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MAY 21 , 2014 VOLUME 25, NO. 98BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS

BIOWORLD TODAYTM

THE DAILY BIOPHARMACEUTICAL NEWS SOURCE

See AMD, page 3 See Takeda, page 4

See IPOs, page 8

See FDA, page 6

See Neostem, page 10

See Arzerra, page 5

THE NEXT STEP

IN THE CLINIC

FINANCINGS

REGULATORY

DEALS AND M&A

DEALS AND M&A

See Perspectives, page 9

See Aadi, page 7

BIOWORLDPERSPECTIVES Neostem, Cellular

Biomed ink liver cancer immunotherapy dealBy Shannon Ellis, Staff Writer

SHANGHAI – Neostem Inc. signed an exclusive license agreement with Cellular Biomedicine Group, of Shanghai, for its patient-specific immunotherapy (DC-TC) to treat late-stage hepatocellular

Arzerra no better than Rituxan in head-to- head lymphoma trialBy Cormac Sheridan, Staff Writer

Shares in Genmab A/S opened Tuesday morning down 11 percent on overnight news that its anti-CD20 antibody Arzerra (ofatumumab) failed to demonstrate a progression-free survival (PFS) benefit

Co-formulation players with anti-VEGF, PDGF are taking ‘shots’ in AMD marketBy Randy Osborne, Staff Writer

Ophthotech Corp.’s potential $1 billion-plus, ex-U.S. deal with Novartis AG for Fovista, the antiplatelet-derived growth factor (PDGF) agent capable of enhancing the efficacy of anti-VEGF therapies in wet age-related macular degeneration (AMD), added juice to a growing $5 billion market – one about to take the next step into co-formulation.Part of the $200 million up-front arrangement disclosed this week between New York-based Ophthotech and Novartis, of Basel, Switzerland, involves a plan to pair

Let the conversation beginBy Mari Serebrov, Washington Editor

“Communication about how certain treatments are working in certain patients is happening through a multitude of media around the globe. These conversations between and among doctors, patients, researchers,

Pacific pride: Abraxis veteran grooms dormant Celgene drug for successBy Michael Fitzhugh, Staff Writer

Aadi LLC, a small new biotech company led by Abraxane (nab-paclitaxel) co-inventor Neil Desai, is in-licensing a once-shelved nanoparticle therapy from Celgene Corp. to develop it for oncology

Searching for cures, lawmakers look to PCAST reportBy Mari Serebrov, Washington Editor

Adequate FDA resources and a greater commitment at the agency to consider expedited approval paths early in drug development would go a long way in advancing cures for rare diseases and

Ardelyx, Kite Pharma seek to keep IPO window propped openBy Marie Powers, Staff Writer

Though biotechs Ardelyx Inc. and Kite Pharma Inc. have virtually nothing in common except headquarters in California, both filed for initial public offerings (IPOs) Monday, hoping to keep

Takeda’s Entyvio gets FDA nod in ulcerative colitis, Crohn’s diseaseBy Jennifer Boggs, Managing Editor

Coming as little surprise after an FDA advisory panel backed Entyvio (vedolizumab) for treatment of severe ulcerative colitis and moderate to severe Crohn’s disease, Takeda Pharmaceutical Co. Ltd.’s drug gained approval on its May 20 PDUFA date, becoming the first integrin inhibitor to hit the market since

WEDNESDAY, MAY 21, 2014 BIOWORLD™ TODAY PAGE 2 OF 13

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STOCK MOVERS 5/20/2014

Company Stock in $ Change in %

Nasdaq Biotechnology -$35.35 -1.46%

Auspex Pharmaceuticals +$1.70 +9.55%

Chimerix Inc. -$2.60 -15.46%

Intercept Pharmaceuticals -$36.66 -14.10%

Ophthotech Corp. +$7.70 +24.48%

Stemline Therapeutics Inc. +$1.35 +10.74%Biotechs showing significant stock changes Tuesday

Coming Thursday in BioWorld Highlights:

LET THE CONVERSATION BEGIN“Communication about how certain treatments are working in certain patients is happening through a multitude of media around the globe. . . . We need to harness the power of the Internet and social networks.” That’s how Reps. Fred Upton (R-Mich.) and Diana DeGette (D-Colo.) described the importance of open communication between drugmakers and doctors in a recently released white paper. For more on this topic, see tomorrow’s edition of BioWorld Highlights, an op-ed e-zine that provides fresh commentary from the BioWorld Highlights blog, http://bioworld.blogs.bioworld.com. Plus, you’ll have access to free articles from BioWorld Today, BioWorld Asia and BioWorld Insight. If you don’t already receive this complimentary e-zine, click here to opt in.

OTHER NEWS TO NOTE

Aradigm Corp., of Hayward, Calif., said the FDA has designated its lead inhaled antibiotic candidate, Pulmaquin, as a qualified infectious disease product for treatment of noncystic fibrosis bronchiectasis patients with chronic lung infections with Pseudomonas aeruginosa. The incentive program, created by the Generating Antibiotic Incentives Now Act, provides priority review and eligibility for fast-track status. If the FDA approves Pulmaquin, it also will be eligible for an additional five-year extension of Hatch-Waxman exclusivity. The company granted an exclusive, worldwide license for Pulmaquin and Lipoquin, its formulations of inhaled ciprofloxacin, for the treatment of severe respiratory diseases to Barcelona-based Grifols SA in May 2013. (See BioWorld Today, May 22, 2013.)Beryllium Inc., of Bedford, Mass., said UCB SA, of Brussels, Belgium, acquired a minority stake in the company. The agreement builds on an ongoing six-year relationship, during which the companies’ joint discovery team has made significant scientific breakthroughs in developing undisclosed small-molecule drugs, Beryllium said.Boston Therapeutics Inc., of Manchester, N.H., signed a marketing agreement with Benchworks SD LLC to drive brand awareness and grow sales of Sugardown, its nonsystemic complex carbohydrate-based food supplement for glycemic health. Terms were not disclosed. Boston Therapeutics also is working on a drug portfolio based on complex carbohydrate chemistry, with polysaccharide candidate PAZ320 in phase IIb testing to reduce postmeal elevation of blood glucose. (See BioWorld Today, Dec. 9, 2013.)Cardiome Pharma Corp., of Vancouver, British Columbia, struck a deal in which Vienna-based AOP Orphan Pharmaceuticals AG will commercialize Aggrastat, Cardiome’s reversible GP IIb/IIIa inhibitor for the treatment of acute coronary syndrome, in selected European countries. The partners did not disclose financial details of the agreement.Cell Therapy Catapult, of London, UCL Business and Imperial Innovations formed a joint venture to accelerate development of a therapy for acute myeloid leukemia (AML) originally

developed at Imperial College and then at UCL by scientists funded by the charity Leukaemia & Lymphoma Research. The therapy is designed to target disorders associated with overexpression of the WT1 antigen, including AML and myelodysplastic syndrome. As part of the deal, Cell Therapy Catapult will work to expedite delivery of phase I/II trials and will invest up to £10 million (US$16.8 million).


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AMD Continued from page 1

in a single drug Fovista and an anti-PDGF compound from Novartis. It’s an approach already in the works by Regeneron Pharmaceuticals Inc. with its marketed therapy Eylea (aflibercept). (See BioWorld Today, May 20, 2014.)Anti-VEGFs available for AMD include Lucentis (ranibizumab), and used off-label for the condition is Avastin (bevacizumab), both from Roche AG, of Basel. The anti-VEGFs block the growth of abnormal blood vessels behind the eye, and Fovista is designed to make them shrivel away. (See BioWorld Insight, July 22, 2013.)The one-two punch is becoming a favored attack in wet AMD. Tarrytown, N.Y.-based Regeneron, which broadened its ophthalmology portfolio about a year ago by acquiring full exclusive rights to early stage antibodies targeting the PDGF family of receptors and to antibodies targeting the ANG2 (angiopoietin2) receptor and ligand, also preclinical. Invented at the company, they were previously included in a collaboration with Paris-based Sanofi SA. Regeneron paid Sanofi $10 million up front, as well as up to $40 million in development milestone payments, and royalties on sales in connection with PDGF antibodies. For the ANG2 batch, the firm gave $10 million up front, a potential $5 million development milestone payment, and royalties on sales. Leerink Partners LLC analyst Joseph Schwartz, in a report, called the Ophthotech/Novartis plan for the co-formulation “a nice hedge” against Regeneron.RBC Capital Markets analyst Adnan Butt found no cause for panic on Regeneron’s part as a result of the Ophthotech/Novartis tie-up, at least not yet. “Though details [of the deal] could be unsettling, they should not be, as they also confirm Regeneron’s strategy,” he wrote in a research report, calling the other companies’ approach “a play out of Regeneron’s playbook.” Regeneron’s research has attained the phase I stage. “Though success is not assured for either company, the strategy underscores our premise that the future of anti-VEGF therapy lies in combination treatment, where Regeneron could be in the lead,” in Butt’s view. “Phase I results could be a meaningful catalyst for Regeneron shares, whether with anti-PDGFR or with ANG2, another product candidate that REGN could put in the clinic with Eylea.”In either case, noted Deutsche Bank analyst Robyn Karnauskas, Ophthotech’s ongoing phase III trial does not use any co-formulation and the drug would enter market, if successful, as a single agent. “Given that Eylea looks the best anti-VEGF, due to its convenience and effect in hard-to-treat patients, we believe Eylea will likely be the best combination treatment option,” she opined in research report.Almost inevitably, Irvine, Calif.-based Allergan Inc. has stakes in the AMD combo game, too, with collaborator Molecular Partners

AG, of Schlieren, Switzerland. In the summer of 2012, the duo inked their second ophthalmology deal, with two parts. The first involved MP0260 (AGN-150998), a bispecific designed ankyrin repeat protein (Darpin) molecule, which binds VEGF and PDGF, in development for exudative or wet AMD. The second part had to do with a discovery alliance, during which the two companies will design and develop Darpins against selected targets involved in serious eye diseases. Allergan got options on three molecules arising from the effort and would be solely responsible for advancing them. (See BioWorld Today, Aug. 22, 2012.)Plenty of cash went into the Molecular Partners deals. In 2011, Allergan paid $45 million up front to begin the relationship, and continuing it cost another $62.5 million. But last year, Allergan said work would be delayed for up to two years because of disappointing phase II data in wet AMD. (See BioWorld Today, May 10, 2011, Aug. 21, 2012, and July 3, 2013.)A smaller but notable player in the field of potential combo AMD therapy is Allegro Ophthalmics LLC, of San Juan Capistrano, Calif., with ALG-1001, which was found to inhibit cell adhesion in vitro and to arrest aberrant blood vessel growth in vivo, both systemically and in the eye. Specifically, the compound blocks adhesion meditated by the alpha-5-beta-1, alpha-v-beta-3 and alpha-v-beta-5 integrins, which are implicated in the angiogenic process and known to be expressed in neovascular ocular tissue from patients with wet AMD and diabetic retinopathy. In wet AMD, ALG-1001 has reached the phase Ib/IIa stage, and might work with an anti-VEGF therapy in AMD and diabetic macular edema. (See BioWorld Today, Dec. 27, 2013.) //

OTHER NEWS TO NOTE

Clovis Oncology Inc., of Boulder, Colo., said the FDA granted breakthrough therapy designation to CO-1686 as a monotherapy treatment for second-line EGFR mutant non-small-cell lung cancer patients with the T790M mutation. That designation was granted based on interim data from an ongoing phase I/II study of the oral, targeted covalent EGFR inhibitor in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M.Endocyte Inc., of West Lafayette, Ind., and partner Merck & Co. Inc., of Whitehouse Station, N.J., said they withdrew the conditional marketing authorization applications (MAAs) from the EMA for vintafolide and its companion imaging components, imaging agent etarfolide and intravenous folic acid, seeking approval for the treatment of adults with folate receptor-positive, platinum-resistant ovarian cancer, in combination with pegylated liposomal doxorubicin (PLD). The decision to pull the MAAs was based on further review of interim data from the PROCEED trial. Enrollment in that study was suspended earlier this month after the data safety monitoring board reported that vintafolide plus PLD vs. PLD alone did not meet the pre-specified criteria for progression-free survival to allow continuation of the study. (See BioWorld Today, May 5, 2014.)




Takeda Continued from page 1

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Biogen Idec Inc.’s Tysabri (natalizumab).Entyvio, which inhibits the alpha2beta7 integrin, is indicated for patients for whom one or more standard therapies, including corticosteroids, immunomodulators and tumor necrosis factor blockers, failed to produce adequate responses. Data stemmed primarily from two clinical trials involving about 900 patients, which showed that a greater percentage of participants treated with Entyvio vs. placebo achieved and maintained clinical responses. The trial data were not without controversy. During the December meeting of the Gastrointestinal Drugs and the Drug Safety and Risk Management advisory committees, members barely voted – 12-9 – that efficacy data were sufficient to

support Entyvio’s use as an induction therapy in patients with Crohn’s who had failed other therapies, with those voting no pointing out that the drug fell short of the FDA’s formal criteria. (See BioWorld Today, Dec. 10, 2013.)Panel members were more confident in the use of Entyvio as a maintenance therapy in Crohn’s, voting unanimously with one abstention, that data supported use in that indication.In a single Crohn’s maintenance trial, the drug hit the primary endpoint of clinical remission and two secondary endpoints. But it fell short in a third secondary endpoint measuring durable clinical remission. The biologic showed a statistically significant treatment difference for the primary endpoint of clinical remission in one Crohn’s induction trial but not for the alternative primary response endpoint or for the secondary endpoint. In a second induction trial of patients who had failed on TNF-alpha antagonists, vedolizumab didn’t demonstrate superiority over placebo, the FDA said.In ulcerative colitis, the data were clearer, with Entyvio demonstrating statistically significant improvements on all endpoints.In Entyvio’s favor, however, is the fact that many ulcerative colitis and Crohn’s patients do not adqueately respond to existing therapies and are in desperate need of new treatments. According to Amy G. Egan, acting deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, the latest approval “provides an important new treatment option for patients who have had an inadequate response to conventional therapy to help control their symptoms.”Data from Entyvio trials showed that the most common side effects included headache, joint pain, nausea and fever. Doctors also are recommended to monitor patients for any neurological side effects, particularly progressive multifocal leukoencephalopathy (PML). While no instances cropped up during Entyvio trials, Biogen’s Tysabri was plagued by cases of the potentially fatal brain infections, resulting in that drug’s temporary removal from the market. Since Entyvio has a similar mechanism of action, the FDA said it will work with Takeda to further investigate the risk of PML through a required postmarketing study and enhanced, expedited adverse event reporting. //

OTHER NEWS TO NOTE

Karyopharm Therapeutics Inc., of Natick, Mass., secured FDA orphan drug status for its lead candidate, Selinexor (KPT-330). The company is developing Selinexor for the third-line treatment of diffuse large B-cell lymphoma, the most common of aggressive non-Hodgkin lymphomas (NHL), accounting for up to 30 percent of newly diagnosed cases of NHL in the U.S. Karyopharm said it had secured another orphan designation for Selinexor, an oral selective inhibitor of nuclear export compound, as a second-line therapy for acute myeloid leukemia.

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Arzerra Continued from page 1over Rituxan (rituximab) in a phase III head-to-head study in patients with diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin’s lymphoma (NHL). As a result, Copenhagen, Denmark-based Genmab and its partner, London-based Glaxosmithkline plc are unlikely to pursue a regulatory filing in DLBCL. The result is another setback for a product that has so far failed to make any significant headway against the juggernaut that is Rituxan, an anti-CD20 antibody first approved back in 1997. Arzerra, which is currently approved for treating patients with refractory chronic lymphocytic leukemia (CLL) and, in the U.S., treatment-naïve CLL patients who are unable to take fludarabine, attained sales of £74.9 million (US$126.1 million) last year. In the same period, Basel, Switzerland-based Roche Holding AG reported CHF7 billion (US$7.8 billion) in sales of Rituxan across five oncology indications, as well as rheumatoid arthritis, granulomatosis with polyangiitis (Wegener’s granulomatosis) and microscopic polyangiitis.According to Peter Welford, analyst at Jefferies International, peak annual sales in DLBCL, which represents about one-third of all NHL cases, could have amounted to $350 million, but the damage to the product’s commercial potential arising from the trial is limited to that indication. “Importantly, we believe clinicians are unlikely to infer too much for CLL/NHL from the DLBCL phase III failure, as these lymphomas are different diseases. Nevertheless, hopes for a differentiated profile versus entrenched Rituxan are thwarted, and Roche may have a greater commercial advantage in the anti-CD20 battle,” he wrote in a research note. Genmab CEO Jan van de Winkel put the peak potential in DLBCL at a much lower figure – about $70 million to $100 million, he told BioWorld Today. “It’s a relatively limited impact,” he said. “The major impact is on the patients – that’s the saddest part.” Genmab still attaches blockbuster ambitions to the product, based on its potential in CLL, follicular lymphoma and other NHLs, as well as in autoimmune disease. Reaching $500 million in annual sales would represent an important milestone, as Genmab’s royalty rate would then rise to 20 percent. The resulting cashflow would cover all of the company’s operational costs. This week, the EMA’s Committee on Human Medicinal Products is due to decide on an application to broaden Arzerra’s label in CLL to include first-line therapy, a designation it received from the FDA in April after a priority review. “We hope we’ll get a very nice label in Europe,” van de Winkel said.A phase III, head-to-head, single-agent study vs. Rituxan in follicular lymphoma patients who have relapsed on the latter drug is ongoing but will not read out until 2016. “We are confident about the potential of Arzerra to outperform rituximab in relapsed follicular lymphoma,” he said, citing preclinical data in which Genmab’s drug consistently

outperformed its rival in terms of cell killing. In the meantime, Roche is ramping up the rollout of Gazyva (obinutuzumab) its much-vaunted Rituxan successor, which gained FDA approval late last year as first-line therapy in CLL, in combination with chlorambucil. It has already beaten Rituxan in a phase III head-to-head study in previously untreated CLL. (See BioWorld Today, Dec. 10, 2013.)In CLL, van de Winkel said Arzerra is competitive with Gazyva, and it offers a more convenient dosing schedule as well as 30 percent cheaper pricing.The rationale for the present study was based on the widespread adoption of Rituxan in first-line regimens for treating CD20-positive DLBCL, which reduces its effectiveness in second-line settings. The trial recruited 447 patients who had relapsed on or who were refractory to front-line therapy comprising rituximab plus a chemotherapy regimen containing anthracycline or anthracenedione, and who were eligible for autologous stem cell transplant (ASCT). Patients were randomized to receive Arzerra plus salvage chemotherapy or Rituxan plus salvage chemotherapy. After three cycles of treatment, those with either a complete or a partial response were given high-dose chemotherapy followed by ASCT. The primary endpoint was PFS. Secondary endpoints include: overall and complete response rate after salvage chemotherapy; two-year overall survival; ability to mobilize at least 2 million CD34-positive cells/kg from peripheral blood; overall and complete response rate three months after ASCT; safety and tolerability; and two-year event-free survival. There was no statistically significant difference in PFS between the two arms. “This is a very tough disease to treat. There is no second-line therapy approved in this indication,” van de Winkel said.The companies will present detailed data at upcoming medical conferences. Although there were no differences between the two treatment arms in terms of adverse events leading to treatment discontinuation or serious adverse events, patients in the Arzerra arm experienced more dose interruptions and treatment delays due to infusion reactions and elevations in serum creatinine, a marker for impaired kidney function. Oncology rights to Arzerra are due to transfer from GSK to Basel-based Novartis AG as part of their complicated three-way asset swap agreed last month. (See BioWorld Today, April 23, 2014.)The impact of the move on Arzerra could be interesting. “In the short term, there may be some uncertainty,” van de Winkel said. “In the longer term, it may mean more focus and a more attractive proposition, with Arzerra being placed in the Novartis oncology portfolio.”Significantly, GSK has retained rights to a subcutaneous formulation of the antibody for autoimmune disease. It has already undergone early stage trials in multiple sclerosis and is in a phase III study in pemphigus vulgaris, a skin condition.

See Arzerra, page 10




FDA Continued from page 1other medical conditions, a House subcommittee was told Tuesday. In its second hearing on the bipartisan 21st Century Cures Initiative, the Energy & Commerce Subcommittee on Health heard from experts who contributed to the President’s Council of Advisors on Science and Technology (PCAST) report on propelling innovation in drug discovery, development and evaluation. Released two years ago, that report called for a doubling in the number of new drug approvals over the next decade, while increasing efficacy and safety. The report cited inefficiency in the conduct of clinical trials and scientific knowledge gaps between basic research and commercial projects as primary causes of the burgeoning cost of drug development, without commensurate increases in drug approvals. (See BioWorld Today, Sept. 27, 2012.)The report noted numerous opportunities that already exist for the FDA to improve the balance between protecting the public from dangerous or ineffective drugs and ensuring timely access to innovative and potentially life-extending therapies. For example, the agency should expand its existing authorities for accelerated approval and confirmatory evidence to all drugs that meet the statutory standard of addressing an unmet need or a serious or life-threatening disease, the council recommended.Congress repeated that recommendation in the FDA Safety and Innovation Act (FDASIA), which encouraged the agency to use innovative and flexible approaches in assessing products under accelerated approval. While the FDA uses accelerated approval prudently, it does not use it frequently, Frank Sasinowski, a director of the National Organization for Rare Disorders, testified Tuesday. Since the 1980s when the FDA was given the authority to use accelerated approval, 87 percent of the drugs approved on the track have been for cancer or HIV/AIDS. Only about 20 drugs for other indications have received accelerated approval. The most recent was Chelsea Therapeutics International Ltd.’s Northera (droxidopa), which was approved in February for neurogenic orthostatic hypotension (NOH), or a sudden drop in blood pressure when the patient stands up. (See BioWorld Today, Feb. 19, 2014.)Although Northera was granted accelerated approval, its approval process was anything but accelerated. The drug, which has been on the market in Japan for 20 years, went through two advisory committee meetings and had to work through a complete response letter before finally getting FDA approval for what had been an unmet need.

EXPAND EXPEDITED APPROVAL PATHSTo get the necessary data in a timely manner, accelerated approval and other expedited paths must be considered early

in the clinical development process, Sasinowski said; otherwise “we forfeit opportunities.” One of the first questions the FDA should consider when meeting early on with sponsors of a potential new drug in any therapeutic space is whether the compound is a candidate for an expedited approval path, he recommended.Accelerated approval is especially critical when developing new treatments for many rare diseases. Using Duchenne muscular dystrophy (DMD) as an example, Sasinowski said it made no sense to require the large trials with long follow-up that are standard to traditional approval. There isn’t enough time or patients to satisfy those requirements, given the progression of DMD.On the other hand, Jeff Allen, executive director of Friends of Cancer Research, praised the FDA for its robust implementation of the breakthrough therapy designation provided under FDASIA to expedite the development and review of promising drug candidates. Intended to give the agency the ability to respond to new science, the designation can be granted to drugs that have preliminary clinical evidence indicating they may demonstrate a substantial improvement on a clinically significant endpoint over other available therapies for a serious condition. (See BioWorld Today, June 26, 2013.)By the end of last year, the FDA had received 121 requests for the designation and had granted it to 36 candidates that showed encouraging early clinical results in areas such as cystic fibrosis and breast cancer. The agency had approved two breakthrough therapies for rare types of cancer and one for hepatitis C. (See BioWorld Today, March 14, 2014.)Because the breakthrough designation provides extensive interaction between the FDA and the sponsor, it is resource-intensive, Allen noted. That can be a challenge given the agency’s current budget constraints.

FDA BUDGET CONSTRAINTSRecognizing those constraints, Garry Neil, global head of R&D at Medgenics Inc., urged Congress to increase and sustain the funding for both the FDA and NIH. At the subcommitee’s first hearing on the 21st Century Cures Initiative earlier this month, much of the discussion centered on the need for more NIH funding. The FDA’s financial needs were not addressed. (See BioWorld Today, May 8, 2014.)Those needs became more central to Tuesday’s discussion, especially since a House Appropriations subcommittee was in the process of marking up the fiscal 2015 agriculture appropriations bill, which includes FDA funding. The bill calls for $4.5 billion in total funding for the FDA, an increase of $98 million, or 2 percent, over this year’s level. All but $23 million of that increase is to come from user fees. Under the House bill, the FDA’s drug safety activities would get an additional $12 million.The bill, which still must be approved by the full Appropriations

See FDA, page 7




Aadi Continued from page 1and cardiovascular indications. Celgene acquired the drug, ABI-009, in its 2010 acquisition of Abraxis Bioscience Inc. and retains an option to reacquire it in the new deal.Desai kept terms of the deal under wraps, but allowed that Celgene has invested a lot in the nanoparticle albumin-bound (NAB) platform on which both Abraxane and ABI-009 are based, so the big biotech will be keeping close tabs on the project.Originated by Abraxis, ABI-009 is a NAB version of the mTOR inhibitor sirolimus, also known as rapamycin. While Celgene tested the drug as a potential treatment for solid tumors in a phase I trial that began in December 2007, Thomson Reuters Cortellis records indicate that two years later, the drug was still listed as sitting in phase I development, and no further updates followed.“Celgene’s busy with a lot of things,” Desai told BioWorld Today. So is Desai. In addition to supervising ongoing enrollment for a combined phase I/II trial of the ABI-009 for bladder cancer, his new company has two more indications in mind: peripheral artery disease and pulmonary arterial hypertension. To advance all three indications through proof of concept in phase II, he’s now seeking additional financing.Desai shepherded Abraxane from the lab straight through clinical development as senior vice president of R&D at Abraxane. He was also involved in early development of ABI-009 during those days. Still convinced that the experimental drug offers a great opportunity to develop an improved mTOR inhibitor, he approached Celgene with a plan to rapidly develop the drug at the Pacific Palisades, Calif.-based company.“If you look at the mTOR inhibitor space, there are several drugs approved with varying profiles of toxicity and efficacy,” he said. “With the NAB platform, we can get great efficacy while at the same time having minimal toxicity.”ABI-009’s safety profile means it can be used in ways that other mTORs cannot, such as administering it locally in the bladder, he said. Furthermore, because bladder cancers are typically treated by urologists instead of oncologists, it’s “a good place to get into the hyper-competitive oncology market,” possibly offering an easier regulatory pathway, Desai said.“With just three new drugs approved for bladder cancer in the last 30 years, there’s a massive unmet need to develop new agents,” he said.The drug has already completed one earlier phase I trial in patients with advanced nonhematologic malignancies, which showed the drug to be well tolerated with evidence of activity in heavily pretreated patients. The company is now recruiting for the combined phase I/II study in recurrent nonmuscle-invasive bladder cancer.As many as 80 percent of the almost 70,000 new bladder cancer cases in the U.S. each year are nonmuscle-invasive

bladder cancers. More than half will recur, even after treatment with bacillus Calmette-Guerin delivered by catheter straight to the bladder, the standard first-line treatment. With an annual death toll of 14,990, the cost per bladder cancer patient is among the highest of all cancers, noted Desai when applying for a grant to fund the study.Aadi recently began recruiting for the study, and has now enrolled three patients in the phase I study, and expects to complete enrollment by year’s end. The study is backed by a fast-track Small Business Technology Transfer grant and a supplemental grant from the National Cancer Institute, totaling about $641,000 in its first phase. New York-based Columbia University will be the primary clinical trial site. Vanderbilt University, of Nashville, Tenn., will provide another site.“It is important that we continue to search for new treatments for bladder cancer patients who are all too often faced with surgical removal of their bladder as their only option,” said James McKiernan, the study’s principal investigator, and interim chairman of the department of urology at Columbia University Medical Center and New York Presbyterian Hospital and professor of urologic oncology.Next, Aadi plans to start a phase I trial of ABI-009 in the treatment of peripheral artery disease in the second half of this year. Desai said the company plans another phase I study in pulmonary arterial hypertension in early 2015, in collaboration with the University of Pittsburgh.Celgene did not return a request for comment. Its shares (NASDAQ:CELG) closed Tuesday at $147.65, up 27 cents. //

Committee and the House itself, is less than the $4.7 billion President Barack Obama had proposed for the FDA. But much of the increase in the president’s budget was to come from new food safety user fees. Like the House bill, the president’s FDA budget includes $2.6 billion in discretionary funding. His budget calls for $25 million to strengthen FDA oversight of compounding pharmacies as it implements the Drug Quality and Security Act.Meanwhile, the Senate is working on its own agriculture appropriations bill. That bill, unveiled Tuesday following a subcommittee markup, also gives the FDA about $2.6 billion in discretionary funding. It includes an increase of $23 million for implementation of the Food Safety Modernization Act and provides $1.5 million to the Health and Human Services Office of Inspector General to increase oversight of FDA programs and operations. //

FDA Continued from page 6

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that wobbly window open.Fremont, Calif.-based Ardelyx, which is developing small-molecule treatments for kidney and gastrointestinal diseases, is seeking to raise up to $69 million, including overallotments. Filing as an emerging growth company, Ardelyx plans to list on Nasdaq under the ticker ARDX. The company has a potential $272.5 million NHE3 inhibitor deal with Astrazeneca plc. NHE3 is the sodium-hydrogen antiporter 3, a key protein in the absorption of sodium in the intestines. The agreement, inked in 2012, provided $35 million up front, with the remainder in development, launch and commercialization milestones. Ardelyx also is entitled to tiered, double-digit sales royalties and it retained an option to co-promote products in the U.S. (See BioWorld Today, Oct. 9, 2012.)The program, tenapanor (RDX5791), is in development for constipation-predominant irritable bowel syndrome (IBS-C) and for prevention of sodium overload in patients with kidney and heart disease. Ardelyx completed a Phase IIa trial in IBS-C and two phase I studies in healthy subjects testing the drug’s ability to divert sodium absorption in the gastrointestinal tract. Last week, Ardelyx picked up a $25 million milestone payment from Astrazeneca for the commencement of a phase IIb trial. Because the drug’s mechanism of action enables the diversion of sodium excretion from the kidney to the feces, thus sparing the kidney and cardiovascular system, the company plans to move into end-stage renal disease (ESRD) and chronic kidney disease (CKD). All told, Ardelyx and Astrazeneca have evaluated tenapanor in more than 750 individuals across eight human trials, with the compound well tolerated in phase I and II studies.Ardelyx is responsible for conducting trials through phase II, with London-based Astrazeneca expected to shoulder subsequent development costs. In its S-1 filing, however, Ardelyx said IPO proceeds will be used, in part, to exercise its right to co-fund the first phase III development program for tenapanor, including additional work on its cell-culture system to simulate gut tissues called Ardelyx Primary Enterocyte and Colonocyte Culture System, or APECCS.In February, Ardelyx also licensed its phosphate transport NaP2b inhibitor program (also known as NaPi2b, Npt2b and SCL34A2) to Paris-based Sanofi SA. The up-front amount was not disclosed, but the companies said the total deal, including development and regulatory milestones, could reach $198 million. Like its Astrazeneca deal, Ardelyx could see sales royalties and retained an option to co-promote in the U.S. Ardelyx’s NaP2b portfolio, designed to treat phosphorus disorders associated with CKD and ESRD, includes candidates in discovery and preclinical stages. Sanofi assumed responsibility for further discovery and development.Ardelyx has several additional internal discovery programs.

IPOs Continued from page 1

RDX009 is focused on nonsystemic TGR5 agonists that stimulate GLP-2 and GLP-1 and have the potential, in combination with a DPP-4 inhibitor, to heal the intestines and reduce inflammation in inflammatory bowel disease. RDX013 is focused on hyperkalemia, or elevated serum potassium, also commonly seen in CKD and ESRD patients, while RDX020 is focused on providing alternate ways to manage fluid overload and kidney function by inhibiting chloride transport in CKD patients, particularly those who also experience acid-base disorders.Founded in 2007 with $1 million in seed funding, the company pulled in a $25 million series A the following year, followed by a $30 million B round in 2011 led by new investor Amgen Ventures LLC, with participation from existing investors New Enterprise Associates and CMEA Capital. In its S-1, Ardelyx reported $33.2 million in cash and equivalents and an accumulated deficit of $71.7 million as of March 31.Citigroup and Leerink Partners are joint bookrunners on the IPO, which is not yet priced.

‘COMPELLING’ DATA COULD SEND KITE TO BLAKite Pharma, which is developing an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is aiming for a much higher raise of up to $115 million, including overallotments. The offering comes just three weeks after the Santa Monica, Calif.-based company closed a $50 million mezzanine convertible note financing. Participants in that transaction were not disclosed but were described as a syndicate of health care-dedicated investors, with many based in the U.S. and first-time investors in Kite. The company raised $15 million in 2011 in an initial private placement with a syndicate of venture investors. In 2013, Kite completed a $35 million series A that included existing investors Commercial Street Capital and Pontifax and several individuals as well as new investor Alta Partners. (See BioWorld Today, May 9, 2011.) Kite’s engineered autologous cell therapy, or eACT, involves the genetic engineering of T cells to express either CARs, or T-cell receptors (TCR). The modified T cells are designed to recognize and destroy cancer cells. The approach – part of the larger cancer immunotherapy space – has taken the cancer drug development world by storm but also has significant competition, with the upcoming American Society of Clinical Oncology meeting virtually swimming in immuno-oncology abstracts. (See BioWorld Today, May 15, 2014.)Kite is funding multiple phase I/IIa trials with CAR- and TCR-based therapies that are being conducted by its collaborator, the Surgery Branch of the National Cancer Institute. Its technology appears promising: In an ongoing trial, patients with relapsed/refractory lymphomas and leukemias treated with CAR-based therapy experienced an objective response rate of 84 percent.

See IPOs, page 11




BIOWORLDPERSPECTIVES

Continued from page 1

BioWorld Perspectives is the official blog for news, analysis, debates, commentary and camaraderie related to the development of biotechnology drugs. Read more at www.bioworld.com/perspectives. All opinions expressed in this article are those of the author and do not reflect the position of BioWorld. To send a Letter to the Editor, please email [email protected].

and scientists in academia and industry should be facilitated. This includes the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients. We need to harness the power of the Internet and social networks.”That’s how Reps. Fred Upton (R-Mich.) and Diana DeGette (D-Colo.) described the importance of open communication between drugmakers and doctors in their recently released white paper 21st Century Cures: A Call to Action, which was intended to launch a national discussion on how to streamline and hasten the development of new cures.Apparently, the FDA didn’t get an advance copy of the memo. Instead of encouraging the free flow of data, research and results, the agency is trying to muzzle it – especially when the exchange involves drugmakers truthfully discussing off-label uses. In revising a 2009 draft guidance on best practices for distributing scientific and medical publications on unapproved uses, the FDA appears to be shrinking drugmakers’ safe harbor for off-label speech, the Pharmaceutical Research and Manufacturers Association (PhRMA) said in comments on the proposed revision.The 2009 draft unambiguously recognized that the dissemination of truthful, nonmisleading medical journal articles about unapproved uses was important in promoting public health. But the revised version waters that down by adding that “this information is in no way a substitute for the FDA premarket approval process.” Such a statement ignores the fact that off-label use is the standard of care for some indications and that Medicare and Medicaid are obligated, by

law, to reimburse for that use.The revision also restricts distribution to articles about adequate and well-controlled studies. If it imposes this new standard, the FDA would prohibit the “dissemination of many types of important and useful scientific information, including certain pharmacoeconomic analyses, meta-analyses, subpopulation analyses, and real world evidence and observational studies that describe significant uses, benefits, and risks of medicines that can improve the effectiveness and/or efficiency of patient care,” PhRMA said.Besides running afoul of drugmakers’ First Amendment rights, such restrictions don’t reflect the reality of health care today, Jeff Francer, PhRMA vice president and senior counsel, told BioWorld. To ensure they’re giving the best care possible, doctors need scientific, accurate, data-driven answers in a timely manner. But given current regulations, all they’re likely to get from an industry rep is a recitation of the professional labeling. If they need more information, they have to go through what can be a lengthy process of requesting it from the company’s medical affairs office.Meanwhile, drugmakers have volumes of scientific data on their products that go well beyond the labeling, Francer said. But even though that information could help doctors determine the best treatment for a specific patient, much of it couldn’t be shared under the FDA’s proposed guidance.If Upton and DeGette seriously want to rethink the status quo, allowing drugmakers to have honest discussions with doctors would be a good place to start.

OTHER NEWS TO NOTE

Morphosys AG, of Martinsried, Germany, said the FDA granted orphan drug designation to MOR208, its humanized Fc engineered monoclonal antibody against CD19, for the treatment of chronic lymphocytic leukemia or small lymphocytic leukemia. The company also received a positive opinion from the EMA for an orphan product application for MOR208 in those indications. MOR208 is in phase II development.Neurotrope Inc., of Plantation, Fla., said it signed an agreement with Stanford University to study and investigate certain analogues of bryostatin, referred to as bryologs, as potential clinical candidates for various neurological disorders. Under the license agreement, Neurotrope has exclusive

rights to make, use or sell certain bryologs for commercial use in therapeutic applications for central nervous system disorders, lysosomal storage diseases, stroke, cardioprotection and traumatic brain injury. Bryostatin is Neurotrope’s phase II candidate in development for Alzheimer’s disease. It is designed to activate the PKCepsilon enzyme and, in preclinical studies, that effect has been shown to play a role in slowing or reversing several neurodegenerative disease processes.Nordic Nanovector AS, of Oslo, Norway, said the lead product candidate Betalutin has been granted orphan drug designation for treatment of follicular lymphoma by the FDA. The compound is described as a radionuclide conjugated to a tumor seeking carrier/antibody, which can be used for irradiation of malignant metastasized tumors with minimal damage to nearby healthy normal tissue.




Neostem Continued from page 1carcinoma (HCC) in China, home to more than 45 percent of the world’s HCC patients. The deal will kick off phase II trials in China. After the first patients are enrolled, Neostem stands to collect a $1 million up-front payment with an additional $30 million in licensing fees and milestones should the project be successful. There is further possibility of payments in royalties and sublicense fees. The partnership is a legacy from New York-based Neostem’s recent acquisition of California Stem Cell (CSC), which closed earlier this month, and shows the deal is already beginning to earn its keep. (See BioWorld Today, April 15, 2014.)“The recent acquisition of CSC allows us to add this platform technology in immunotherapy, which we believe is one of the hottest areas in biotechnology. The idea is that if you can create the target for your particular cancer cells toward the particular cancer cells that will replicate and metastasize – you can help your body destroy those cells,” Robin L. Smith, chairman and CEO of Neostem, told BioWorld Today. CSC developed the relationship with the Chinese partner, CBMG, having collaborated on the phase I trial. It has now become a wholly owned subsidiary, Neostem Oncology LLC, to develop targeted immunotherapies for cancer.CBMG will assume the costs of the trial and will take on the responsibility for all clinical, marketing and possible commercialization activities in China. It is expected that CBMG will have the rights to China, as well as surrounding countries.Neostem, which runs a U.S.-based contract management organization as well as conducts cellular therapy discovery, will be responsible for the regulatory filings and controlling the manufacturing process.“The manufacturing will be done in China; we are sort of controlling the manufacturing – collaborating yet controlling – but it will all be done in China,” Smith said. DC-TC treatment is based on recent findings that a small number of cancer-initiating stem cells may be the cause of the rapid proliferation of cancer in the body. The technology in question has refined the isolation and expansion of those cancer-initiating cells, which are combined with autologous dendritic cells. Those are then introduced into the patient with subcutaneous injections to bolster the immune system, enabling it to fight the cancer stem cells.In addition to being home to 45 percent of the world’s HCC patients, China reported 395,000, or roughly 50 percent, of new cases in 2012. “There is a huge population with liver cancer,” Smith said, “a huge unmet need where we believe we can create a therapy for those diseases.”“The planned phase II study in China is seeking to assess the efficacy and safety of our new DC-TC platform technology in treating hepatocellular carcinoma, and we look forward to

working with CBMG to develop this indication in Asia,” she added. CBMG reported its successful phase I trials in December, which marked the first immune cell clinical trial of its kind in China. “We are very pleased with the positive results of this [phase I] trial, which show the DC-TC therapy to be safe and are now in a position to plan a phase II trial,” said William Cao, CEO of CBMG.The treatment is particularly valuable for patients with late-stage liver cancer who are not eligible for curative resection or transplantation. Currently, the most common therapies used to treat most HCC patients are surgery and local chemotherapy, with a two-year recurrence rate of 51 percent.The phase I trial was an open-label, single-center trial conducted on eight primary HCC patients following resection. Each patient received patient-specific DC-TC therapy. Patients received weekly injections for three consecutive weeks and were evaluated over a two-month period for the therapy’s safety.The last patient received treatment in December and, after a two-month follow-up, the safety data from the trial showed no adverse events related to the injection site, a few transient adverse events mitigated with drug treatment and one serious adverse event deemed to be a pre-treatment tumor recurrence. //

Much of Genmab’s attraction to investors lies in its anti-CD38 antibody, daratumumab, which is partnered with Johnson & Johnson, of New Brunswick, N.J., and which is undergoing phase III trials in multiple myeloma. The company’s stock (COPENHAGEN:GEN) recovered most of its losses during trading Tuesday, to close at DKK205 (US$37.60), down less than 2 percent. //

Arzerra Continued from page 5

OTHER NEWS TO NOTE

Novelmed Therapeutics Inc., of Cleveland, reported data showing that its humanized monoclonal antibody demonstrated dramatic effects in two animal models of osteoarthritis in reducing cartilage degeneration and osteophyte formation by greater than 90 percent vs. controls. Recent toxicology studies in primates demonstrated no adverse effects, including complete lack of microscopic histological findings, and phase I studies are planned by the end of this year.Orexo AB, of Uppsala, Sweden, said Orexo U.S. Inc. and Inventiv Health Inc., of Somerset, N.J., will work together to commercialize Zubsolv (buprenorphine and naloxone) for opioid addiction in the U.S. The new partnership, effective July 1, has a three-year term. The deal calls for Orexo to take responsibility for sales management and direct sales force expenses, while Inventiv will employ and support individual sales representatives.




IPOs Continued from page 8

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TWO CHINAS EMERGING AS BIOPHARMAS SHIFT TOWARD INNOVATIVE DRUGS

Although innovation is the topic of much conversation in China’s biopharma industry, Western companies are more likely to observe that the notion of innovative drug development in China is more hype than reality. However, participants at the Chinabio Partnering Forum, held in Suzhou earlier this month, offered compelling evidence that Chinese biotechs are, indeed, transforming cutting-edge discoveries into drug pipelines, with partnering opportunities very much welcomed.

COMPANIES JUMPING ON SGC MODULATORS POTENTIAL PAYOFF

Merck & Co. Inc.’s new billion-dollar collaboration with Bayer AG threw a spotlight on soluble guanylate cyclase (sGC) modulators, a relatively young class of drugs that are part of a new generation of treatments for cardiopulmonary and gastrointestinal diseases. With Bayer and Ironwood Pharmaceuticals Inc. already leveraging FDA approvals of their sGCs, others are now jumping in to find new profit in modulating the enzyme.

BIOTECH SECTOR CONTINUES TO SLIDE AS GENERAL MARKETS ALSO TUMBLE

With the general markets sliding over concerns about a weakening economy, biotech companies followed suit this week and there were plenty of red numbers all round. BioWorld Insight takes the sector’s “temperature” with a close look at the performance of BioWorld Biotech Indices. BioWorld Today subscribers can add BioWorld Insight for a special discounted rate. Call (770) 810-3144 or (800) 477-6307 and mention Editor Peter Winter for a free trial.

With the IPO funding, Kite plans to conduct a phase I/II trial next year for lead candidate KTE-C19, a CAR-based therapy, in patients with relapsed/refractory diffuse large B-cell lymphoma. Provided the data are “compelling,” the company then would go straight to the FDA, filing a biologics license application for accelerated approval of KTE-C19 as third-line therapy in the indication, where it already has orphan drug designation.Kite’s pipeline includes several additional TCR-based T-cell therapies. The company has an exclusive license with the NIH for intellectual property (IP) relating to a TCR-based T-cell

therapy targeting the antigen SSX2 to treat head and neck cancer, hepatocellular carcinoma, melanoma, prostate cancer and sarcoma, and a co-exclusive license to the same IP to treat additional cancer types. Kite also holds an option to negotiate commercialization licenses from the NIH to additional IP related to TCR-based candidates the company is funding under a Cooperative Research and Development Agreement. Kite indicated in its filing that it is negotiating a license with the NIH for IP related to a candidate targeting NY-ESO-1.Kite reported $18.6 million in cash and equivalents and an equivalent accumulated deficit as of March 31, with 5.6 million common shares outstanding on that date. The company plans to list on Nasdaq as KITE. Jefferies, Credit Suisse and Cowen and Co. are joint bookrunners on the deal, which is not yet priced.In other financings news:Chimerix Inc., of Durham, N.C., is offering to sell 6.2 million shares of its common stock in an underwritten public offering. Chimerix will also grant to the underwriters a 30-day option to purchase up to an aggregate of 930,000 additional shares of common stock. Morgan Stanley & Co. LLC and J.P. Morgan Securities LLC are acting as joint book-running managers for the offering, and Cowen and Co. LLC is acting as co-lead manager. //

OTHER NEWS TO NOTE

Pluristem Therapeutics Inc., of Haifa, Israel, said the South Korean Ministry of Food and Drug Safety recently cleared the company’s upgraded manufacturing process in its new facility in Haifa. The cells produced in that facility will be used by Korean sites joining the large phase II study conducted by Pluristem of Placental Expanded, or PLX, cells in intermittent claudication patients. Pluristem is operating in South Korea under an exclusive partnership with CHA Bio & Diostech Co. Ltd., of Seoul, South Korea. Under the terms, CHA will perform and fund multiple clinical trials in South Korea using the PLX cells and, upon the first regulatory approval for a PLX product in South Korea, the two companies will establish a joint venture.Proteo Inc., of Irvine, Calif., said its German subsidiary, Proteo Biotech AG, entered an agreement with Biotech Development Corp. (BDC), of Farmington, Utah. Proteo is developing the orphan medicinal product tiprelestat (Elafin) for prophylactic treatment of acute postoperative inflammatory complications after resection of esophageal cancer in the European Union. In February, Proteo received protocol assistance from the EMA’s Committee for Medicinal Products for Human Use with respect to the strategy for further clinical development and marketing authorization. Under the terms of the agreement, BDC will support the future development, including a pivotal clinical study, by providing Proteo with total funds of €3.5 million (US$4.8 million) in return for a share of future revenues for Elafin in that indication.




Relypsa Inc., of Redwood City, Calif., entered a multiyear commercial manufacturing and supply agreement with DSM Fine Chemicals Austria NFG GMBH & Co. KG, of Linz, Austria, for the active pharmaceutical ingredient in patiromer, the company’s polymer in development for the treatment of hyperkalemia. Terms were not disclosed.Replicel Life Sciences Inc., of Vancouver, British Columbia, said its RCH-01 licensing partner, Shiseido Co. Ltd., of Tokyo, opened its new cell processing facility at the Kobe Biomedical Innovation Cluster in Port Island, Japan. The facility will focus on the continued R&D and commercialization of Replicel’s RCH-01 hair regeneration technology. The two companies inked a collaboration and tech transfer agreement last year, granting Shiseido rights to the technology in Japan, China, South Korea, Taiwan and the ASEAN countries.

OTHER NEWS TO NOTE

IN THE CLINIC

Biospecifics Technologies Corp., of Lynbrook, N.Y., said new analyses of data evaluating the use of Xiaflex (collagenase clostridium histolyticum) in adult men with Peyronie’s disease were presented at the American Urological Association meeting in Orlando, Fla., by partner Auxilium Pharmaceuticals Inc., of Chesterbrook, Pa. Data from the pivotal IMPRESS studies showed that 75 percent of men treated with Xiaflex had clinically meaningful improvements in their penile curvature deformity by the end of the studies. Those subjects also reported an improvement of 25 percent or greater in penile curvature deformity. Xiaflex gained FDA approval in Peyronie’s disease late last year. (See BioWorld Today, Dec. 9, 2013.)Dendreon Corp., of Seattle, presented data at the American Urological Association meeting in Orlando, Fla., from the phase II ProACT and phase III IMPACT studies suggesting that prostate cancer vaccine Provenge (sipuleucel-T) elicits an immune response associated with an overall survival benefit. Data showed evidence that antigen spread may occur after Provenge treatment, indicating that the immune response evolves over time to target multiple prostate antigens. Genprex Inc., of Austin, Texas, said it enrolled the first patient in a phase II trial to test lead candidate Oncoprex in combination with Tarceva (erlotinib, Roche AG and Astellas Pharma Inc.) in late-stage lung cancer patients. The study will evaluate the combination in patients with activating EGFR mutations who have received prior chemotherapy or in patients with the activating EGFR mutation whose cancer has progressed after treatment with Tarceva. About 40 patients will be enrolled. Oncoprex is a targeted biologic incorporating pan-kinase inhibitor TUSC2, which inhibits oncogenic kinases via multiple pathways.Immunomedics Inc., of Morris Plains, N.J., reported stabilization of disease, as measured by computed tomography (CT) according to RECIST criteria, in a phase I/II trial in

pancreatic cancer patients with advanced disease who previously failed one to five therapies. In a group of 13 CT-assessable patients receiving repeated doses of antibody-drug conjugate IMMU-132, a median time to progression of 12.7 weeks was reported (range of 4.3 weeks to 21.4 weeks), compared to the median eight weeks (range of four weeks to 36 weeks) estimated from their last prior therapies. Results were presented at the American Association for Cancer Research Special Conference on Pancreatic Cancer in New Orleans.Immunovaccine Inc., of Halifax, Nova Scotia, reported results from a phase I/Ib study showing early evidence of clinical activity of cancer vaccine candidate DPX-Survivac in ovarian cancer patients, including one patient who experienced a partial response, defined as a shrinking of tumor size by at least 30 percent using RECIST. That response was accompanied by a reduction in levels of commonly used ovarian cancer biomarker CA125 and a significant increase in vaccine-induced immune responses.Insmed Inc., of Monmouth Junction, N.J., reported additional results from the phase II study of Arikayce, or liposomal amikacin for inhalation, for the treatment of patients with treatment-resistant nontuberculous mycobacterial (NTM) lung infections at the American Thoracic Society meeting in San Diego. At the conclusion of the 84-day, double-blind phase of the trial, 78 of 80 patients agreed to receive once-daily Arikayce plus standard of care for an additional 84 days. Data from 68 of those patients from the open-label phase showed that 21 were culture-negative for NTM at day 168. Arikayce has orphan drug, fast-track and qualified infectious disease product designations in the U.S. and orphan status from the EMA. Insmed also has applied for breakthrough therapy designation in the U.S.

NEGOTIATE LUCRATIVE BIOPHARMA LICENSING DEALS

BIOPHARMACEUTICAL ROYALTY RATES ANALYSIS:ESSENTIAL BENCHMARKS FOR DEALMAKING

New data from BioWorld reveal that biotechnology companies are now garnering higher royalty rates from pharmaceutical partners, higher than other biotech partners.

BioWorld Data’s new resource, Biopharmaceutical Royalty Rates Analysis: Essential Benchmarks for Dealmaking, analyzed hundreds of licensing deals. According to the Royalty Rates Analysis, the average royalty rate for deals with a pharma licensee is 14.9% at the high end and 11.7% at the low end.

This critical negotiation and analysis tool contains:

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PHARMA: IN THE CLINIC

Glaxosmithkline plc, of London, presented data at the American Thoracic Society meeting in San Diego, showing that the addition of umeclidinium (UMEC) at either dose to inhaled corticosteroid and long-acting beta2 agonist combination fluticasone proprionate and salmeterol (FSC) resulted in a statistically significant improvement in lung function when compared with placebo plus FSC in patients with chronic obstructive pulmonary disease over 12 weeks. Compared with placebo added to FSC 250/50 mcg, both doses of UMEC (62.5 mcg and 125 mcg) added to FSC 250/50 mcg, demonstrated statistically significant improvements in trough FEV1 at day 85 (both p < 0.001) and 0 to six-hour WM FEV1 at day 84 (both p < 0.001).

REGULATORY FRONT

Colorado Gov. John Hickenlooper on Saturday signed the “Right To Try” bill, which passed unanimously in the Colorado state legislature, allowing terminally ill patients to obtain experimental drugs without getting federal approval. Similar bills are awaiting signatures in Missouri and Louisiana. The SEC charged two California-based doctors this week with insider trading, alleging that they used their knowledge as investigators in a prostate cancer trial sponsored by Gtx Inc. to sell Gtx stock prior to the public announcement that the

IN THE CLINIC

Isis Pharmaceuticals Inc., of Carlsbad, Calif., said it started a phase I study of ISIS-PKKrx, an antisense drug in development to treat patients with hereditary angioedema (HAE). ISIS-PKKrx is designed to target prekallikrein, a protein produced in the liver that plays a role in the activation of inflammatory mediators associated with acute attacks of HAE.Novabay Pharmaceuticals Inc., of Emeryville, Calif., said results from a phase II trial presented at the American Urological Association meeting in Orlando, Fla., showed significant benefits from a new catheter irrigation solution. In the trial, nine of 14 catheters collected from patients that irrigated twice a week with saline solution, the only current treatment option, became completely encrusted. In contrast, none of those treated with an irrigation solution containing antimicrobial candidate auriclosene became significantly encrusted.

FDA had halted the study due to safety concerns. After Gtx disclosed the trial’s termination, the Memphis, Tenn.-based biotech’s stock dropped more than 36 percent. The SEC alleges that Franklin M. Chu and Daniel J. Lama, who practice at the San Bernardino Urological Associates Medical Group in San Bernardino, Calif., made more than $45,000 in illicit profits. The two doctors have agreed to settle the SEC’s charges by paying a combined total of $116,864.

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