BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) has concluded it can successfully make the case to gain approval for drisapersen to treat Duchenne muscular dystrophy after it acquires Prosensa Holding N.V. (NASDAQ:RNA) for $680 million in cash up front and up to $160 million in milestones.
GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) returned rights to drisapersen to Prosensa in January, ending a 2009 licensing deal, after the compound missed the primary endpoint of improving 6-minute walk distance (6MWD) from baseline to week 48 vs. placebo (see BioCentury, Sept. 30, 2013).
Seeing the data differently, BioMarin on Monday said it will pay $17.75 per share for Prosensa, which is eligible for up to two $80 million milestones if drisapersen is approved to treat DMD, the first for FDA approval by May 15, 2016 and the second for EMA authorization by Feb. 15, 2017. In a conference call on Monday, BioMarin executives said the dates were negotiated to reward Prosensa if drisapersen is approved on first pass in the U.S. and EU, which would make the deal accretive to BioMarin's GAAP earnings in 2017.
Prosensa has expected to complete its rolling submission of the drisapersen NDA to FDA by 1Q15 and to start two confirmatory studies to support accelerated approval in 1H15. The timeline also calls for an MAA submission to EMA in 2015.
The antisense oligoribonucleotide that induces exon 51 skipping on the dystrophin gene has Fast Track, Orphan Drug and breakthrough therapy designation in the U.S. and Orphan Drug status in the EU, Australia and Japan.
BioMarin also will purchase a $50 million convertible note from the Dutch company that will convert into 4.4 million Prosensa shares if the deal is not completed.
BioMarin CFO Daniel Spiegelman said the company can complete the deal with cash on hand, which was $1.1 billion at Sept. 30, but it expects to raise money to replenish its reserves. Prosensa had about $78.6 million in cash at Sept. 30.
On the conference call, BioMarin CMO Henry Fuchs said the company believes the case for approval is supported by efficacy data from existing trials, including a Phase II study. In particular, BioMarin noted the Phase III broaded the enrollment criteria to include older patients, and that duration of treatment affected the outcome.
Spiegelman anticipates FDA will ask an advisory committee to review drisapersen.
BioMarin expects its tender offer for Prosensa shares to close in 1Q15. The Dutch biotech's shares jumped over the upfront price on Monday, gaining $7.16 (63%) to $18.60. BioMarin was up $2.11 to $87.94.
Bristol-Myers Squibb Co. (NYSE:BMY) and Five Prime Therapeutics Inc. (NASDAQ:FPRX) will jointly evaluate a combination of BMS's Opdivo nivolumab and Five Prime's FPA008 in a Phase Ia/Ib study to treat non-small cell lung cancer (NSCLC), melanoma, head and neck cancer, pancreatic cancer, colorectal cancer and malignant glioma. Opdivo is a human IgG4 mAb against programmed cell death 1 (PDCD1; PD-1; CD279). FPA008 is a humanized mAb that inhibits colony-stimulating factor 1 receptor (CSF1R; C-FMS; CD115).
BMS will pay Five Prime $30 million up front and pay for the study, which Five Prime expects to begin by 2H15. The deal gives each partner an exclusive opt-in right if the other proposes to study combinations of PD-1 or programmed cell death 1 ligand 1 (PD-L1) (B7-H1) (CD274) antagonists with anti-CSF1R antagonists in additional tumor types. If Five Prime seeks a partner for FPA008, BMS has a right of first refusal for three months.
Opdivo has Fast Track designation from FDA to treat NSCLC, melanoma and renal cell carcinoma (RCC). It has a March 30, 2015, PDUFA date for previously treated advanced melanoma, for which it has breakthrough designation.
Under an expanded deal, BMS has worldwide rights to Opdivo from Ono Pharmaceutical Co. Ltd. (Tokyo:4528), excluding Japan, Korea and Taiwan, where Ono and BMS are partnered for the product. Japan approved Opdivo for unresectable melanoma in July.
Five Prime shares rose $4.95 (31%) to $20.70 on Monday.
The Janssen unit of Johnson & Johnson (NYSE:JNJ) and Transposagen Biopharmaceuticals Inc. (Lexington, Ky.) have started a three-year research collaboration to develop allogeneic CAR T therapies using Transposagen's piggyBac Footprint-Free Gene Editing System. Unlike autologous chimeric antigen receptor T cell therapies, allogenic CAR T therapies have the potential to be used off-the-shelf.
Janssen will pay upfront and milestone fees of $292 million, plus tiered royalties, for exclusive rights to each CAR T therapy developed under the collaboration. Janssen also obtained a non-exclusive license to use Transposagen's gene editing technologies, while Transposagen retained rights to develop CAR T therapies using Natural Killer or NK-like cells.
Janssen's Barry Springer, VP, Strategy & External Innovation, Biotechnology Center of Excellence, would not disclose additional financial details or the indications upon which the partners intend to focus, but noted that CAR T therapies "have shown promise in hematologic cancers."
Pfizer Inc. (NYSE:PFE) made a similar move in June when it partnered with Cellectis S.A. (Euronext:ALCLS) to develop and commercialize allogenic CAR T therapies for several oncology targets (see BioCentury, July 14).
FDA granted breakthrough therapy designation to JCAR015 from Juno Therapeutics Inc. (Seattle, Wash.) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia. Juno partner Memorial Sloan Kettering Cancer Center (MSKCC) filed for the designation.
JCAR015 comprises autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. Juno, which filed this month to raise $150 million in an IPO, aims to start a Phase II trial of the product in mid-2015 in ALL.
In an ongoing Phase I trial, results through July 1 showed that JCAR015 treatment led to a 91% complete remission rate among 22 evaluable patients. MSKCC briefly halted the study of JCAR015 in a variety of settings in March to review two treatment-related deaths before resuming all five trials a month later under a protocol revised with FDA (see BioCentury, April 21).
H. Lundbeck A/S (CSE:LUN) CEO Ulf Wiinberg resigned after failing to disclose that he received 55 shares of Stratified Medical Ltd. (London, U.K.) from the company's founder in 2013. Lundbeck later invested DKK19 million ($3.2 million) in the company.
"Ulf Wiinberg has not only acknowledged but also apologized for his erroneous actions, but this does not change the fact that Lundbeck has a clear and unmistakable Code of Conduct for all employees," Lundbeck Chairman Hakan Bjorklund said in a statement.
Wiinberg will receive a severance package of up to DKK19 million ($3.2 million) over 18 months.
Bjorklund will serve as interim CEO.
Merck & Co. Inc. (NYSE:MRK) has paid $30 up front for exclusive worldwide rights to develop and commercialize the Ebola vaccine VSV-EBOV from NewLink Genetics Corp. (NASDAQ:NLNK). The biotech also will receive $20 million upon the start of an efficacy trial, expected in 1Q15, and is eligible for tiered royalties. Merck will also have exclusive rights to any follow-on products.
The recombinant vesicular stomatitis virus (rVSV) vaccine expressing an Ebola virus protein is in Phase I testing at the Walter Reed Army Institute of Research. VSV-EBOV was originally developed by the Public Health Agency of Canada, which has retained non-commercial rights (see BioCentury Extra, Oct. 13).
NewLink shares fell $0.89 to $34.44 on Monday.
The Janssen Research & Development unit of Johnson & Johnson (NYSE:JNJ) submitted an NDA for Yondelis trabectedin to treat patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy.
The submission comes more than three years after the pharma withdrew an NDA for Yondelis to treat relapsed ovarian cancer after FDA recommended an additional Phase III trial (see BioCentury Extra, Oct. 13). The drug already is approved in Europe as monotherapy to treat advanced or metastatic STS and in combination with Caelyx pegylated liposomal doxorubicin for relapsed platinum-sensitive ovarian cancer.
The cytotoxic alkaloid binds to the minor groove of DNA. The product has Orphan Drug status in the EU and Orphan Drug designation in the U.S. for ovarian cancer and STS.
Janssen is also opening its expanded access program to offer Yondelis to eligible U.S. patients with liposarcoma and leiomyosarcoma.
The pharma has rights outside of Europe and Japan from PharmaMar, a subsidiary of Zeltia S.A. (Madrid:ZEL).
Amgen Inc. (NASDAQ:AMGN) terminated all company-sponsored clinical trials of rilotumumab to treat advanced gastric cancer after an independent data monitoring committee found an increase in deaths among patients treated with rilotumumab plus chemotherapy vs. those receiving chemotherapy alone in a Phase III trial.
Rilotumumab is a human mAb against human hepatocyte growth factor/scatter factor (HGF/SF). It was one of five compounds put into the Amgen Astellas BioPharma K.K. joint venture created last year in Japan with Astellas Pharma Inc.(Tokyo:4503), and underwent a Phase I trial in Japan (see BioCentury, June 17, 2013).
Amgen said results of the Phase III RILOMET-1 study will be submitted for presentation and publication.
Aveo Pharmaceuticals Inc. (NASDAQ:AVEO) is developing ficlatuzumab (AV-299), a human IgG1 mAb antagonist of HGF/SF ligand, in a different indication. The biotech plans to conduct a Phase II study of the compound in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients stratified using a biomarker identifed with the VeriStrat test from Biodesix inc. (Broomfield, Colo.) (see BioCentury, April 14).
Ficlatuzumab missed the primary endpoints in a Phase II trial in 2012 (see BioCentury Extra, May 2, 2012).
Amgen gained $1.37 to $164.18 on Monday, while Aveo was flat at $0.91. The Tokyo stock exchange was closed.
Polaris Partners closed its oversubscribed seventh fund with $450 million, with about half to be invested in healthcare and the balance in technology. The firm typically invests $10-$20 million per company and plans to invest the new Polaris Partners VII in about 35-40 companies. Spokesperson Emily Mendell said Polaris already has made a few commitments from the fund, but declined to disclose details.
Since 2013, 10 Polaris healthcare portfolio companies have gone public, including cancer and drug delivery company Bind Therapeutics Inc. (NASDAQ:BIND), Orphan disease play Acceleron Pharma Inc. (NASDAQ:XLRN) and Receptos Inc. (NASDAQ:RCPT), which has a compound in Phase II/III for multiple sclerosis and Phase II for ulcerative colitis.
Polaris' active life science portfolio includes genome editing company Editas Medicine (Cambridge, Mass.) and Syros Pharmaceuticals Inc. (Watertown, Mass.), which is creating maps of a class of regulatory DNA regions called super-enhancers - master switches responsible for maintaining cell identity - to identify novel targets. Syros raised $53 million in a series B round last month (see BioCentury, Nov. 3).
Polaris closed its sixth fund in 2011 at $375 million. Including the seventh fund, the firm has almost $4 billion under management.
In the wake of two deals to acquire HBV assets, OnCore Biopharma Inc. (Doylestown, Pa.) on Monday said it had submitted draft registration materials to SEC for a proposed IPO.
OnCore was founded in 2012 by former Pharmasset Inc. executives, including one credited with inventing HCV blockbuster Sovaldi sofosbuvir before the biotech was acquired by Gilead Sciences Inc. (NASDAQ:GILD). The company has said it intends to create the first oral HBV cure and plans to bring multiple combination therapies to clinic next year (see BioCentury Extra, Oct. 1).
Last month, OnCore acquired infectious disease company Enantigen Therapeutics Inc. and gained two HBV programs, an s-antigen secretion inhibitor and a capsid assembly inhibitor. In September, OnCore licensed the sangamide-based cyclophilin inhibitor NVP018 to treat HBV from NeuroVive Pharmaceutical AB (SSE: NVP).
OnCore said the date of the IPO, number of shares, and price have not been determined. CEO Patrick Higgins did not respond to inquiries for more details. In August, the company anounced a venture round of undisclosed size.
The Sinopharm Group Co. Ltd. (Hong Kong:01099) subsidiary of China National Pharmaceutical Group Corp. (Sinopharm) said it will raise HK$5.6 billion ($727.8 million) through the sale of 198.8 million shares at HK$28.40 in a follow-on. The price represents a 7.5% discount to the healthcare conglomerate's Nov. 21 closing price of HK$30.70. CICC; Morgan Stanley; and UBS are placement agents.
The proceeds will be used to expand the company's pharmaceutical distribution and retail network.
Sinopharm dipped HK$1.85 to HK$28.85 on Monday.
Lexicon Pharmaceuticals Inc. (NASDAQ:LXRX) raised $150 million from an affiliate of Invus by selling shares in a private placement at $1.005 per share. The deal was disclosed in an SEC filing that also described the biotech's $50 million follow-on offering and raising of $80 million in senior notes (see BioCentury, Nov. 3).
Invus now holds 60.6% of the company's outstanding shares. Three of the firm's partners hold seats on Lexicon's nine-member board, and Invus has the right to designate a number equal to its ownership percentage, rounded up. On Monday, Invus declined to discuss whether it would designate more directors or say how much it has invested in Lexicon to date.
Lexicon added $0.04 to $0.99 on Monday, after losing $0.05 on Friday after the fundraising arrangements were announced. The company is collecting $23 million up front in last month's deal giving Ipsen Group (Euronext:IPN;Pink:IPSEY) an exclusive license to commercialize telotristat etiprate outside of North America and Japan.
Lexicon, which also is eligible for up to $122 million in milestones, plus royalties, expects top-line data in 3Q15 from Phase III trial of the tryptophan hydroxylase inhibitor in carcinoid syndrome.
The Vyrix Pharmaceutical Inc. subsidiary of Ampio Pharmaceuticals Inc. (NYSE-M:AMPE) withdrew its proposed IPO on NYSE MKT, citing market conditions. In April, Vyrix filed to raise up to $28.8 million. Aegis Capital and Fordham were underwriters.
In December 2013, Ampio carved out its sexual dysfunction business into Vyrix. The subsidiary's lead product is Zertane tramadol, an oral fast-dissolving tablet formulation of tramadol hydrochloride in development to treat premature ejaculation.
In its prospectus, Vyrix said it planned to submit an IND in 2H14 for Zertane and begin two U.S. Phase III trials soon afterward. On Monday, the company did not reply to inquiries about whether it still planned to submit an IND this half.
Ampio was up $0.11 to $3.52 on Monday.
House Reps. Gus Bilirakis (R-Fla.) and G.K. Butterfield (D-N.C.) introduced a bill intended to spur companies with approved drugs to repurpose them to treat rare diseases. H.R. 5750, the Orphan Product Extensions Now Accelerating Cures and Treatments Act of 2014 (OPEN Act), would offer companies an additional six months of market exclusivity for adding a rare disease indication to the label of an approved drug. The bill was referred to the Committee on Energy & Commerce.
Julia Jenkins, executive director of the EveryLife Foundation for Rare Diseases, told BioCentury the extra six months of exclusivity would offer an economic incentive that could offset "perceived risks" associated with testing an approved drug in a "very sick population." She said companies fear that a serious adverse event might hurt the drug's larger market.
Jenkins added that label expansions are typically cheaper than developing new drugs since clinical safety analyses have already been completed.
"Drug companies already try to repurpose drugs," she said. "They're just not necessarily looking at rare diseases. This would be give them a reason to."
FDA's Anti-Infective Drugs Advisory Committee (AIDAC) is being asked to weigh in on the feasibility of clinical trial designs to streamline the development of antibacterial drugs in the face of "more commonplace bacterial resistance."
In briefing materials released ahead of the Dec. 4 meeting, the agency said it will ask AIDAC to discuss whether smaller than usual clinical studies would be acceptable in a streamlined development program despite increased uncertainty concerning safety and efficacy. The panel also will consider trials at single body sites with larger than usual non-inferiority margins, as well as superiority trials that pool data from multiple infection sites.
AIDAC will discuss whether smaller safety databases of 300-400 patients are acceptable, and trial design options for narrow-spectrum antibacterials where use is limited to one or two microorganisms.