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Adding Four More, Omeros Has Now Unlocked 46 Orphan GPCRs

SEATTLE, Oct. 24, 2012 /PRNewswire/ -- Omeros Corporation (NASDAQ: OMER) today announced that it has identified compounds that functionally interact with each of four additional orphan G protein-coupled receptors (GPCRs). Without compounds that functionally interact with orphan GPCRs, developing drugs targeting those receptors is extremely difficult. Omeros has now unlocked 46 Class A orphan GPCRs, representing almost 60 percent of these targets and equaling the number of GPCRs that are targeted by over 30 percent of all marketed drugs. There are approximately 120 orphan GPCRs and Omeros expects to unlock an even larger percentage of them, focusing first on Class A orphans.

The four additional orphan GPCRs unlocked by Omeros are GPR65/TDAG8, GPR82, MRGE and MRGF. GPR65/TDAG8 has been linked to several types of cancer and to inflammatory disorders, such as asthma. GPR82 is linked to appetite and body weight. MRGE has been linked to pain, and MRGF, which like MRGE is expressed in dorsal root ganglia, is also likely associated with pain. Omeros is in the process of filing broad patent applications around the orphan GPCRs that it has unlocked and compound optimization efforts are in progress.

"Using our proprietary high-throughput assay, we continue to unlock orphan GPCRs – finding functionally  active and structurally diverse compounds – and, for a number of those receptors, generating compelling preclinical data," said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros.  "Through medicinal chemistry, we are selectively optimizing some of these compounds. The results of these collective efforts further expand our intellectual property estate, and we expect that we will exclusively control the commercial rights to each of the GPCRs that we unlock."

Ongoing GPCR Program

Omeros is screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput cellular redistribution assay (CRA). The CRA detects receptor antagonists, agonists and inverse agonists. Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with 46 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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