [email protected]. For photocopy rights or reprints, please contact Tyler Beatty toll free at (855) 260-5607 or, outside the U.S. and Canada, at (646) 223-7585, or by email at tyler.beatty@ thomsonreuters.com. Send all press releases and related information to [email protected]. BUSINESS OFFICE Donald R. Johnston (Senior Director, Current Awareness), Sarah Cross (Marketing Director), Penney Holland (Web Production Manager), Tracie Webb (Customer Service Manager) CONTACT US Jennifer Boggs, (770) 810-3120 // Anette Breindl, (770) 810-3134 // Sarah Cross, (770) 810-3138 // Michael Fitzhugh, (770) 810-3064 // Penney Holland, (770) 810-3047 // Donald R. Johnston, (770) 810-3118 // Nuala Moran, 44-7778-868-579 // Randy Osborne, (770) 810-3139 // Marie Powers, (770) 810-3136 // Mari Serebrov, (770) 810-3141 // Cormac Sheridan, 353-876864323 // Tracie Webb, (770) 810-3130 // Peter Winter, (770) 810-3142 // Lynn Yoffee, (770) 810-3123 MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY JPM Continued from page 1 a wild ride, and they might need to hold onto their hats for the foreseeable future. Despite inching up early Friday, the Dow Jones Industrial Average closed in the red at 16,346.45, shedding more than 6 percent of its value during the first week of the New Year. The Nasdaq Composite – arguably the sector’s more important index – was off more than 7 percent in the week leading to JPM after losing more ground Friday to close at 4,643.63. The Nasdaq Biotechnology Index, the subset of 190 of the sector’s biggest names, also remained in the red Friday for a one-week drop of nearly 11 percent, finishing at 3,160.21. Still, the losses didn’t prevent a stunning number of biopharmas from turning to the markets with IPO filings during the first week of 2016 – eight offerings collectively seeking some $680 million – while 22 additional companies filed or priced follow-ons set to exceed $2.6 billion. (See BioWorld Today, Jan. 7, 2016, and Jan. 8, 2016.) “Although biotech investors have headed for the sidelines for now, the industry’s fundamentals remain strong,” said Peter Winter, editor of BioWorld Insight and a seasoned observer of the industry’s financial and business trends. “Investors will be listening closely to company presentations at JPM on how executives plan to deliver value going forward,” he observed. “After a massive inflow of cash in 2015, biopharma companies are well placed to pull the trigger on acquiring assets through M&A or ambitious partnering deals, in addition to the usual share buybacks. If investors like what they hear, expect them to return to the fold later this month.” WHAT WILL BIOPHARMA DO WITH ALL THAT CASH? The industry is poised to see more multibillion-dollar mergers, which could be announced as early as this quarter – even during JPM, as the long-simmering offer by Shire plc, of Dublin, to acquire Baxalta Inc., of Bannockburn, Ill., heated up again last week. (See BioWorld Today, Aug. 5, 2015.) Winter also pointed to Gilead Sciences Inc., of Foster City, Calif., which is sitting on $10 billion raised in September 2015, only a fraction of which was used last month to purchase rights to the Janus kinase 1-selective inhibitor, filgotinib (GLPG0634), from Galapagos NV, of Mechelen, Belgium. (See BioWorld Today, Dec. 18, 2015.) Analysts had questions about what biopharmas will do with all that cash – 70 pages worth from the J.P. Morgan Healthcare team. For example, the team wants Alkermes plc, of Dublin, to explain how the company will prioritize the use of its $800 million in cash in light of its ongoing phase III program for ALKS 5461 in major depressive disorder and upcoming pivotal programs for multiple sclerosis candidate ALKS 8700 and schizophrenia drug ALKS 3831. (See BioWorld Today, Feb. 25, 2015.) PAGE 3 OF 15 For Celgene Corp., of Summit, N.J., the question is more about capital allocation and providing the most value from its cash, reported as $7.5 billion as of Sept. 30. For Dynavax Technologies Corp., of Berkeley, Calif., which posted upbeat phase III data last week on its hepatitis B vaccine, Heplisav-B, the J.P. Morgan team asked whether the cash runway is sufficient to finance the product launch. (See BioWorld Today, Jan. 8, 2016.) For Vertex Pharmaceuticals Inc., of Boston, which is “sitting on a nice sum of cash,” inquiring minds want to know about capital allocation – whether the company plans “to keep this cushion or consider M&A/additional collaborations,” asked the J.P. Morgan analysts. In October, Vertex paid $105 million up front, including $75 million in cash and a $30 million equity investment, to Crispr Therapeutics AG, of Basel, Switzerland, on a collaboration to discover and develop treatments for genetic diseases, including cystic fibrosis and sickle cell disease, that could ultimately exceed $2.6 billion. (See BioWorld Today, Oct. 27, 2015.) For Mannkind Corp., of Valencia, Calif., questions focus more on prospects for solvency. Last week, the company lost its commercial partnership with Paris-based Sanofi SA, for the inhaled insulin product, Afrezza, and saw shares plummet. The J.P. Morgan analysts want to know how long the company’s cash resources will last, how to think about its capital structure and future financing needs and whether it can raise additional capital in Israel. (See BioWorld Today, Jan. 6, 2016.) ‘WE’RE LOOKING FOR THE SAME OLD-FASHIONED STUFF’ Although pundits like to look back when assessing the mood at JPM, participants remain scrupulously consistent. They arrive with meticulous meeting lists and focus on checking off their boxes as they slog cheek-to-cheek through the congested halls of the Westin St. Francis – indeed, through the streets, eateries and hotels lining Union Square. There’s no template for success at JPM. The agendas are as varied as the attendees. “It’s always a little bit of zoo,” admitted Oleg Nodelman, founder and managing director of Ecor1 Capital LLC. “But everyone in the world of health care comes to San Francisco, so it’s amazingly efficient.” As he always does, Nodelman will look for “the most interesting things” – processes, technologies and data – to stand out while the rest of the PowerPoints fade into background noise. “We’re fundamentally driven so we’re looking for the same old-fashioned stuff,” he told BioWorld Today, stressing two of his favorite questions: “What is the market missing? Or is the market not missing anything? There’s no magic buzzword. We’re always looking for companies that are well funded – you can’t save your way to success in this sector – but at the same time we like companies that are spending money prudently.” A staggering amount of public and private capital flowed See JPM, page 10 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY PAGE 4 OF 15 Tensha malignancies and advanced solid tumors. (See BioWorld Today, Dec. 19, 2014.) and extra terminal domain (BET) inhibitor specialist Tensha Therapeutics Inc. drew Roche AG to the table for a takeover valued at up to $535 million. “Hopefully, we’ve provided them with the foundation of monotherapy data to take [lead small-molecule TEN-010] forward in a very smart way, as they’ve historically done in [other] fields of novel mechanisms,” CEO Douglas Onsi told BioWorld Today. In Tensha’s hands, the compound has reached phase I trials in solid tumors and hematological malignancies. BET drugs bear promise in combination regimens for cancer, too, making Basel, Switzerland-based Roche a good fit, he said. The pair is expected to make public their deal today and tie up loose ends in the first quarter of this year. Specifically, Roche agreed to pay $115 million up front and as much as $420 million in milestone payments related to clinical and regulatory goals. Founded by James Bradner, formerly of the Dana-Farber Cancer Institute, and managed and funded by Healthcare Ventures, Tensha brings an epigenetic technology that disrupts BET proteins, which contribute to cancer cell memory by binding to the genome as molecular “bookmarks.” An investigatorinitiated phase II trial with TEN-010 in TNBC is set to open at Dana-Farber shortly. Results in NUT midline carcinoma were offered by the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in November. (See BioWorld Today, Jan. 7, 2016.) The chemical probe for BET, JQ1, was freely shared by Bradner – over the last five years, more than 500 labs have received it – “with the expectation that the global research community could provide more scientific support and direction for our clinical candidate more efficiently and effectively than any one company, particularly a venture capital-backed biotech company, could do on its own,” Onsi said. “It’s been a tremendous success. We and the entire field have benefited from the publications and the enthusiasm that all of those investigators have had for JQ1 and for BET inhibition.” Bradner also was the originator of suberohydroxamic acid (4-methoxycarbonyl) phenyl ester, or SHAPE, the topical histone deacetylase inhibitor that ended up with Tetralogic Pharmaceuticals Corp., of Malvern, Pa., which recently began an interim analysis of a randomized phase II experiment. The trial was designed to investigate the safety and efficacy of three SHAPE dosing regimens in patients with earlier-stage cutaneous T-cell lymphoma. Onsi said both of Bradner’s programs “went from his academic labs to clinical trials in two years, and in both cases were able to demonstrate proof-of-concept data within a couple of years thereafter.” (See BioWorld Today, Jan. 8, 2016.) Roche’s move is not the first pharma bid in BET inhibitors. Kenilworth, N.J.-based Merck & Co. Inc. bought Oncoethix SA, of Lausanne, Switzerland, for $110 million up front and $265 million in potential milestone payments in late 2014. Oncoethix had advanced OTX015 to phase Ib trials for hematological RESISTANCE COULD LIE AHEAD Continued from page 1 Farthest along clinically in BETs is Resverlogix Corp., of Calgary, Alberta. In November, the firm dosed the first patient in the phase III trial called BETonMACE with lead drug apabetalone (RVX-208) in high-risk patients with coronary artery disease and type 2 diabetes. The primary outcome measure will assess the effect of apabetalone on time to first occurrence of major adverse cardiovascular events (MACEs). In the fall of 2014, Resverlogix disclosed data showing the compound gained a 77 percent reduction in MACEs in diabetic patients. Resverlogix spinout Zenith Epigenetics Inc., of San Francisco, has next-generation oncology work under way with BET inhibitors. Others active in the space include Aptose Biosciences Inc., of San Diego; Foster City, Calif.-based Gilead Sciences Inc.; and Incyte Pharmaceuticals Inc., of Wilmington, Del. As long ago as 2013, analyst Andrew Fein with H.C. Wainwright tagged BET inhibitors as “the most underappreciated early stage small-molecule class in oncology. Since then,” he wrote in an April 2014 report, “the BET space has crowded fast, with many new small companies emerging and several big pharmas also joining the movement with in-house programs. We count at least 16 active BET inhibitor programs, although, notably, the number of companies that have recently ‘dabbled’ in the space may be twice as large.” But a paper in Nature recently tempered the optimism, pointing out that “tumor cells are likely to become resistant to these drugs. Anticipated mechanisms of resistance have now been described.” Several reports lately suggest that “BET inhibitors might have a broader potential than had previously been realized,” the paper conceded. “They also highlight the possibility that BET inhibitors could be used in combination with other drugs to overcome both innate and acquired drug resistance. Although the reported resistance mechanisms seem to reflect an adaptation to drug pressure, the root cause of resistance remains unknown. Does a specific mutation cause Wnt or CK2 activation, or are these adaptive changes that drive resistance through reversible epigenetic mechanisms? A complete mechanistic understanding of resistance remains to be defined.” // OTHER NEWS TO NOTE Bamboo Therapeutics Inc., of Chapel Hill, N.C., said it acquired the viral gene therapy manufacturing facility (Vector Core) from the University of North Carolina at Chapel Hill. Financial details were not disclosed. The Vector Core was founded in 1993 as a full-service viral vector production organization with extensive experience in vector design and process development, as well as manufacturing of research and clinical-grade vectors. Bamboo has developed a suspension cell-based production platform that utilizes serum free/chemically defined media to increase scalability, efficiency and purity. For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY Zai Continued from page 1 Capital and Orbimed. The trio of Zai’s series A backers – Qiming Ventures, Sequoia and TF Capital – also continued their support in this second round. Zai is a biopharma focused on discovering and developing new medicines for oncology, inflammatory and autoimmune diseases for the China market but also with potential for global markets. The Chinese character for Zai, which means “once more” or “again,” refers to the history many of its key people have had in China’s relatively fledgling biotech space, namely with pioneering firm Hutchison Medipharma. Not least among that group is Samantha Du, former head of Hutchison and CEO and founder of Zai. Her goal from the outset has been to establish a globally respected Chinese biopharma capable of working to the highest industry standards, and Zai’s in-licensing deals and strategic moves show the firm has earned the confidence to be considered among the most relevant players in the industry after just a few short years. Firms such as Sanofi SA, UCB SA and Hanmi Pharmaceuticals Co. Ltd. have all felt comfortable signing over key assets to Zai for local and/or global development. (See BioWorld Today, Aug. 20, 2014, Sept. 23, 2015, and Nov. 25, 2015.) Zai’s pipeline consists of ZL2301 for hepatocellular cancer and ZL2303 for non-small-cell lung cancer (NSCLC), both at a late stage, entering phase III studies. Three other candidates, ZL 2302 for NSCLC, ZL2102 for asthma and chronic obstructive pulmonary disease and ZL1101 for graft-vs.-host disease and inflammatory bowel disease, are all in the preclinical or phase I stage. Zai has a recently launched internal discovery program in large molecules for oncology as well. That diversified, multishots-at-the-target pipeline approach has allowed Zai to be in the enviable position of picking the cream of the crop for investment partners, benefiting from an ongoing trend that there are often more Chinese investors on the hunt for a good investment vehicle than there are good Chinese companies in which to invest. Advantech is a newly formed fund from venture capitalist Jianming Yu, who has successfully managed one of China’s largest funds, New Horizon. Advantech Capital will focus on innovation-driven growth capital, investing in technology, media and telecommunications, e-services and health care companies in China. “What impressed me about Advantech Capital is that Jianming Yu and I have the same dreams,” Du told BioWorld Today. “He is looking to make Zai one of the largest pharma companies up to a global standard coming out of China; we hope to be the best. He has a lot of patience stemming from his own background and training – he obtained a doctorate in molecular biology from Harvard – and has a global network of resources, all sure to help our company as well.” With that added financial leverage, Zai’s goal is to continue its three-prong offensive: advance the pipeline in the clinic, in- PAGE 5 OF 15 license more candidates for China (and the globe) and expand its newly formed biological discovery unit. (See BioWorld Today, Oct. 28, 2015.) “We still have $20 million left [from previous rounds of investment],” said Du. “With this over $100 million round we have a pretty solid financial base to support the company to move toward the next three years.” Zai received $30 million in series A financing more than a year ago. (See BioWorld Today, Sept. 2, 2014.) The company also joins a relatively exclusive club of Chinese biotechs that have entered the $100 million-plus venture capital financing club. Also on the list are Ascletis Pharmaceuticals Co. Ltd., Innovent Biologics Inc. and Beigene Co. Ltd. And along with Innovent, Zai is one of the few Chinese biotechs invited to give a company presentation at this week’s J.P. Morgan Healthcare Conference in San Francisco. A ‘VERY BIG AMBITION’ The latest round of financing, Du said, was driven at the outset from repeated investor interest, prompting the firm to quietly solicit a few investors with deep knowledge of the industry. It did not take long to line up Advantech and Orbimed and to see enthusiastic support from existing series A investors as well. Du said there are many investors in China looking to enter the biopharma field, but without the requisite scientific background, there is a concern they may underestimate the risks. Over the long term, that could create a dangerous bubble as those VCs offer capital along with pressure for quick returns, but little in the way of patience or understanding that it takes biopharmas a long time to make a return for investors. While Du said her investors have that patience, with decadelong investment windows, her timetable, if all goes according to plan, may not require it. Zai is looking to start ramping up commercial efforts in 2017, with hopes that approvals will be in hand not long after. Du pointed to her team’s track record at Hutchison for securing green channel approval from regulatory authorities and extensive experience working with the CFDA and the CDE, as key indicators of that future success. Those relationships also help potential licensing deals as well, since Zai has demonstrated local know-how in getting candidates over China’s considerable regulatory hurdles. “We hope to license a few more blockbuster drugs – early stage global rights and later-stage China rights – because the team by now has very strong capabilities, very good communication with the CDE and very strong operation and technical background. We want to continue this momentum and the team has the capability to handle multiple programs,” said Du. “Even though we are not a big pharma – we consider ourselves a medium-sized biotech – we have the know-how to ask the right questions, which has impressed our global partners. We have a very big ambition,” she added. “That is why the $100 million can help continue our efforts. It is the right valuation with the right investors; we really think it is a great move.” // For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY Momenta Continued from page 1 fuel future growth, while giving Momenta access to a global distribution and commercial capacity that would be hard to build on its own. Mylan will pay Momenta $45 million up front and as much as $200 million in six contingent early development milestone payments. Each company will share equally in the costs of the collaboration and in its profits. The deal also provides Mylan CEO Heather Bresch with an opportunity to extend and build upon what Momenta President and CEO Craig Wheeler said was a close alignment between the two executives on their vision for the future of the biosimilars marketplace, an area in which they’ve worked together in recent years to hammer out favorable policies via participation in biosimilars industry groups. Shares of Momenta (NASDAQ:MNTA) closed Friday at $14.48, up 92 cents, while Mylan shares (NYSE:MYL) dipped, losing $2.19 before closing at $49.42. At the head of the deal is Momenta’s lead biosimilar candidate, M834, a version of the rheumatoid arthritis (RA) drug Orencia (abatacept, Bristol-Myers Squibb Co.). Clinical trials testing the biologic are expected to begin midyear. The deal also includes five other biosimilars for which only the following names were shared: M615, M706, M710, M730 and M740. Wheeler said all six programs target branded biologics with aggregate worldwide 2014 sales of greater than $12 billion and could be expected to launch between 2020 and 2025, starting with M834. Evercore ISI analyst Umer Raffat said that, based on Momenta’s patent filings, it’s possible that the remaining five products may include biosimilars for Rituxan (rituximab, Biogen Inc./ Roche AG), Prolia/Xgeva (denosumab, Amgen Inc.), Vectibix (panitumumab, Amgen Inc.), Xolair (omalizumab, Genentech Inc./Roche AG) and Campath (alemtuzumab, Sanofi SA). The Orencia biosimilar holds big potential for the partners due to a combination of factors. First, it’s the only CTLA4-Ig fusion protein approved for use in RA and juvenile idiopathic arthritis, a position that helped it generate worldwide revenues of nearly $1.7 billion in 2014. Furthermore, there could be a fair bit more money on the table: With several other indications in development, a consensus forecast including models from seven analysts predicts global sales will peak at $2.4 billion by 2019, followed by the expiration of a U.S. composition of matter patent on the drug that year and a very gradual projected decline in sales after that. Momenta has already filed for an inter partes review (IPR) challenging BMS’s formulation patent and expects the Patent Trial and Appeal Board to issue the IPR this month. Although costs are split equally, the work behind the deal is divided roughly between early and later tasks. Momenta is taking primary responsibility for preclinical development, process development and scale-up for all products, as well as all clinical development activities for M834 and phase I development activities for the five other products. It expects PAGE 6 OF 15 to receive $60 million out of the potential $200 million this year, Momenta’s chief financial officer, Rick Shea, said. The extra cash could help Momenta manage its near-term operating expense increase in the face of both its novel drug and biosimilar development programs. Momenta will also be responsible for all regulatory activities in the U.S. through approval. Mylan will be responsible for pivotal or phase III activities for all products except M834, regulatory activities outside the U.S. and inside the U.S. post-approval and worldwide commercialization of all products. Clearance under the Hart-Scott-Rodino Antitrust Improvements Act is expected by the end of March, after which the partners will work closely to prioritize each program. Closing a broad biosimilar deal with economic terms that would allow it to retain substantial downstream value has been a top priority for Momenta, said Wheeler, during a conference call held Friday. He said the Mylan deal accomplished not only that but marked a “defining moment” in the growth of the company’s biosimilar business. Wheeler also spoke to the breadth of the company’s biosimilars portfolio following the Mylan deal, something he said would help smooth revenue flow and allow the company to achieve scale, technology and regulatory synergies. The latter factors could help Momenta achieve differentiation through early interchangeability designations from the FDA. “Our common goal through this collaboration is to reduce development costs and potentially eliminate the need for significant marketing investments once the products are launched,” he said. Mylan’s Bresch said the collaboration with Momenta would be “highly complementary” to Mylan’s partnership with Bangalore, India-based Biocon Ltd., which is focused on more near-term biosimilar opportunities. That partnership, first formed in 2009, now includes a follow-on of Herceptin (trastuzumab, Roche AG), launched in India in early 2014, as well as biosimilar versions of Neulasta (pegfilgrastim, Amgen Inc.), Humira (adalimumab, Abbvie Inc.), Avastin (bevacizumab, Genentech Inc./Roche AG), Enbrel (etanercept, Amgen Inc.) and Neupogen (filgrastim, Amgen Inc.), plus three insulin analogues – a generic of Sanofi SA’s Lantus, Lispro, a generic of Eli Lilly and Co.’s Humalog and Aspart, and a generic of Novo Nordisk A/S’ Novolog. Although both Mylan and Momenta are optimistic about the endeavor, their hopes could be frustrated by what has been, to date, a slower than expected uptake for biosimilars. A decade after the first biosimilar was approved in Europe, research carried out by IMS Health for the European Commission has suggested that the market still has lots of room to mature. The report found that uptake of biosimilars has been slow there. Furthermore, cost savings that biosimilars are expected to deliver have not always been as dramatic or market-changing as expected in the face of complicating factors like price reductions for reference products or the arrival of new versions of off-patent biologics that promise more convenient dosing. (See BioWorld Today, Jan. 7, 2016.) // For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY Lodo Continued from page 1 investment syndicate partners that days earlier propelled Petra Pharma Corp. out the door: Abbvie Inc., Alexandria Venture Investments, Arch Venture Partners, Eli Lilly and Co., Harris & Harris Group Inc., Innovate NY Fund, Johnson & Johnson Innovation/JJDC Inc., The Partnership Fund for New York City, Pfizer Venture Investments, Watson Fund and Wuxi Pharmatech. (See BioWorld Today, Jan. 6, 2016.) This time, they were joined by the Bill & Melinda Gates Foundation, which had a pre-existing collaboration with Lodo co-founder Sean Brady, associate professor and head of the Laboratory of Genetically Encoded Small Molecules at Rockefeller University – an Accelerator partner institution. Lodo – the Spanish word for mud – will seek to translate discoveries from Brady’s lab, which focuses on the discovery, biosynthesis and characterization of genetically encoded small molecules from microbial sources, particularly those produced by uncultured soil bacteria and the human microbiome. The start-up is Brady’s first. The company’s formation was a case of “perfect timing, where people are wandering around the world and find each other,” Brady told BioWorld Today. His group had worked for roughly a decade on methods to access the chemical and biosynthetic potential of uncultured, previously inaccessible bacteria directly from environmental samples – a field known as metagenomics. “We had come to the point where we had shown all of the proof of principle and were thinking of ways to try to scale this,” with the goal of improving human health, Brady said. “We came to the conclusion that such work had to be done outside an academic lab.” Two years ago, a chance meeting with the Gates Foundation led to a collaboration on finding, identifying and proving molecules that could have applications in infectious diseases, such as tuberculosis, that affect patients in the world’s poorest countries. Around the same time, Accelerator was ramping up in New York and seeking to marshal biotech efforts at the city’s major research and medical institutions. “It’s an exciting time in New York, seeing biotech develop,” Brady said. “Accelerator provided the right people at the right time.” ‘WE’RE GOING BACK TO THE ROOTS OF DRUG DISCOVERY’ As part of its model, Accelerator will oversee the early operations of Lodo, which will have office and lab headquarters in Accelerator’s facilities at New York’s Alexandria Center for Life Science. Lodo co-founder David Pompliano – a former senior scientist at Glaxosmithkline plc and Merck & Co. Inc. before turning to consulting and venture investment – will serve as interim chief scientific officer. With expertise in the PAGE 7 OF 15 discovery and development of anti-infective and oncology drugs, Pompliano sits on numerous scientific boards, including the Gates Foundation Tuberculosis Drug Accelerator. Lodo inked a license agreement with Rockefeller to expand Brady’s technology platform, which also offers potential therapeutic applications in oncology, metabolic disorders and rare diseases. “We think we have an approach that allows us to think about a global screen for natural products,” Brady explained. “We’re no longer limited by what one can culture or see in fermentation broth. The idea of metagenomics is that we can go out and look and just ask, ‘What does nature have for us?’” Although “maybe it’s forgotten in the drug development community,” until a few decades ago the vast majority of therapeutic agents came from nature, he added. Metagenomics allows scientists to peek into nature “in excruciating detail, all the way down to its genetic code, and see very broadly and very deeply, what’s going on.” By using a sequencing-based approach, Brady said he believes Lodo has the opportunity to discover molecules in nature that are better than those discovered in the lab. “As productive as the fermentation-based approach has been, it’s missed most of the chemistry out there,” he maintained. “We’re taking a systematic look to see if we can have a renewed age of natural products. We’re going back to the roots of drug discovery, but with modern tools.” Thong Le, CEO of Accelerator, called Brady “an incredibly special researcher” who developed “really, really cool technology.” The series A is designed to explore the therapeutic potential of the platform, but metagenomics also has potential applications in the food and agriculture industries and Lodo holds the intellectual property for all uses, Le said. “The Accelerator model allows us to take on platform technologies and rapidly, in a step-wise fashion, refine specific applications,” Le said. “That’s exactly the way we’ve structured the financing for this company, so we can build on the technology, expand upon it where appropriate and identify a small handful of test cases.” Whether to develop Lodo as a standalone company or spin out various applications remains to be seen. “All possibilities are on the table,” Le said. “We have to start with the science. We have some very specific things that we need to see the science do. Assuming that the technology delivers, we have a lot of options for the company.” For now, Lodo is focused on developing targeted therapeutic applications, and potential partners are already calling. “A number of firms in our syndicate and others have reached out to us in a very aggressive way to work with the technology,” Le said, citing prospects in pharma, biotech and other industries. “We’re going to stay as focused as we can and let the science lead us.” // For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY Risk Continued from page 1 University have reported that in an unselected population, the carriers of two gene variants that are considered potentially pathogenic for heart disease had neither a higher incidence of arrhythmia nor longer QT intervals than those without such variants. The work shows that “these genetic variants are not deterministic,” first author Sara Van Driest, an assistant professor of pediatrics at Vanderbilt University Medical Center, told BioWorld Today. When a risk variant is detected, “we are talking about probabilities here, and not about diagnoses.” Genome and exome sequencing is not quite yet in routine clinical use. But with massive advances in sequencing technology has come a deluge of genetic data. As more and more patients undergo such sequencing, there are important questions about what to do with so-called incidental findings – gene variants that have no bearing on the original reason for the testing, but might indicate a risk for another disease. For example, if the whole genome or exome of a cancer patient is sequenced, the resulting sequence data also include that patient’s ApoE variant, which predicts their risk of developing Alzheimer’s disease. Compared to those individuals with two copies of the protective ApoE2 variant, carriers of two highrisk ApoE4 variants have approximately 10 times the risk of developing Alzheimer’s disease by age 75. Most risk-conferring variants, though, have far more modest effects. And many have been identified by testing individuals with clinical disease. A gene variant that is useful for an accurate diagnosis where disease is already present, though, may not be predictive of that same disease in a larger, unselected population. As a result, there is a lively and ongoing debate on what to do with incidental findings. (See BioWorld Today, Feb. 19, 2013.) When the evidence for harmful effects of such incidental findings is weak, there is a complex mix of factors that comes into play with respect to reporting them. There is an argument to be made for patient autonomy – patients have a right to their own medical information, and keeping such information from them is paternalistic. On the other hand, when patients are informed of biological measurements of dubious information value, overtreatment can cause harm. The prostate-specific antigen (PSA) test and hormone treatment for postmenopausal women are two examples of tests that have led to overtreatment, and there is currently a heated debate on whether screening mammograms do more harm than good. For gene variants, specifically variants of unknown significance, in the BRCA gene could lead affected women to seek a PAGE 8 OF 15 mastectomy and/or ovariectomy. The cardiac equivalent might be a defibrillator, though Van Driest pointed out that in practice, “in the cardiac rhythm world, the nice thing is that we have an easier test to do” before making decisions on invasive procedures – the electrocardiogram, which is noninvasive and can show whether a risk variant is actually leading to problems. In the current study, which Van Driest and her colleagues published in the Jan. 5, 2016, issue of the Journal of the American Medical Association (JAMA), the team sequenced the genes for two ion channels, SCN5A and KCNH2, in a group of more than 2,000 patients. In its 2013 “Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” the American College of Medical Genetics and Genomics (ACMG) called variants in SCN5A and KCNH2 known pathogenic or expected pathogenic in two cardiac syndromes, Long QT syndrome and Brugada syndrome. According to the ACMG recommendations, “reporting these incidental findings to the ordering clinician will offer the clinician, or an appropriate consulting clinician, the opportunity to re-evaluate the patient’s personal and family history and consider appropriate surveillance or intervention for patients and their family members who are deemed to be at increased risk for these conditions.” In the work now published in JAMA, the variants identified in the sequencing were sent to three different laboratories for “variant calling,” that is, deciding whether a given variant within the genes was likely to cause disease. The team also looked at the database Clinvar to identify variants as potentially pathogenic. The first finding of the study was that there was much more disagreement than agreement on whether variants within the two genes were problematic. Overall, 223 individuals had at least one rare variant in one of the two genes. Between them, the three laboratories and the Clinvar database named 42 variants in 63 individuals as pathogenic or likely pathogenic. The majority of those variants, however, were called out as problematic by only one of the four sources. The team looked for evidence of clinical disease, in the form of arrhythmias or long QT syndrome, in the electronic medical records of those individuals where at least one of the labs had identified a pathogenic gene variant. That study showed no difference between the group with variants and the rest of the cohort, which served as a control, in either the prevalence of arrhythmias or long QT syndrome. Several uncertainties remain about the relationship between rare variants in the two channels and disease. The bleakest possibility is that such variants are harmful after all, and the reason the study failed to detect that harm was survivor bias – that is, the patients that had rare variants that had led to disease did not live long enough to enter the study. Van Driest and her colleagues said they think it is more likely, See Risk, page 11 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY Nanobiotix Continued from page 1 trial in the U.S. and a bold new program stepping into the fastdeveloping field of immuno-oncology. Late last month, the FDA approved Nanobiotix’s lead product, NBTXR3, as an investigational new drug (IND) for a clinical study in prostate cancer at three reference radiation oncology centers. Prostate cancer is a new indication for NBTXR3, and the FDA approval of the nanomedicine as a drug compound is also a first for the company, as NBTXR3 is approved as a medical device in clinical programs concurrently being run in Europe and Asia for soft tissue sarcoma, head and neck cancer, rectal cancer and liver cancer. At the same time, Nanobiotix also said it would enter the burgeoning field of immuno-oncology, exploring the use of NBTXR3 in combination therapies, a departure from the approach in current trials testing the efficacy of the nanoparticles for enhancing the effects of radiotherapy. Based on inorganic hafnium oxide crystals measuring on average 50 nanometers, NBTXR3 is injected locally at a tumor site and binds to cancer cell membranes to amplify the energy used in radiotherapy by as much as ninefold. SPANNING THE GLOBE CEO Laurent Levy said the U.S. approval completes a global reach for clinical development as the company now has programs running across Europe, as well as in Asia through a partnership with Pharmaengine Inc., a biopharmaceutical company based in Taipei, Taiwan. While the company reported a cash balance at the end of June 2015 of €25 million (US$27 million), Levy told BioWorld Today that with the launch of the immuno-oncology program, “we have reached a point where we are going to stop expanding clinical development and focus on bringing NBTXR3 to market by the end of this year.” Publicly traded on the Euronext Paris exchange, Nanobiotix (EPA:NANO) is capitalized at €221 million. Shares closed Friday at €15.92 (US$17.39). “The stock price is good and it is stable at this moment with many investors waiting to see our results in 2016,” said Levy, who added that there will be a steady news flow with four different clinical trials delivering data this year. “These results could create an interesting potential for an inflection in the value of the company,” he said. Interim findings for the pivotal phase of the soft tissue sarcoma trial in are expected by the middle of the year. “This should bring a validation of the proof of concept we demonstrated in 2014, and these data will allow us to proceed to the CE mark and the commercialization of the product for this indication,” said Levy. “This clinical trial is a fast track to market for our product,” he said. PAGE 9 OF 15 He views the trial for NBTXR3 in head and neck cancer as an extension of the product into a new indication, “a validation of the transferability of the product from one cancer to another.” Levy said he expects the company will also be able to communicate on the first findings from that phase I trial ahead of the soft tissue sarcoma results. A clinical trial applying NBTXR3 in radiotherapy for several forms of liver cancer is due in the second half of the year, he said. That phase I/II trial should help establish the value of the therapy using NBTXR3 by demonstrating the treatment can kill tumors and extend the lives of patients where the standard of care cannot be used or does not exist. MARKET ACCESS FOCUS SHOULD HASTEN RELEASE Over the past year, Levy said the focus at Nanobiotix has been on market access, “preparing all the actions necessary so that on the day we get the CE mark we can press a button to start selling and deploying NBTXR3.” Asked if the FDA approval of NBTXR3 as a drug would slow the time to market, compared to the designation as a medical device in Europe, Levy said, “at the end of the day what we need to put our product on the market is to demonstrate the benefit to the patient against any risk, and the amount of data we will need to demonstrate this does not depend on the regulatory status of the product.” “The technology is new,” Levy added. “We are not working with biological or chemical interactions but physics, bringing a new mode of action to eradicate cancerous cells. “If you apply cytotoxins to a cancer cell, the cell is equipped to resist these interactions and at some point cancer cells may escape, but no cancer cell can build resistance to the physical effect of heating a cell to 80 degrees Celsius, which will kill it no matter what biological strategy it develops,” he said. At the same time, a biological reaction of the tumor to the physical effect is behind the decision to enter the new frontier of immuno-oncology. “As long as there is a tumor that can be recognized by the immune system, then boosting the immune system to recognize and then kill the tumor makes sense, yet not every tumor naturally expresses sufficient proteins or markers that will identify the tumor for the immune system,” he explained. “We know that radiotherapy boosts some expression at the tumor that can be recognized by the immune system. This has been demonstrated. Our proposal is to show that our product can boost this expression even greater than radiotherapy alone, and thereby create a better response from the immune system,” he said. “The bet here, which has been confirmed in two clinical settings, is that when you irradiate part of metastatic melanoma, and it is combined with an immuno-oncology therapy, the immune system recognizes the tumors and can start the attack on the other metastasis present in other parts of the body.” // For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY JPM Continued from page 3 into biopharma in 2014 and 2015 – more than $105 billion, combined, in private rounds, IPOs and follow-ons, according to BioWorld Snapshots. Some companies plowed those investments into “really important drugs that are going to have a significant therapeutic benefit for diseases that have no great treatment,” Nodelman said. Others, however, allocated funds inefficiently, and that shakeout “is happening as we speak,” he added. But recent wobbles in the capital markets have a silver lining, according to Nodelman. “The lower the expectations are, the more upside we could see,” he observed. Although conversations, and perhaps market performance, may be dominated this year by political rhetoric, “the fundamentals are stronger than they’ve ever been,” Nodelman said. “We have more approvals than ever, M&A is stronger than ever and innovation is clearly the strongest it’s ever been.” He cited CRISPR/Cas9 gene-editing technology as an example of the compelling platforms propelling biopharma’s trajectory, calling the system’s use by three independent groups of researchers to improve the symptoms of Duchenne muscular dystrophy in mice “mind-bending.” (See BioWorld Today, Jan. 4, 2016.) Despite the hype around CRISPR, “when you compare it to other revolutionary technologies, like RNAi or monoclonal antibodies, the development of CRISPR is moving at an exponentially faster pace,” he said. ‘WE’RE IN THE MIDDLE OF A LONG INNOVATION CYCLE’ Jim Healy, general partner at Sofinnova Venture Partners, was more cautious about CRISPR, citing the complicated intellectual property landscape and lack of clear regulatory guidance from the FDA. “We’re intentionally watching from the sidelines at this point in time,” Healy said. Nevertheless, he acknowledged the accelerating pace of innovation in gene therapy, from lentivirus to adeno-associated virus approaches and now CRISPR – which, he added, lit up the field with its prospect to offer durable cures even in replicating cells. Healy will look to hear more during meetings at JPM. “Our general approach to J.P. Morgan is to spend a lot of time interacting with big pharma, looking for what types of new products they’re looking to acquire or partner with,” he told BioWorld Today. Healy also attends company presentations and said he’ll be in the audience for New York-based BristolMyers Squibb Co., which he called “the innovation leader in the immuno-oncology field.” Sofinnova is tracking that trend “in an important therapeutic area.” Sofinnova also uses JPM as an opportunity to touch base with public companies in its portfolio. Healy cited biosimilars PAGE 10 OF 15 specialist Coherus Biosciences Inc., of Redwood City, Calif., and gene therapy developer Spark Therapeutics Inc., of Philadelphia, as two that could create some buzz at the meeting. With three programs in the clinic and numerous upcoming milestones, Coherus “should be a beneficiary of discussions around trying to put cost-containment controls around new drugs,” he said. That concern is heightened by the trajectory of more-expensive biologics approvals in the U.S., which have risen fourfold over the past two years, compared to the 20042008 time period, and now account for more than one-fourth of FDA drug approvals, according to a BioWorld Today analysis. (See BioWorld Today, Jan. 8, 2016.) Spark, meanwhile, reported positive phase III data in October for its lead program, SPK-RPE65, in blindness-causing, RPE65mediated inherited retinal dystrophies and could be the first gene therapy approved in the U.S. (See BioWorld Today, Oct. 6, 2015.) Healy also is optimistic about prospects for 2016, coming on top of two “terrific” years. The positives, he said, begin with the regulatory environment, where the FDA picked up the pace of drug approvals and is seeking to be more transparent about its decision-making process. M&A activity was steady, and IPOs remained strong, albeit with a slight falloff in 2015 as markets turned “choppy” in the second half of the year. If that pullback continues in 2016, “our expectation is that pharma is going to use that to their advantage to step in and fill up their pipelines,” Healy said. But biotech could have strong staying power. Through December, in generalist funds, fund flow was negative in every sector except biotech, he pointed out. Even in the fourth quarter, when the biotech sector dropped 20 percent, “we were still seeing positive fund flows,” Healy said. “We hope that’s an indicator for this year.” Despite election year rhetoric, macroeconomic jitters and concerns about drug prices, “we’re in the middle of a long innovation cycle, and we believe that will continue,” he added. ‘A THREAD THAT’S CONSISTENT AMONG THE PRESENTATIONS’ Scientific innovation also is the draw for Jim Robinson, U.S. president for Astellas Pharma Inc., of Tokyo, who carves out time at JPM to attend big and specialty pharma presentations. “I try to see if there’s a thread that’s consistent among the presentations,” he said. “Clearly, the bulk of the presentations are about the innovation that each company is driving – their future focus in terms of investment and their greatest opportunities for success in the short and long term.” Robinson keeps an ear to the ground for trends in therapeutic areas, regulatory oversight and industry activity. But, from a personal viewpoint, “I really enjoy the science aspect of the biopharmaceutical industry,” he said. At this year’s JPM, Robinson expects to attend a broad crosssection of pharma presentations. He’ll also take in talks by See JPM, page 11 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY JPM Continued from page 10 pharmacy benefit managers and retail pharmacy companies to get their take on industry challenges. “I don’t have a particular pattern,” he said. “I just try to have an opportunity to meet with as many folks as possible to communicate the message about Astellas and to educate myself on trends in the industry.” Robinson also was upbeat going in to JPM. “I’m fairly bullish,” he told BioWorld Today. “If you look at the investment that’s been made over the last decade in specialty therapeutics, I’m pretty excited about what is actually coming from the pipelines of companies around the world. I’m an optimist by nature, and I’m very optimistic, in light of what I’ve seen during the last couple of years, about emerging oncology and specialty products. As an industry, we have an opportunity to continue to focus on invention, as well as innovation.” Biopharma investors may have a clearer read of the sector’s pulse at the end of JPM than the beginning, but the early sense is that 2016 will play out pretty much as business as usual. “The biopharma sector is in good shape as it enters the New Year,” BioWorld’s Winter said. “While we will likely not see a massive run-up in valuation during 2016, it should be able to exhibit slow and steady growth.” // Risk Continued from page 8 however, that the variants really are not predictive of disease, and that whether to report them when they show up as incidental findings should be carefully considered. Van Driest said her take on the return of incidental findings is that “we will all be much more enthusiastic about returning results as we gain more confidence in the results.” For now, though, “genes are like people,” she said. “They are more complex than you think.” // OTHER NEWS TO NOTE Cytos Biotechnology Ltd., of Schlieren, Switzerland, said it is to be renamed as Kuros Biosciences Ltd. Dual Therapeutics LLC, of Cleveland, said it signed a strategic collaboration with Bristol-Myers Squibb Co., of New York, to advance small-molecule compounds for the treatment of cancer and other diseases. Dual’s small-molecule modulators simultaneously block multiple cancer-promoting pathways, particularly the growth and survival pathways, allowing a more comprehensive assault on cancer cells while sparing normal cells. BMS will gain exclusive, worldwide rights to develop and commercialize the small-molecule therapeutics discovered by Dual in exchange for an undisclosed up-front fee and development costs. Dual will be eligible to receive development and regulatory milestones that could total more than $255 PAGE 11 OF 15 million for a successful compound approved in multiple indications in addition to royalties on future sales of products discovered in the collaboration. Enumeral Biomedical Holdings Inc., of Cambridge, Mass., announced the presentation of research findings for the company’s class of anti-PD-1 antibodies at the Function of the Tumor Microenvironment in Cancer Progression conference in San Diego. The anti-PD-1 antibodies can reverse T-cell suppression in ex vivo assays by eliciting high levels of T-cell activation as measured by increased secretion of effector cytokines such as interferon-gamma and increases in expression of the IL-2 receptor alpha chain, CD25. Further, in an in vivo preclinical model harboring a reconstituted human immune system, the company’s fully humanized anti-PD-1 antibodies exhibited significant antitumor efficacy against a human lung adenocarcinoma xenograft. Grünenthal Group, of Aachen, Germany, said it established a joint global drug development program with Akashi Therapeutics Inc., of Cambridge, Mass., for HT-100 (delayedrelease halofuginone), an orally available small-molecule drug candidate designed to reduce fibrosis and inflammation and to promote healthy muscle fiber regeneration in Duchenne muscular dystrophy patients. Grünenthal will be responsible for commercialization in Europe and Latin America, while Akashi will retain rights for the U.S. and all other markets. HT-100 is currently in phase Ib/IIa trials. Under the terms of the agreement, Grünenthal will make up-front and milestone payments to Akashi. In addition, it will assume all post-phase II global development costs through commercialization of an approved product. Akashi will receive royalties on net sales. In total, Grünenthal plans to commit more than $100 million to the partnership and will receive royalties on U.S. net sales in exchange for funding development of Akashi’s U.S. commercial infrastructure. APPOINTMENTS AND ADVANCEMENTS Acorda Therapeutics Inc., of Ardsley, N.Y., appointed Burkhard Blank interim chief medical officer. Achillion Pharmaceuticals Inc., of New Haven, Conn., added Frank Verwiel to its board. Aclaris Therapeutics Inc., of Malvern, Pa., named Brett Fair senior vice president of commercial operations. Aimmune Therapeutics Inc., of Brisbane, Calif., appointed Jeffrey H. Knapp chief operating officer, effective Feb. 1. Alimera Sciences Inc., of Alpharetta, Ga., named Richard S. Eiswirth Jr. president and chief financial officer. C. Daniel Myers will remain CEO. Ariad Pharmaceuticals Inc., of Cambridge, Mass., appointed Paris Panayiotopoulos president and CEO. Assembly Biosciences Inc., of New York, added Alan J. Lewis to its board. Catabasis Pharmaceuticals Inc., of Cambridge, Mass., named Deirdre Cunnane senior vice president, general counsel. For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY OTHER NEWS TO NOTE Healios K.K., of Tokyo, and Athersys Inc., of Cleveland, said they entered a partnership and license agreement that will focus on the development and commercialization of cell therapy treatments, including Multistem, in Japan. Multistem, an off-the-shelf stem cell therapy being developed by Athersys, initially is being developed for ischemic stroke. Healios will gain exclusive rights for the development of Multistem for treating ischemic stroke in Japan, where it will develop and commercialize the product. Athersys will provide the manufactured product and support to Healios, while retaining all rights outside of Japan. In addition, Healios will obtain an exclusive option for development of two additional Multistem clinical indications in Japan, including the treatment of acute respiratory distress syndrome (ARDS), which is currently in clinical development by Athersys in the U.S. and the U.K, and another indication in the orthopedic area. Healios will also obtain an exclusive license to incorporate Athersys technology in the development and commercialization of its organ bud technology, initially for transplantation to treat liver disease or dysfunction, which may be expanded upon exercise of the option. Athersys will receive an initial license fee of $15 million, as well as have the opportunity to earn milestone and royalty payments upon the successful accomplishment of specific development and commercialization objectives, including the achievement of certain sales milestones. The milestones for stroke could total $30 million, in addition to sales milestones that could reach $185 million based on successful commercialization and the achievement of substantial sales of an approved product for treating stroke in Japan. Athersys will also receive tiered, double-digit royalties increasing into the high teens on product sales and will be responsible for providing manufactured product to Healios, subject to receiving reimbursement under a manufacturing supply arrangement. In addition, if Healios elects to expand the partnership following the successful completion of Athersys’ ongoing clinical trial in ARDS, it will receive a license expansion fee of $10 million for the exclusive rights to two additional indications in Japan, with the corresponding potential for further milestones based on successful achievement of specific development and commercialization objectives. Shares of Athersys (NASDAQ:ATHX) gained 22 cents, or 21.4 percent, to close Friday at $1.25. Immune Design Corp., of Seattle, said the FDA granted orphan status for LV305 and G305 for the treatment of soft tissue sarcoma. LV305 and G305 are the complementary agents that comprise CMB305, Immune Design’s prime boost cancer immunotherapy candidate currently in a phase Ib trial in patients with locally advanced, relapsed or metastatic solid cancers whose tumors express NY-ESO-1 and in a phase II trial in combination with anti-PD-L1 drug atezolizumab (MPDL3280A, Genentech Inc./Roche AG) in patients with soft tissue sarcoma. PAGE 12 OF 15 Moderna Therapeutics Inc., of Cambridge, Mass., and Pharmaceutical Product Development LLC, of Wilmington, N.C., said they entered a collaboration to support Moderna’s evolution as a clinical-stage company. Under the terms of the agreement, PPD will play a significant role in the company’s clinical development efforts, including support for investigational new drug planning, as well as for clinical trial design and execution. Moderna’s pipeline is composed of a series of drug modalities that include infectious disease vaccines, personalized cancer vaccines, intracellular/ transmembrane liver proteins, intratumoral cancer therapy and secreted antibodies and proteins. Moderna is leveraging these modalities to advance drugs across a broad spectrum of therapeutic areas via its four ventures, including Valera, focused on infectious diseases; Elpidera, focused on rare diseases; Onkaido, focused on oncology; and Caperna, focused on personalized cancer vaccines. Pfizer Inc., of New York, and Adaptive Biotechnologies Corp., of Seattle, entered a translational research collaboration to leverage next-generation sequencing of the adaptive immune system to advance Pfizer’s growing immuno-oncology franchise. Under the terms of the agreement, the companies will seek to combine drug development and platform technology biomarker expertise to identify patients who may preferentially benefit from immunotherapy. PTC Therapeutics Inc., of South Plainfield, N.J., said it completed its rolling submission of a new drug application to the FDA for Translarna (ataluren), an oral protein restoration therapy for the treatment of nonsense mutation Duchenne muscular dystrophy. PTC has also fulfilled the principal requirement of the EMA in connection with its approval of Translarna in August 2014 by submitting the results of its phase III ACT DMD trial to the agency. (See BioWorld Today, May 27, 2014.) Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and Sanofi SA, of Paris, said the FDA has accepted for review the biologics license application for sarilumab with a target action date of Oct. 30, 2016. Sarilumab is a human monoclonal antibody directed against the interleukin-6 (IL-6) receptor that is intended for the treatment of patients with active, moderate to severe rheumatoid arthritis (RA). IL-6 is the most abundant cytokine in the serum and synovial fluid of patients with RA and levels correlate with both disease activity and joint destruction, the firms noted. Theravance Inc., of South San Francisco, changed its name to Innoviva Inc. Tiziana Life Science plc, of London, said its research agreement with Cardiff University, focused on the development of Bcl-3 inhibitors for cancer, led to the identification of a lead candidate, CB1, with antimetastatic activity and in vivo efficacy and safety. The company said it plans to file an investigational new drug application and move CB1 into the clinic before the end of this year. For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY OTHER NEWS TO NOTE Wuxi Apptec Co. Ltd., of Shanghai, started construction of a state-of-the-art integrated biologics solution center at the company’s headquarters. The company plans to invest a total of $120 million in that dedicated, 250,000-square-foot facility, which will be operational in 2017 and accommodate 800 scientists. The facility will provide integrated solutions from ideas to the clinic for biologics discovery, development and clinical manufacturing on a consolidated campus, Wuxi said. IN THE CLINIC Abbvie Inc., of North Chicago, Ill., said it started a large phase III program to study the use of ABT-494, a once-daily, oral selective JAK1 inhibitor for the treatment of rheumatoid arthritis (RA). The program will include adult patients with inadequate responses to conventional or biologic disease-modifying antirheumatic drugs (DMARDs), as well as methotrexate-naive patients. The first two trials out of the five phase III studies planned have opened for enrollment in the U.S. One study will evaluate ABT-494 in combination with methotrexate in adult patients with moderate to severely active RA who have had an inadequate response to prior treatment with methotrexate, and will include Humira (adalimumab) as an active comparator. The second study will include patients who have had an inadequate response or intolerance to conventional synthetic DMARDs. The studies will include assessments of safety and tolerability, as well as key measures of efficacy, including American College of Rheumatology criteria for responses and levels of disease activity. The other three phase III trials will begin enrollment early this year and will include patients with an inadequate response to biologics and patients who are methotrexate-naive. Acelrx Pharmaceuticals Inc., of Redwood City, Calif., said it received comments from the FDA’s Division of Anesthesia, Analgesia and Addiction Products on the company’s proposed protocol for a phase III study (IAP312) designed to assess the overall performance of Zalviso (sufentanil sublingual tablet system). In response to the comments, the protocol has been amended to track additional Zalviso use by patients in a clinical setting. Acelrx plans to initiate the study in the first quarter. The IAP312 study will include about 310 postoperative patients and collect information requested by the division to supplement the three phase III trials already completed. Acelrx is developing Zalviso for the management of moderate to severe acute pain in adult patients in the hospital setting. Beigene Ltd., of Beijing, said the FDA cleared the firm’s investigational new drug application for phase Ia/IIb studies of BGB-A317, a humanized monoclonal antibody against immune checkpoint receptor PD-1. That will allow the firm to include U.S. sites in the ongoing open-label, dose-escalation study in patients with relapsed or refractory solid tumors. As of Nov. 30, a total of 51 patients in Australia had been dosed in the study, which is evaluating pharmacokinetics and antitumor activities. Beigene plans to develop BGB-A317 as a monotherapy and PAGE 13 OF 15 as a combination agent with small-molecule therapeutics for various solid organ and blood-borne cancers. Biocryst Pharmaceuticals Inc., of Durham, N.C., said that when compared to Western subjects administered the same dose level of BCX7353, its oral plasma kallikrein inhibitor, plasma drug levels in healthy Japanese trial volunteers were moderately higher. Kallikrein inhibition on day seven of daily dosing with 250 mg in Japanese subjects was similar to that seen at the 350-mg daily and 500-mg daily dose levels in Western subjects. The patients were added to the phase I trial to support development of BCX7353 in Japan under the Sakigake accelerated R&D designation. BCX7353 has been generally safe and well tolerated in a total of 96 Western and Japanese healthy volunteers treated, Biocryst said. Biogaia AB, of Stockholm, Sweden, reported that its subsidiary, Infant Bacterial Therapeutics (IBT), said an investigational new drug application seeking permission to test a therapy for the prevention of necrotizing enterocolitis has been accepted by the FDA. IBT also received approval from the Medical Product Agency to conduct a trial in Sweden, it said. Dermira Inc., of Menlo Park, Calif., said patient enrollment was completed for the DRM01 phase IIb trial in patients with facial acne vulgaris, with top-line data expected in the second quarter. DRM01 is a topical, small-molecule sebum inhibitor. The company also reported that top-line data from its two phase III trials of DRM04, a topical, small-molecule anticholinergic product, in axillary hyperhidrosis are expected in mid-2016, compared to the previous guidance of the second half of 2016. Foamix Pharmaceuticals Ltd., of Rehovot, Israel, reported top-line results from a phase I maximum use pharmacokinetics study of FMX-101, a topical foam containing 4 percent minocycline, in development to treat moderate to severe acne. The study, intended to characterize the systemic absorption of minocycline after repeated maximum dose applications, indicated that the relative bioavailability (systemic exposure) of FMX-101 was more than 100 times lower than that for Solodyn (minocycline HCl). FMX-101 was well tolerated, and no serious adverse events were reported. Genentech Inc., of South San Francisco, a unit of Roche AG, said The New England Journal of Medicine published a letter to the editor reporting results of a 10-year study using Rituxan (rituximab) in combination with intravenous immune globulin for the treatment of pemphigus vulgaris, a potentially fatal autoimmune blistering disease that affects the skin and mucous membranes. Findings showed that, following discontinuation of Rituxan, all patients continued to remain in remission without recurrence of the disease. Kolltan Pharmaceuticals Inc., of New Haven, Conn., said KTN0158, a humanized anti-KIT monoclonal antibody drug candidate, was administered to the first cancer patient in phase I trial. The open-label, dose-escalating study involves patients with gastrointestinal stromal tumors and other tumors expressing KIT. For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY IN THE CLINIC Molecular Partners AG, of Zurich, Switzerland, said it plans to conduct a phase II trial of MP0250, a multi-DARPin drug candidate designed to block vascular endothelial growth factor and hepatocyte growth factor, in multiple myeloma. The trial will test MP0250 in combination with Velcade (bortezomib, Takeda Oncology Inc.) and dexamethasone in patients who have developed resistance to Velcade and have received at least two prior regimens, including Velcade and an immunomodulatory drug. Molecular Partners aims to enroll the first patient in the second half of this year. Ocera Therapeutics Inc., of Palo Alto, Calif., reported further details from a phase I study testing oral formulations of OCR002, ornithine phenylacetate, in healthy subjects. Top-line data, reported in November, showed a robust, extendedrelease profile for all three pilot OCR-002 formulations. Those pilot formulations were evaluated on their ability to provide extended release of phenylacetate (PAA), a potent ammonia scavenger, and on the formation of phenylacetylglutamine (PAGN), the end-product responsible for clearing ammonia. Levels of plasma PAA and PAGN exceeded those achieved with the ammonia-lowering agent glycerol phenylbutyrate, branded Ravicti (Horizon Pharma plc), a pre-prodrug of phenylacetate. The company plans to conduct additional phase I testing after further formulation optimization. Oncomed Pharmaceuticals Inc., of Redwood City, Calif., said a manuscript published in Cancer Research describes the company’s efforts to develop therapeutics against R-spondin (RSPO) targets and elucidates the link between expression of the RSPO cancer stem cell pathway and tumor growth. Oncomed is conducting a phase Ia/Ib trial of its anti-RSPO3 antibody, OMP-131R10. Prescient Therapeutics Ltd., of Melbourne, Australia, said it secured FDA approval for a phase Ib/II trial in acute myeloid leukemia (AML). The study will combine the firm’s lead candidate, Akt inhibitor PTX-200, with chemotherapeutic agent cytarabine in refractory or relapsed AML. The first part will enroll 15 to 18 patients in an open-label, dose-escalation design, while the second part will be an open-label study testing the recommended dose of PTX-200 for two 21-day cycles. Protagonist Therapeutics Inc., of Milpitas, Calif., said it started treating subjects with lead candidate PTG-100, an orally stable alpha-4-beta-7 integrin-specific peptide antagonist for inflammatory bowel disease, in a phase I study. The randomized, double-blind, placebo-controlled, dose-escalation trial will involve 70 normal healthy volunteers. The first part of the study consists of single ascending doses of PTG-100 in 40 volunteers, while the second part will involve administration of PTG-100 over 14 consecutive days in 30 additional subjects. Primary endpoints are safety and tolerability, and secondary endpoints are the identification of the maximally tolerated dose and evaluation of pharmacokinetic and pharmacodynamic parameters. PAGE 14 OF 15 Roche AG, of Basel, Switzerland, reported updated results from its pivotal phase II IMvigor 210 study testing immunotherapy candidate atezolizumab (MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma (mUC), with median overall survival of 11.4 months in people with higher levels of PD-L1 expression, and 7.9 months in the overall study population. The study also showed that 84 percent (38/45) of people who responded to atezolizumab continued to respond regardless of their PD-L1 status, when the results were assessed with longer median follow-up of 11.7 months. Median duration of response has not yet been reached. Atezolizumab was well tolerated and adverse events were consistent with those observed in previous updates. Data were presented at the 2016 Genitourinary Cancers Symposium in San Francisco. Valor Biotherapeutics LLC, of Bryan, Texas, said the first patient was dosed in a phase I study of lead candidate IGN002 in non-Hodgkin lymphoma. The study is designed to assess the safety and tolerability of IGN002 administered weekly for up to 26 weeks, evaluate the pharmacokinetic profile of escalating doses of IGN002 and assess the antitumor activity, objective response rate and duration of responses. Valor, a joint venture between Immungene Inc., of Camarillo, Calif., and Caliber Biotherapeutics LLC, also of Bryan, has partnered with the Leukemia & Lymphoma Society on preclinical development, manufacturing and an initial proof-of-concept clinical study of IGN002. Vectura Group plc, of Chippenham, U.K., said it completed a clinical trial for VR315, a generic inhaled combination therapy comprising fluticasone and salmeterol, in the U.S. for asthma and chronic obstructive pulmonary disease. VR315 is delivered using Vectura’s dry powder inhaler and formulation technology. Xbiotech Inc., of Austin, Texas, said it completed data analysis for its phase III European study of Xilonix in advanced, symptomatic colorectal cancer. In addition to previously announced positive results regarding the primary endpoint of the pivotal study, complete data analysis further demonstrated that key secondary measures of antibody activity were also improved. Inhibition of IL-1 alpha on the surface of platelets may represent an antitumor, disease-modifying activity, due to the mechanism of action of Xilonix, and median platelet counts among placebo patients in the study were found to be increased fivefold compared to patients who received Xilonix, whose platelet counts remained near baseline levels during the treatment cycle (p=0.003). (See BioWorld Today, Dec. 8, 2015.) BIOWORLD HIGHLIGHTS A free, weekly e-zine offering unique viewpoints on developments within the biotechnology industry. Sign-up today and get a fresh outlook on topics that you can’t find elsewhere! Go to BioWorld.com and click on “Highlights”! For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MONDAY, JANUARY 11, 2016 BIOWORLD™ TODAY APPOINTMENTS AND ADVANCEMENTS Decibel Therapeutics, of Boston, added Jeff Jonas, to its board. Derma Sciences Inc., of Princeton, N.J., named Stephen T. Wills interim executive chairman and principal executive officer. Dicerna Pharmaceuticals Inc., of Cambridge, Mass., named John “Jack” Green interim chief financial officer. Dimerix Ltd., of Melbourne, Australia, added Liz Jazwinska to its board. Immunocore plc, of Oxford, U.K., appointed James Sandy chief development officer and Julian Hirst director of corporate finance; they will be based in Oxford. The company also opened a U.S. office in Conshohocken, Pa. Kite Pharma Inc., of Santa Monica, Calif., appointed Shawn Tomasello chief commercial officer. Merus BV, of Utrecht, the Netherlands, appointed Hui Liu chief business officer. Novavax Inc., of Gaithersburg, Md., named Mark Twyman vice president, marketing. Redhill Biopharma Ltd., of Tel Aviv, Israel, appointed Micha PAGE 15 OF 15 Ben Chorin chief financial officer, effective March 1. Rodin Therapeutics Inc., of Cambridge, Mass., added Samantha Singer to its board. Theravectys SAS, of Paris, named Alain Clergeot CEO. Turing Pharmaceuticals AG, of Zug, Switzerland, appointed Ron Tilles interim CEO. Uniqure NV, of Amsterdam, the Netherlands, named Dan Soland CEO. Vical Inc., of San Diego, added Thomas E. Shenk to its board. IN THE CLINIC Xcovery Inc., of Needham, Mass., updated data from its ongoing phase I/II trial of tyrosine kinase inhibitor (TKI) X-396 in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. Key data showed an objective response rate of 88 percent in ALK-TKI treatment-naïve patients and 84 percent in Xalkori (crizotinib, Pfizer Inc.)-resistant patients. Data also showed responses in patients with brain metastases. The most common adverse event (AE) related to treatment was rash in 49 percent of patients, and no other related AEs were observed in greater than 30 percent of patients. CLEARLY CORTELLIS Accelerate your strategic clinical development decisions— and advance personalized medicine and patient care. Access global clinical trials information covering biomarkers, devices, biologics and drugs. Integrated with extensive scientific information and competitive intelligence from Thomson Reuters. Explore Cortellis Clinical Trials Intelligence — the most effective resource for fast clinical trial development and strategic portfolio decisions. When you want clarity – fast: thomson reuters cortellis. go.thomsonreuters.com/cti cortellis™ clinical trials intelligence For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email [email protected]. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. BENCH PRESS BioWorld looks at translational medicine By Anette Breindl, Senior Science Editor Pandemic take 3 Pandemic flu gives insights into vaccine response Scientists at the British King’s College London have reported results from long-term high-throughput immune monitoring of a cohort of roughly 180 individuals after they were vaccinated with adjuvanted Pandemrix, the vaccine against the 2009 pandemic “swine flu” strain. Because seasonal influenza strains do not vary that much from year to year, the immune response to seasonal influenza vaccination is predetermined to a significant extent by an individuals’ vaccination history. By looking at immune responses to the vaccine for a pandemic flu strain – which is pandemic precisely because there is not the same kind of immune crossreactivity as with annual strains – the authors were able to look at how individual immune characteristics determined the vaccination response. They found that there was an early complex immune response that included myeloid cell responses, currently thought to be a late component of immunity. Furthermore, they were able to show that an adverse vaccine response did not exacerbate underlying immune abnormalities, and linked the probability of such a response to a specific immune signature. Beyond their findings with respect to the pandemic vaccine, the authors said that “the trial’s outcomes confirmed the practicality of high-throughput immune monitoring, which will be important as immunotherapies are more widely adopted.” The findings appeared in the Jan. 4, 2016, issue of Nature Immunology. Pandemic redux Another team, this one from New York University and the University of Hong Kong, has looked at the co-transmission of pandemic H1N1 and seasonal H3N2 flu strains in 2009 to understand within-host genetic diversity and how it affected the transmission of the flu. In their work, the authors took an in-depth look at viral sequences in donor-recipient pairs, where one caught influenza from the other, within the same household. They used those data to estimate that during a typical infection event, about 100 to 200 viral particles are transmitted, which allowed for the co-transmission of multiple lineages, The authors said their work “allows a better understanding of influenza virus transmission in humans and provides more accurate information for modeling epidemics and for disease control strategies.” It appeared in the Jan. 4, 2016, issue of Nature Immunology. MONDAY, JANUARY 11, 2016 Finally, a team at the British Imperial College London has gained new insights into why bird or avian influenza viruses cannot easily breach the species barrier. Avian influenza viruses cause the most serious disease in humans when they do become easily transmissible, but most fail to do so. Several reasons for that failure to launch have been identified, including differences in the anatomical distribution of the receptors influenza virus uses to enter cells. Another reason is that avian polymerase, which copies the viral RNA, does not work particularly well in mammals. Previous work by the same team had shown that the reason is that avian cells have a specific factor that turbo-charges the polymerase, rather than the presence of a specific inhibitory protein in mammalian cells. In the current follow-up, the team showed that the difference in polymerase activity is due to species differences in the protein ANP32A, which interacts with the viral polymerase. Avian ANP32A has 33 amino acids more than its mammalian counterpart, and the shorter mammalian versions led to reduced polymerase activity and, therefore, reduced viral replication. The exact nature of the interaction between ANP32A and polymerase remains to be determined, but the authors concluded that “disrupting the interaction of the virus with ANP32A may be a novel means for virus control” of influenza viruses that infect humans, because efficient replication is paramount to viral success. The findings appeared in the Jan. 6, 2016, advance online edition of Nature. CRISPR’s helpmate goes high-fidelity Scientists from Massachusetts General Hospital have engineered a Cas9 nuclease that had greatly reduced off-target effects, which has been one of the major stumbling hurdles for CRISPR’s use in clinical application. Cas9 is the enzyme that induces DNA breaks at sites that are determined by the sequence of CRISPR. CRISPR, however, consists of more than just the targeting part. The authors originally hypothesized that the nontargeting part of the enzyme might be responsible for off-target effects through nonspecific binding, and they substituted several amino acids that they predicted would be most likely to be responsible for such effects. The resulting version of Cas9, which the authors dubbed SpCas9-HF1, “rendered all or nearly all off-target events undetectable” for standard targeting sequences, and greatly reduced offtarget effects even for atypical repetitive sequences, where BIOWORLD™ TODAY EXTRA Continues on next page PAGE 1 OF 2 BENCH PRESS Continued from previous page off-target activity is harder to prevent. The authors noted that their original hypothesis for why engineering Cas9 at the sites they chose should decrease off-target effects was likely too simple. Nevertheless, they concluded that “with its exceptional precision, SpCas9-HF1 provides an alternative to wild-type SpCas9 for research and therapeutic applications. More broadly, our results suggest a general strategy for optimizing genome-wide specificities of other CRISPR-RNA-guided nucleases.” The team published its work in the Jan. 6, 2016, advance online edition of Nature. T cells’ expansion strategies, deciphered Scientists from the University of Pennsylvania have identified factors that affected whether T cells expanded in vitro. Such expansion is a necessary prerequisite for emerging T-cell therapies such as chimeric antigen receptor (CAR) T cells, and it strongly predicts whether T cells will be active in vivo once they are re-infused into patients. In the clinic, about a quarter of children being considered for the University’s CD19 CAR T clinical trial had T cells that did not expand sufficiently during testing for them to be able to enter the trial itself. In a new trial, the team studied 50 children with different leukemias and lymphomas, both upon enrollment and after each cycle of chemotherapy the children received. They found that the ability to expand correlated with higher levels of early lineage T cells that were still stem-like in some aspects. Chemotherapy specifically depleted those cells, but culturing cells with the cytokines interleukin-7 and interleukin-15 could restore their expansion capabilities. The authors concluded that “early lineage cells are essential to T cell fitness for expansion, and enrichment of this population either by timing of T cell collection or culture method can increase the number of patients eligible to receive highly active engineered cellular therapies.” They published their results in the Jan. 6, 2016, issue of Science Translational Medicine. Metabolic reprogramming is neuroprotective Scientists from the Belgian KU Leuven have shown that inhibiting or deleting the oxygen-sensing protein prolyl hydroxylase domain 1 (PHD1) could reduce the infarct size in animal models of stroke. Cell death during and after a stroke does not occur at one fell swoop. Instead, there is a core zone where neurons die immediately. But around that zone is the so-called penumbra, where neurons are damaged but not necessarily fated to die. In their experiments, the authors showed that they could limit the damage within that penumbra through inhibiting PHD1, either through genetic deletion or through pharmacological inhibitors. Inhibiting PHD1 changed neuronal metabolism in a way that ultimately allowed the cells to buffer free radicals, which are a major source of damage MONDAY, JANUARY 11, 2016 in ischemic stroke. The authors concluded that “these data identify PHD1 as a regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke.” They published their results in the Jan. 7, 2016, online issue of Cell Metabolism. Treat the liver without making things worse A team at the University of Texas Southwestern Medical Center has developed a nanoparticle that improved survival in a mouse model of late-stage liver cancer. Liver cancer has a high fatality rate and is particularly difficult to treat because most drugs are more toxic to a cancerous liver than a healthy one. MicroRNAs (miRNAs) could potentially be an answer to that conundrum, but delivering them presents the same toxicity challenges. The authors tested more than 1,500 dendrimer nanoparticles to identify those with the best combination of low toxicity and high delivery efficacy, and tested the five most promising candidates’ ability to deliver let-7 miRNAs in an aggressive model of liver cancer. They showed that the approach significantly extended the animals’ survival. The authors concluded their particles had promise for the treatment of liver cancer but also that, more broadly, “the interface between chemical design, cancer biology, and the clinical disease setting must be carefully appreciated to develop the next generation of oligonucleotide-based cancer therapies.” The findings appeared in the Jan. 4, 2016, online issue of the Proceedings of the National Academy of Sciences. Deciphering the stress response Two independent research teams, one from Duke University and one from the German Max Planck Institute of Biochemistry, have gained new insights into the structural features of heat-shock factors (HSFs). HSFs bind to heat-shock proteins, chaperone proteins that help other proteins fold correctly. As such, they play a role in a wide variety of cellular processes. Their role is further broadened because their interaction partners include proteins that are critical in the DNA damage response. There are two HSFs, HSF1 and HSF2, and the authors looked at the structural details of how both bind to DNA. The Munich group focused on HSF1 and found that single amino acid changes can alter its binding characteristics, revealing the structural basis for its specificity. The Duke team looked at both HSF1 and HSF2, and found that in addition to assembling in groups of three identical subunits of one type, the two can form trimers with each other. Such HSF1-HSF2 interaction, the authors said, “add an additional layer of complexity to the stress response but may also provide cells with a rheostat facilitating more precise transcriptional output.” The papers appeared back to back in the Jan. 4, 2016, issue of Nature Structural and Molecular Biology. LET US KNOW WHAT YOU THINK We welcome your feedback. Contact Anette Breindl at [email protected], or (770) 810-3134. 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