Omeros Corporation Unlocks Six Additional Class A Orphan GPCRs and Identifies Small Molecules Targeting Two Commercially Validated Class B GPCRs
Published: Oct 03, 2013
SEATTLE, Oct. 3, 2013 /PRNewswire/ -- Omeros Corporation (NASDAQ: OMER) today announced that it has identified compounds that functionally interact with each of six additional orphan G protein-coupled receptors (GPCRs) that have been linked to a wide range of diseases in the areas of neurologic disorders, cardiovascular disease and oncology. Identification of compounds that functionally interact with orphan GPCRs facilitates the development of drugs that target those receptors. Omeros has now unlocked 52 Class A orphan GPCRs, representing approximately 65 percent of these targets.
The six additional orphan GPCRs unlocked by Omeros are GPR37, GPR37L1, GPR132, GPR174, GPR176 and LGR5. GPR37 has been linked to Parkinson's disease. GPR37L1, GPR132 and GPR176 are associated with cardiovascular indications, specifically hypertension and cardiac hypertrophy (GPR37L1 and GPR132) and atherosclerosis (GPR176). GPR174 has been linked to melanoma and Grave's disease, while LGR5 is expressed in cancer stem cells and has been associated with esophageal adenocarcinoma.
In addition, using its proprietary Cellular Redistribution Assay (CRA) technology, which has already successfully "unlocked" 52 Class A orphan GPCRs, Omeros has identified small molecules that interact with two non-orphan Class B GPCRs; the glucagon-like peptide 1 receptor (GLP-1R) and the parathyroid hormone 1 receptor (PTH-1R). Both of these receptors are established drug targetsGLP-1R for diabetes and PTH-1R for osteoporosis. The marketed drugs currently available that target these receptors are all injectable, with 2012 annual sales of GLP-1R agents and PTH-1R agents exceeding $2.0 billion and $1.1 billion, respectively. Omeros' identification of small molecules targeting GLP-1R and PTH-1R could lead to the development of oral medications for these diseases that provide dosing advantages over the injectable agents on the market. Omeros is in the process of filing broad patent applications around its discoveries, and compound optimization efforts are in progress.
"Using our proprietary technology, we continue to add to the number of druggable Class A orphan GPCRs now 52 and spanning a broad range of important disorders that we believe Omeros exclusively controls," said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "Our team has now also turned to Class B GPCRs, starting with two receptors that are commercially validated but whose corresponding marketed drugs are only peptides or proteins, requiring daily or weekly injections. By identifying small molecules that functionally interact with these receptors, Omeros is opening the door to new oral treatments for diabetes and bone loss."
Ongoing GPCR Program
Omeros is screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput CRA technology. 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 52 orphan receptors linked to metastatic melanoma and lung cancer (GPR19), renal cell carcinoma, ovarian cancer and inflammatory conditions (GPR65/TDAG8), ovarian cancer, prostate cancer, bone diseases and asthma (GPR68/OGR1), hepatocellular carcinoma (GPR80), squamous cell carcinomas, bladder carcinoma, hepatocellular carcinoma and lung cancer (GPR87), ovarian cancer (GPR150), metastatic epithelial cancers, congenital cataracts and birth defects of the brain and spinal cord (GPR161), melanoma and Grave's disease (GPR174), cancer stem cells and self-renewal and maintenance of adult stem cells (LGR4, LGR5), esophageal adenocarcinoma (LGR5), leukemia (P2Y8/P2RY8), arterial stiffness (GPR25), hypertension and cardiac hypertrophy (GPR37L1), atherosclerosis (GPR132 and GPR176), multiple sclerosis, spinal cord injury, traumatic brain injury (GPR17),anxiety disorders (GPR31), Parkinson's disease (GPR37), schizophrenia (GPR52, GPR153), autism (GPR63), bipolar disorder (GPR78), anxiety, post-traumatic stress disorder, body weight abnormalities and autoimmune diseases (GPR83), motor control (GPR139), schizophrenia, cognitive impairments and mood disorders (GPR151), cognitive impairments, blood pressure abnormalities and colon cancer (MAS1), pain (MRGE), circadian rhythm irregularities and sleep disorders (OPN4), obesity, cognitive impairments and motor disorders (GPR12), obesity and diabetes (GPR21), obesity-related type-2 diabetes (GPR39), obesity, metabolic disorders, thermoregulation, mood disorder and bipolar disorder (GPR50), appetite control (GPR82, GPR101), metabolic and psychotic disorders (SREB1/GPR27, SREB2/GPR85, SREB3/GPR173), rheumatoid arthritis (CCRL2), rheumatoid arthritis and HIV-mediated enteropathy (GPR15), osteoarthritis (GPR22), acute inflammatory responses (GPR32), humoral immunity (GPR183), regulation of hematopoietic stem cell differentiation (GPR171), long-term wound repair, including the formation of new hair follicles (LGR6). In addition, Omeros has unlocked GPR20, GPR45, GPR135, GPR141, GPR162, GPR182, MRGF and OPN5, which are expressed preferentially in the gastrointestinal tract (GPR20), brain (GPR45, GPR135, GPR162 and OPN5), dorsal root ganglia (MRGF), bone marrow, spleen, skin and lung (GPR141) and throughout the body (GPR182).
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, and compounds acting through serotonin and dopamine receptors.
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 82 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 small-molecule and protein therapeutics targeting inflammation, coagulopathies and disorders of the central nervous system. Derived from its proprietary PharmacoSurgery® platform, the Company's lead drug product, OMS302 for lens replacement surgery, is currently under review for marketing approval by both the US Food and Drug Administration and the European Medicines Agency with commercial launch planned for 2014. Omeros' five other clinical programs are focused on schizophrenia, Huntington's disease and cognitive impairment; addictive and compulsive disorders; complement-related diseases; and preventing problems associated with surgical procedures. Omeros also has a proprietary GPCR platform, which is making available an unprecedented number of new GPCR drug targets and corresponding compounds to the pharmaceutical industry for drug development.
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, which are subject to the "safe harbor" created by those sections for such statements. These statements include, but are not limited to, statements regarding the number of orphan GPCRs that Omeros expects to unlock; the potential development of new drugs, including oral medications that provide dosing advantages over injectable agents on the market; the potential indications of the orphan GPCRs unlocked by Omeros; Omeros' potential patent rights for each unlocked orphan GPCR; its exclusive control over Class A orphan GPCRs; Omeros' expectations regarding its ability to unlock GPCRs; and the planned commercial launch of OMS302 in 2014. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Omeros' actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors described under the heading "Risk Factors" in the Company's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 9, 2013. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future.
SOURCE Omeros Corporation
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