Tonix Pharmaceuticals Presented Preclinical Data on Gastric Cancer Models at the American Association for Cancer Research (AACR) 2025 Annual Meeting
Tonix Pharmaceuticals presented promising preclinical data for gastric cancer treatment at the AACR 2025 Annual Meeting in Chicago. The research focused on a combination therapy using TFF2 with anti-PD1 antibody, showing positive results in activating cancer-killing CD8+ T cells.
The study demonstrated that TFF2-MSA, when combined with anti-PD1 antibody, effectively reduces immunosuppression in the tumor microenvironment. The company is developing TNX-1700 (TFF2-HAS) as their lead immuno-oncology program.
Key findings revealed that TFF2-MSA selectively reduces immunosuppressive neutrophils and cancer-driven granulopoiesis. The research also identified a potential negative correlation between TFF2 and PMN-MDSCs levels in gastric cancer patients, suggesting therapeutic potential for treating gastric and colorectal cancers.
Tonix Pharmaceuticals ha presentato dati preclinici promettenti per il trattamento del cancro gastrico al AACR 2025 Annual Meeting di Chicago. La ricerca si è concentrata su una terapia combinata che utilizza TFF2 insieme all'anticorpo anti-PD1, mostrando risultati positivi nell'attivazione delle cellule CD8+ T citotossiche.
Lo studio ha dimostrato che TFF2-MSA, combinato con l'anticorpo anti-PD1, riduce efficacemente l'immunosoppressione nel microambiente tumorale. L'azienda sta sviluppando TNX-1700 (TFF2-HAS) come programma principale di immuno-oncologia.
I risultati chiave hanno evidenziato che TFF2-MSA riduce selettivamente i neutrofili immunosoppressivi e la granulopoiesi indotta dal cancro. La ricerca ha inoltre identificato una possibile correlazione negativa tra i livelli di TFF2 e PMN-MDSCs nei pazienti con cancro gastrico, suggerendo un potenziale terapeutico per il trattamento dei tumori gastrici e del colon-retto.
Tonix Pharmaceuticals presentó datos preclínicos prometedores para el tratamiento del cáncer gástrico en la AACR 2025 Annual Meeting en Chicago. La investigación se centró en una terapia combinada que utiliza TFF2 junto con anticuerpo anti-PD1, mostrando resultados positivos en la activación de células CD8+ T citotóxicas.
El estudio demostró que TFF2-MSA, combinado con el anticuerpo anti-PD1, reduce eficazmente la inmunosupresión en el microambiente tumoral. La compañía está desarrollando TNX-1700 (TFF2-HAS) como su programa principal de inmuno-oncología.
Los hallazgos clave revelaron que TFF2-MSA reduce selectivamente los neutrófilos inmunosupresores y la granulopoyesis inducida por el cáncer. La investigación también identificó una posible correlación negativa entre los niveles de TFF2 y PMN-MDSCs en pacientes con cáncer gástrico, sugiriendo un potencial terapéutico para tratar cáncer gástrico y colorrectal.
토닉스 파마슈티컬스는 시카고에서 열린 AACR 2025 연례 회의에서 위암 치료를 위한 유망한 전임상 데이터를 발표했습니다. 연구는 TFF2와 항-PD1 항체를 결합한 병용 요법에 초점을 맞추었으며, 암을 공격하는 CD8+ T 세포 활성화에 긍정적인 결과를 보였습니다.
연구는 TFF2-MSA가 항-PD1 항체와 결합할 때 종양 미세환경 내 면역 억제를 효과적으로 감소시킨다는 것을 입증했습니다. 회사는 주요 면역항암제 프로그램으로 TNX-1700 (TFF2-HAS)을 개발 중입니다.
주요 발견사항은 TFF2-MSA가 면역 억제성 호중구와 암 유도 과립구생성을 선택적으로 감소시킨다는 점입니다. 또한 연구는 위암 환자에서 TFF2와 PMN-MDSCs 수치 간에 부정적 상관관계가 있을 가능성을 확인하여, 위암 및 대장암 치료에 대한 치료적 잠재성을 시사합니다.
Tonix Pharmaceuticals a présenté des données précliniques prometteuses pour le traitement du cancer gastrique lors du AACR 2025 Annual Meeting à Chicago. La recherche s'est concentrée sur une thérapie combinée utilisant TFF2 avec un anticorps anti-PD1, montrant des résultats positifs dans l'activation des cellules CD8+ T tueuses de cancer.
L'étude a démontré que TFF2-MSA, lorsqu'il est combiné à l'anticorps anti-PD1, réduit efficacement l'immunosuppression dans le microenvironnement tumoral. L'entreprise développe TNX-1700 (TFF2-HAS) comme programme principal en immuno-oncologie.
Les résultats clés ont révélé que TFF2-MSA réduit sélectivement les neutrophiles immunosuppresseurs et la granulopoïèse induite par le cancer. La recherche a également identifié une corrélation négative potentielle entre les niveaux de TFF2 et de PMN-MDSCs chez les patients atteints de cancer gastrique, suggérant un potentiel thérapeutique pour le traitement des cancers gastriques et colorectaux.
Tonix Pharmaceuticals präsentierte vielversprechende präklinische Daten zur Behandlung von Magenkrebs auf dem AACR 2025 Annual Meeting in Chicago. Die Forschung konzentrierte sich auf eine Kombinationstherapie mit TFF2 und einem Anti-PD1-Antikörper, die positive Ergebnisse bei der Aktivierung von krebsbekämpfenden CD8+ T-Zellen zeigte.
Die Studie zeigte, dass TFF2-MSA in Kombination mit dem Anti-PD1-Antikörper die Immunsuppression im Tumormikroumfeld effektiv reduziert. Das Unternehmen entwickelt TNX-1700 (TFF2-HAS) als ihr führendes Immunonkologie-Programm.
Wichtige Erkenntnisse zeigten, dass TFF2-MSA selektiv immunsuppressive Neutrophile und krebsbedingte Granulopoese reduziert. Die Forschung identifizierte zudem eine potenzielle negative Korrelation zwischen TFF2- und PMN-MDSCs-Spiegeln bei Patienten mit Magenkrebs, was auf ein therapeutisches Potenzial für die Behandlung von Magen- und Darmkrebs hindeutet.
- Positive preclinical data showing TFF2-MSA + anti-PD1 combination reduces immunosuppression in tumor models
- TNX-1700 advancing as lead program in immuno-oncology pipeline
- Data demonstrates TFF2-MSA selectively reduces immunosuppressive neutrophils
- Treatment combination induced robust anti-tumoral CD8+ T cell responses
- Still in early preclinical development stage - no human trials yet
- No efficacy data in human patients presented
- Multiple development stages required before potential commercialization
Insights
Tonix's preclinical data shows TFF2 reduces immunosuppressive cells in gastric cancer models, enhancing anti-PD1 therapy effectiveness.
Tonix Pharmaceuticals has presented preclinical data for their compound TNX-1700 (TFF2-HAS) at the AACR Annual Meeting. The data demonstrates that in animal models of gastric cancer, a fusion protein of trefoil factor 2 (TFF2) selectively reduces immunosuppressive neutrophils called polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs).
The mechanism involves TFF2 acting as a partial agonist of CXCR4, which differs from complete CXCR4 antagonism. This partial agonism appears to suppress the generation of PMN-MDSCs, which are known to inhibit anti-tumor immune responses. When combined with anti-PD1 antibody therapy, the treatment induced robust anti-tumoral CD8+ T cell responses and inhibited tumor invasion in the tested animal models.
An additional finding shows correlation between TFF2 reduction and elevated PMN-MDSCs in gastric cancer patients, suggesting potential clinical relevance. The company is developing TNX-1700 for gastric and colorectal cancers, where new therapeutic approaches are needed.
This represents early-stage progress in Tonix's immuno-oncology pipeline, though considerable development work remains before human clinical trials can begin. The combination approach with checkpoint inhibitors like anti-PD1 antibodies suggests a complementary strategy rather than a standalone therapy.
Tonix advances preclinical oncology pipeline with positive animal data for TNX-1700, positioning it as potential combination therapy with checkpoint inhibitors.
Tonix Pharmaceuticals has demonstrated positive preclinical results for TNX-1700 (TFF2-HAS) in gastric cancer models, representing progress in their oncology pipeline development. The data presented at the AACR Annual Meeting shows that their trefoil factor 2 (TFF2) compound, when combined with anti-PD1 antibody treatment, effectively reduces immunosuppression in the tumor microenvironment of animal models.
This approach specifically targets polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which inhibit anti-tumor immune responses. By reducing these immunosuppressive cells, TNX-1700 appears to enhance the effectiveness of checkpoint inhibitor therapy, creating a more favorable environment for immune-based cancer killing.
For Tonix, which describes itself as a "fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates," this represents advancement in their immuno-oncology portfolio. The company has positioned TNX-1700 as their lead program in immuno-oncology, targeting gastric and colorectal cancers.
The preclinical stage of this program indicates that human trials have not yet begun. The development path for oncology drugs typically involves multiple phases of clinical trials spanning several years before potential regulatory approval. These early positive results, while promising, represent just the initial step in a lengthy development process.
Combination treatment of TFF2 with anti-PD1 antibody was associated with the activation of cancer-killing CD8+ T Cells and limiting immune evasion by tumor cells
TNX-1700 is in preclinical development for gastric and colorectal cancers
CHATHAM, N.J., April 29, 2025 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, presented data in a poster presentation at the American Association for Cancer Research (AACR) 2025 Annual Meeting, held April 25-30, 2025, in Chicago, IL. 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 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.
“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.
1Kim W, et al. PD-1 Signaling Promotes Tumor-Infiltrating Myeloid-Derived Suppressor Cells and Gastric Tumorigenesis in Mice. Gastroenterology. 2021 Feb;160(3):781-796
2Veglia F, et al. Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice. J Exp Med. 2021 Apr 5;218(4):e20201803.
3Colligan SH, et al. Inhibiting the biogenesis of myeloid-derived suppressor cells enhances immunotherapy efficacy against mammary tumor progression. J Clin Invest. 2022 Dec1;132(23):e158661.
4Dubeykovskaya Z, et al. Secreted trefoil factor 2 activates the CXCR4 receptor in epithelial and lymphocytic cancer cell lines. J Biol Chem. 2009 Feb 6;284(6):3650-62.
5Dubeykovskaya Z, et al. Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer. Nat Commun. 2016 Feb 4;7:10517.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a fully-integrated biopharmaceutical company focused on transforming therapies for pain management and vaccines for public health challenges. Tonix’s development portfolio is focused on central nervous system (CNS) disorders. Tonix’s priority is to advance TNX-102 SL, a product candidate for the management of fibromyalgia, for which an NDA was submitted based on two statistically significant Phase 3 studies for the management of fibromyalgia and for which a PDUFA (Prescription Drug User Fee act) goal date of August 15, 2025 has been assigned for a decision on marketing authorization. The FDA has also granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS study funded by the U.S. Department of Defense (DoD). Tonix’s immunology development portfolio consists of biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an Fc-modified humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. Tonix also has product candidates in development in infectious disease, including a vaccine for mpox, TNX-801. Tonix recently announced a contract with the U.S. DoD’s Defense Threat Reduction Agency (DTRA) for up to
* Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication.
Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. All other marks are property of their respective owners.
This press release and further information about Tonix can be found at www.tonixpharma.com.
Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, 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 of our products; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (the “SEC”) on April 1, 2024, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.
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FAQ
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