Technology & Products

GNTbm prioritizes the development of innovative cancer immunotherapies due to their exceptional therapeutic efficacy in advanced malignancies, demonstrating the potential to prolong recurrence-free survival (RFS) and offer broad clinical applicability. However, the success of immunotherapy is highly dependent on the state of the tumor microenvironment (TME).

Based on immune activity, tumors are categorized into three distinct phenotypes:

Hot Tumors (Inflamed): Characterized by an inflamed TME with robust infiltration of cytotoxic T lymphocytes (CTLs), capable of inducing strong anti-tumor immune responses.

Cold Tumors (Non-inflamed): Lacking inflammatory signals and exhibiting sparse CTL infiltration, resulting in limited immune recognition.

Immune-Excluded Tumors: A transitional state where CTLs are present at the tumor periphery but are physically or chemically prevented from infiltrating the tumor core.

While immune checkpoint inhibitors (ICIs) have been commercially available for over a decade and show significant efficacy as monotherapy in hot tumors, the majority of solid tumors remain "cold." To enhance clinical outcomes, ICIs must be combined with synergistic agents (Agent X) designed to convert cold or immune-excluded tumors into "hot" phenotypes, thereby amplifying the immune response.

The key to this conversion lies in the dynamic remodeling of the TME. Specifically, the TME must be re-engineered into a pro-inflammatory state to recruit extensive CTL infiltration while preventing premature T-cell exhaustion. Despite numerous clinical trials over the years, success rates have remained low due to unmanageable combinatorial toxicity or failure to meet primary efficacy endpoints.

The R&D team at GNTbm has long focused on developing "Agent X" candidates capable of TME remodeling, particularly two classes of therapeutics for ICI combination. Among these, epigenetic immunoactivators regulate gene expression within TME cells through epigenetic modulation. These agents effectively:

• Promote CTL infiltration into the TME;

• Induce vascular normalization and alleviate hypoxia;

• Enhance antigen presentation effects;

• Inhibit the recruitment of immunosuppressive cell populations;

• Facilitate the formation of immunological memory.

By integrating these characteristics, GNTbm’s therapeutic candidates drive the conversion of cold tumors into hot tumors, ultimately maximizing the curative potential of cancer immunotherapy.

The development of drug X

The TME varies greatly depending on the type of cancer, but most solid tumors are classified as cold tumors, making them difficult to be treated with single-agent ICIs. On the other hand, ICIs do not possess the activity of remodeling the TME. To bridge this gap, combing ICI with drug X is crucial for reprogramming the TME and eliciting a synergistic anti-cancer effects. GNTbm has independently developed two drugs, the first drug epigenetic immunoactivator GNTbm-38, involves gene regulation as its main pharmacological mechanism, accompanied by a potent tumor immune-stimulatory activity. The second drug is a multi-tyrosine kinase inhibitor GNTbm-TKI with strong immune activation effects. They are described as follows:

1. GNTbm-38

(1) Unique Tumor Immune Mechanism: GNTbm-38 is an epigenetic immune-activating drug independently developed by GNTbm for cancer immunotherapy. GNTbm-38 monotherapy is applied to lymphomas and hematologic cancers, its combination with ICI plus anti-angiogenesis drug can transform cold tumors into hot tumors, will significantly broaden therapeutic indications and enhance the benefits of cancer immunotherapy.
(2) Class of epigenetic-regulatory drugs: GNTbm-38 is the benzamide-based class I HDAC inhibitor, classified as a new chemical entity new drug, administered orally.
(3) Drug with activity of epigenetic immune activation: GNTbm-38 differs significantly from past epigenetic modulators in that it possesses activity of potent tumor immune activation, selected through a preclinical animal testing platform with robust immune responses.
(4) Essential component for cancer combination immunotherapy: GNTbm-38 can be combined with ICI for enhancing the treatment effect of cold tumors; it can also be combined with ICI and anti-angiogenesis drug for the immunotherapy of cold tumors. Therefore, it is reasonable to expect that GNTbm-38 can provide better cancer immunotherapy efficacy when combined with anti-PD-1/VEGF or anti-PD-L1/VEGF bispecific antibody.

2. GNTbm-TKI

(1) Unique immune-regulating multi-tyrosine kinase inhibitor: Although many multi-tyrosine kinase inhibitors have been approved by the US FDA, there are not many that are primarily focused on immune regulation. GNTbm has independently developed the orally administered GNTbm-TKI, which is a potent inhibitor of TYRO-3, AXL, c-MER, BTK, ROS1, NTRK2, MET, and VEGFR2, demonstrating strong immune regulation, tumor growth inhibition, metastasis and invasion suppresion, and anti-angiogenesis activity.
(2) Multi-tyrosine kinase inhibitor with potent immune modulation: The inhibition of those targets primarily obtains synergistic and potent immune modulation activity, which can remodel TME. When combined with ICI, it is expected to achieve superior therapeutic benefits.
(3) Compared to marketed drugs, it has an absolute competitive advantage: GNTbm-TKI has demonstrated stronger immune-regulating activity than Cabozantinib and Zanzalintinib in head-to-head animal models, highlighting its superior potential for cancer immunetherapy.
(4) Essential component for the new generation of cancer combination immunotherapy: Next-generation immunotherapy relies on the strategic combination of checkpoint inhibitors or bispecific antibodies with synergistic agents. GNTbm-TKI possesses a unique mechanism that provides a robust synergistic foundation, markedly enhancing the therapeutic benefits of established immunotherapies.
(5) Treatment for different indications: GNTbm-TKI monotherapy for neuroendocrine tumors; combination therapy for various solid tumors, including advanced renal cell carcinoma, colorectal cancer, and head and neck cancer.

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