BIOBUSINESS BRIEFS NATURE REVIEWS REVIEWS NATURE is already approved forthetreatment of disorders, such as rheumatoid arthritis. subsets ofpatientswithotherautoimmune and dermatomyositis, and potentially in be particularly relevant to lupus, polymyositis Rosen. He expects S1PR modulation to also difficult ability tohaveanimpactonanumberof cascade, [S1PR modulators] have a unique multipoint interdiction oftheautoimmune and stromal cells.“Because oftheir cells distributed on lymphocytes, endothelial The S1PRs targeted by ozanimod are broadly and oneinpatientswithulcerative colitis. with relapsing–remitting multiple sclerosis, currently in two Phase III trials: one in patients to become a marketed drug. Ozanimod is ozanimod (previously known as RPC1063) the initiativehasalsoprovided thebasisfor molecules andexpertiseremain. chemical probes, ended in 2012, but legacy molecules that could be optimized into screening capacityneededtoidentifysmall researchers accesstothelarge-scale was establishedin2003toprovide biomedical receptor 1 (S1PR1). The MLP initiative, which agonists ofthesphingosine-1-phosphate the NIH MLP collection to identify from TSRI.Theresearchers hadscreened Rosen and his colleague, Edward Roberts, compounds identifiedinthelaboratories of Diego, USA, who co‑discovered ozanimod. at The Scripps Research Institute (TSRI) in San into Phase III,” says Hugh Rosen, a professor was discovered inacademiaandhasmadeit “This isaveryrare exampleofacompoundthat Health (NIH) Molecular Libraries Program (MLP). originated from the US National Institutes of its portfolio, including one — ozanimod — that candidates fortreating autoimmunediseasesto Celgene addstwoclinical-stagedrug Receptos for US$7.2 billion. In doing so, Celgene isbuyingthebiotechcompany In its third major acquisition in 3 months, autoimmunity candidate Celgene betsbigonScripps-originated S1PRs are targeted by one drug that Soon itwillbecomeapparent whether In 2009, Receptos licensed a series of DEALWATCH - to - treat autoimmune diseases,” says |
DRUG DISCOVERY
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© 2015 Macmillan Publishers Limited. Allrights reserved diseases. of multiplesclerosis andotherautoimmune alongside thesenewcomersforthe treatment that ozanimod will eventually have a place In acquiring Receptos, Celgene has bet heavily number of circulating CD20 ocrelizumab (Roche), which decreases the a CD25 daclizumab high the treatment of multiple sclerosis by 2017: compounds are settoentertheclinic for infections couldbetreated more effectively. Hemmer, which means that opportunistic faster than you can fingolimod,” explains infection, you can get this drug out much half multiple sclerosis. Thesecondistheshorter that ithasgreater efficacyinpatientswith relative to fingolimod, which could mean penetrance of ozanimod into the brain Hemmer. Thefirstisthereportedly higher treatment of multiple sclerosis, according to it anedgeoveritsdirect competitorsinthe an active comparator”. a Phase III trial with clinical end points and “one hastoseehowthedrugperformsin in multiple sclerosis. However, he cautions, München, Munich, Germany, and an expert a professor at Technische Universität less with ozanimod,” says Bernhard Hemmer, to me like the cardiac side effects are a bit among S1PR — mean there is room for improvement both ofwhichwere observedinclinicaltrials zoster virus and decreases in heart rate, most notably, fatal infections with varicella effective. Safety issues with fingolimod — interferon patients withactivediseaseforwhom In Europe, fingolimod is only approved for (Novartis) and ponesimod (Actelion). that are in Phase III trials, siponimod fingolimod (Novartis) — and by two others relapsing–remitting multiple sclerosis — Two characteristics of ozanimod may give Two otherpromising immune-modulating - life of ozanimod. “If a patient has a severe - specific monoclonal antibody, and ‑ β andglatiramer acetateare not - targeting compounds. “It looks - yield process (Biogen/AbbVie), - expressing B cells. Megan Cully
NEWS &ANALYSIS VOLUME 14 | SEPTEMBER 2015
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