Omeros Announces Unlocking of Class A Orphan GPCRs

The unlocking of the compounds, according to the company, could lead to new treatments for autism, osteoarthritis neuropsychiatric disorders.

Omeros Corp. announced that it has identified compounds that functionally interact with each of five 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 42 Class A orphan GPCRs, representing over half of these targets. There are approximately 120 orphan GPCRs and Omeros expects to unlock a large percentage of them, focusing first on Class A orphans.

The five additional orphan GPCRs unlocked by Omeros are GPR22, GPR45, GPR63, GPR162 and GPR171. GPR22 has been linked to osteoarthritis and is highly expressed in osteoarthritic cartilage while almost absent in healthy cartilage. GPR63 has been connected to autism, a developmental disorder affecting social and communication skills in an estimated 1 in 88 children in the United States. GPR162 is predominantly expressed in the brain, specifically in regions such as the hypothalamus, amygdala, striatum and hippocampus, which are associated with a variety of neuropsychiatric disorders. While the physiological roles of GPR45 and GPR171 have yet to be definitively determined, GPR45 appears to be exclusively expressed in the brain and GPR171 is thought to regulate differentiation of hematopoietic stem cells. 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.

"We continue to add to our estate of unlocked orphan GPCRs and are methodically building a patent position around each," said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros.  "Our proprietary screening assay has identified as many as 80 discrete compounds against a given receptor with potencies as low as 20 nanomolar.  Together with our ongoing efforts to strengthen the biology around these targets and optimize selected compounds, we expect that our collective achievements will result in Omeros exclusively controlling the rights to develop and commercialize drugs targeting each of these important receptors."

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 42 orphan receptors linked to metastatic melanoma (GPR19), esophageal squamous cell carcinoma and obesity-related type-2 diabetes (GPR39), hepatocellular carcinoma (GPR80), 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" (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 (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 hematopoietic stem cell differentiation (GPR171), cancer stem cells and the self-renewal and maintenance of adult stem cells (LGR4) and long-term wound repair, including the formation of new hair follicles (LGR6). In addition, Omeros has unlocked GPR20, GPR45, GPR135, GPR162 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 and spinal cord (OPN5).

About G Protein-Coupled Receptors

GPCRs, which mediate key physiological processes in the body, are one of the most valuable families of drug targets. According to Insight Pharma Reports, GPCR-targeting drugs represent 30 to 40 percent of marketed pharmaceuticals. Examples include Claritin® (allergy), Zantac® (ulcers and reflux), OxyContin® (pain), Lopressor® (high blood pressure), Imitrex® (migraine headache), Reglan® (nausea) and Abilify® (schizophrenia, bipolar disease and depression) as well as all other antihistamines, opioids, alpha and beta blockers, serotonergics and dopaminergics.

The industry focuses its GPCR drug discovery efforts mostly on non-sensory GPCRs. Of the 363 total non-sensory GPCRs, approximately 240 have known ligands (molecules that bind the receptors) with nearly half of those targeted either by marketed drugs (46 GPCRs) or by drugs in development (about 70 GPCRs). There are approximately 120 GPCRs with no known ligands, which are termed "orphan GPCRs." Without a known ligand, drug development for a given receptor is extremely difficult.

Omeros uses its proprietary high-throughput CRA to identify small-molecule agonists and antagonists for orphan GPCRs, unlocking them to drug development. Omeros believes that it is the first to possess the capability to unlock orphan GPCRs in high-throughput, and that currently there is no other comparable technology. Unlocking these receptors could lead to the development of drugs that act at these new targets. There is a broad range of indications linked to orphan

GPCRs including cardiovascular disease, asthma, diabetes, pain, obesity, Alzheimer's disease, Parkinson's disease, multiple sclerosis, schizophrenia, learning and cognitive disorders, autism, osteoporosis, osteoarthritis and several forms of cancer.

About Omeros Corporation

Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing products targeting inflammation, coagulopathies and disorders of the central nervous system. The Company's most clinically advanced product candidates are derived from its proprietary PharmacoSurgery platform designed to improve clinical outcomes of patients undergoing a wide range of surgical and medical procedures. Omeros has four ongoing clinical

development programs. Omeros may also have the near-term capability, through its GPCR program, to add a large number of new drug targets and their corresponding compounds to the market. Behind its clinical candidates and GPCR platform, Omeros is building a diverse pipeline of protein and small-molecule preclinical programs targeting inflammation, coagulopathies and central nervous system disorders.

Source: Omeros Corp. via PR Newswire

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