Deals of the Week: Prime Time For Parkinson's

Parkinson’s disease is about to receive plenty of media attention. Most of that will come as NBC’s The Michael J. Fox Show makes its debut Sept. 26, returning its star to center stage in a sitcom that deals with neurodegenerative disease. But here at Deals of the Week, we’re pointing our camera at a small but potentially influential Big Pharma bet on a company whose early progress in Parkinson’s is funded by the foundation that bears Fox’s name.

Biogen Idec and Amicus Therapeutics revealed a tie-up this week that will fund continued research on the link between the glucocerebrosidase, or GCase, enzyme and Parkinson’s. Known primarily for its research in rare lysosomal disorders such as Fabry disease and Pompe disease, Amicus specializes in repairing lysosomal enzyme function related to protein instability and misfolding. There’s a connection between those disorders and Parkinson’s: Scientists have known since the late 1990s about a connection between Gaucher disease, another lysosomal storage disorder, and Parkinson’s; mutations in the GBA1 gene cause Gaucher, and are a known risk factor for Parkinson’s. And indeed, Amicus’s continued research on a first-generation Gaucher product showed early promise in treating Parkinson’s as well.

The Michael J. Fox Foundation, one of the best-known Parkinson’s charities, has funded preclinical research on Amicus’s AT3375 since 2006. Beginning with a predecessor compound, AT2101, Cranbury, N.J.-based Amicus learned that pharmacological chaperones could be used to stimulate GCase activity, prevent buildup of alpha-synuclein – a protein associated with Parkinson’s – in mice’s brains, and improve motor function. That led to the development of AT3375, a more potent and selective next-generation product, and a series of MJFF grants.

The Biogen Idec deal includes discovery, development and commercialization of new molecules that address GCase activity. The companies didn’t disclose specific terms, but said Biogen Idec will own the candidates, fund the projects, and reimburse Amicus for its employees’ time, while Amicus can receive milestone payments and “modest” royalties if a product succeeds in the clinic and is commercialized.

It’s the latest among several Parkinson’s deals for Biogen Idec, including its 2010 purchase of an alpha-synuclein-targeting compound from Neurimmune Holdings. The pharma has also invested in neurodegeneration start-up Knopp Biosciences, most recently in November 2012.

Overall, the Parkinson’s field is still dominated by generic drugs. In light of some recent discoveries, it's possible that both symptomatic and disease-modifying treatments could reach the market within several years, though none will imminently. The clinical failure of Merck’s Phase III candidate preladenant in May raised some doubts about one class, adenosine A2A agonists.

But if the Biogen/Amicus deal is a modest step forward, it’s still another sign that a pharma will commit capital to an early-stage Parkinson’s project with a lot yet to prove. Other recent alliances include a couple of university deals. AstraZeneca partnered with Tufts University in a broader neuroscience pact in July. And last year, Bristol-Myers Squibb licensed a group of metabotropic glutamate receptor 4 modulators from Vanderbilt Center for Neuroscience Drug Discovery. Plus, watch for coverage of Civitas Therapeutics’s latest venture funding, another bet on Parkinson’s disease that’s likely to be featured in Deals of the Week’s cousin, Financings of the Fortnight, next week. --Paul Bonanos

Which other deals are ready for prime time? We'll do our best Don Pardo voice to introduce...

Biogen Idec/Isis: Biogen has been an active dealmaker lately, and struck another partnership with a familiar ally. In a move that capitalizes on the already-existing relationship, Biogen teamed with Isis Pharmaceuticals for a fourth partnership – one that broadens their discovery work in antisense technology and raises the stakes financially. The two companies announced what Isis refers to as ‘Biogen 4’ on Sept. 9. The broad, six-year strategic research collaboration will use Isis’s antisense technology to discover and advance compounds that treat neurological conditions. Biogen will pay $100 million upfront – the payment will be reflected in its third quarter R&D expenses – and Isis is eligible to receive as much $220 million in milestone payments, as well as royalties and clinical trial expenses. Once targets are validated the team can choose to utilize Isis’ antisense technology or opt to develop a small molecule or biologic. Should antisense be chosen, Isis will receive an additional $10 million milestone payment and have the opportunity to earn an additional $250 million in pre-commercial milestone payments. If not, Isis still will receive a $5 million milestone and have the potential for another $85 million in milestones. The strategic relationship builds on three earlier collaborations inked in the last two years, including one around a Phase II program to develop a treatment for spinal muscular atrophy. –Lisa LaMotta 

Merck/AstraZeneca: AstraZeneca’s in-licensing of Merck's MK-1775 for study in certain types of ovarian cancer is the UK drug maker’s latest move to build a dynamic oncology portfolio and highlights its keen focus on the DNA damage response area and efforts to induce cancer cell death. Under the Sept. 11 deal, Merck will receive $50 million upfront, and will be eligible for undisclosed development and regulatory milestone payments, as well as tiered royalties. MK-1775 is currently in Phase IIa clinical studies in combination with standard of care therapies for treating patients with P53-deficient ovarian cancer. WEE1 helps to regulate the cell-division cycle and WEE1 inhibitor MK-1775 is designed to cause certain tumor cells to divide without undergoing the normal DNA repair processes, ultimately leading to cell death. For AstraZeneca, the addition of WEE1 inhibitor MK-1775 gives it yet another agent that targets tumor-specific DNA damage response dependencies, such PARP inhibitor olaparib and first-in-class AZD6738. Preclinical evidence suggests that MK-1775 can enhance anti-tumor properties in conjunction with DNA damage-inducing chemotherapy agents.  AstraZeneca intends to study the compound in a range of solid tumor cancer types as part of a concerted push in oncology, part of a larger turn-around plan. Merck will continue to focus on its later stage oncology candidates, MK-3475 and vintafolide. In the spring, FDA granted breakthrough status to MK-3475, or lambrolizumab, a PD-1 specific monoclonal antibody for the treatment of advanced malignancy. Vintafolide is a treatment for a variety of tumor types expressing folate receptors, including ovarian and lung cancers, which Merck licensed from Endocyte Inc. in April 2012. It is paired with a radio-labeled imagingn agent to identify high-responding patients whose tumors express folate receptors. – Sten Stovall

Roche/Inovio: Roche announced a deal Sept. 10 to license two preclinical assets, one of which will be used as a potential combination with other cancer immunotherapy candidates in the Swiss pharma’s pipeline. Its partner, Inovio Pharmaceuticals gets $10 million upfront in exchange for rights to INO-5150 for prostate cancer and INO-1800 for hepatitis B, as well rights to use an electroporation delivery technology for the two candidates. Both candidates are multi-antigen DNA immunotherapies well into preclinical work. Inovio CEO Joseph Kim said ‘5150, which targets both prostate-specific antigen and prostate-specific membrane antigen, could move into clinical development before the end of the year. In a release, Roche said it plans to use ‘5150 in combination with cancer immunotherapies in its pipeline in hopes of developing next-generation approaches to treating a variety of cancers. Roche also gets an option to license additional back-up vaccine candidates that Inovio will discover and develop, as well as an exclusive license for use of the biotech’s Cellectra electroporation technology in the development of ‘5150 and ‘1800. In addition to the upfront payment, Roche also will finance the remaining preclinical work for the two candidates. Inovio could earn development and commercial milestones up to $412.5 million for the two programs and up to double-digit tiered royalties on product sales. – Joseph Haas

Cellceutix/PolyMedix: One company’s loss may be another’s gain. In this case, Cellceutix is taking advantage of PolyMedix’s bankruptcy to acquire the company’s assets at an affordable price and strengthen its own portfolio. Cellceutix said Sept. 9 it will acquire the Phase II antibiotic brilacidin and eight other compounds previously in development at PolyMedix for $2.1 million in cash and 1.4 million shares of Cellceutix stock, in a deal orchestrated in bankruptcy court. Financially distressed PolyMedix filed for Chapter 7 bankruptcy protection April 1, after it ran into trouble in May 2012 while testing a different product, PMX-60056, in development for reversing the anticoagulant activity of unfractionated heparin in patients undergoing percutaneous coronary intervention procedures. Brilacidin will be Cellceutix’s latest-stage compound in clinical development, and the company said it is anxious to begin Phase III trials testing the first-in-class defensin mimetic. The question now for Cellceutix is if it will be able to succeed where PolyMedix failed and turn brilacidin and other molecules in the portfolio into valuable late-stage drugs. - Jessica Merrill

GSK/Suntory: By arranging the sale of its iconic drink brands Lucozade and Ribena to Suntory Beverage & Food of Japan for net proceeds of £1.3 billion ($2.11 billion), GlaxoSmithKline has disposed of two valuable non-core assets, freeing itself to focus on its late-stage drug and vaccine pipeline. The Sept. 9 divestment had been expected after GSK in April said it had put Lucozade and Ribena on the auction block. Introduced in 1927 and 1937 respectively, the two drinks deliver strong cash flow and together generate annual sales of around £600 million ($915 million). Both drinks are well-loved in Glaxo’s home country, but lack global reach, especially in the emerging markets that are now becoming the focus of the British drugmaker's consumer health business. Proceeds from the sale will be used to reduce GSK’s debt. SBF, the number 4 supplier of soft drinks globally in 2012, will get global rights to the two brands and GSK’s Coleford, UK, manufacturing site in the Forest of Dean. Most employees at the site and those working on Lucozade and Ribena in commercial and R&D functions will transfer to SBF. In Nigeria, GSK will continue to manufacture and distribute Lucozade and Ribena under license. The deal is part of a number of housekeeping moves set in motion early in 2013 by GSK’s chief executive Andrew Witty. They include hiving off some 50 medicines, including stomach acid treatment Zantac (ranitidine), migraine medication Imitrex (sumatriptan) and anti-nausea treatment Zofran (ondansetron), into a separate global established products portfolio. - S.S.

Bayer/Broad Institute: MIT and Harvard-backed cancer research center The Eli & Edythe L. Broad Institute turns 10 this year, and is solidifying its status as a key partner for pharmas. Its latest ally is Bayer: the German giant inked a five-year oncogenomics deal under which the pair will attempt to discover new drugs that target genomic alterations selectively. The two didn’t release financial terms of the Sept. 10 deal, but the early-stage collaboration gives Bayer an exclusive option to license the compounds discovered jointly, at the pre-clinical stage. Bayer and the Broad Institute will share their compound libraries, screening platforms, and expertise, and establish a joint steering committee to decide which candidates to pursue. Established in 2003 with a $200 million gift, the Broad Institute was enlarged in 2008 when its namesake benefactors donated another $400 million. The Cambridge, Mass.-based Institute struck a two-year antibiotics research deal with AstraZeneca in September 2012, and a multi-year agreement with Roche to explore repurposed drugs in December 2012. It also granted NanoString Technologies Inc. rights to a genetic signature implicated in liver disorders, invented by Broad Institute CSO Todd Golub, in April. – P.B.