SEATTLE--(BUSINESS WIRE)--Omeros Corporation (Nasdaq: OMER) last week presented new data directed to its novel cancer immunotherapy target GPR174 at the European Society for Medical Oncology (ESMO) 2019 Immuno-Oncology Congress in Geneva, Switzerland. In addition to previously reported findings, which revealed enhanced anti-tumor immune responses in GPR174-deficient mice and synergism between adenosine receptor antagonists and GPR174 antagonists in promoting interleukin-2 (IL-2) and interferon-γ (IFN-γ) production from human T cells, this presentation included new data from human ex vivo studies demonstrating that GPR174 inhibition results in downregulation of checkpoint and tumor-promoting factors.
The findings, presented by Marc Gavin, Ph.D., Omeros’ Director of Immunology, show that GPR174 suppresses T lymphocytes through the cyclic adenosine monophosphate (cAMP) signaling pathway. In addition to suppressing T-cell function, cAMP signaling is known to enhance production of both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and amphiregulin (AREG), both important drivers of tumor development. CTLA-4 is an immune checkpoint molecule targeted by FDA-approved drugs such as Yervoy® (ipilimumab), and AREG is a cell growth factor involved in promoting tumor growth. The data demonstrate that, using either GPR174 small-molecule inhibitors or in GPR174-deficient mice, the T cell-suppressing effect of cAMP is blocked, resulting in enhanced “tumor-killing” T-cell activation. In addition, the new data show that GPR174 inhibitors reduce both CTLA-4 and AREG levels in T cells, suggesting that multiple pathways – including checkpoint and tumor-promoting factors – downstream of GPR174 inhibition may be inactivated, further augmenting anti-tumor immunity and blocking tumor growth.
“The data show that GPR174 inhibitors enhance anti-tumor immune responses through multiple pathways, including increased production of tumor-fighting cytokines IL-2, IFN-γ, and TNF while suppressing expression of CTLA-4 and AREG,” said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. “Among our ongoing activities, we are exploring the effect of GPR174 inhibition on other checkpoints, including PD-1, and their inhibitors. We are increasingly confident in the role of GPR174 in immuno-oncology and look forward to moving our GPR174 inhibitors into the clinic as quickly as possible with the hope of improving survival for cancer patients.”
Dr. Gavin’s recent presentation at ESMO can be accessed on the company’s website at https://investor.omeros.com/presentations.
About Omeros Corporation
Omeros is an innovative biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers. In addition to its commercial product OMIDRIA® (phenylephrine and ketorolac intraocular solution) 1%/0.3%, Omeros has multiple Phase 3 and Phase 2 clinical-stage development programs focused on complement-mediated disorders and substance abuse, as well as a diverse group of preclinical programs including GPR174, a novel target in immuno-oncology that modulates a new cancer immunity axis recently discovered by Omeros. Small-molecule inhibitors of GPR174 are part of Omeros’ proprietary G protein-coupled receptor (GPCR) platform through which it controls 54 new GPCR drug targets and their corresponding compounds. The company also exclusively possesses a novel antibody-generating platform.
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