Therapy Areas: Central Nervous System
Omeros' Newly Presented GPR174 Immuno-oncology Data at ESMO Immuno-Oncology Congress Show Inhibition of Both Checkpoint and Tumor-Promoting Factors
19 December 2019 - - US-based biopharmaceutical company Omeros Corp. (NASDAQ: OMER) last week presented new data directed to its novel cancer immunotherapy target GPR174 at the European Society for Medical Oncology 2019 Immuno-Oncology Congress in Geneva, Switzerland, the company said.

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 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 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, 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.

Omeros is an 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 programmes focused on complement-mediated disorders and substance abuse, as well as a diverse group of preclinical programmes 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 platform through which it controls 54 new GPCR drug targets and their corresponding compounds.

The company also exclusively possesses a novel antibody-generating platform.