Omeros’ Proprietary Orphan GPCR Program Delivers New Target and Approach in Cancer Immunotherapy
-- Small-Molecule Inhibitors Enhance Immune System and
In assays with human peripheral blood mononuclear cells (PBMCs)
evaluating T-cell proliferation and survival following T-cell
These results demonstrate that GPR174 inhibition potentiates the activity of effector T cells, which produce cytokines and are known to be integral to combatting cancer. Also, reducing the level of Tregs is a key objective in cancer immunotherapy, and high levels of Tregs in solid tumors frequently correlates with poor patient outcomes. In addition, signaling and mechanistic studies support that GPR174 suppresses anti-tumor activity, and inhibitors of GPR174 are expected to counteract that detrimental suppression.
“The data from Omeros’ GPR174 program are exciting, as they may lead to
a new approach to increase immune function through simultaneous
modulation of multiple immune cell subsets,” stated
Based on the collective data, small-molecule inhibitors of GPR174 could provide a significant advance in cancer immunotherapy with meaningful potential advantages over current cancer immunotherapies in development, including CAR-T cell therapy and checkpoint inhibitors. Small molecules, unlike antibodies, can be formulated for oral, intravenous, intralesional and topical delivery, addressing some of the administration and procedural limitations of other immunotherapies. Small-molecule compounds, because of their shorter half-life than antibodies, should not have the same safety concerns (e.g., acute, life-threatening immune reactions due to extended duration of drug activity) associated with CAR-T cell and checkpoint therapies. GPR174 inhibitors act on both CD4 (helper) and CD8 (cytotoxic) T-cells and should not rely on the presence of specific tumor cell-surface receptors to be effective as do checkpoint inhibitors. GPR174 inhibitors represent a class of agents that could treat a broad range of cancers – the primary mechanistic limitation of a GPR174 inhibitor is expected to be a cancer cell that is recognized by the body’s immune system as fully “self,” i.e., a cancer cell without mutation, which is quite rare.
“Omeros’ proprietary orphan GPCR program continues to generate new drug
targets, and GPR174 is one of our current areas of focus,” stated
About Omeros’ GPCR Program
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 with nearly half of those targeted either by marketed drugs (46 GPCRs) or by drugs in development (about 82 GPCRs). There are approximately 120 orphan GPCRs, which have no known ligands. Without a known ligand, drug development for a given receptor is extremely difficult.
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. All statements
other than statements of historical fact are forward-looking statements,
which are often indicated by terms such as “anticipate,” “believe,”
“could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,”
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“would” and similar expressions and variations thereof. 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, risks associated with product
commercialization and commercial operations, unproven preclinical and
clinical development activities, regulatory oversight, intellectual
property claims, competitive developments, litigation, and 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
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Cook Williams Communications, Inc.
Jennifer Cook Williams
Investor and Media Relations