Io Therapeutics, Inc., presents today at the San Antonio Breast Cancer Symposium preclinical studies demonstrating effectiveness of IRX4204, the company's clinical stage retinoid X nuclear receptor (RXR) agonist compound, for synergistically promoting killing of HER2+ breast cancer cells in combination with HER2-targeted chimeric antigen receptor modified T-cells (CAR-T).

SPRING, Texas, Dec. 11, 2025 (GLOBE NEWSWIRE) -- Io Therapeutics, Inc., a privately held pharmaceutical company headquartered in Spring, Texas; announced today presentation at the San Antonio Breast Cancer Symposium, in San Antonio, TX; of data from preclinical studies demonstrating effectiveness of IRX4204, the company's phase II clinical stage retinoid X nuclear receptor (RXR) agonist compound, for promoting killing of HER2+ breast cancer cells in combination with HER2-targeted chimeric antigen receptor modified T-cells (CAR-T). IRX4204 demonstrated synergistic killing with HER2-targeted CAR-T cells of human HER2+ breast cancer cells in vitro. The presentation by Drs. Martin E. Sanders, M.D., and Vidyasagar Vuligonda, Ph.D., is titled, “The RXR agonist IRX4204 promotes cytotoxicity of HER2+ breast cancer by HER2 targeted CAR-T cells.”

CAR-T cells targeting various types of hematologic cancers, such as multiple myeloma and lymphomas have been highly clinically effective. However, progress in developing effective CAR-T cells against solid tumors, such as breast cancers, has been slow. It has previously been reported that IRX4204 has synergistic HER2+ breast cancer killing effects in combination with HER2-targeted antibodies and HER2-selective tyrosine kinase inhibitors (Moyer, C., et. al., Clinical Cancer Research, June, 2024). Based on these reported combination effects of IRX4204 with anti-HER2-targeted agents on HER2+ breast cancers, we hypothesized that IRX4204 may have combination effects with HER2-targeted CAR-T cells on killing of HER2+ breast cancer cells.

IRX4204 did not affect expression of cell surface HER2 on breast cancer cells. However, IRX4204 increased expression of a T-cell adhesion molecule called ICAM-1 on HER2+ breast cancer cells. This effect promotes T-cell adhesion, tumor infiltration, and cytotoxic tumor cell killing. IRX4204 increased infiltration of CAR-T cells into spheroids of cultured HER2+ breast cancer cells. IRX4204 alone had cytotoxic effect on HER2+ breast cancer cells, however, in combination with HER2-targeted CAR-T, IRX4204 synergistically promoted killing of HER2+ breast cancer cells.

Dr. Sanders, Chief Executive Officer of Io Therapeutics, stated “IRX4204 is a clinical stage compound which was invented by Dr. Vuligonda, Chief Science Officer of Io Therapeutics. IRX4204 more potently and more selectively activates RXR than earlier generation RXR agonists. It has demonstrated an excellent chronic dosing safety profile in clinical trials in patients with lung, prostate, and other cancers. The IRX4204 safety profile likely will be suitable for chronic treatment of HER2+ breast cancer in combination with HER2-targeted CAR-T cells, and other HER2-targeted agents. IRX4204 previously showed anti-cancer activity in phase I and II clinical trials in patients with various types of solid tumor malignancies. The new findings that IRX4204 has synergistic killing effects against HER2+ breast cancer cells in combination with HER2-targeted CAR-T cells adds to the drug's scope of potential clinical utilities, and may result in increase of the number of HER2+ breast cancer patients achieving durable responses to combination treatments for their cancers.”

More information about Io Therapeutics, Inc., and its product development programs is available on the company's web site: www.io-therapeutics.com

Forward Looking Statements: This new release contains "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995.

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