8-K: Tonix Pharmaceuticals Unveils Promising Preclinical Data for Cancer Immunotherapy Candidate TNX-1700 in Gastric Cancer

Tonix Pharmaceuticals announced the publication of preclinical data in Cancer Cell journal, demonstrating that its investigational drug mTNX-1700 significantly improved survival and reduced metastases in animal models of gastric cancer when combined with anti-PD-1 immunotherapy.

Summary

• Tonix Pharmaceuticals announced the publication of a paper in the peer-reviewed journal Cancer Cell, detailing preclinical data for murine TNX-1700 (mTNX-1700).
• The study, a collaboration with Columbia University's Medical School, showed that mTNX-1700 treatment increased survival and decreased metastases in animal models of gastric cancer.
• When combined with anti-PD-1 antibody, mTNX-1700 was associated with increased survival and decreased metastases relative to anti-PD-1 treatment alone.
• mTNX-1700 treatment activated cancer-killing CD8+ T Cells and limited neutrophil-mediated immune evasion.
• The human version, TNX-1700 (hTFF2-HSA fusion protein), is currently in preclinical development for the treatment of gastric and colorectal cancers.
• The data supports further development of TNX-1700 as an approach to overcome resistance to anti-PD-1 immunotherapy in gastric cancer and other tumors.
• The study demonstrated that mTNX-1700 plus anti-PD-1 shrank primary tumors, cut liver and lung metastases, and increased survival in several mouse models compared to anti-PD-1 alone.
• TFF2-MSA, a component of mTNX-1700, selectively reduces immunosuppressive neutrophils (PMN-MDSCs) and cancer-driven granulopoiesis.
• TFF2 reduction correlated with elevated PMN-MDSCs in gastric cancer patients, suggesting a potential negative correlation between TFF2 and PMN-MDSCs levels while promoting a T-cell rich microenvironment.

Sentiment

Score: 7

Explanation: The announcement presents strong positive preclinical data for a novel cancer therapeutic approach, addressing a significant unmet need in immuno-oncology. While preclinical, the results are compelling and published in a high-impact journal, indicating promising early-stage development.

Positives

• Preclinical data showed mTNX-1700 increased survival and decreased metastases in animal models of gastric cancer.
• Combination treatment of mTNX-1700 with anti-PD1 antibody significantly improved outcomes compared to anti-PD1 alone.
• mTNX-1700 treatment activated cancer-killing CD8+ T Cells, indicating a robust anti-tumoral immune response.
• The drug candidate effectively limited neutrophil-mediated immune evasion, a key hurdle in immunotherapy.
• The findings support TNX-1700's potential to overcome resistance to anti-PD-1 immunotherapy, addressing a significant unmet medical need.
• The study demonstrated that fine-tuned modulation of CXCR4 can dismantle neutrophil-driven immune suppression and revive checkpoint efficacy without compromising normal myelopoiesis.
• Collaboration with Columbia University and Dr. Timothy Wang, an expert in carcinogenesis, strengthens the scientific foundation of the research.

Risks

• Risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations.
• Risks related to the failure to successfully market any products.
• Risks related to the timing and progress of clinical development of product candidates.
• The need for additional financing to support ongoing development.
• Uncertainties of patent protection and litigation.
• Uncertainties of government or third-party payor reimbursement.
• Limited research and development efforts and dependence upon third parties.
• Substantial competition in the pharmaceutical industry.
• Significant inherent risks in the development, regulatory approval, and commercialization of new pharmaceutical products.

Future Outlook

The company believes the published preclinical data supports further development of TNX-1700 as an approach to overcome resistance to anti-PD-1 immunotherapy in the treatment of gastric cancer and other tumors. They plan to continue studies to identify potential clinical biomarkers through preclinical models and enhance understanding of TFF2's role in overcoming anti-PD1 resistance in the tumor microenvironment.

Management Comments

• Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals, stated, 'Addressing the root causes of resistance to immunotherapy in solid tumors is a hurdle for the successful application of immuno-oncology to anti-PD-1 resistant cancers.'
• Dr. Lederman also commented, 'The combination therapy of mTFF2-MSA with anti-PD1 treatment shows significant promise in reducing the ability of tumors to evade anti-PD-1 therapy in animal models.'
• Dr. Lederman added, 'We believe the published data support further development of TNX-1700 as an approach to overcome resistance to anti-PD-1 immunotherapy in the treatment of gastric cancer and other tumors.'
• Dr. Lederman further noted, 'The study showed that in several mouse models, mTNX-1700 plus anti-PD-1 shrank primary tumors, cut liver and lung metastases, and increased survival compared to anti-PD-1 alone.'
• Dr. Lederman highlighted, 'These data show that fine-tuned modulation of CXCR4 can dismantle neutrophil-driven immune suppression and revive checkpoint efficacy without compromising normal myelopoiesis.'
• Dr. Lederman expressed excitement, stating, 'We are excited, through our collaboration with Columbia University, to continue studies to identify potential clinical biomarkers through preclinical models while enhancing our understanding of the relationship between the role of TFF2 in overcoming resistance to anti-PD1 therapy in the tumor microenvironment (TME).'

Industry Context

This announcement is highly relevant to the immuno-oncology field, particularly addressing the significant challenge of resistance to anti-PD-1 therapies in solid tumors. The focus on targeting immunosuppressive neutrophils (PMN-MDSCs) and modulating CXCR4 represents a novel and promising approach within the broader landscape of cancer treatment, aiming to enhance the efficacy of existing checkpoint inhibitors.

Comparison to Industry Standards

• The findings address a critical unmet need in immuno-oncology: overcoming resistance to anti-PD-1 therapy, a challenge faced by many existing cancer treatments.
• The mechanism of action, involving the selective reduction of immunosuppressive neutrophils and activation of CD8+ T cells, positions TNX-1700 as a potentially differentiated approach compared to other investigational or approved immunotherapies.
• The collaboration with Columbia University and Dr. Timothy Wang, a recognized expert in the molecular mechanisms of carcinogenesis, lends significant scientific credibility to the preclinical findings, aligning with industry best practices for early-stage drug development.

Stakeholder Impact

• Shareholders: Potential positive impact due to promising preclinical data for a new drug candidate, which could increase the company's long-term value.
• Patients: Potential for a new therapeutic option to overcome resistance to existing cancer immunotherapies, particularly for gastric and colorectal cancers.
• Scientific Community: Contribution of new research findings to the understanding of cancer immunology and immunotherapy resistance mechanisms.
• Employees: Positive impact on morale and potential for continued research and development opportunities.

Next Steps

• Further development of TNX-1700 for the treatment of gastric cancer and other tumors.
• Continue studies to identify potential clinical biomarkers through preclinical models.
• Enhance understanding of the relationship between the role of TFF2 in overcoming resistance to anti-PD1 therapy in the tumor microenvironment.

Key Dates

Keywords

Tonix Pharmaceuticals, TNX-1700, Gastric Cancer, Immunotherapy, Anti-PD-1 Resistance, Cancer Cell Journal, Preclinical Data, CXCR4 Partial Agonist, Immunosuppressive Neutrophils, CD8+ T Cells, Colorectal Cancer, Biopharmaceutical, Oncology