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Omeros Announces That GPR17 Antagonists Improve Function In Model Of Multiple Sclerosis

SEATTLE, April 10, 2013 /PRNewswire/ -- Omeros Corporation (NASDAQ: OMER) today announced positive data in the most commonly used model for studying the clinical and pathological features of multiple sclerosis (MS), further advancing its development program of GPR17-targeting compounds for the treatment of MS. Compounds previously discovered by Omeros that inhibit GPR17, an orphan G protein-coupled receptor (GPCR) unlocked by Omeros, significantly improved function from experimental autoimmune encephalomyelitis (EAE) in mice. Using its proprietary high-throughput Cellular Redistribution Assay (CRA), Omeros believes that it alone has identified compounds that functionally interact with GPR17 and has patents pending that are broadly directed to any such compounds active at the receptor.

Having discovered compounds that functionally interact with GPR17, Omeros previously showed that GPR17 antagonists promote generation of mature oligodendrocytes, the cells that produce myelin. Myelin is a key component of the proper functioning of the central nervous system, and myelin deficiency is a hallmark of a large number of neurodegenerative autoimmune diseases, including MS. In this EAE model, animals treated with GPR17-targeting compounds, compared to untreated animals, significantly improved mean clinical scores, which quantify disease progression by measuring motor dysfunction and are used as a surrogate indicator of demyelination.

"Our GPCR platform – built around our proprietary CRA – continues to unlock wholly new drug targets, and we expect that our sole knowledge of the identities of their interacting compounds together with our patent positions will give Omeros exclusive control of those receptors," stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "GPR17 is one of those receptors, and the EAE data further underscore the potential for the compounds that we have identified with our CRA. There are no approved remyelinating therapeutics – all approved agents for the treatment of MS are anti-inflammatories. The GPR17 antagonists that we are developing could lead to the first drug able to promote remyelination and restore neural function in patients with MS."

Ongoing GPCR Program

Omeros is screening orphan and difficult-to-drug Class A and Class B GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput cellular redistribution assay (CRA). The CRA detects receptor antagonists, agonists, inverse agonists and allosteric modulators for a given GPCR without requiring the receptor's ligand or any knowledge of the receptor's signaling pathway(s). Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with 46 Class A orphan receptors linked to metastatic melanoma (GPR19), esophageal squamous cell carcinoma and obesity-related type-2 diabetes (GPR39), hepatocellular carcinoma (GPR80), several types of cancer (GPR65/TDAG8), squamous cell carcinoma (GPR87), ovarian cancer (GPR150), pancreatic cancer (GPR182), acute lymphoblastic leukemia (P2Y8/P2RY8), ovarian and prostate cancer (OGR1), arterial stiffness (GPR25), sleep disorders (OPN4), cognitive disorders (GPR12), torpor or "suspended animation" and bipolar disorder (GPR50), anxiety disorders (GPR31), schizophrenia (GPR52, GPR153), autism (GPR63), bipolar disorder and schizophrenia (GPR78), memory and inflammatory conditions (GPR83), psychotic and metabolic disorders (GPR27, GPR85, GPR173), cognition (GPR151), cognitive impairments (MAS1), inflammatory responses (GPR32), obesity and diabetes (GPR21), appetite control (GPR82, GPR101), immunological disorders (CCRL2), rheumatoid arthritis and HIV-mediated enteropathy (GPR15), respiratory and immune disorders (GPR141), humoral immunity (GPR183), multiple sclerosis (GPR17), osteoarthritis (GPR22), motor control (GPR139), congenital cataracts and birth defects of the brain and spinal cord (GPR161), regulation of hematopoietic stem cell differentiation (GPR171), cancer stem cells and the self-renewal and maintenance of adult stem cells (LGR4), long-term wound repair, including the formation of new hair follicles (LGR6) and pain (MRGE). In addition, Omeros has unlocked GPR20, GPR45, GPR135, GPR162, MRGF and OPN5, which have not yet been definitively tied to any specific indications but are expressed preferentially in the gastrointestinal tract (GPR20), brain (GPR45, GPR135 and GPR162) and eye, brain, testes, spinal cord (OPN5) and dorsal root ganglia (MRGF).

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