NEWS & ANALYSIS BIOBUSINESS BRIEFS DEAL WATCH Celgene bets big on Scripps-originated autoimmunity candidate In its third major acquisition in 3 months, relapsing–remitting multiple sclerosis — Celgene is buying the biotech company fingolimod (Novartis) — and by two others Receptos for US$7.2 billion. In doing so, that are in Phase III trials, siponimod Celgene adds two clinical-stage drug (Novartis) and ponesimod (Actelion). candidates for treating autoimmune diseases to In Europe, fingolimod is only approved for its portfolio, including one — ozanimod — that patients with active disease for whom originated from the US National Institutes of interferon‑β and glatiramer acetate are not Health (NIH) Molecular Libraries Program (MLP). effective. Safety issues with fingolimod — “This is a very rare example of a compound that most notably, fatal infections with varicella Ryan McVay/Photodisc was discovered in academia and has made it zoster virus and decreases in heart rate, into Phase III,” says Hugh Rosen, a professor both of which were observed in clinical trials at The Scripps Research Institute (TSRI) in San — mean there is room for improvement Diego, USA, who co‑discovered ozanimod. among S1PR-targeting compounds. “It looks In 2009, Receptos licensed a series of to me like the cardiac side effects are a bit compounds identified in the laboratories of less with ozanimod,” says Bernhard Hemmer, Rosen and his colleague, Edward Roberts, a professor at Technische Universität from TSRI. The researchers had screened München, Munich, Germany, and an expert the NIH MLP collection to identify allosteric in multiple sclerosis. However, he cautions, agonists of the sphingosine-1-phosphate “one has to see how the drug performs in receptor 1 (S1PR1). The MLP initiative, which a Phase III trial with clinical end points and was established in 2003 to provide biomedical an active comparator”. researchers access to the large-scale Two characteristics of ozanimod may give screening capacity needed to identify small it an edge over its direct competitors in the molecules that could be optimized into treatment of multiple sclerosis, according to chemical probes, ended in 2012, but legacy Hemmer. The first is the reportedly higher molecules and expertise remain. penetrance of ozanimod into the brain Soon it will become apparent whether relative to fingolimod, which could mean the initiative has also provided the basis for that it has greater efficacy in patients with ozanimod (previously known as RPC1063) multiple sclerosis. The second is the shorter to become a marketed drug. Ozanimod is half-life of ozanimod. “If a patient has a severe currently in two Phase III trials: one in patients infection, you can get this drug out much with relapsing–remitting multiple sclerosis, faster than you can fingolimod,” explains and one in patients with ulcerative colitis. Hemmer, which means that opportunistic The S1PRs targeted by ozanimod are broadly infections could be treated more effectively. distributed on lymphocytes, endothelial Two other promising immune-modulating cells and stromal cells. “Because of their compounds are set to enter the clinic for multipoint interdiction of the autoimmune the treatment of multiple sclerosis by 2017: cascade, [S1PR modulators] have a unique daclizumab high-yield process (Biogen/AbbVie), ability to have an impact on a number of a CD25-specific monoclonal antibody, and difficult-to-treat autoimmune diseases,” says ocrelizumab (Roche), which decreases the Rosen. He expects S1PR modulation to also number of circulating CD20-expressing B cells. be particularly relevant to lupus, polymyositis In acquiring Receptos, Celgene has bet heavily and dermatomyositis, and potentially in that ozanimod will eventually have a place subsets of patients with other autoimmune alongside these newcomers for the treatment disorders, such as rheumatoid arthritis. of multiple sclerosis and other autoimmune S1PRs are targeted by one drug that diseases. is already approved for the treatment of Megan Cully NATURE REVIEWS | DRUG DISCOVERY VOLUME 14 | SEPTEMBER 2015 | 595 © 2015 Macmillan Publishers Limited. All rights reserved.