On February 26, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company, reported that the company presented preclinical data on its investigational compounds KROS 101 and KROS 401 during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) conference held in Los Angeles from February 23-26, 2025 (Press release, Kairos Pharma, FEB 26, 2025, View Source [SID1234650631]). The data highlighted positive preclinical outcomes with the Company’s glucocorticoid-induced tumor necrosis factor receptor (GITR) agonist KROS101 in melanoma and glioblastoma as well as its peptide inhibitor for macrophages KROS 401 in glioma animal models.
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In the presentation, titled "KROS 101: A Next Generation GITR agonist boosting anti-tumor T cell responses and reprogramming the tumor environment," study authors demonstrated that KROS significantly inhibited tumor growth in a preclinical melanoma model. The same team of scientists also showed that KROS 101 increased the proliferation of helper and cytotoxic T cells (CD4+ and CD8+), while decreasing T reg cell growth in a melanoma model. Further, T cells treated with KROS 101 showed cytotoxicity against glioblastoma cell lines and glioma cancer cells, which study authors, Admasu, et. al., concluded KROS 101 demonstrated potent anti-tumor activity compared to a previously used antibody against the GITR receptor TRX518 that was in clinical trials. Most importantly, the authors demonstrated KROS 101 but not TRX518 to prevent the exhaustion of T cells in the tumor.
The second presentation, titled "Targeting M2 macrophage polarization: The anti-tumor effects of IL-4/IL-13 blocking peptide and iron oxide nanoparticles," demonstrated the Company’s peptide inhibitor KROS 401 may effectively reprogram macrophages — types of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances – to inhibit tumor growth. The preclinical study demonstrated that KROS 401 exhibited an anti-tumor effect in glioma-bearing mice following a decrease in M2 macrophages, which are known to facilitate tumor growth.
Dr. John Yu, CEO of Kairos Pharma and co-inventor, commented, "We continue to receive validation of our preclinical data demonstrating our KROS platform’s development of anti-tumor therapies. KROS 101 addresses an Achille’s heel of all T cell immunotherapies and that is the development of exhaustion in anti-tumor T cells. KROS 101 appears to prevent the development of exhaustion by T cells enabling them to continue to kill tumor cells."
Dr. Ram Murali, VP of Research and Development stated, "KROS 401 is designed to reverse the M1 to M2 transition of macrophages in the tumor microenviroment. What this translates to is changing pro-tumor macrophages into anti-tumor macrophages. This leads to tumor-killing activity by both macrophages and T cells."
The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) encompasses the very best of basic, translational, and clinical research in immunology, inflammation, and immunotherapies for cancer, including immuno-oncology (IO) drugs, inflammatory modulators, vaccines, and cellular therapies. The cutting-edge AACR (Free AACR Whitepaper) IO 2025 program will appeal to a wide audience of basic scientists, translational researchers, clinical investigators, regulators, industry, investors, and lay press. A mix of keynote lectures, major symposia, spotlight sessions, educational sessions, special sessions, and poster sessions with exhibits will cover the spectrum of the IO field—including late-breaking clinical trials sessions highlighting new agents and IO combinations, and the results of practice-changing clinical trials.