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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 cellular redistribution assay (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.

Omeros has begun screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput CRA. In addition to Class A orphan GPCRs, we have also begun screening orphan and non-orphan Class B receptors. Class B GPCRs have large extracellular domains and their natural ligands are generally large peptides, making the development of orally active, small-molecule drugs against these receptors, such as glucagon and parathyroid hormone, a persistent challenge. Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with the following orphan receptors:

GPCRMetabolic Indications GPCROncology Indications
GPR12Obesity, Cognitive Impairments, Motor Disorders GPR19Metastatic Melanoma
GPR21Obesity, Diabetes GPR39Esophageal Cancer
GPR25 Arterial Stiffness GPR65 Cancer
GPR37L1 Hypertension, Cardiac Hypertrophy GPR80 Hepatocellular Carcinoma
GPR50Metabolic Disorders GPR87Squamous Cell Carcinoma
GPR82Appetite, Body Weight GPR150Ovarian Cancer
GPR132 Atherosclerosis GPR161 Metastatic Epithelial Cancers, Cancer Stem Cells
GPR176 Atherosclerosis GPR174 Melanoma, Grave’s Disease
GPR101Eating Disorders LGR4Cancer Stem Cells, Bone Diseases
SREB1/GPR27Obesity, Schizophrenia LGR5Cancer Stem Cells, Esophageal Adenocarcinoma
SREB2/GPR85Obesity, Schizophrenia OGR1/GPR68Ovarian, Prostate Cancers
SREB3/GPR173Obesity, Schizophrenia P2Y8Acute Lymphoblastic Leukemia
GPCRCNS Indications GPCR Miscellaneous Indications
GPR17Multiple Sclerosis GPR15HIV Enteropathy, Rheumatoid Arthritis
GPR31Anxiety Disorders GPR22 Osteoarthritis
GPR37 Parkinson’s Disease GPR32 Acute Inflammatory Responses
GPR52Schizophrenia GPR183Humoral Immunity
GPR63Autism CCRL2Rheumatoid Arthritis, Immune Disorders
GPR78Bipolar Disorder, Schizophrenia LGR6Hair Follicle Stem Cells, Wound Repair
GPR83Memory and Inflammatory Conditions Orphans Unlocked with No Known Indictations
GPR139Motor Disorders GPR20, GPR45, GPR135, GPR141, GPR171, GPR182, OPN5
GPR151 Cognition; PTSD  
GPR162Neuropsychiatric Disorders
MAS1Cognitive Impairments
OPN4Circadian Rhythm, Sleep Disorders

In parallel, Omeros is executing on its intellectual property strategy to protect each unlocked target through a multipronged approach directed to compound structures, uniquely identified signaling pathways and associated therapeutic indications. Collectively, this approach provides Omeros the opportunity to establish broad and enforceable protection for each unlocked receptor.


We are optimizing compounds against GPR17, a G protein-coupled receptor (GPCR) which is linked to myelin formation. Myelin is an insulating layer rich in lipids and proteins that forms a sheath around the nerve fibers, which is essential for the proper functioning of the nervous system. Loss of the myelin sheath is the hallmark of several diseases, including multiple sclerosis, acute disseminated encephalomyelitis, Neuromyelitis Optica, transverse myelitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, central pontine myelinosis, inherited demyelinating diseases such as leukodystrophy, and Charcot-Marie-Tooth disease. We believe GPR17 inhibitors have the potential to promote remyelination and improve the outcome of these diseases as well as traumatic brain injury and spinal cord injury, conditions that have been associated with GPR17.

Discovering GPR17 inhibitors has previously been challenging to the pharmaceutical industry because this receptor is an orphan GPCR. However, using our proprietary CRA, we have been able to identify over 100 compounds that functionally interact with GPR17. We are now in the process of developing lead molecules targeting GPR17, which we intend to evaluate in remyelination assays in cell culture systems as well as in animal models.

Patent Position

As of February 15, 2014, we owned five issued patents and 10 pending patent applications in the U.S., and 43 issued patents and eight pending patent applications in foreign markets , which are directed to previously unknown links between specific molecular targets in the brain and a series of CNS disorders, our cellular redistribution assay and other research tools that are used in our GPCR program and to orphan GPCRs and other GPCRs for which we have identified functionally interacting compounds using our cellular redistribution assay.