On April 29, 2025 Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, reported data in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting, held April 25-30, 2025, in Chicago, IL (Press release, TONIX Pharmaceuticals, APR 29, 2025, View Source [SID1234652325]). A copy of the Company’s presentation is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. The presentation titled, "TFF2-mediated CXCR4 partial agonism outperforms CXCR4 antagonism in reducing murine gastric cancer by suppressing PMN-MDSC generation," demonstrated positive data in gastric cancer animal models. In the AACR (Free AACR Whitepaper) presentation, a fusion protein of murine trefoil factor family member 2- murine serum albumin (mTFF2-MSA) was studied. Tonix is developing human TFF2-human serum albumin (hTFF2-HAS) as TNX-1700.
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"The combination therapy of mTFF2-MSA with anti-PD1 treatment shows promise in reducing immunosuppression in the tumor microenvironment (TME) in animal models," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "We are excited to develop TNX-1700 (TFF2-HAS) as the lead program in our immuno-oncology pipeline, by testing potential dosing strategies, and establishing potential clinical biomarkers through preclinical models."
Immunosuppressive neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a major component in solid tumors that significantly hinder anti-tumor activity1,2. Despite being short-lived, their continuous replenishment from the bone marrow sustains their potent immunosuppression in the TME3. Stromal cells in the TME promote immunosuppression by recruiting MDSCs via secretion of CXCL12. Trefoil Factor 2 (TFF2), a secreted peptide of the trefoil factor family, has displayed activity as a partial agonist of CXCR44,5. Data presented in the poster demonstrated that TFF2-MSA selectively reduces immunosuppressive neutrophils and cancer-driven granulopoiesis. Treatment with TFF2-MSA, in combination with an anti-PD1 antibody, induced robust anti-tumoral CD8+ T cell responses, inhibiting tumor invasion. TFF2 reduction correlated with elevated PMN-MDSCs in gastric cancer patients, highlighting the potential negative correlation between TFF2 and PMN-MDSCs levels.
About Trefoil Factor Family Member 2 (TFF2)
Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. The inventor of the core technology at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells. He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth. Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment.