Tonix Pharmaceuticals Holding Corp. 8-K

Exhibit 99.01

Tonix Pharmaceuticals Presented Preclinical Data on Gastric Cancer Models at the American Association for Cancer Research (AACR) 2025 Annual Meeting

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 – 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 activity^1,2. 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 CXCR4^4,5. 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 $34 million over five years to develop TNX-4200, small molecule broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick, Md. Tonix Medicines, our commercial subsidiary, markets Zembrace^® SymTouch^® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.

* 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.

Investor Contact

Jessica Morris

Tonix Pharmaceuticals

investor.relations@tonixpharma.com

(862) 799-8599

Peter Vozzo

ICR Healthcare

peter.vozzo@icrhealthcare.com

(443) 213-0505

Media Contact

Ray Jordan

Putnam Insights

ray@putnaminsights.com

(949) 245-5432

Indication and Usage

Zembrace^® SymTouch^® (sumatriptan succinate) injection (Zembrace) and Tosymra^® (sumatriptan) nasal spray are prescription medicines used to treat acute migraine headaches with or without aura in adults who have been diagnosed with migraine.

Zembrace and Tosymra are not used to prevent migraines. It is not known if Zembrace or Tosymra are safe and effective in children under 18 years of age.

Important Safety Information

Zembrace and Tosymra can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency help if you have any signs of a heart attack:

Zembrace and Tosymra are not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam shows no problem.

Do not use Zembrace or Tosymra if you have:

Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements.

Zembrace and Tosymra can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert.

Zembrace and Tosymra may cause serious side effects including:

The most common side effects of Zembrace and Tosymra include: pain and redness at injection site (Zembrace only); tingling or numbness in your fingers or toes; dizziness; warm, hot, burning feeling to your face (flushing); discomfort or stiffness in your neck; feeling weak, drowsy, or tired; application site (nasal) reactions (Tosymra only) and throat irritation (Tosymra only).

Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Zembrace and Tosymra. For more information, ask your provider.

This is the most important information to know about Zembrace and Tosymra but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit https://www.tonixpharma.com or call 1-888-869-7633.

You are encouraged to report adverse effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Tonix Pharmaceuticals Holding Corp. 8-K

Exhibit 99.02

Conclusion 1. Kim 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. 2.Veglia 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. 3. Colligan SH, et al . Inhibiting the biogenesis of myeloid - derived suppressor cells enhances immunotherapy efficacy against mammary tumor progression. J Clin Invest. 2022 Dec 1;132(23):e158661.4.Dubeykovskaya 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. 5.Dubeykovskaya Z, et al . Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer. Nat Commun. 2016 Feb 4;7:10517.6.Chen X, et al . Histidine decarboxylase (HDC) - expressing granulocytic myeloid cells induce and recruit Foxp3+ regulatory T cells in murine colon cancer. Oncoimmunology. 2017 Feb 10;6(3):e1290034. Background • Immunosuppressive neutrophils, also known as polymorphonuclear myeloid - derived suppressor cells (PMN - MDSCs), are a major component in solid tumors that significantly hinder anti - tumor immunity. These cells comprise a heterogeneous group of neutrophils pathologically programmed by cancer - derived signals 1,2 . • Despite being short - lived, their continuous replenishment from aberrant myelopoiesis in the bone marrow (BM) sustains their potent immunosuppression in the tumor microenvironment (TME) 3 . • CXCR4 is a key bone marrow retention signal for hematopoietic stem and progenitor cells (HSPCs) and neutrophils . In many cancers, stromal cells in the TME highly secreted CXCL 12 , promoting immunosuppression by recruiting MDSCs . Tumor - derived signals also dampen the CXCL 12 - CXCR 4 bone marrow retention signal, leading to accelerated neutrophil mobilization and increased granulopoiesis . • Trefoil Factor 2 (TFF 2 ), a secreted peptide of the trefoil factor family, acts as a partial agonist of CXCR 4 , dampening CXCL 12 - mediated intense signaling while eliciting weak CXCR 4 signaling 4 , 5 . The Tff 2 gene is epigenetically silenced during gastric preneoplasia . • Histidine decarboxylase (Hdc), an enzyme that catalyzes histamine synthesis, is expressed in immature granulocytes that predominate in cancer, suggesting its potential utility in distinguishing tumor PMN - MDSC 6 . Graphic Abstract Figure 1. TFF2 - MSA showed synergy with anti - PD - 1 antibody in inhibition of s.c. and orthotopic ACKP xenograft growth. Figure 2. TFF2 - MSA inhibited tumor invasion, and reduced Hdc - GFP+ PMN - MDSCs in the tumor. Figure 3. TFF2 - MSA in combination with anti - PD - 1 activated anti - tumor immunity and it reduced tumor - driven granulopoiesis .  TFF2 - MSA, a CXCR4 partial agonist, sensitizes mouse gastric cancer to anti - PD - 1.  TFF2 - MSA selectively reduces immunosuppressive neutrophils and cancer - driven granulopoiesis.  TFF2 - MSA plus anti - PD - 1 induces robust anti - tumoral CD8 + T cell responses  TFF2 reduction correlates with elevated PMN - MDSCs in gastric cancer patients. Tumor Volume % Tumor volume change Vehicle Anti - PD - 1 (%TGI=17.93%) TFF2 - MSA (%TGI=24.57%) Combo (%TGI=78.29%) 30 0 0 500 1000 1500 Tumor volume (mm 3 ) Treatment ns ns ٓ ٓ ٓ ٓ A B C Vehicle Tumor Imaging TFF2 - MSA Anti - PD - 1 Combo D E 7 14 21 28 10 10 10 9 10 8 10 7 10 6 10 5 10 4 10 3 ٓ ٓ ٓ ٓ ٓ ٓ ٓ ٓ 500 1000 1500 2000 0 - 100 Vehicle Anti - PD - 1 TFF2 - MSA Combo 10 20 Days after cell innoculation Luminescence (p/sec/cm 2/ sr) A A. Schematic representation of the treatment scheme of ACKP ((Atp4b - Cre; Cdh1 - / - ; LSL - KrasG12D; Trp53 - / - ) xenografts. B. Tumor growth curve of s.c. implanted ACKP tumors in response to anti - PD1 antibody, TFF2 - MSA or their combination. C. Tumor volume change relative to the initial volume of each tumor. Each bar represents one tumor. TGI: Tumor Growth Inhibition. Tumor Positive or negative value represents volume increase or decrease respectively. D . Representative bioluminescence images showing orthotopically injected ACKP tumors with different treatments. E. Bioluminescent intensity curves showing changes of orthotopic tumors. **P < 0.01, ***P < 0.001, ****P < 0.0001. A. Representative H&E staining images of autochthonous GC in Mist1 - CreERT; Cdh1flox/flox; LSLRHOAY42C/Y42C; Hdc - GFP mice and quantification of tumor invasion depths following treatments at 10 months post - tamoxifen induction (n=10). B. Survival curve of the mice in A (n=10) . C. Imaging flow cytometry showing the nuclear segmentation in Hdc - GFP - and Hdc - GFP+ subsets of neutrophils (CD45+CD11b+LY6G+LY6C - /low). D . T cell proliferation co - cultured with HDC - GFP+ or HDC - GFP - LY6G+ PMNs. E. Flow cytometry showing the Hdc - GFP+ PMN in subcutaneous ACKP tumors following the treatments (n=6). *P < 0.05, ***P < 0.001, ****P < 0.0001. References A. Tumor growth curve of subcutaneous ACKP tumors following the indicated treatments (n=8). B. Hdc - GFP+ PMNs in the tumor and bone of the subcutaneous ACKP model (n=5). C. GMP in the BM of the subcutaneous ACKP model (n=5). D. PMN - MDSC, TFF2 plasma level, and their correlation in the blood of healthy donors (n=10) or gastric cancer patients (n=8). *P < 0.05, A. scRNA - seq of tumor CD45+ cells following the treatments.. B . Tumor PMN changes in the scRNA - seq Representative flow cytometry plots of CXCR4 in tumor PMNs. C. Immunostaining of CD8+ T cells in the treated tumors.. D. CD8+ T cell changes in the scRNA - seq. E. Granulocyte - monocyte progenitor (GMP) percentage in the bone marrow (BM) by flow cytometry. F . Cxcr4 - GFP expression in LSK (Lin - C - kit+Sca - 1+) and MP (myeloid progenitor) cells in the BM of Cxcr4 - GFP mice with subcutaneous ACKP tumors (n=3). G. Frequency of GMP after culture of sorted MP (myeloid progenitor, Lin - C - kit+Sca - 1 - ) cells in myeloid differentiation media for 5 days (n=3). ***P < 0.001, **** P < 0.0001. Figure 4. TFF2 - MSA outperforms CXCR4 antagonist AMD3100 by reducing PMN - MDSC generation, and shows promise in targeting PMN - MDSC in human GC patients . Day 0 ACKP syngeneic gastric cancer cell s.c. inoculation Vehicle TFF2 - MSA PD - 1 Antibody Combination i.p. every 3 days Day 10 Start treat me nt at volume 150 - 200 mm 3 Host: HDC - GFP mice Day 28 Terminate experiment Extract and analyze tumor CD15 B C Tumor CD45+ cell Tumor PMN Tumor CD8+ T cell Tumor CD8+ T cell F G A B C D A B C D E D E • Lead contact: Timothy C. Wang M.D. Email: tcw21@cumc.columbia.edu Chief, Division of Digestive and Liver Diseases Silberberg Professor of Medicine Department of Medicine Irving Cancer Research Center Columbia University Medical Center TFF2 - mediated CXCR4 partial agonism outperforms CXCR4 antagonism in reducing murine gastric cancer by suppressing PMN - MDSC generation Jin Qian 1 , Chenkai Ma 2 , Quin T. Waterbury 1 , Xiaofei Zhi 1 , Christine S. Moon 1 , Ruhong Tu 1 , Hiroki Kobayashi 1 , Feijing Wu 1 , Biyun Zheng 1 , Yi Zeng 1 , Hualong Zheng 1 , Yosuke Ochiai 1 , Ruth A. White 1 , David W. Harle 1 , Jonathan S. LaBella 1 , Leah B. Zamechek 1 , Lucas ZhongMing Hu 1 , Ryan H. Moy 1 , Arnold S. Han 1 , Bruce L. Daugherty 3 , Seth Lederman 3 , Timothy C. Wang . g 1 * 1. Irving Cancer Research Center, Columbia University Medical Center, New York, NY 10032, USA. 2. Integrated Diagnostic, Human Health, Health and Biosecurity, CSIRO, Westmead, New South Wales 2070, Australia 3. Tonix Pharmaceuticals, Inc., 26 Main Street, Suite 101, Chatham, NJ 07928 Result