IRX4647 / Io Therap - LARVOL DELTA

RAR gamma agonist compounds inhibit tumor growth, promote effector memory tumor infiltrating T-cells, and inhibit tumor infiltrating myeloid derived suppressor cells in multiple cancer models (SITC 2024) - "We performed in vivo evaluation of three RARg agonist compounds: IRX4647, IRX5010, and tazarotenic acid, in syngeneic murine models of NSCLC (Lewis Lung Cancer), triple negative breast (EMT6), colorectal (MC38), and prostate cancer (MyC-CaP). These data support that RARg agonism is a potential new approach for immunotherapy of cancers. They expand studies recently published by our collaborators at the Frederick National Laboratory for Cancer Research with ourselves, which demonstrated effects of our first generation RARg agonist IRX4647 on tumor growth and immune microenvironment in a murine model of NSCLC, with increased TILs, and combination treatment effects on lung tumor growth with anti-PD-L1 checkpoint inhibitor.2"

IO biomarker • Myeloid-derived suppressor cells • Preclinical • Breast Cancer • Colorectal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • B2M • CD8 • HER-2 • RARG

Io Therapeutics, Inc., Announces Publication of Data on a Novel Compound Promoting Anti-Cancer Immune Responses (GlobeNewswire) - "Io Therapeutics, Inc., announced today the publication in Scientific Reports – Nature Publishing Group, of results from studies done with the company’s novel anti-cancer compound IRX4647, an agonist of the retinoic acid nuclear receptor gamma, discovered in the company’s oncology drug program....The studies showed that oral treatment with IRX4647 in combination with an immune checkpoint inhibitor (anti-PD-L1) resulted in suppression of a typically checkpoint inhibitor treatment-resistant syngeneic lung cancer in mice. IRX4647 did not appreciably impact growth of the lung tumor cells in cultures, indicating that the compound alone is not directly toxic to lung cancer cells."

Preclinical • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A novel retinoic acid receptor-γ agonist antagonizes immune checkpoint resistance in lung cancers by altering the tumor immune microenvironment. (PubMed, Sci Rep) - "To augment ATRA's anti-tumorigenicity without promoting its pro-tumorigenic potential, an RARγ agonist (IRX4647) was used since it regulates T cell biology...Yet, RARα antagonist (IRX6696)-treatment with anti-PD-L1 did not repress syngeneic lung cancer growth. Together, these findings provide a rationale for a clinical trial investigating an RARγ agonist to augment check point blockade response in cancers."

IO biomarker • Journal • Lung Cancer • Oncology • Solid Tumor • CD38 • CD4 • CD8 • IL13 • IL5 • RARA