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AUGUST 17 , 2016 VOLUME 27, NO. 159BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS

See Oncogenex, page 3 See Vertex, page 4

See HDAC, page 7

See Tioma, page 5

SITTING BULL-ISH ON WHAT COULD BE CUSTIRSEN’S LAST STAND

FINANCINGS

IN THIS ISSUE

JAPAN INSIGHT

See Japan, page 6

Failures clusterin: AFFINITY fizzle bums hizzle post-SYNERGY, Oncogenex hopeful ENSPIRITBy Randy Osborne, Staff Writer

With the second phase III failure of antisense oligonucleotide custirsen in castrate-resistant prostate cancer (CRPC), Oncogenex Pharmaceuticals Inc. investors have turned their eyes to non-small-cell lung cancer (NSCLC), where the clusterin inhibitor is undergoing late-stage tests in combination with docetaxel. CEO Scott Cormack acknowledged the NSCLC field is crowded, but pointed out during a brief conference call on the latest data – a call that fielded just one question – that “unfortunately those therapies don’t provide cures. We see that the landscape

Futility sinks Vertex combo trial in difficult cystic fibrosis subgroupBy Michael Fitzhugh, Staff Writer

Vertex Pharmaceuticals Inc. is ending a phase III study testing VX-661 with the company’s already-approved Kalydeco (ivacaftor) in a hard-to-treat subgroup of cystic fibrosis patients (CF) after learning that the combination failed to deliver a pre-specified improvement in lung function.

Combination treatments with HDAC inhibitors showing promiseBy Peter Winter, Editor

Histone deacetylases (HDACs), the cellular enzymes whose functions include turning gene expression off and on, are promising targets in current drug development for cancer therapy. While treatment with HDAC inhibitors as monotherapies has demonstrated clinical benefit for patients with various hematological and solid tumor malignancies, there is excitement surrounding early results of their use together with other cancer therapeutics. That has spurred an increase in the research and development of treatment combinations with therapeutics such as checkpoint inhibitors. Lexington, Mass.-based Curis Inc., for example, is developing its CUDC-907 – a synthetic, orally available, small molecule that has the potential to inhibit the activity of HDAC – combined

Activity, opportunity picking up for Japan’s biosimilar marketBy Richard Smart, Staff Writer

TOKYO – A flurry of activity over the past month suggests that the adoption of biosimilars in Japan is about to accelerate. Partnerships with Indian and U.S. companies are bringing new biosimilars to the market, while an association for the drugs was launched to help promote awareness of their benefits.Fujifilm Pharma Co. Ltd. earlier this year released a biosimilar insulin glargine onto the Japanese market after licensing it from the Indian company Biocon Ltd. as part of a broader push in Japan to bring cheaper versions of biopharmaceutical treatments to patients. “Sales of the drug are going well and [it has been] well accepted,” said Kana Matsumoto, of Fujifilm’s corporate communications division.The treatment, which is similar to Sanofi

Tioma gets $86M series A ‘wake-up’ call for anti-CD47 antibodiesBy Marie Powers, News Editor

Tioma Therapeutics Inc. hauled in $86 million in its series A to support development of a pipeline of anti-CD47 antibodies to treat solid and hematologic cancers. The stunning size of the round

Other news to note, p. 2 & 10

Financings, p. 8

In the clinic, p. 8 & 12

Regulatory front, p. 11

WEDNESDAY, AUGUST 17, 2016 BIOWORLD™ TODAY PAGE 2 OF 12

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OTHER NEWS TO NOTE

Adherium Ltd., of Melbourne, Australia, said it will provide its Smartinhalers for London-based Astrazeneca plc’s Australia commercial pilot program this year. The program will use Adherium’s devices, mobile app and cloud platform and aims to show how those devices improve medication adherence in patients with asthma and chronic obstructive pulmonary disease. Terms were not disclosed.Astrazeneca plc, of London, said it completed the licensing agreement with Leo Pharma A/S, of Ballerup, Denmark, for the global rights to the interleukin-13 monoclonal antibody tralokinumab in skin diseases. (See BioWorld Today, July 5, 2016.)Axovant Sciences Ltd., of Hamilton, Bermuda, and Qaam Pharmaceuticals LLC, of Canandaigua, N.Y., entered an exclusive license agreement under which Axovant expects to develop and, if successful, commercialize products that combine cholinesterase inhibitors with peripheral muscarinic receptor antagonists, including glycopyrrolate, which could mitigate the peripheral side effects of cholinesterase inhibitors. Axovant will initially develop RVT-103, a combination of glycopyrrolate and donepezil (Aricept, Pfizer Inc.). In addition, Axovant expects to develop RVT-104, a combination of glycopyrrolate and high-dose rivastigmine (Exelon, Novartis AG). Axovant said it believes the intellectual property portfolio licensed from Qaam as part of the transaction provides a strong exclusivity position in this area, the company said. Terms were not disclosed.Chiasma Inc., of Waltham, Mass., is reducing its workforce by about 44 percent, primarily in the company’s research and general and administrative functions, to lower its operating expenses and extend its cash runway. The action follows Chiasma’s announcement of a corporate restructuring plan in June 2016, which included an initial workforce reduction composed primarily of the company’s commercial personnel. Chiasma intends to focus its resources on the continued development of Mycapssa (octreotide) capsules for the maintenance treatment of adult patients with acromegaly, the

company said.Eleven Biotherapeutics Inc., of Cambridge, Mass., signed an exclusive licensing deal with Roche Holdings AG, of Basel, Switzerland. Eleven has granted Roche an exclusive, worldwide license to develop and commercialize EBI-031 and all other interleukin-6 (IL-6) antagonist antibody technology owned by Eleven. EBI-031 is a humanized monoclonal antibody that potently binds IL-6 and inhibits all known forms of IL-6 cytokine signaling. EBI-031 is currently in development for the treatment of ocular diseases. Eleven is entitled to receive $30 million in payments from Roche, including a $7.5 million up-front payment in connection with the effectiveness of the license agreement, and a $22.5 million milestone payment based on the IND for EBI-031 becoming effective. Under the terms, Eleven could receive up to an additional $240 million upon the achievement of certain regulatory, development and commercialization milestones. In addition, Eleven could be entitled to receive royalties for net sales of potential future products containing EBI-031 or any other potential future products containing other Eleven IL-6 compounds.Emergent Biosolutions Inc., of Gaithersburg, Md., said the FDA approved the company’s supplemental BLA for the manufacture of Biothrax (anthrax vaccine adsorbed) in Building 55, the company’s large-scale manufacturing facility located in its 12.5-acre campus in Lansing, Mich.

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Oncogenex Continued from page 1

certainly can have room for something like this.”Shares of Oncogenex (NASDAQ:OGXI) closed Tuesday at 53 cents, down 36 cents, or 40 percent, not far from its 52-week low of 45 cents. The company, which last month reported $39.7 million in cash and equivalents – enough to last until the third quarter of 2017 – said it has engaged MTS Health Partners LP as its advisor to help explore strategic alternatives.In the most recent setback, the firm’s AFFINITY phase III trial, testing custirsen in metastatic CRPC patients whose disease has progressed after treatment with docetaxel, missed the primary endpoint of statistically significant improvement in overall survival. Patients treated with custirsen in combination with cabazitaxel, a form of chemotherapy, plus the steroid prednisone, were compared to those given cabazitaxel/prednisone alone. The AFFINITY news follows the late-stage blowup in newly diagnosed CRPC called SYNERGY. Data were disclosed in April 2014, which is about when Oncogenex’s stock began to slide seriously. Yet to report outcomes is the NSCLC phase III trial known ENSPIRIT with custirsen, a compound once partnered with Petah Tikva, Israel-based Teva Pharmaceutical Industries Ltd., in a deal that ended in April 2015. After losing Teva, Oncogenex revised (with the FDA’s blessing) AFFINITY’s protocol, inspiring hope in some company watchers. (See BioWorld Today, April 29, 2014.)The ongoing ENSPIRIT trial is testing custirsen with second-line docetaxel. “Obviously the plan that we have is to advance to an early analysis of ENSPIRIT,” CEO Cormack said during the conference call. “Since the trial has fast track designation, our hope is that a meeting will occur in a timely manner in order to obtain the FDA’s feedback” and, “depending on the outcome of our discussions with the agency, we expect that final survival results could be available early in the fourth quarter of this year.” “While we are [blinded] to the ENSPIRIT results, we remain encouraged by the two rigorous futility analyses that have already been performed in which the futility boundaries were not crossed,” Cormack said. “We believe our proposed plan for an expedited analysis of the ENSPIRIT data will conserve capital that otherwise would be required to continue this phase III trial to completion and will extend our cash runway. Our plan to accelerate the timeline will also allow us to gain a better understanding of custirsen’s value in NSCLC and act on this knowledge faster.”

HSP27 CANDIDATE STILL KICKINGMeanwhile, Oncogenex settled this month the lawsuit filed by Ionis Pharmaceuticals Inc., of Carlsbad, Calif. In the action filed in January of this year, Ionis claimed that Oncogenex was in breach of an amended and restated license agreement

between the pair that dated back to 2008. The deal granted Ionis a share of certain forms of non-royalty revenue received by Oncogenex, but no share of revenue collected for R&D reimbursement. Ionis wanted 30 percent of the $23.2 million breakup fee Oncogenex gained from Teva, money that was described as an advance reimbursement for continuing R&D related to custirsen and other antisense clusterin inhibitors. Oncogenex filed a motion to dismiss the lawsuit in March. The settlement puts Ionis in line for a $1.4 million payment followed by more if custirsen meets with success.Also ahead, probably in the fourth quarter of this year, are data from phase II BOREALIS-2, which is testing Oncogenex’s apatorsen in combo with docetaxel in bladder cancer. RBC Capital Markets analyst Douglas Miehm noted in a research report that the company has met with the FDA to discuss an IND submission for a phase I/II study evaluating apatorsen for intravesical administration in combination with the current standard of care, Bacillus Calmette-Guerin, in non-muscle invasive bladder cancer. “Management anticipates that it will complete an IND,” he wrote, “but gave no timeline on when it intends to submit this IND to the FDA.” Designed to inhibit heat-shock protein 27, which is linked to treatment resistance and more aggressive cancer phenotypes, apatorsen (formerly OGX-427) has been the subject of multiple trials. It chalked up a phase II failure in pancreatic cancer in the effort called RANIER last year. In January, Oncogenex said the phase II SPRUCE trial testing apatorsen as a combo therapy in NSCLC fell short of statistically significant improvement in progression-free survival. (See BioWorld Today, Sept. 24, 2015, and BioWorld Insight, Jan. 26, 2016.)Also underway is the phase II PACIFIC experiment, an investigator-sponsored, randomized study evaluating apatorsen in metastatic CRPC who are experiencing rising prostate-specific antigen levels while on Zytiga (abiraterone acetate, Janssen Biotech Inc.). PACIFIC aims to discover the potential benefit of adding apatorsen to Zytiga plus prednisone for patients with metastatic CRPC by measuring the treatments’ ability to extend time without disease progression. The trial is backed by the Hoosier Cancer Research Network in Indianapolis.But the attention Tuesday landed on custirsen, and interest still percolates around clusterin (the protein is also known as alipoprotein J), which is implicated not only in cancer but in Alzheimer’s disease and infectious diseases such as hepatitis C. A study in the current issue of Allergy and Asthma Proceedings suggests that serum levels of clusterin may turn out to be a biomarker for children atopic dermatitis, too. //

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Vertex Continued from page 1

Despite progress on a broader phase III program in CF expected to underpin filing of an FDA new drug application for the combo in the second half of 2017, Vertex shares (NASDAQ:VRTX) fell $2.48 to close at $100 on Tuesday.The trial to be wound down tested VX-661, a corrector of the CF transmembrane regulator (CFTR) trafficking defect, with ivacaftor, a CFTR stimulator, in about 150 people with one copy of the F508del mutation and one copy of a mutation that results in minimal CFTR protein function (F508del het/min). While no safety concerns were identified — good news for the program overall — a planned interim futility analysis at the conclusion of the first of the study’s two parts led members of an independent data safety monitoring board to recommend stopping the trial.Vertex did not outline the criteria it had established for determining futility of the study, though Jeff Chodakewitz, the company’s chief medical officer, did speak to it briefly during a recent earnings call. “There’s a certain tension as you make a decision based on partial information,” he said. “We want to try, if the drug is not benefiting patients, to stop the trial. Conversely, there is uncertainty and we also want to be careful about not missing a positive result. Therefore, there always is a certain overlap. And what we tend to do is then say it’s clearly not working. We stop.”Patients from the first part of the study who enrolled in the long-term extension study — part two — will be transitioned off the combination.

IF NOT TWO, THEN THREEFollowing the futility decision on Tuesday, Chodakewitz said the results “suggest that a triple combination regimen may provide this group of people with CF the best chance at obtaining a meaningful benefit,” referring to the company’s plans to begin the first study of a next-generation corrector together with VX-661 and ivacaftor in F508del het/min patients later this year. The decision will follow the arrival of data from ongoing phase I studies of the triplet in healthy volunteers. Neither Chodakewitz nor Vertex CEO and President Jeff Leiden were available for comment on Tuesday.Analysts universally said the doublet’s failure to help F508del het/min patients was no big surprise in light of low odds for its success and, like Vertex, looked to the triplet as a potential ticket to better results for those patients. “We believe adding a second corrector is the critical part of improving efficacy, as they have shown 100 percent to 200 percent better data in assays,” wrote RBC Capital Markets analyst Michael Yee.Vertex has yet to say which of two next-gen CFTR correctors in its pipeline that it will include in a phase II study of triplet, VX-152 or VX-440. But in vitro data the company has published in the past has shown enhanced CFTR function in cells with triple combination therapy vs. Orkambi.

Both of the next-gen correctors are designed to further improve processing and trafficking of the CFTR protein to the surface of human bronchial epithelial cells, beyond that observed with a single corrector combined with ivacaftor, which may enable increased CFTR chloride transport, a measure of the function of the CFTR protein at the cell surface.

MORE STUDIES UNDERWAYDespite the setback in F508del het/min CF patients, Vertex is moving ahead with tests of the combo in other subgroups. It completed enrollment for a 500-patient phase III study in people with two copies of the F508del mutation, a group for which it expects an ivacaftor + VX-661 combo may have an improved benefit-risk profile compared to Orkambi. Results from the trial, which will study 24 weeks of treatment with the combination, are expected in the first half of 2017. (See BioWorld Today, March 7, 2016, and April 29, 2016.)In September, the company expects to complete enrollment in a 200-patient phase III study in people with one F508del mutation and one residual function mutation. The crossover study includes two eight-week dosing periods, separated by an eight-week washout period. In addition to the combination arm, it also includes ivacaftor monotherapy and placebo arms. Data from the study are expected in the first half of 2017.“This is important as it could convert patients from old Orkambi (ivacaftor + lumacaftor) into new ‘661 doublet due to better tolerability and safety as well as bring back patients into the market who had previously discontinued Orkambi,” wrote Yee.By late 2016 or early 2017, enrollment is also expected to be complete for a study designed to evaluate VX-661 in combination with ivacaftor in people with gating mutations that have been shown to be responsive to ivacaftor alone. The hypothesis there is that the combo may provide enhanced clinical benefits over ivacaftor monotherapy. The study is expected to enroll approximately 200 patients and is evaluating eight weeks of treatment with VX-661 in combination with ivacaftor.Vertex has patents in the U.S. and European Union covering the composition of matter of VX-661 that expire in 2027 and 2028, respectively, subject to potential extensions. //

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Tioma Continued from page 1was designed to enable the company, founded a decade ago in St. Louis, Mo., as Vasculox Inc., to open a corporate office in Brisbane, Calif., and achieve an ambitious clinical program by advancing multiple candidates through proof of concept, both as monotherapy and in combination regimens. “We have a pretty fat portfolio of anti-CD47 antibodies, and we wanted to put together a syndicate and a financing amount that would allow us to do the right scope of work, test these things in the clinic and determine if, how and to what extent CD47 inhibition benefits patients suffering from cancer,” explained John Donovan, Tioma’s president and CEO. Proving that thesis will involve not only an initial safety study but also safety and efficacy studies in a multiple settings.“It’s a robust scope of work,” Donovan told BioWorld Today. The round was co-led by seed investor Rivervest Venture Partners, including its 3×5 Rivervest Fund, along with Novo Ventures, Roche Venture Fund and Glaxosmithkline plc’s venture arm, S.R. One. John McKearn, Rivervest managing director, was named chairman of Tioma’s board, where he was joined by Novo’s Peter Moldt, Carole Nuechterlein of Roche and S.R. One’s Jill Carroll.Scientific founder William Frazier, professor of biochemistry, molecular biophysics, cell biology and biomedical engineering at Washington University School of Medicine, formed Vasculox with Pamela Manning, the company’s vice president of R&D, based on research from his laboratory and that of collaborators at the NIH. A pioneer in the field of CD47-mediated signaling pathways, Frazier discovered that CD47 is a receptor for thrombospondin-1, or THBS1, and advanced the company’s research with seed rounds, grants “and the traditional shoestring approach,” Donovan said.Donovan credited McKearn with the vision for assembling the institutional round after Rivervest become a seed investor last year. In mid-2015, Vasculox closed on a financing of approximately $5 million that was intended to be first tranche of a larger syndicated round – expected, at the time, to be in the range of about $45 million, according to an SEC filing. In February, the company recruited Donovan, who most recently was a co-founder of Alios Biopharma Inc., where he served as chief business officer and chief financial officer until its 2014 acquisition by Johnson & Johnson for $1.75 billion. (See BioWorld Today, Oct. 1, 2014.)The expanded executive team – including Robert Karr, who joined the company in 2010 as chief scientific officer and had been serving as interim CEO – and investors sat down together to review the existing data, determine the company’s strategy and assess the amount of work that would be needed to prove the science. Based on the existing data and the desire to execute a robust development plan, the company garnered support from its syndicate to increase the size of the planned A round. “We decided to finance the whole thing through proof of concept,”

Donovan said. “We can now turn our attention to research and development and not get side-tracked every six or 12 months looking for additional capital.”

NOTHING ‘PREVENTING US FROM TAKING THIS ALL THE WAY’Although Alios was developing therapies to treat respiratory syncytial virus and hepatitis C virus, Donovan said his attraction to Tioma had the same appeal of his previous firm.“I came up on the business side of this industry, so I always start with the people,” he said, citing “a great group of investors” for bringing him to the table, where he was intrigued by the biology. “I was convinced pretty quickly that the team assembled here knows as much about the CD47 biology as anyone in the world,” Donovan maintained.By targeting CD47, a protein expressed on most tumor cells, Tioma is pursuing a less-traveled approach in immuno-oncology – a field bent on waking the body’s immune system to pursue and destroy cancer cells. But the integrin associated protein has appeal; in February, start-up Forty Seven Inc. landed a $75 million round to advance its humanized IgG4 kappa anti-CD47 monoclonal antibody through dual phase I studies. (See BioWorld Today, Feb. 25, 2016.)Tioma is keeping details about its fully owned technology under wraps until it has more data in hand. The biology is complicated and unproven in the clinic, Donovan conceded, but the prospect that CD47 antibodies may be used to treat a broad number of oncology indications is equally compelling.“There are multiple mechanisms of action at play here, mediated by the CD47 receptor,” he said. “Therefore, CD47 inhibitors have the ability to exhibit a wide variety of functional characteristics. We think it’s very intriguing biology, with a tremendous amount of potential.”The company’s clinical plan is designed to investigate whether and to what extent CD47 inhibition improves coordination between the innate and adaptive immune systems to harness attacks against tumors and, if demonstrated successfully, in which patient populations. “We’re going to do robust clinical investigations that look at a variety of different cancers in a variety of different settings, including combination and monotherapy,” Donovan said. “Our approach isn’t just to put this into the clinic, put it in a few patients and then pinch your nose and hope for the best.”Tioma expects to advance its lead candidate to the clinic in the first half of 2017.The company has fewer than 20 employees and Donovan expects to keep the head count in that vicinity for the next few years, selectively adding development officials at the Brisbane headquarters. The company plans to retain its scientists, research facilities and wet labs in St. Louis.Long term, “there’s nothing inherently preventing us from taking this all the way,” Donovan said. “We don’t want to partner right now. We feel like this is a great venture play. Our business case is to build a company with a viable stand-alone future.” //

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Japan Continued from page 1SA’s Lantus, received approval in March and was released into the market last month. It is still too early to tell whether the release in Japan of the insulin biosimilar will be successful, but Kiran Mazumdar-Shaw, Biocon’s chairman and managing director, said he was confident the agreement would bear fruit. “We believe with Fujifilm Pharma’s commercial network, we will enable access to this world-class, prefilled disposable pen for better diabetes management for patients in Japan,” he said.Glargine is registered by Biocon in 20 countries, and a biosimilar is expected to begin selling in Malaysia early next year, after recently receiving approval from authorities in Kuala Lumpur to put the drug on the market. The Japanese market for glargine is worth around $144 million and treats around 7.2 million people afflicted with the disease, according to the International Diabetes Federation. For Fujifilm, the deal with Biocon may prove to be a one-off, as it has a joint venture with Kyowa Hakko Kirin Co. Ltd. to develop and launch biosimilars in Japan. “There is no decision on whether FujiFilm Pharma will license-in other insulin [products] from Biocon,” Matsumoto told BioWorld Today.Still, its release in Japan shows that companies in the Northeast Asian nation, and the government, are looking for ways to cut costs beyond cutting the prices of drugs on the National Health Insurance scheme and introducing simple generics to the market. Biosimilars are one option.In April, the Japan Biosimilar Association (JBSA) launched with a mission to get more products to the market through information exchange, research and lobbying. The organization will include six committees tackling drug safety, research and development, public relations, general affairs, health care systems and matters relating to medicine. Its first chairman is Tatsuo Kurokawa, a former bureaucrat at the Ministry of Health, Labour and Welfare.The JBSA’s first four members are Nichi-iko Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Meiji Seika Kaisha Ltd. and Mochida Pharmaceutical Co. Ltd. “Both the benefits and definition of biosimilars are yet to become common knowledge in Japan,” Kurokawa said upon taking the chairmanship of the new association.Outside of the new association, Daiichi Sankyo Co. Ltd. and Thousand Oaks, Calif.-based Amgen Inc. last month signed an agreement to commercialize nine biosimilars to Japan, including those for adalimumab (Humira, Abbvie Inc.), bevacizumab (Avastin, Roche Holdings AG) and trastuzumab (Herceptin, Roche Holding AG). Financial terms for the agreement were not disclosed, but Daiichi Sankyo will handle marketing approval, commercialization and distribution in Japan, while Amgen maintains control of manufacturing and development responsibilities. (See BioWorld Today, July 18, 2016.)

Fujifilm’s Matsumoto views the biosimilar market as having potential. “The biosimilars market is set to expand rapidly throughout the world against the backdrop of escalating medical costs and patent expiration of a series of innovative biopharmaceuticals through to 2020,” she said.Targeting the market, Fujifilm Kyowa Kirin Biologics Co. Ltd., was launched in 2012, equally co-funded with Kyowa Hakko Kirin. The joint venture currently has two biosimilars in development, one for adalimumab and another for bevacizumab. The company aims to become a leader in biosimilars by combining Kyowa Hakko Kirin’s pharmaceuticals technologies with production and quality control methods used by Fujifilm during the years when it was primarily a manufacturer of photographic film. It was launched with ¥100 million (US$998,223) in capital. The biosimilar for adalimumab, which treats rheumatoid arthritis, is currently in phase II trials in countries including the U.S. The biosimilar for bevacizumab, which can be used to treat colorectal and non-small-cell lung cancers, is in phase I trials in Europe. Last year, Fujifilm Kyowa Kirin Biologics set up a joint venture with Astrazeneca plc, of London, to get the drug to market. In exchange for allowing the new venture to market the drug, the Japanese company received a payment of $45 million. (See BioWorld Today, Aug. 4, 2015.)While the market for biosimilars is likely to grow, Matsumoto said the drugs and technology will not likely face the same sort of commoditization that has damaged the market for standard pharmaceuticals. “Biosimilars will require an advanced level of reliability and quality equivalent to that of their original counterparts as well as low costs in order to achieve broad proliferation and expansion,” she said. //

Coming Thursday in BioWorld Highlights:

Will biosimilar carve-outs put R&D for older MAbs on ice?

Unintended consequences. It’s a term that’s bandied about all too often in Washington these days, as it’s become the PC way for lawmakers and agencies like the FDA to save face when they have to admit, “Oops, we didn’t think that one through very well” when confronted with the negative impacts of the laws and regulations they’ve created. To read more, see tomorrow’s edition of BioWorld Highlights, a free weekly ezine that provides articles from BioWorld Today, BioWorld Insight and BioWorld Asia, plus insight and opinion from the BioWorld Perspectives blog, http://bioworld.blogs.bioworld.com. If you don’t already receive this complimentary e-zine, click here to opt in.

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HDAC Continued from page 1with phosphatidylinositol 3 kinase (PI3K) inhibitors. In June, the company updated data from a phase I trial of CUDC-907 in 75 patients with relapsed/refractory lymphoma or multiple myeloma at the European Hematology Association’s annual meeting. Data from 21 response-evaluable patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) showed objective responses reported in nine of them, including three patients with complete responses. Additionally, a retrospective post-hoc analysis showed that among six response-evaluable DLBCL patients whose tumors were characterized with MYC alterations, five experienced objective responses, including three patients with complete responses. All five patients with MYC-altered disease who experienced objective responses also had alterations in BCL-2, including two patients with BCL-2 gene translocations. The company is currently enrolling relapsed/refractory DLBCL patients in a phase II monotherapy trial of CUDC-907 to assess its efficacy specifically in patients with MYC-altered DLBCL. Data from are expected next year.Analyst Chris Shibutani at Cowen and Co. said he believes CUDC-907 has the potential to advance relatively quickly.

EXPANDING PIPELINEClinical development is growing and there are approximately 130 trials that are currently recruiting or in the planning stages, according to Cortellis Clinical Trials Intelligence. (See HDAC inhibitor clinical trials by phase of testing, p. 9.)Syndax Pharmaceuticals Inc., which completed its IPO in March, is collaborating with Merck KGaA, of Darmstadt, Germany, and Pfizer Inc. to evaluate avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in combination with Syndax’s entinostat, an oral HDAC inhibitor, in patients with heavily pre-treated, recurrent ovarian cancer. Syndax will be responsible for conducting a phase Ib/II trial. Speaking on the importance of the study, Luciano Rossetti, head of global research and development of the biopharma business of Merck KGaA, said, “Combination therapy is the next frontier in immuno-oncology and a key strategy for the alliance.” Syndax also has a clinical collaboration with Genentech Inc., a unit of the Roche Group, of Basel, Switzerland, to evaluate entinostat in combination with atezolizumab (MPDL3280A), a fully humanized monoclonal antibody (MAb) targeting PD-L1 in patients with triple-negative breast cancer. (See BioWorld Today, March 4, 2016.)In a phase III program, the company is testing a entinostat in advanced HR-positive breast cancer, and proceeds from the recent IPO will help support those ongoing trials, the filing of a new drug application and manufacturing of registration batches of active pharmaceutical ingredient and final drug

product. The company plans to use other funds from the offering to support various combination trials.The company said it has completed enrollment for a dose confirmation stage of ENCORE 601, a phase Ib/II trial evaluating the combination of entinostat plus Merck & Co. Inc.’s anti-PD-1 blocking therapy, Keytruda (pembrolizumab), in patients with advanced metastatic or recurrent non-small-cell lung cancer (NSCLC) or melanoma. It is moving ahead with the phase II portion of the study. San Diego-based MEI Pharma Inc. attracted Swiss pharma Helsinn Group for an exclusive licensing, development and commercialization agreement for HDAC inhibitor pracinostat, a phase III-ready candidate for the treatment of acute myeloid leukemia (AML) and other potential indications. (See BioWorld Today, Aug. 9, 2016.)A phase III study is expected to start early next year and will take about two and a half years to enroll approximately 525 patients, mostly in the U.S. and Western Europe, with a primary endpoint of overall survival based on an analysis about a year and a half after the last patient is enrolled. At the beginning of this month, the company reported that the FDA had granted breakthrough therapy designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are 75 or older or who are unfit for intensive chemotherapy. The designation was supported by data from a phase II study, which showed a median overall survival of 19.1 months and a complete response (CR) rate of 42 percent (21 of 50 patients). Those data compare favorably to a phase III study of azacitidine (AZA-AML-0011), which showed a median overall survival of 10.4 months with azacitidine alone and a CR rate of 19.5 percent in a similar patient population.

See HDAC, page 9

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Advaxis Inc., of Princeton, N.J., agreed to sell approximately 2.2 million common shares at $13.50 apiece in a registered direct offering, generating gross proceeds of approximately $30 million. The offering price represented an 8.8 percent discount to the stock’s (NASDAQ:ADXS) closing price of $14.81 on Monday, Aug. 15. The company did not disclose specific use of proceeds. Jefferies LLC and Barclays Capital Inc. are lead placement agents, with Cantor Fitzgerald & Co. and Guggenheim Securities LLC as co-placement agents. Earlier this month, Advaxis granted global rights to its preclinical cancer immunotherapy, ADXS-NEO, to Amgen Inc., of Thousand Oaks, Calif., for up to $540 million. On Tuesday, the company’s shares closed at $14.06 for a loss of 75 cents. (See BioWorld Today, Aug. 3, 2016.)Arno Therapeutics Inc., of Flemington, N.J., completed a private placement of its common shares and warrants to purchase additional shares for gross proceeds of approximately $2.8 million. Pricing was not disclosed. The financing was led by the company’s existing investors, including affiliates of its chairman, Arie Belldegrun, along with Miami-based Opko Health Inc., Commercial Street Capital LLC, Pontifax, Bonderman Family Limited Partnership, Perceptive Advisors LLC and Auriga Capital Management. Arno said proceeds will fund ongoing development of lead candidate, onapristone. On Tuesday, the company’s shares (OTCQB:ARNI) closed at 62 cents for a loss of 7 cents.Oculis ehf, of Reykjavik, Iceland, closed a series A financing led by Brunnur Ventures and Silfurberg. The company did not disclose the amount of the round, designed to support continued

FINANCINGS development of its solubilizing nanoparticle drug delivery platform and drug candidates, including topical eye drops to treat diabetic macular edema. In connection with the financing, Árni Blöndal of Brunnur and Stefan Jökull Sveinsson, former global head of R&D at Actavis plc (now Allergan plc), joined the company’s board. Recro Pharma Inc., of Malvern, Pa., priced an underwritten public offering of approximately 1.99 million common shares at $7.50 apiece for gross proceeds of about $15 million. The price represented a discount of about 14.7 percent to the stock’s (NASDAQ:REPH) close at $8.79 on Monday, Aug. 15. Recro said proceeds will fund the ongoing phase III pivotal trial and safety studies of injectable meloxicam. Piper Jaffray & Co. is sole book-running manager and representative of the underwriters, with Janney Montgomery Scott as co-manager. On Tuesday, the company’s shares closed at $8.60, down 19 cents.Zosano Pharma Corp., of Fremont, Calif., agreed to sell 4.8 million common shares and warrants to purchase 9.6 million additional shares at $1.57 per unit in a private placement to qualified institutional buyers, institutional accredited investors, accredited investors and certain members of the company’s management and board. The financing is expected to generate gross proceeds of approximately $7.5 million from sale of the units, and Zosano is eligible to receive up to another $14.4 million upon exercise of the warrants. The company’s shares (NASDAQ:ZSAN) closed Tuesday at $1.35, up 3 cents. Zosano said proceeds will advance its M207 program toward FDA registration. Guggenheim Securities LLC served as lead placement agent and Roth Capital Partners LLC served as co-placement agent. //

IN THE CLINIC

Anthera Pharmaceuticals Inc., of Hayward, Calif., said the data and safety monitoring board voted that the phase III SOLUTION study of Sollpura in cystic fibrosis patients with exocrine pancreatic insufficiency continue without modification after completing its first pre-planned safety review of the trial. Sollpura is designed as a soluble, stable and non-pig-derived pancreatic enzyme replacement therapy.Armo Biosciences Inc., of Redwood City, Calif., said clinical safety and efficacy data on its lead investigational immuno-oncology drug, AM0010 (pegylated Interleukin-10), in patients with advanced solid tumors has been published in the Journal of Clinical Oncology. In a phase I study, 51 patients with advanced solid tumors were treated with AM0010 monotherapy, first in a dose-escalation study and subsequently in a dose-expansion cohort in patients with renal cell cancer (RCC). The primary endpoint was safety and secondary endpoints included objective tumor responses, progression free survival and immune activation. AM0010 led to systemic immune activation with elevated immune stimulatory cytokines and a reduction in the immune suppressive cytokine TGF-beta in the serum. It was well-tolerated in that heavily pretreated patient population

who had failed a median of four prior therapies for metastatic resistant or refractory disease. Partial responses were observed in one patients with uveal melanoma and in four of the 15 (27 percent) evaluable RCC patients treated at 20 mcg/kg. CASI Pharmaceuticals Inc., of Rockville, Md., said its phase II trial of ENMD-2076 in fibrolamellar carcinoma has met its stage I endpoint of objective response for non-futility based on the pre-specified interim analysis criteria and will advance to stage II development.Collegium Pharmaceutical Inc., of Canton, Mass., said an article published in Current Medical Research and Opinion included results from multiple in vitro studies and clinical pharmacokinetic studies demonstrating that Xtampza ER (oxycodone extended-release), an abuse-deterrent, extended-release opioid, can be administered by sprinkling on to soft food, administering the capsule contents through enteral tubes (nasogastric and gastrostomy) or crushed/chewed without affecting the drug release profile of the formulation. The results suggest that Xtampza ER could provide a treatment option, especially in those patients who have dysphagia or an aversion to swallowing tablet formulations and for whom alternative therapies are not a viable therapeutic option.

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HDAC Continued from page 7

COLLABORATIONSMirati Therapeutics Inc., of San Diego, initiated a trial for the combination study of mocetinostat, an HDAC inhibitor, with the Astrazeneca/Medimmune anti-PD-L1 checkpoint inhibitor, durvalumab, in patients with NSCLC. That trial is exploring the potential of mocetinostat to enhance the effectiveness of checkpoint inhibitors in NSCLC. The company said it believes the dual effect of class I HDACs on tumor cells, as well as on immune cells, may enhance the effect of checkpoint inhibitors in all indications where checkpoint inhibitors have demonstrated efficacy.Mirati struck a deal with Astrazeneca/MedImmune last year in which it will conduct and pay for the first phase I/II study in NSCLC, with London-based Astrazeneca’s Medimmune arm providing supply of durvalumab. Medimmune holds an option to negotiate a license if the experiment succeeds. (See BioWorld Today, Aug. 6, 2015.)In June, Boston-based Acetylon Pharmaceuticals Inc. presented positive results from multiple clinical trials evaluating the safety and efficacy of two selective HDAC6 inhibitors in combination with pomalidomide (Pom) (Pomalyst, Celgene Corp.) and dexamethasone (Dex) for the treatment of relapsed or relapsed-and-refractory multiple myeloma at the European Hematology Association meeting.

The results of the phase II ACE-MM-102 trial indicated that treatment with ricolinostat in combination with Pom and Dex was very well-tolerated, and toxicities were predominantly low grade. Pharmacokinetic and pharmacodynamic analysis demonstrated selective inhibition of HDAC6 at therapeutic doses. Analysis of 67 efficacy-evaluable patients enrolled at least six months prior to the data cut confirmed an overall response rate of 46 percent, a clinical benefit rate of 58 percent, nine months duration of response and seven months progression-free survival. In 2013, the company signed a strategic collaboration agreement with Celgene Corp., which includes an exclusive option for the future acquisition of Acetylon.The company also has on ongoing partnership with the Hereditary Neuropathy Foundation (HNF), of New York. As a supplement to HNF’s longstanding collaboration with University of Sheffield, Acetylon will provide an HDAC6 inhibitor compound for testing in a preclinical model of Charcot-Marie-Tooth, the most common inherited peripheral neuropathy. Huya Bioscience International LLC is working with Japanese pharmaceutical company Eisai Co. Ltd. for the commercialization of its HBI-8000 class I-selective oral HDAC inhibitor, approved in China for the treatment of peripheral T-cell lymphoma. (See BioWorld Today, Feb. 3, 2016.)HBI-8000 inhibits class I HDAC1, HDAC2, HDAC3, as well as class IIb HDAC10 and stimulates accumulation of acetylated histones H3 and H4 in tumor cells. //

HDAC INHIBITOR CLINICAL TRIALS BY PHASE OF TESTING

Source: Cortellis

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rights, Aram will pay Rockwell an undisclosed up-front licensing fee, a high double-digit royalty on product sales and commit to annual minimum purchase quantities. Aram also will assume responsibility for all clinical and regulatory expenses for the territories. (See BioWorld Today, Jan. 27, 2015.)Scintilla Pharmaceuticals Inc., a subsidiary of Sorrento Therapeutics Inc., of San Diego, has entered a binding term sheet to acquire Semnur Pharmaceuticals Inc., of Los Altos, Calif., whose lead program is resiniferatoxin (RTX) for the treatment of intractable cancer pain. On Aug. 8, Scintilla said it entered a binding term sheet to acquire Scilex Pharmaceuticals Inc., of Mission Viejo, Calif., and following the closing of those acquisitions it will operate as a stand-alone company focused on pain management. Scintilla will pay Semnur’s equity holders an initial payment of $60 million, consisting of $40 million in cash and $20 million in shares of common stock of Sorrento. In addition, up to $140 million may be paid upon achievement of certain development, product approval and commercial milestones. Vyriad Inc., of Rochester, Minn., said it signed a license collaboration deal with Imanis Life Sciences LLC, also of Rochester, to develop in vitro and in vivo theranostic tests that assess the probability that a cancer patient will be responsive to Vyriad’s oncolytic virus therapeutics. The tests use recombinant vesicular stomatitis viruses (VSV) that have been engineered to incorporate theranostically informative reporter genes and permit their safe handling as diagnostic reagents in the hospital laboratory setting. The test kits are being developed and preclinically validated at Imanis, while clinical validation is anticipated in Vyriad-sponsored clinical trials through 2017 and beyond. For any approved tests, Imanis will grant Vyriad a nonexclusive license to use the companion diagnostics to accelerate development of its oncolytic viruses derived from the company’s VSV, measles virus or other Vyriad platforms. Financial details were not disclosed. Xycrobe Therapeutics Inc., of La Jolla, Calif., said it entered a research agreement with Johnson & Johnson Consumer Inc., a unit of New Brunswick, N.J.-based Johnson & Johnson. Facilitated by Johnson & Johnson Innovation, the deal focuses on further understanding therapeutic and commercial applications of Xycrobe’s platform technology developed to treat inflammatory skin diseases. Xycrobe’s technology consists of a library of commensal strains from the skin microbiome engineered to grow and secrete biotherapeutics as needed to help treat an array of skin issues. //

Glycomimetics Inc., of Rockville, Md., reported that during a preclinical study, GMI-1271 reduced the cellular interactions that often lead to a buildup in inflammatory response and unstable atherosclerotic plaque formation after a heart attack. The candidate is currently being evaluated as a potential treatment for acute myelogenous leukemia in a phase I/II trial. The preclinical study showed that GMI-1271-induced E-selectin inhibition significantly reduced the numbers of stem and progenitor cells leading to reduced numbers of inflammatory monocytes and neutrophils in the blood, Glycomimetics said. The candidate appeared to also inhibit the cells’ infiltration into existing plaques leading to the stabilization of atherosclerotic plaques after an myocardial infarction in animal models. Data were published in Arteriosclerosis, Thrombosis, and Vascular Biology.Janssen Research & Development LLC, of Boston, a unit of Johnson & Johnson, gained an FDA breakthrough designation for esketamine, an investigational antidepressant for people with major depressive disorder at imminent risk for suicide. The candidate received FDA breakthrough status in November 2013, too, but for treatment-resistant depression, a phase III indication for which the company is running six ongoing trials. If approved, it would be one of the first new approaches to treat major depressive disorder available to patients in the last 50 years, the company said.Knight Therapeutics Inc., of Montreal, pledged to invest $1 million in Genesys Ventures III LP, a Canadian-based life sciences venture capital fund managed by Genesys Capital Management Inc. The investment in Genesys Fund is the eighth life sciences equity fund investment Knight has made to date, having committed more than $125 million of the $130 million earmarked for the strategy. (See BioWorld Insight, Sept. 15, 2014.)Oncoceutics Pharmaceuticals Inc., of Philadelphia, won a $1.7 million orphan grant from the FDA to support phase II evaluation of its lead molecule, ONC201, a selective antagonist of DRD2 that belongs to the superfamily of G protein-coupled receptors, in a relapsed/refractory multiple myeloma trial.Rockwell Medical Inc., of Wixom, Mich., signed an exclusive license and manufacturing supply agreement with Saudi firm Aram Medical for the rights to commercialize Rockwell’s Triferic and Calcitriol in the Middle East to serve a market of about 375,000 hemodialysis patients. Triferic is Rockwell’s iron replacement and hemoglobin maintenance drug for treating anemia in hemodialysis patients. Calcitriol is Rockwell’s generic injection for treatment of secondary hyperparathyroidism in dialysis patients. Under the terms of the agreement, Aram will become the exclusive distributor for Triferic and Calcitriol in 13 countries, including the Kingdom of Saudi Arabia, Kuwait, Bahrain, Qatar, Oman, Lebanon, Jordan, United Arab of Emirates, Yemen, Syria, Algeria, Tunisia and Egypt for an initial commercial term of 10 years. In consideration for the exclusive

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New EMA guidelines on good pharmacovigilance practices for biologics went into effect Tuesday. The guidelines – which apply to new biologics, biosimilars and other follow-ons – provide guidance on how to better monitor and manage the safety of biologics. The document advises on how to address specific challenges in pharmacovigilance for biologics and outlines the roles and responsibilities of the drug company and the various regulators.The FDA revised its 2013 guidance on the classification of co-crystals for small-molecule drugs in an effort to encourage the development of the crystals, which can expand opportunities for engineering solid-state forms of APIs. Composed of two or more different molecules in the same crystal lattice, co-crystals can be tailored to enhance drug product bioavailability and stability, as well as the processability of APIs. The 2013 guidance classified co-crystals as a “drug product intermediate,” creating uncertainty about the good manufacturing practices that applied to their production, according to an FDA notice slated for publication in Wednesday’s Federal Register. Responding to stakeholder concerns, the FDA reconsidered the classification. The new draft guidance discusses the appropriate classification of co-crystal solid-state forms, the data needed to support the classification and the regulatory implications. Comments on the draft are due by Oct. 16.The FDA this week rolled out its first major revision of its web-based version of the Orange Book, a database of approved small-molecule drugs and their therapeutic equivalence evaluations. The new look features an updated design with user-friendly search options. First published online in 1997, the Orange Book includes information about patents and exclusivity for the listed drugs and is one of the most searched-for features on the FDA’s website.German regulators advised other EU regulators to prohibit the entry of simvastatin API made at an Artemis Biotech facility in Hyderabad, India. The recommendation followed an inspection in which a German team noted 35 observations, including five major deficiencies that could potentially lead to a risk to human and veterinary patients. Most of the major deficiencies had to do with quality assurance (QA) issues. For instance, repackaging operations were conducted without any documentation and QA approval, inadequate controls were noted in the issuance of labels for raw materials and APIs, and the plant’s instrumental laboratory violated basic principles on data integrity, according to a statement of noncompliance. While the inspection team didn’t recommend an immediate recall of batches already imported, it advised a complete retest of all the batches. Artemis is a division of Themis Medicare Ltd., of Mumbai.The FDA reported Tuesday that it placed Laxachem Organics Pvt. Ltd., of Maharashtra, India, on import alert

REGULATORY FRONT for refusing to allow FDA investigators to inspect its facility. The company manufactures APIs for repackagers, labelers and wholesale drug distributors. Laxachem will remain on import alert until it has been inspected by the FDA and found to meet U.S. standards. In the meantime, U.S. companies that have received an API from Laxachem are not to distribute it or products containing it, the FDA said.Noven Pharmaceuticals Inc., of Miami, received an FDA warning letter citing several manufacturing problems involving its transdermal drug delivery systems such as Minivelle and Daytrana. The Aug. 5 warning letter, posted Tuesday, is based on an FDA inspection conducted more than a year ago. The investigator claimed the company’s scientifically unsound testing methods could be masking product failures, noting that the complaint rate for Minivelle had increased by 50 percent from fiscal 2013 to fiscal 2014. However, Noven failed to determine why complaints had increased. The inspector also observed calibration issues with the adhesive testing machine and undocumented deviations from required laboratory control mechanisms, according to the letter. In addition, the inspection revealed repeat problems, including the handling of complaints and failure to thoroughly investigate discrepancies in components or batches. //

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Millendo Therapeutics Inc., of Ann Arbor, Mich., said it started a phase IIb trial of oral candidate MLE4901, a nonhormonal therapy for treating polycystic ovary syndrome (PCOS). The double-blind, randomized, parallel-group, placebo-controlled study will test the drug, an antagonist of the neurokinin 3 receptor, in PCOS patients over a seven-month dosing period. The primary endpoint will assess its impact in improving menstrual regularity in women with amenorrhea or oligomenorrhea resulting from PCOS.Oncosec Medical Inc., of San Diego, said research published in the Journal of Clinical Investigation showed that partially exhausted CD8-positive cells infiltrating melanoma tumors accurately predicted most patients’ responses to anti-PD-1 therapies. Findings showed that the response to Keytruda (pembrolizumab, Merck & Co. Inc.) strongly correlated to the percent of CD8-positive tumor-infiltrating lymphocytes that expressed high levels of both PD-1 and CTLA-4. That exhaustion marker is currently being used to select patients for the ongoing phase II investigator-sponsored trial evaluating the combination of Oncosec’s investigational therapy, Immunopulse IL-12, and Keytruda in patients with unresectable metastatic melanoma.Radius Health Inc., of Waltham, Mass., said results from the phase III ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial were published in the Journal of the American Medical Association. The study enrolled 2,463 patients to evaluate the safety and efficacy of abaloparatide for the treatment of postmenopausal women with osteoporosis. Results showed that patients treated with daily abaloparatide for 18 months had a significantly greater reduction in the incidence of new vertebral fractures (p < 0.001) and nonvertebral fractures (p = 0.049) compared to placebo. The drug is under FDA review. (See BioWorld Today, Dec. 22, 2014.)Regen Biopharma Inc., of San Diego, said the Pan Am Cancer Treatment Center in Tijuana, Mexico, which has a nonexclusive license to test Hemaxellerate in a first-in-human proof-of-concept study, presented interim data on the first five patients with chemotherapy-induced bone marrow suppression, showing all tolerated Hemaxellerate with no side effects. At one month post treatment, two patients (40 percent) had dramatic increases in their circulating white blood cells to levels even above the normal range, and two other patients had their white blood cells return to the normal range. Those patients continued to benefit, and all five patients showed increased number of white blood cells after three months. Four of five patients also had increased numbers of red blood cells, and all patients had increased numbers of platelets three months after treatment compared to after one month. Hemaxellerate comprises cells extracted from a patient’s own fat tissue and processed to induce a biological response in the patient that heals damaged bone marrow and restores the

body’s ability to generate healthy blood cells. The product has received FDA clearance for phase I testing in aplastic anemia patients.Repros Therapeutics Inc., of The Woodlands, Texas, provided a six-month update on results from its ongoing 15-month study of secondary hypogonadal men in which diet and exercise alone is compared to diet and exercise in combination with enclomiphene treatment. Using LC/MS/MS assessments for total testosterone (T) and free T, it was determined diet and exercise alone increased total T from a mean of 264 ng/dL at baseline to 368 ng/dL (p = 0.0055) at six months but only raised free T from 55.6 pg/mL to 57.1 pg/mL (p = 0.0802). On the other hand, the 12.5-mg and 25-mg doses of enclomiphene achieved levels of both total T and free T beyond levels reached without the addition of diet and exercise in previous studies. Using LC/MS/MS assessments, the 12.5-mg group exhibited an increase in mean morning T from 298 ng/dL to 723 ng/dL (p = 0.0002) at six months, while mean morning T for the 25-mg group increased from 255 ng/dL to 864 ng/dL (p = 0.0082). All subjects in the first six-month phase were provided a commercially available prepared diet along with enrollment in a health club with a personal trainer. During the second six-month phase, men will continue their current treatment with enclomiphene or placebo but will no longer be provided the commercial diet. Exercise with the assigned trainer will continue during this period. In the last three months of the study, the subjects will no longer receive treatment but will stay enrolled in the health club, though without a trainer.Viiv Healthcare Ltd., of London, said it started a phase III program to support regulatory filings for a two-drug regimen of Tivicay (dolutegravir) and Epivir (lamivudine) as a treatment of HIV-1 infection in adults who have not received prior antiretroviral therapy. The program will consist of two identical studies – GEMINI 1 and 2 – comparing the two-drug regimen with the three-drug regimen comprising dolutegravir plus Truvada (tenofovir/emtricitabine, Gilead Sciences Inc.). A total of 1,400 HIV patients will be enrolled. Both trials are designed to demonstrate noninferiority, and the primary efficacy endpoint will be measured at week 48. The study will continue to evaluate the long-term antiviral activity, tolerability and safety through week 148.Vtv Therapeutics Inc., of High Point, N.C., said it completed enrollment in the phase II LOGRA (aLosteric Oral Glp1 Receptor Agonist) study, a randomized, double-blind, placebo-controlled trial testing TTP273, an oral, small-molecule GLP-1 receptor agonist. The trial is assessing the safety and efficacy of TTP273 in type 2 diabetics on stable doses of metformin. The primary endpoint is the change from baseline in HbA1c at three months, with secondary endpoints including body weight, plasma glucose, lipids insulin, lactate, C-peptide, glucagon and GLP. Top-line data are expected late this year. //

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