Taiwan-based GNTbm (stock code: 7427) has unveiled promising preclinical data for GNTbm-38, a novel epigenetic immune activator designed for cancer immunotherapy, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
The data, presented on June 2, 2025, highlights GNTbm-38's potential as a breakthrough treatment component for advanced microsatellite stable (MSS) colorectal cancer, a type of "cold tumor" that currently lacks effective immune checkpoint inhibitor (ICI) based combination therapies.
Novel Mechanism of Action
GNTbm-38 functions as a class I histone deacetylase inhibitor (HDACi) with a unique dual mechanism. Unlike other epigenetic drugs, it combines epigenetic regulation of gene expression with immune activation properties. This oral drug candidate works by remodeling the tumor microenvironment (TME) through specific epigenetic regulatory mechanisms.
Dr. Alex Chen, Chief Scientific Officer at GNTbm, explained, "GNTbm-38 represents a significant advancement in our approach to treating cold tumors. Its ability to transform the tumor microenvironment could potentially overcome one of the biggest challenges in cancer immunotherapy today."
Impressive Preclinical Results
The preclinical studies demonstrated that when combined with tyrosine kinase inhibitors (TKIs), GNTbm-38 significantly improved tumor response rates and survival through multiple synergistic effects:
- Normalization of tumor vessels
- Enhanced tumor antigen presentation
- Increased infiltration of activated CD8+ T cells into tumors
- Induction of memory T cell persistence
- Inhibition of immunosuppressive cell mobilization into tumors
When combined with anti-PD-1 antibodies in the CT-26 colon cancer model, the compound showed "greatly improved tumor response rate and survival rate with a strong synergistic effect," according to the presentation.
Particularly noteworthy was the performance in a humanized mouse model, where treatment with pembrolizumab and GNTbm-38 resulted in 46.5% inhibition of tumor growth in mice subcutaneously injected with B-hPD-L1 CT-26 cells.
Addressing Unmet Clinical Needs
Advanced MSS colorectal cancer represents a significant unmet clinical need. Unlike microsatellite instability-high (MSI-H) colorectal cancers, MSS tumors typically show poor response to current immunotherapies due to their immunologically "cold" nature.
"The current treatment landscape for MSS colorectal cancer is limited," noted Dr. Sarah Johnson, an oncologist not affiliated with the study. "A compound that can effectively convert these cold tumors into hot tumors could potentially change the standard of care for these patients."
Development Timeline and Future Applications
GNTbm expects to complete its US Investigational New Drug (IND) application by the end of 2025, with clinical studies to follow. The company envisions multiple applications for GNTbm-38:
- As monotherapy for hematological tumors
- In combination with multi-kinase inhibitors for solid tumors
- In combination with immune checkpoint inhibitors for various cancer types
Broader Implications for Cancer Immunotherapy
The development of GNTbm-38 aligns with the growing interest in epigenetic regulators as critical components of combination cancer therapies. Class I HDAC inhibitors have emerged as particularly promising agents that can enhance the efficacy of existing immunotherapies.
GNTbm, which has already developed and marketed a treatment for advanced breast cancer in Taiwan, continues to focus on innovative mechanisms for next-generation cancer immunotherapy. The company aims to address unmet medical needs for patients with advanced cancers globally.
"These preclinical results provide a strong rationale to explore the combination of GNTbm-38 with anti-VEGF TKI with or without ICI," the company stated in their presentation. "GNTbm-38 has been shown to display powerful induction of immune activation and immune memory in combination therapy against colon CT-26 cold tumor."
Based on the comprehensive preclinical package, including in vitro and in vivo studies, GNTbm-38 has demonstrated "markedly superior pharmacokinetics, tolerability, and efficacy in animal models," positioning it as a promising candidate for further clinical development.
