On December 16, 2019 Omeros Corporation (Nasdaq: OMER) reported new data directed to its novel cancer immunotherapy target GPR174 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Immuno-Oncology Congress in Geneva, Switzerland (Press release, Omeros, DEC 16, 2019, View Source [SID1234552404]). 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.
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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 (Free ESMO Whitepaper) can be accessed on the company’s website at View Source