Tonix Pharmaceuticals Announces Peer-Reviewed Publication in Cancer Cell Journal Highlighting Positive Preclinical Data of mTNX-1700 in Gastric Cancer Animal Models Combination treatment of mTNX-1700 (mTFF2-MSA fusion pr

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Announces Peer-Reviewed

Publication in Cancer Cell Journal Highlighting Positive Preclinical Data of mTNX-1700 in Gastric Cancer Animal Models

Combination treatment of mTNX-1700 (mTFF2-MSA

fusion protein) with anti-PD1 antibody was associated with increased survival and decreased metastases in animal models of gastric cancer

relative to anti-PD1 treatment alone

mTNX-1700 treatment was associated with activation

of cancer-killing CD8+ T Cells and limiting neutrophil-mediated immune evasion

TNX-1700 (hTFF2-HSA fusion protein) is in

preclinical development for gastric and colorectal cancers

CHATHAM, N.J., July 2, 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, today announced the publication of a paper entitled, "A CXCR4 Partial Agonist, Improves Immunotherapy

by Targeting Immunosuppressive Neutrophils and Cancer-Driven Granulopoiesis,"1 in the peer-reviewed journal Cancer

Cell, that represents a collaboration between scientists at Tonix and Columbia University's Medical School and presents data

demonstrating that treatment with murine TNX-1700 (mTNX-1700) increased survival and decreased metastases in animal models of gastric

cancer. The manuscript can be accessed here: www.sciencedirect.com/science/article/pii/S1535610825002569.

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," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "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.

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."

The published studies examined mTNX-1700, which is

a fusion protein of murine trefoil factor-2 (mTFF2) and murine serum albumin (MSA). The human version, TNX-1700 is a fusion protein of

human TFF2 (hTFF2) and human serum albumin (HSA) that is under development for the treatment of gastric and colorectal cancers.

"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. These data show that fine-tuned modulation of CXCR4 can dismantle neutrophil-driven immune

suppression and revive checkpoint efficacy without compromising normal myelopoiesis. 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

Immunosuppressive neutrophils, also known as

polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a major component in solid tumors that significantly hinder anti-tumor

activity2,3. Despite being short-lived, the continuous replenishment of PMN-MDSCs from the bone marrow sustains

their potent immunosuppression in the TME4.

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 CXCR45,6. The Cancer Cell publication describes

data demonstrating 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. This combination

of the mTNX-1700 with anti-PD1 therapy has been shown to reduce tumor size and increase survival in these animal models. TFF2 reduction

correlated with elevated PMN-MDSCs in gastric cancer patients, highlighting the potential negative correlation between TFF2 and PMN-MDSCs

levels while promoting a T-cell rich microenvironment and inducing an increase in CD8+ T cells in the tumor.

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 for the treatment of gastric and colorectal 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

recombinant TFF2 in combination with other therapies in cancer prevention and early treatment.

1Qian, J. et al. Cancer Cell. 2025. on-line: https://doi.org/10.1016/j.ccell.2025.06.006.

2Kim W, et al. Gastroenterology. 2021. 160(3):781-796

3Veglia F, et al. J Exp Med. 2021. 218(4):e20201803.

4Colligan SH, et al. J Clin Invest. 2022. 132(23):e158661.

5Dubeykovskaya Z, et al. J Biol Chem. 2009. 284(6):3650-62.

6Dubeykovskaya Z, et al. Nat Commun. 2016. 7:10517.

Tonix Pharmaceuticals Holding Corp.*

Tonix is a fully-integrated biotechnology 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's infectious disease portfolio includes

TNX-801, a vaccine in development for mpox and smallpox, as well as TNX-4200 for which Tonix has a contract with the U.S. DoD's

Defense Threat Reduction Agency (DTRA) for up to $34 million over five years. TNX-4200 is a small molecule broad-spectrum antiviral agent

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, 2024, as filed with the Securities and Exchange Commission

(the "SEC") on March 18, 2025, 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