Friday, September 06, 2013

Deals Of The Week: Hunting For Dengue Fever Drugs Amid Climate Change

                                      Aedes aegypti busily transmitting virus

Dengue fever is on the move. This mosquito-borne viral disease is invading new parts of the world, helped by climate change, urbanization and increased travel. Europe last autumn had its first big outbreak since 1920 on the Portuguese island of Madeira, while in Florida, where Dengue fever was largely eradicated in the 1930s, around 10 cases were reported in August.

With no approved vaccines on the market to fight the virus, this DOTW reporter was heartened to learn that Johnson & Johnson’s Janssen Inc. is joining the hunt for drugs to treat the world's fastest-spreading tropical disease by linking with academic researchers in Belgium and Britain’s Wellcome Trust medical charity.

The tie-up between Janssen and researchers at the University of Leuven, who have received backing from Wellcome, will build on the discovery of a series of chemical compounds that are highly potent in preventing the replication of dengue virus. The compounds, which have yet to be tested in clinical trials, are active against all four types of the virus and have been shown to work in animal tests. Janssen will have the option of an exclusive, worldwide license to progress and commercialize compounds developed through the research program. Financial terms were not disclosed but Janssen will make upfront, milestone and royalty payments to the University of Leuven.

The collaboration, although long-term, reflects confidence in the feasibility of making an effective medicine against Dengue fever, which is sometimes known as tropical flu. Dengue fever is spread by the Aedes aegypti mosquito, which is now found in 150 countries. To put concerns in context: malaria causes more deaths, but it is on the decline and affects fewer than 100 countries, according to the World Health Organization (WHO). Dengue fever, on the other hand, affected only a handful of areas in the 1950s, but is now officially present in more than 125 countries, exposing half the world's population to the disease. The danger is greatest in the developing world, but the disease is also prevalent in the southern U.S. and parts of southern Europe. Aedes mosquitoes are now present in 18 European countries, often arriving via the importation of bamboo and second-hand tires.

No treatment exists for Dengue fever and vaccines are still in the research stage. Hopes for an effective dengue vaccine were set asunder in 2012, when an experimental tetravalent dengue vaccine from Sanofi Pasteur proved less effective than hoped in a mid-stage clinical trial in Thailand, producing only 30% efficacy. More successful, we hope, will be the latest crop of deals of the week, including: - Sten Stovall

Sanofi/Pozen: Sanofi Pasteur’s parent Sanofi has signed a license agreement with Pozen Inc. on the commercialization of Pozen's new-and-improved aspirin therapies, being developed to reduce gastric ulcers in cardiovascular patients. The deal, which could generate more than $35 million for the U.S.-based company, gives Sanofi exclusive U.S. rights to commercialize all of Pozen's combination drugs containing the proton pump inhibitor immediate-release omeprazole and 325 mg or less of enteric-coated aspirin. This refers currently to Pozen's PA8140 and PA32540 tablets.

PA32540/PA8140 layers 40 mg immediate-release omeprazole (Prilosec) around aspirin to provide the cardiac benefits of once-daily aspirin therapy while reducing the risk of aspirin-induced gastric ulcers. PA32540 contains 325 mg aspirin while PA8140 contains 81 mg aspirin.

The Chapel, Hill N.C.-based company has built a business around developing fixed-dose combination drugs, which are sold through its partners GlaxoSmithKline PLC and AstraZeneca PLC. Prozen previously said it planned to go it alone on PA32540 after frustrating relationships with its big pharma partners and disappointing sales of its migraine treatment Treximet (sumatriptan/naproxen) and pain reliever Vimovo (naproxen/esomeprazole). Its latest deal will see Sanofi pay Pozen $15 million up front, with Pozen eligible to receive pre-commercial milestone payments of $20 million and additional payments upon achievement of certain sales milestones. Pozen will also get double-digit tiered royalties on sales of licensed products by Sanofi and its affiliates in the U.S. Sanofi will have responsibility for all sales, marketing, ongoing manufacturing and future development for the licensed PA products in the U.S. Pozen will keep responsibility for obtaining approval of the NDA, after which Pozen will transfer the application to Sanofi. The application was submitted on March 27 and accepted for filing in May by FDA. - S.S.

Otsuka/Astex: While the California biotech wouldn’t reveal how long it’s been on the block, Astex Pharmaceuticals Inc. said it found its highest bidder in Japan’s Otsuka Pharmaceutical Co. Ltd.  The deal, revealed Sept. 4 by a Japanese news organization, has Otsuka paying $8.50 per share for all outstanding shares of Astex, a 48% premium to the company’s 30-day moving average, and above its close of $6.68 on Sept. 3, the day prior to the deal announcement. Otsuka is expected to issue a tender offer within 10 days that will remain open 20 days. The transaction has been approved by the boards of both companies. The deal is expected to close in the fourth quarter.

Otsuka, which is trying to shore up its top-line from the bloodshed it expects when its blockbuster schizophrenia drug Abilify (aripiprazole) goes off patent in 2015, will benefit from the royalties that Astex brings in on its already-marketed leukemia drug Dacogen (decitabine), which another Japanese drugmaker - Eisai Inc. - has worldwide exclusive rights to commercialize. With Eisai required to pay 20% royalties on sales, escalating to a maximum of 30%, Dacogen accounts for about $60 million to $70 million in royalty revenues for Astex annually. Astex also has a fragment-based discovery platform dubbed Pyramid that turns out small-molecule drug candidates with a variety of mechanisms of action, amplifying the effects of existing drugs or resensitizing cancers to their effects - Lisa LaMotta

Ultragenyx/Kyowa Hakko Kirin: Rare disease company Ultragenyx Pharmaceutical Inc. has partnered with Kyowa Hakko Kirin Co. Ltd. to develop and commercialize a treatment for X-linked hypophosphatemia (XLH). This is the first pharma partnership for the high-profile biotech, which raised a $75 million Series B round in late 2012 that included several crossover investors.

At that time, it planned an IPO for the first half of 2014.. The pair will collaborate to develop the candidate, KRN23, for the U.S., Canada and EU with Ultragenyx leading development in the XLH indication and the pair sharing marketing and profits in the U.S. and Canada. KHK will be responsible for the commercialization of KRN23 in the EU. Ultragenyx plans to develop and commercialize KRN23 in Mexico, Central and South America. Financial details of the deal were not disclosed. KRN23 is in a Phase I/II trial in adults with XLH; the partners plan to initiate a pediatric XLH trial in 2014. XLH is a metabolic bone disorder caused by excessive loss of phosphate in the urine leading to severe hypophosphatemia. The resulting inadequate bone mineralization leads to various abnormalities. These patients have low serum phosphate levels due to high levels of FGF23, a hormone that represses the reabsorption of phosphate from the urine. KRN23 is intended to bind to and render FGF23 inactive, leading to an increase in kidney tubular absorption of phosphate and increased serum phosphate levels. This would be the first disease-modifying treatment for XLH, according to the company. The current treatment for XLH is oral phosphate and vitamin D (calcitriol) therapy; patients must be closely monitored and are at risk for various complications. - Stacy Lawrence

Baxter/Coherus: Pfizer Inc. and Amgen Inc.’s blockbuster Enbrel (etanercept) may have won extended patent coverage in the U.S., but at least two biosimilars that could challenge the drug in certain territories are under development. The latest will come from a Sept. 3 partnership between Baxter International Inc. and Redwood City, Calif.-based biosimilar specialist Coherus BioSciences Inc., which will collaborate on development of an etanercept alternative in Europe, Canada, Brazil, and other unspecified locales.  Baxter will pay Coherus $30 million up front, plus up to $216 million in additional payments contingent on clinical development and regulatory milestones, according to the deal terms. It’s not yet clear whether they’ll pursue approval in Enbrel’s largest indication, rheumatoid arthritis, or whether the companies will aim for psoriasis, psoriatic arthritis, ankylosing spondylitis or another autoimmune-related indication.

Enbrel generated $4.2 billion in 2012 sales; Amgen shares co-promote rights to the drug in the U.S. and Canada with Pfizer under a deal that ends Oct. 31, with Amgen taking back all rights. Sandoz is already developing an etanercept biosimilar, although that company is hoping to gain its first approval in psoriasis. That company believes it can challenge Enbrel’s extended exclusivity, including two U.S. patents that expire in 2028 and 2029. Baxter has teamed with Momenta Pharmaceuticals Inc. in a December 2011 deal that is expected to yield between two and six new biosimilars. - Paul Bonanos

Novartis/Regenerex: Novartis AG and Regenerex LLC have inked an exclusive global licensing and research collaboration based on the Kentucky-based biotech’s hematopoietic stem cell-based FCRx platform. Regenerex’s Facilitating Cell Therapy (FCRx ) has shown encouraging results in Phase II trials involving 15 kidney transplant recipients, inducing stable immunological tolerance and graft survival without the need for lifelong immunosuppression.  Currently, solid organ transplant recipients need immunosuppressive drugs for life to prevent rejection. FCRx is an allogeneic hematopoietic stem cell based therapy platform that also contains facilitating cells derived from a donor. The platform supports the development of tolerance, or "bone marrow chimerism," in transplant recipients and the two hope chimerism will eventually render recipients tolerant to cell, tissue or organ transplants from the same donor, enabling transplant patients to discontinue immunosuppressive medications after building stable immunological tolerance. Beyond transplant, the partners will study FCRx’s potential for correcting serious genetic deficiencies such as inherited metabolic storage disorders and hemoglobinopathies, examples being metachromatic leukodystrophy and sickle cell disease. The companies did not provide financial details or timeframe for their collaboration in the Sept. 6 announcement. Novartis did say that the FCRx platform will broaden its current cell therapy portfolio, which includes two novel cell therapy platforms initially being investigated in hematological malignancies. HSC835, currently in a Phase II trial in patients with high-risk hematological malignancies, is a novel cell therapy approach that enables an expanded single umbilical cord blood derived hematopoietic stem cell transplant in patients with limited treatment options. A second cell therapy product, CTL019 is a chimeric antigen receptor T cell therapy currently in Phase II development in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). - S.S.

Thrombogenics/Bicycle: ThromboGenics NV has signed its second licensing deal in three months involving novel targets for diabetic eye disease, this time with U.K.-based Bicycle Therapeutics Ltd.  Bicycle's bicyclic peptide technology will be used to identify and optimize bicyclic peptides that inhibit what is believed to be a new target involved in vascular permeability, and ThromboGenics will have exclusive rights to clinically develop and commercialize the products. In return, Bicycle will receive an undisclosed upfront fee, development and regulatory milestones and royalties on sales, and will also collaborate with ThromboGenics on preclinical development. Their licensing pact was announced on Sept. 5. Now that ThromboGenics's lead product, the vitreomacular adhesion product Jetrea (ocriplasmin), has reached the market in the U.S and Europe, the Belgian biotech is casting around for new avenues to explore in ophthalmic diseases. It has nearly €200 million in cash, including milestone payments totaling €90 million from Jetrea's European licensee, Alcon (Novartis), so has the financial muscle to do so. In May, it licensed technology from Cambridge, Mass.-based Eleven Biotherapeutics to develop protein therapeutics aimed at another novel biologic target involved in diabetic macular edema (DME) and diabetic eye diseases. DME is of increasing interest to pharma companies because of its increasing prevalence and the possibility of improving on the current standard of care, lasers or VEGF inhibitor therapy. - John Davis

Santhera/Takeda: Santhera Pharmaceuticals AG of Switzerland reached agreement with Takeda Pharmaceutical Co. Ltd. on Sept. 3 to license back the European rights to its Phase III Duchenne muscular dystrophy (DMD) drug Catena (idebenone), increasing the Swiss company’s commercial flexibility. In return, Takeda gets an undisclosed percentage of future licensing and/or sales income generated by Santhera in DMD. Takeda acquired exclusive marketing rights for the medicine in Europe in 2005. Idebenone is a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) capable of transferring electrons directly onto complex III of the mitochondrial electron transport chain, thereby capable of restoring cellular energy levels.

The drug is in a DMD Phase III study conducted in Europe and the U.S. Santhera also obtained the right to cross-reference Takeda's idebenone data for regulatory use in any indication in any territory. If Santhera makes use of the cross-references, Takeda is eligible to obtain a percentage from future licensing and/or sales income generated by Santhera in such indications. The two companies also ended a 2005 agreement for idebenone’s use treating Friedreich's ataxia. Santhera's €1 million ($1.3 million) contingent liability payable to Takeda under that has been waived, but Takeda is eligible to receive €1 million  as a percentage from future income generated by Santhera to offset this.- S.S.

Photo credit: Wikimedia Commons.

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