Ikena Oncology Announces Publication in Nature Communications of Preclinical Data Supporting the Therapeutic Potential of AHR Blockade
Scientific Research Conducted in Collaboration with the Jedd Wolchok Lab at Memorial Sloan Kettering Cancer Center
Data Demonstrate that AHR Blockade Reverses Tumor Immunosuppression
Results Support the Clinical Investigation of IK-175 Alone and in Combination with Anti-PD-1 Therapy
Boston, Mass. – August 12, 2020 – Ikena Oncology, a clinical-stage biotechnology company that discovers and develops patient-directed, biomarker-driven therapies, today announced the publication in Nature Communications of a preclinical collaboration with the Jedd Wolchok and Taha Merghoub team at Memorial Sloan Kettering Cancer Center (MSK). The manuscript, titled, “Blockade of the AHR restricts a Treg-Macrophage suppressive axis induced by L-Kynurenine,” (Campesato, et al) describes the preclinical activity of aryl hydrocarbon receptor (AHR) blockade, alone and in combination with anti-PD-1 immunotherapy. It further supports the potential of IK-175, Ikena’s internally developed, orally administered, selective AHR antagonist currently in Phase 1 clinical development.
“AHR is known to be expressed by several cell types within the tumor microenvironment (TME), to play an important role in modulation of the body’s immune response to tumors, and to be activated in tumor and immune cells,” said Jason Sager, M.D., Chief Medical Officer of Ikena Oncology. “These newly published data notably establish that selective AHR inhibition overcomes those immunosuppressive features in the TME and can additionally sensitize otherwise immune resistant tumors to clinically approved anti-PD-1 inhibitors. Collectively, it supports our recently initiated Phase 1 study evaluating IK-175 as a single-agent in patients with urothelial carcinoma and other advanced solid tumors. These data also point towards the potential for evaluating IK-175 in combination with an anti-PD-1 inhibitor.”
In this preclinical study, which includes use of an Ikena AHR antagonist similar to IK-175, researchers demonstrated that AHR blockade reverses IDO/TDO-mediated immunosuppression. This immunosuppression allows a tumor to evade the immune system and is a key driver of tumor growth and progression. Moreover, the study supports a previously undescribed role for AHR signaling in regulatory T cells to modulate tumor associated macrophages and mediate immune resistance. The data also demonstrated that AHR inhibition, in combination with immune checkpoint blockade, led to prolonged survival in tumor-bearing mice when compared to single-agent anti-PD-1 treatment.
Mark Manfredi, Ph.D., President and Chief Executive Officer of Ikena Oncology, commented, “We are honored to collaborate with Jedd Wolchok and his research team at MSK. The findings published today are especially compelling because they suggest that blocking the AHR pathway has the potential to overcome the limitations of prior IDO targeting agents. We believe this research provides important rationale for implementing a personalized approach to immunotherapy. Together, with key Ikena translational findings to identify which patients may benefit most, the data presented in this manuscript is significant in informing the design of future clinical trials investigating single-agent and combination strategies with IK-175.”
The manuscript can be accessed online here.
IK-175 (formerly known as KYN-175) is an internally-developed, orally-administered, selective aryl hydrocarbon receptor (AHR) antagonist which prevents AHR-modulated tumor promotion through its influence on both the tumor and the immune system. Ikena Oncology has commenced a first-in-human, single-arm, open-label, dose-escalation and expansion Phase 1 clinical study (NCT04200963) designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of IK-175 as a single-agent in patients with locally advanced or metastatic solid tumors, including urothelial carcinoma. US Patent 10,570,138 with claims directed to IK-175 has been issued by the United States Patent and Trademark Office. The AHR antagonist program is the subject of a global strategic collaboration with Bristol Myers Squibb (formerly Celgene).
About Ikena Oncology
Ikena Oncology is a clinical-stage biotechnology company that discovers and develops patient-directed, biomarker-driven therapies for cancer patients who need life-saving treatment, by understanding what drives their disease. Ikena is advancing five clinical, preclinical, and discovery programs: IK-007, an EP4 receptor antagonist; IK-175, an AHR antagonist; IK-412, a kynurenine-degrading enzyme (“Kynase”); discovery-stage molecules targeting the Hippo signaling pathway; and a discovery-stage program against an undisclosed target. Ikena has entered into a global strategic collaboration with Bristol Myers Squibb on the AHR antagonist and Kynase programs. Ikena has raised capital from top tier investors OrbiMed Advisors and Atlas Venture.