Royalty Pharma (New York, N.Y.) raised its offer to acquire Elan Corp. plc (NYSE:ELN) on Monday shortly after Elan announced a flurry of proposed moves, including two proposed acquisitions, a spinout, a share buyback and an $800 million note deal. Royalty increased its bid to $12.50 per share from $11.25, valuing Elan at $6.4 billion. The bid is contingent on Elan shareholders rejecting Monday's deals, as well as this month's proposed deal to pay Theravance Inc. (NASDAQ:THRX) $1 billion in cash in exchange for a 21% interest in the royalties Theravance is eligible to receive from partner GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) for four respiratory programs (see BioCentury, May 20).
Elan plans to raise the $800 million through the sale of senior notes due 2021, and said it will repurchase $200 million in shares under a new buyback program. Elan also proposing to buy rare disease company AOP Orphan Pharmaceuticals AG (Vienna, Austria) and acquire a 48% stake in NewBridge Pharmaceuticals Ltd. (Dubai, UAE). It also plans to spin out ELND005 into a newco (see below). Elan expects to have about $1.2 billion in pro forma cash following the deals, all of which are subject to shareholder approval at a June 17 extraordinary general meeting.
Elan was up $0.37 to $12.04 on Monday. Theravance was off $2.58 to $37.01.
Elan Corp. plc (NYSE:ELN) announced two proposed acquisitions on Monday, including a proposal to buy rare disease company AOP Orphan Pharmaceuticals AG (Vienna, Austria) for EUR 175.7 million ($225.5 million) in cash and EUR 87.8 million ($112.7 million) in Elan shares, plus up to EUR 270 million ($346.5 million) in milestones. AOP had 2012 revenues of about EUR 59 million ($75.7 million), according to Elan. The company also said it will pay $40 million to acquire a 48% stake in NewBridge Pharmaceuticals Ltd. (Dubai, UAE), which in-licenses products approved in the U.S., Europe and Japan to commercialize in the Middle East, Africa, Turkey and Caspian regions. Elan will have an option to acquire the remaining stake in NewBridge for $244 million by 2015.
Additionally Elan said it will spin out ELND005 -- which is in Phase II testing to treat agitation and aggression in patients with Alzheimer's disease (AD) and for the maintenance treatment of bipolar I disorder -- into newco Speranza Therapeutics Ltd. Elan will provide $70 million in funding, plus up to an additional $8 million. Elan CMO Menghis Bairu will be CEO of Speranza. Elan is developing ELND005, a small molecule that disaggregates beta amyloid fibrils, with Transition Therapeutics Inc. (TSX:TTH; NASDAQ:TTHI) under an amended 2006 deal.
The proposed deals came alongside plans for an $800 million note deal and a $200 million share buyback, as well as an increased bid from Royalty Pharma (New York, N.Y.) to acquire Elan (see above).
On Monday, Elan was up $0.37 to $12.04.
Generics company Actavis Inc. (NYSE:ACT) will acquire specialty pharma Warner Chilcott plc (NASDAQ:WCRX) in a stock deal that values Warner Chilcott at about $5 billion. Warner Chilcott shareholders will receive 0.16 Actavis shares per Warner Chilcott share held or about $17.09 per share based on Actavis' close of $106.81 on May 9, before the companies announced they were in negotiations to merge. Actavis will also assume about $3.4 billion of Warner Chilcott's net debt (see BioCentury Extra, May 10).
The deal, which has been approved by the boards of both companies and is subject to shareholder approval, is slated to close by year end. Warner Chilcott shareholders will own about 23% of the new company, which will be named Actavis plc and be incorporated in Ireland. BofA Merrill Lynch and Greenhill are advising Actavis; Deutsche Bank is advising Warner Chilcott.
Actavis reported $5.9 billion in 2012 revenues, and Warner Chilcott reported $2.5 billion. On Monday, Actavis was up $1.65 to $127.15. Warner Chilcott was up $0.39 to $19.60 on the day.
FDA reviewers said insomnia candidate suvorexant from Merck & Co. Inc. (NYSE:MRK) is effective at promoting sleep, but questioned the product's safety profile as well as the pharma's proposed dosing levels. In briefing documents released ahead of Wednesday's Pulmonary-Allergy Drugs Advisory Committee meeting to discuss an NDA for the dual orexin receptor antagonist, the reviewers said suvorexant doses that are lower than those proposed by Merck may offer similar efficacy and better safety. The reviewers noted that fewer patients received the lower doses in clinical trials.
The reviewers also outlined their suvorexant safety concerns, including daytime somnolence, narcolepsy-like syndrome and suicidal ideation. The lowest dose of suvorexant for which Merck is seeking approval is 15 mg, but the reviewers note that, "if a dosage strength lower than 15 mg is unavailable, we would need to consider if the drug could be marketed safely at all, if we believe that a substantial proportion of the indicated population needs a lower dose." FDA is asking the committee to discuss whether a 10 mg dose would be an "appropriate recommendation as a starting dose." The questions also note that FDA believes the 15 mg dose "results in excessive suvorexant exposure" in some populations, including obese women and patients taking metabolic inhibitors.
Merck has not disclosed the PDUFA date for suvorexant; a standard review would put the PDUFA date in September.
Effector Therapeutics Inc. (San Diego, Calif.) raised $45 million in a tranched series A round co-led by U.S. Venture Partners; Abingworth; Novartis Venture Funds; and SR One. Astellas Venture Management; Osage University Partners; and Mission Bay Capital also participated. Effector, which declined to disclose details of the tranches, plans to develop small molecules to selectively regulate translation of oncogenes for cancer indications.
Abingworth's Ken Haas, Novartis Venture Funds' Markus Goebel and SR One's Simeon George joined Effector's board. The newco also appointed Carol Gallagher as chairman. Gallagher was CEO of Calistoga Pharmaceuticals Inc., which Gilead Sciences Inc. (NASDAQ:GILD) acquired in 2011.
Cancer company Karyopharm Therapeutics Inc. (Natick, Mass.) raised $48.2 million in a series B round led by an undisclosed private investor. New investor Delphi Ventures and additional undisclosed investors participated. Delphi Ventures' Deepa Pakianathan will join Karyopharm's board.
Karyopharm's KPT-330 is in Phase I testing to treat advanced hematologic malignancies and solid tumors, with data slated to be presented at the American Society of Clinical Oncology meeting later this month. The company plans to start pivotal trials of the oral selective inhibitor of nuclear export (SINE) protein exportin 1 (XPO1;CRM1) in at least two indications in 1H14.
Ironwood Pharmaceuticals Inc. (NASDAQ:IRWD) and NPS Pharmaceuticals Inc. (NASDAQ:NPSP) both announced plans late Monday to raise money in follow-ons. Ironwood proposed to sell 10.5 million shares in a follow-on underwritten by JPMorgan; BofA Merrill Lynch; and Morgan Stanley. If sold at Ironwood's close on Monday of $13.83, the company would raise $145.2 million. Ironwood and partner Forest Laboratories Inc. (NYSE:FRX) launched Linzess linaclotide in the U.S. in December to treat irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). The European Commission approved the guanylate cyclase C (GCC; GUCY2C) agonist for IBS-C in November.
NPS plans to sell 6 million shares in a follow-on underwritten by JPMorgan and Morgan Stanley. If sold at NPS's Monday close of $14.11, the company would raise $84.7 million. NPS markets Gattex teduglutide in the U.S. to treat short bowel syndrome. Earlier this month, the company reported $654,000 in the first quarter sales of the analog of glucagon-like peptide-2 (GLP-2), which NPS launched in February (see BioCentury, March 25).
Ironwood was off $0.56 on Monday, while NPS was off $0.17.
Diagnostics company NanoString Technologies Inc. (Seattle, Wash.) filed to raise up to $86.3 million in an IPO underwritten by JPMorgan; Morgan Stanley; Leerink; and Baird. Earlier this year, NanoString launched its Prosigna Breast Cancer Prognostic Gene Signature Assay in the EU and Israel to subtype breast cancer tumor and estimate the probability of cancer recurrence in postmenopausal women. The intrinsic subtying assay runs on NanoString's marketed nCounter Analysis System, an automated system for digital gene expression analysis, and uses the PAM50 gene signature, to which NanoString has exclusive, worldwide rights from Bioclassifier LLC (St. Louis, Mo.).
Athyrium Capital Management and partner Neuberger Berman closed a life sciences private credit fund, Athyrium Opportunities Fund L.P., at $507 million, well above the original target of $350 million. The fund, which the partners formed in 2011, makes structured investments -- including loans, royalties or royalty-backed investments and debt -- in the healthcare and life science sectors, with a focus on public and private companies with approved products, royalty income or direct product sales. The fund will commit $25-$75 million in financings in small- to medium-sized companies including pharmaceutical, medical device and diagnostic companies in the U.S., Europe and Asia. The fund has already made five investments representing 20% of the committed capital.
Pfizer Inc. (NYSE:PFE) said it discontinued the Phase III B1931008 trial evaluating inotuzumab ozogamicin to treat relapsed or refractory CD22-positive aggressive non-Hodgkin's lymphoma. The move came after an interim analysis by an independent DMC showed once-monthly inotuzumab ozogamicin plus rituximab would not meet the primary endpoint of improving overall survival (OS) vs. investigator's choice of rituximab plus either bendamustine or gemcitabine. The open-label trial was slated to enroll about 377 patients who are not candidates for intensive high-dose chemotherapy.
Pfizer said it will review the data to determine if there are subsets of patients that benefited from treatment with inotuzumab ozogamicin, a humanized mAb against CD22 linked to the calicheamicin cytotoxin. The pharma said it will also continue to evaluate the product in the Phase III INO-VATE ALL (B1931022) trial to treat adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL). Pfizer, which announced the news late Monday, is co-developing inotuzumab ozogamicin with UCB Group (Euronext:UCB), which was up EUR 0.11 to EUR 44.56 on the day.
Biogen Idec Inc. (NASDAQ:BIIB) and Genentech Inc., a unit of Roche (SIX:ROG; OTCQX:RHHBY), co-market rituximab as Rituxan in the U.S., while Roche markets it as MabThera elsewhere. Cephalon Inc., which Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA) acquired in 2011, markets bendamustine as Treanda.
XenoPort Inc. (NASDAQ:XNPT) fell $1.03 (15%) to $5.72 on Monday after discontinuing development of arbaclofen placarbil based on top-line data showing that twice-daily doses of the product missed the co-primary endpoints in a Phase III trial to treat spasticity in multiple sclerosis (MS) patients. XenoPort had an SPA from FDA for the trial, which enrolled 228 patients. In 2011, XenoPort discontinued development of arbaclofen placarbil -- a transported prodrug of R-baclofen, a GABA B receptor agonist -- to treat gastroesophageal reflux disease (GERD) (see BioCentury, May 23, 2011).
XenoPort markets Horizant gabapentin enacarbil, a transported prodrug of gabapentin, to treat restless legs syndrome (RLS) and to manage postherpetic neuralgia (PHN). The company's next most advanced product is XP21279, a sustained-release transported prodrug of L-dopa in Phase II testing to treat Parkinson's disease (PD).
Aduro BioTech Inc. (Berkeley, Calif.) stopped early a Phase II trial evaluating CRS-207 plus GVAX Pancreas cancer vaccine and cyclophosphamide to treat pancreatic cancer after the combination met the primary endpoint of improving overall survival (OS) vs. GVAX Pancreas and cyclophosphamide alone (6 vs. 3.4 months, p=0.0114). The open-label, U.S. trial enrolled 90 patients with metastatic pancreatic ductal adenocarcinoma (PDA) who received or refused one or more prior chemotherapy regimen. Data are slated to be presented at the American Society of Clinical Oncology meeting in June. Aduro declined to disclose next steps for CRS-207, a live attenuated strain of Listeria monocytogenes that expresses human mesothelin.
Earlier this year, Aduro acquired all assets related to GVAX cancer vaccines from BioSante Pharmaceuticals Inc. (NASDAQ:BPAX). Aduro already had rights to GVAX vaccines to treat pancreatic and prostate cancer. GVAX Pancreas, which has completed a Phase II trial to treat operable pancreatic cancer, is an allogeneic cancer vaccine engineered to secrete GM-CSF.
H. Lundbeck A/S (CSE:LUN) and partner Takeda Pharmaceutical Co. Ltd. (Tokyo:4502) presented additional data on Monday showing that some doses of Brintellix vortioxetine significantly improved depression rating scores while other doses did not in four Phase III trials for the acute treatment of major depressive disorder (MDD). An NDA for the serotonin modulator and stimulator is under FDA review to treat MDD, with an Oct. 2 PDUFA date. An MAA for the product is also under review for the indication in Europe. Lundbeck said both the NDA and MAA include a 5-20 mg Brintellix dose range. Data from all of the trials are included in the applications.
In Study 315, once-daily 20 mg Brintellix met the primary endpoint of reducing Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline to week eight vs. placebo (p=0.023), while a once-daily 15 mg dose missed the endpoint (p-value not disclosed). In Study 13267A, once-daily 15 and 20 mg doses of Brintellix each met the primary endpoint (p<0.0001 for both), while in Study 316 once-daily 20 mg Brintellix met (p=0.002) but once-daily 10 mg missed the primary endpoint (p=0.58). In Study 317, once-daily 10 and 15 mg doses of Brintellix each missed the primary endpoint (p-values not disclosed). The double-blind trials enrolled 2,141 patients aged 18-75. Data from all the trials were presented at the American Psychiatric Association meeting in San Francisco.
Lundbeck partnered with Takeda to co-develop and co-commercialize Brintellix in the U.S. and Japan in 2007. On Monday, Lundbeck was unchanged at DKK115.80.
FDA will hold a public meeting on June 14 to discuss HIV, including the impact of HIV on daily life and experience with currently available therapies, as well as patient views on issues related to HIV cure research, including perceived benefits and acceptable risk. The meeting is the second under FDA's Patient-Focused Drug Development initiative, under which the agency is holding public meetings on a range of disease areas to discuss topics including the impact of the disease, the measures of benefit that matter most to patients and the adequacy of existing treatment options.
Last month, FDA released a list of 16 disease areas for which it will hold the first round of public meetings in FY13-15 (see BioCentury, May 6).
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