TAIPEI, May 23, 2025 /PRNewswire/ -- GNTbm (stock code: 7427, Taiwan) announced the preclinical data on GNTbm-38, an novel epigenetic immune activator for cancer immunotherapy. GNTbm-38 was presented as posters at the 2025 American Association of Clinical Oncology (ASCO) Annual Meeting, which is held in Chicago, USA, from May 30 to Jun 04, 2025.
Abstract: 2574
Title: Preclinical development of GNTbm-38, a novel class I histone deacetylase inhibitor, while combined with anti-VEGFR TKI or anti-PD-1 Ab: Assessment of immune activation and immune memory in cancer immunotherapy.
Session Date/Time: 6/2/2025, 1:30 PM-4:30 PM CT
Poster Board Number: 221
At present, there is no ICI-based drug combination for the treatment of advanced MSS colorectal cancer, which is a cold tumor. Studies have shown that epigenetic regulators such as class I HDAC inhibitors are an emerging and important drug component for combination therapy that can greatly increase the anti-cancer benefits of cancer immunotherapy. Therefore, rational drug combinations, containing class I HDACi, may provide opportunities in cancer immunotherapy.
GNTbm-38 is a new drug candidate independently developed by GNTbm. GNTbm-38 acts as a TME reprogramming regulator in immunotherapy. When combined with TKI, GNTbm-38 significantly improved tumor response rate and survival rate through synergistic effect by normalizing tumor vessels, increasing tumor antigen presentation, increasing activated CD8+ T cell infiltration into tumors, inducing memory T cell persistence, and inhibiting mobilization of immunosuppressive cells into tumors. On the other hand, treatment with GNTbm-38 plus anti-PD-1 antibody in the CT-26 model showed greatly improved tumor response rate and survival rate with a strong synergistic effect. Furthermore, in B-hPD-1/hPD-L1 mice (humanized model) subcutaneously injected with B-hPD-L1 CT-26 cells, treatment of pembrolizumab and GNTbm-38 resulted in a 46.5% inhibition on tumor growth. Therefore, our data provided a strong rationale to explore the combination of GNTbm-38 with anti-VEGF TKI with or without ICI. From these data GNTm-38 has been shown to display powerful induction of immune activation and immune memory in combination therapy with TKI/ICI against colon CT-26 cold tumor. Based on the in vitro, in vivo and preclinical studies, these data show that GNTbm-38 exhibits markedly superior pharmacokinetics, tolerability, and efficacy in animal models. It is expected to complete the US IND application by the end of 2025 and enter the clinical study.
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