Io Therapeutics, Inc. announces publication in Scientific Reports – Nature, of studies showing synergistic efficacy of its RXR agonist IRX4204 with the standard of care drug lenalidomide against multiple myeloma.

SPRING, Texas, March 25, 2026 (GLOBE NEWSWIRE) -- Io Therapeutics, Inc., a privately held pharmaceutical company headquartered in Spring, Texas; announced today publication online in Scientific Reports – Nature, of collaborative studies with Duke University scientists on effects of the company’s anti-cancer compound IRX4204, on human multiple myeloma, a fatal form of bone marrow cancer. The studies were conducted under the leadership of Professor of Medicine Yubin Kang, M.D., in his laboratory at Duke.

The publication reports data from preclinical studies in in vitro and xenograft mouse models demonstrating effectiveness of IRX4204, a retinoid X nuclear receptor (RXR) agonist compound, against human multiple myeloma. IRX4204 also had synergistic efficacy against human multiple myeloma in combination with a standard of care anti-myeloma drug lenalidomide.

The paper reports data showing that IRX4204 induces ferroptosis (a mechanism of cell death) in multiple myeloma cells via the HMOX1/GPX4 axis and thereby enhances lenalidomide efficacy. The studies demonstrated that IRX4204 promotes ferroptosis in human multiple myeloma plasma cells by activating the PPARα/RXRα-HMOX1 axis and suppressing GPX4/SLC7A11-mediated antioxidant defense. This effect synergistically enhances the therapeutic efficacy of IRX4204 with lenalidomide. In vivo, combination treatment with IRX4204 and lenalidomide significantly reduced tumor growth compared to lenalidomide alone and significantly prolonged median survival in the xenograft mouse model without increased systemic toxicity. Tumor analysis confirmed increased HMOX1 and decreased GPX4 expression in combination-treated mice.

The authors also reported that bioinformatic analysis of multiple myeloma patients show that high HMOX1 expression in their plasma cells correlates with significantly improved overall survival (HR=0.51, p<0.001), while advanced-stage multiple myeloma patient plasma cells show progressively lower HMOX1 levels.

Dr. Kang stated: "These studies have multiple important clinical implications. The data identify a druggable ferroptosis pathway in multiple myeloma and provide a mechanistic rationale for combining RXR agonists such as IRX4204 with established therapies such as lenalidomide. Further, our finding of a strong statistical correlation between HMOX1 expression in myeloma patient plasma cells and patient survival suggests potential for biomarker-guided therapy selection.

While multiple myeloma remains largely incurable, treatments such as the standard of care drug lenalidomide and CAR-T cells effectively prolong survival. But almost all myeloma patients eventually relapse and succumb to the disease. Using new combinations of effective treatments including an RXR agonist such as IRX4204 is a rational approach to improving patient outcomes, including potentially cure in more patients.”

Martin E. Sanders, M.D., Chief Executive Officer of Io Therapeutics stated “IRX4204 is a clinical stage compound which was invented by Vidyasagar Vuligonda, Ph.D., 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 various types of cancer. The IRX4204 safety profile likely will be suitable for chronic treatment of multiple myeloma in combination with lenalidomide. IRX4204 previously showed anti-cancer activity in animal models and in phase I and II clinical trials in patients with solid tumor malignancies including lung, breast, prostate and other cancers. The new findings that IRX4204 has synergistic efficacy against multiple myeloma, a hematologic cancer of bone marrow, when combined with a standard of care anti-myeloma drug lenalidomide, adds to the drug’s scope of potential clinical utilities, and may result in increases of the proportions of multiple myeloma patients achieving cure or long-term maintenance of complete responses of 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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