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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 Gastric and Colorectal Cancers NASDAQ: TNXP Version PO6102 Oct 2, 2025 (Doc 1619)
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© 2025 Tonix Pharmaceuticals Holding Corp. 2 © 2025 Tonix Pharmaceuticals Holding Corp. Cautionary Note on Forward-Looking Statements Certain statements in this presentation regarding strategic plans, expectations and objectives for future operations or results are “forward-looking statements” as defined by 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” 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, the risks related to 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; risks related to the failure to successfully launch and commercialize Tonmya and any of our approved products; 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. The forward- looking statements in this presentation are made as of the date of this presentation, even if subsequently made available by Tonix on its website or otherwise. Tonix does not undertake an obligation to update or revise any forward-looking statement, except as required by law. 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 and current 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.
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© 2025 Tonix Pharmaceuticals Holding Corp. 3 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Table of Contents 3 No. Section Contents Slide 1 Background, TNX-1700 (hTFF2-HSA1) Targeting Gastric Cancer, Colorectal Cancer 4 2 Tumor microenvironment Targeting MDSCs2 7 3 Trefoil Factor-2 Structure Domains, CXCR4 interaction, Migration 10 4 Protein Design Albumin fusion proteins 14 5 TNX-1700 (hTFF2-HSA1) Structure, Safety 16 6 Target Validation In Vitro Studies 18 7 Target Validation Chemoprevention Studies, Murine AOM/DSS3 In Vivo model 20 8 Therapeutic Studies Synergy with PD-1 blockade, mTFF2-MSA4 8a Gastric ACKP murine model 22 8b Colorectal MC38 and CT26.wt murine models 26 9 Summary 30 1human trefoil family factor 2 – human serum albumin fusion protein 2myeloid-derived suppressor cells 3azoxymethane/dextran sodium sulfate 4murine TFF-2 – murine serum albumin fusion protein
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© 2025 Tonix Pharmaceuticals Holding Corp. 4 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO People living with colorectal cancer in the US3 TNX-1700: Targeting Gastric and Colorectal Cancer1 Gastric and colorectal cancer are leading cancers in the US. Colorectal cancer is the 2nd most common cause of cancer deaths for men and women combined.2 >1.4M Current standard of care: • PD-1 blockade − Response rate in gastric cancer is 10-20%, however, tumors which exhibit high levels of microsatellite instability or deficient mismatch repair, response reaches 30-50%, but these patients are rare (10-15% of all gastric cancer)5,6 Large unmet need: • Gastric and colorectal cancer have a relative 5-year survival rate of 37.9% and 65.4%, respectively3,4 − Despite advances in the field, patients are still in need of life saving treatment 1TNX-1700 is in the pre-IND stage and has not been approved for any indication. 2American Cancer Society, accessed March 2025 - https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html 3NIH, accessed October 2025 - https://seer.cancer.gov/statfacts/html/colorect.html 4NIH, accessed October 2025 - https://seer.cancer.gov/statfacts/html/stomach.html 5Kono et al., Gastric Cancer 2020; 23:565-578 6Amonkar et al., J. Clin. Onc. 2019; 37; suppl >140K People living with gastric cancer in the US4
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© 2025 Tonix Pharmaceuticals Holding Corp. 5 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO TNX-1700 (hTFF2-HSA): A Potential Treatment for Gastric and Colorectal Cancers Pre-IND Candidate Targeted as a treatment for cancer • Particularly for gastric and colorectal cancer • Mechanism of Action (MOA) is different from checkpoint inhibitors • Potential synergy with anti-PD-1 or anti-PD-L1 monoclonal antibodies Patents and patent applications directed to recombinant TFF2 (rTFF2) • Issued patent licensed from Columbia University Inventor: Dr. Timothy Wang, MD • Chief, Division of Digestive and Liver Diseases at Columbia University and Cancer Research Center and Silberberg Professor of Medicine • Investigated the molecular mechanisms of gastrointestinal carcinogenesis for decades • Leadership roles in gastroenterology and cancer biology fields Targeting a Condition with Significant Unmet Need Pre-clinical evidence for inhibiting growth of cancer cells • Several studies have shown rTFF2 to be active in the treatment of cancer 1-2 1Dubeykovskaya Z, et al. Nat Commun. 2016 7:1-11 2Dubeykovskaya ZA, et al, Cancer Gene Ther. 2019 26(1-2):48-57
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© 2025 Tonix Pharmaceuticals Holding Corp. 6 © 2025 Tonix Pharmaceuticals Holding Corp. ❖Mechanism of Action • Partial agonist for the chemokine receptor CXCR4 • Distinct from prototypical agonist SDF-1 • Activates anti-cancer CD8+ T cells by altering the tumor microenvironment (TME) via suppression of myeloid-derived suppressor cells (MDSCs) • Redirects granulocyte differentiation towards anti-tumorigenic neutrophils and away from MDSCs • Promotes differentiation of MDSCs to a non- immunosuppressive cell type • Inhibits myelopoiesis/normalizes hematopoiesis • Synergizes with anti-PD-1 • Activity of TFF2 is distinct from CXCR4 antagonists • Prototypical antagonist of CXCR4 is Mozobil® (plerixafor/AMD3100) • Hematopoietic Stem Cell (HPSC) mobilizing agent – FDA approved for stem cell transplantation • Blocks recruitment and migration Dubeykovskaya Z, et al., Nat Commun. 2016 7:1-11 Dubeykovskaya Z, et al., Cancer Gene Ther. 2019 26(1-2):48-57 Qian, et al., Cancer Cell. 2025 Aug 11;43(8):1512-1529 TNX-1700 (TFF2-HSA): Fighting Gastric (GC) and Colorectal Cancer (CRC) by Targeting the Tumor Microenvironment Trefoil Factor-2 (TFF2) Targeted as an Immunotherapy Treatment for Cancer ❖Target Validation • Human Gastric Cancer • TFF2 epigenetically silenced in GC • CXCR4+ PMN-MDSC expanded and negatively correlated with serum TFF2 level and CD8+ T cell abundance • CXCR4+PMN-MDSCs highly expressed immunosuppressive genes • Low TFF2 expression in tumor tissue in patients with diffuse-type or intestinal type GC correlated with poor overall survival • Mouse CRC Tumor Models: • TFF2 knock-out in mice leads to faster tumor growth • Transgenic overexpression of TFF2 suppresses tumor growth • Adenoviral delivery suppresses tumor growth
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 (hTFF2-HSA) Fusion Protein Tumor Microenvironment, MDSCs
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© 2025 Tonix Pharmaceuticals Holding Corp. 8 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Cancers Create Toxic, Immunosuppressive Tumor Microenvironments (TME) • Tumors are surrounded by endothelial and stroma cells, and invading immune cells, both innate and adaptive1,2 • Complex regulatory network supports tumor growth, enabling cancers to thrive by evading immune surveillance and destruction2-3 • The TME sabotages tumor- killing cytotoxic CD8 T cells1 • Myeloid-derived suppressor cells (MDSCs) interfere with anticancer immunity2,3 1Belli C, et al. Cancer Treat Rev. 2018;65:22-32. 2Roma-Rodriguez C, et al. Int J Mol Sci. 2019;20(4):840. 3Tsai M, et al. ISRN Biochem. 2014:351959. Tumors Create a Toxic, Immunosuppressive Microenvironment1-3 Key The TME supports tumor growth and enables cancers to thrive by evading immune surveillance and destruction Healthy cell Malignant cell Myeloid-derived suppressor cell (MDSC) Cancer-associated fibroblast Exhausted CD8 T cell Cytotoxic CD8 T cell CD4 T cell Dendritic cell (DC) B cell Natural Killer (NK) cell Macrophage Neutrophil
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© 2025 Tonix Pharmaceuticals Holding Corp. 9 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO MDSCs Are a Major Treatment Target • Levels of MDSCs tend to correlate with tumor stage, patient survival, and metastatic burden and may predict poor response to certain cancer treatments1 • MDSCs represent a central mechanism of immunosuppression in cancer; targeting these cells could significantly improve our ability to fight cancer2,3 • Therapeutic strategies include3: Promoting the differentiation of MDSCs to a non-immunosuppressive cell type Blocking MDSC immunosuppressive functions Inhibiting MDSC expansion Eliminating MDSCs 1Condamine T, et al. Annu Rev Med. 2015;66:97-110. 2Tuccito A, et al. Virchows Arch. 2019;474(4):407-420. 3Gabrilovitch DI, et al. Nat Rev Immunol. 2009;9(3):162-174.
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TFF2 Structure Domains, CXCR4 Interaction, Cell Migration
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© 2025 Tonix Pharmaceuticals Holding Corp. 11 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO TFF2 Contains 2 Trefoil Domains, Each Containing 5 Conserved Residues Carr et., PNAS (1994) Crystal structure Simplified view (top) Rotate Rotate Space-filling model (side) Domain 1 Domain 2 Carr M, et al. Biochemistry, 1994 91:2206-2210
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© 2025 Tonix Pharmaceuticals Holding Corp. 12 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO TFF2 Signals Through CXCR4 • Importantly, TFF2 activates CXCR4 and may therefore modulate immune and tumorigenic responses, specifically by reducing the expansion or migration of immunosuppressive MDSCs1-3 • TFF2 upregulates ApoE fifty-fold in myeloid progenitor cells; ApoE has been shown to suppress MDSCs4 TFF2 Modulates MDSC Function via CXCR4 Signaling1-3 Migration Proliferation Survival TFF2 CXCR4 MDSC cell membrane 1Dubeykovskaya Z, et al. J Biol Chem. 2009;284(6):3650-3662. 2Balkwill F. Semin Cancer Biol. 2004;14(3):171-179. 3Teixidó J, et al. Int J Biochem Cell Biol. 2018;95:121-131. 4Tavazoie MF et al, Cell 2018; 172:825-840.
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© 2025 Tonix Pharmaceuticals Holding Corp. 13 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Chemokines Direct Immune Cell Production and Migration • Immune cells constantly migrate from the blood into and out of lymphoid organs, processes known as homing and egress1,2 • Homing and egress are regulated by chemokines1,2 • CXCL12-CXCR4 is a crucial chemokine signaling axis that regulates1-3: Proliferation and mobilization of hemopoietic stem cells (HSCs) Retention of developing immune cells within the bone marrow 1Griffith JW, et al. Annu Rev Immunol. 2014;32:659-702. 2Schultz O, et al. Annu Rev Immunol. 2014;34:203-242. 3Balkwill F. Semin Cancer Biol. 2004;14(3):171-179. CXCR4 Signaling Directs Mobilization and Egress1-3 Spleen Lymph nodes Bone marrow CXCR4 CAR cell Developing B cell Developing monocyte HSCs Mobilization CXCL12 Developing neutrophil Egress HSCs and immature immune cells express CXCR4. Decreases in CXCR4 levels induce: Proliferation and mobilization of HSCs Egress of immune cells from the bone marrow to the spleen and lymph nodes
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 Protein Design Albumin Fusion Proteins
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© 2025 Tonix Pharmaceuticals Holding Corp. 15 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Strategies for Half-Life Extension: Albumin Fusion • Albumin ‒ Most abundant plasma protein ‒ Involved in transport of nutrients in the body ‒ Interaction with cellular receptors Gp18, Gp30, and Gp60, which regulate transcytosis/endocytosis of albumin across the endothelial cell surface ‒ High circulatory half-life of ~ 19 days mediated mainly due to neonatal Fc (FcRn)-mediated recycling • Marketed albumin fusions, conjugates and albumin binders ‒ Levemir ‒ Tanzeum ‒ Victoza ‒ Abraxane ‒ Idelvion ‒ Tresiba ‒ Ozempic ‒ Mounjaro
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 (hTFF2-HSA) Fusion Protein Structure, Preliminary Safety
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© 2025 Tonix Pharmaceuticals Holding Corp. 17 © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 is a Fusion Protein of TFF2 and Human Serum Albumin (HSA) Human Trefoil Factor 2 106 AA GGGGS Linker Human Serum Albumin 585 AA Size Exclusion SDS PAGE Fusion of TFF2 with HSA for half-life extension Theoretical MW = 78.1 kDa Vehicle TNX-1700 Mouse Toxicity Study No observable toxicity at efficacious dose Mice: C57BL/6; n=3/group Dose: murine TNX-1700; 22.5 mg/kg or vehicle IP Frequency: 3x/week; 6 weeks • No effect on WBC count and body weight • No inflammation in lymphoid and non-lymphoid organs Preliminary Safety of TNX-1700 Murine TNX-1700 generated for mouse studies 99.3% 8.95 min 0.7% 8.21 min Qian, et al., Cancer Cell. 2025 Aug 11;43(8):1512-1529 Body WeightWBC Count Vehicle TNX-1700 NH2 Thymus Spleen Node Kidney Liver Heart Lung Lymph
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 (hTFF2-HSA) Fusion Protein Target Validation, In Vitro
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© 2025 Tonix Pharmaceuticals Holding Corp. 19 © 2025 Tonix Pharmaceuticals Holding Corp. Target Validation Chemotaxis Calcium flux TFF2 blocks SDF-1 induced chemotaxis mTNX-1700 and AMD3100 block Akt phosphorylation mSDF-1 mTNX-1700 mSDF-1 mTNX-1700 AMD3100 Qian, et al., Qian, et al., Cancer Cell. 2025 Aug 11;43(8):1512-1529 Dubeykovskaya Z. et al., JBC. 2009 284: 3650 Plasma TFF2 % CXCR4+ in PMN-MDSC TFF2, pg/mL % % PMN-MDSC in PBMC % Spearman correlation of TFF2 vs. CXCR4+ PMN-MDSC in GC Probability Low TFF2 High TFF2 % of CXCR4+ PMN-MDSC in GC Time, months TFF2, pg/mL p<0.05 Kaplan-Meier TFF2 in diffuse-type GC Reduced Level of TFF2 Correlates with Elevated CXCR4+ PMN-MDSCs in GC TFF2/TNX-1700 is a Partial CXCR4 Agonist (and an Antagonist to SDF-1α) in vitro N=241 p<0.01 *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 (hTFF2-HSA) Fusion Protein Chemoprevention Studies Murine AOM/DSS Model, Target Validation, In Vivo
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© 2025 Tonix Pharmaceuticals Holding Corp. 21 © 2025 Tonix Pharmaceuticals Holding Corp. Target Validation in vivo: Efficacy in the AOM/DSS CRC Induction Model in C57BL/6 Mice Tumor number MDSC, % spleen Week 0 1 2 3 4 16 20 AssessmentAOM DSS Study #2 Ad-TFF2-CTP-FLAG 2x/month MDSC, % spleen Study #2 • Ad-TFF2-CTP-FLAG • Control • N=4/group Study Design Study #1 • TFF2-Transgenic (Tg) • Wild-Type (WT) • TFF2-KO • N=6/group Tumor number Tumor Burden MDSC Number *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 Dubeykovskaya Z, et al., Nat Commun. 2016 7:1-11 Dubeykovskaya Z, et al., Cancer Gene Ther. 2019 26(1-2):48-57
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. Therapeutic Studies Synergy with PD-1 Blockade Gastric Cancer (GC) ACKP, PC, Orthotopic Syngeneic Murine Models
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© 2025 Tonix Pharmaceuticals Holding Corp. 23 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO mTNX-1700 Exhibits Synergy with anti-PD-1 mAb in Decreasing Tumor Volume, Blocking Metastasis and Increasing Survival in a Syngeneic Mouse Model of GC ns, non-significant, **p<0.01, ***p<0.001, ****p<0.0001 Qian, et al., Cancer Cell. 2025 Aug 11;43(8):1512-1529 Tumor Volume, mm3 Days post-inoculation Days post-inoculation Probability of Survival mTNX-1700 + anti-PD-1 Total area/total liver area (%) CXCR4 partial agonism + checkpoint blockade has superior efficacy in mouse model ACKP Model **** **** CD8+/tumor area Vehicle Anti-PD-1 mTNX-1700 mTNX-1700+ Anti-PD-1 Tumor Inhibition Blocking Liver Metastasis Increasing Survival Tumor CD8+ T cell Vehicle Anti-PD-1 mTNX-1700 mTNX-1700+ Anti-PD-1 N=10-12/group N=5/group N=10/group
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© 2025 Tonix Pharmaceuticals Holding Corp. 24 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO 00 Efficacy of mTNX-1700 on Tumor Growth in Multiple Syngeneic Murine Models of Gastric Cancer (GC) and Colorectal Cancer (CRC) Qian, et al., Cancer Cell. 2025 Aug 11;43(8):1512-1529; Daugherty et al., AACR 2023; Daugherty et al., SITC 2023 PC s.c. GC ❖TNX-1700 is Active in Multiple Models in Two Cancer Types: • Autochthonous GC model • ACKP lung metastasis model • MC38 s.c. CRC model • CT26.wt s.c. CRC model • CT26-Luc orthotopic CRC model Luminescence, p/sec/cm2/sr Days post cell inoculation Days post cell inoculation Days post cell inoculation Tumor Volume, mm3 Days post cell inoculation Fold change No Efficacy in CXCR4-KO PMN, CXCR4 mRNA ns ACKP-Luc Orthotopic GCACKP s.c. GC Tumor Volume, mm3 Tumor Volume, mm3 Target Validation Vehicle Anti-PD-1 mTNX-1700 mTNX-1700+ Anti-PD-1 Vehicle Anti-PD-1 AMD3100 AMD3100+Anti-PD-1 mTNX-1700 mTNX-1700+Anti-PD-1 PC s.c. GC ns, non-significant; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 N=8/group N=5/group N=10/group N=6/group N=3/group
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© 2025 Tonix Pharmaceuticals Holding Corp. 25 © 2025 Tonix Pharmaceuticals Holding Corp. The CXCR4 Partial Agonist mTNX-1700 Reduces PMN-MDSCs in the TME, Blood and Biogenesis in the Bone Marrow Qian, et al., Cancer Cell. 2025 Aug 11;43(8):1512-1529 The CXCR4 full antagonist AMD3100 has the opposite effect Bone Marrow PMN Bone Marrow GMP Tumor PMN-MDSC Blood PMN-MDSC mTNX-1700 AMD3100 ACKP GC Model Vehicle Anti-PD-1 mTNX-1700 mTNX-1700 + Anti-PD-1 Vehicle AMD3100 AMD3100 + Anti-PD-1 % of Live Cells % of Live Cells % of CD45+ % of CD45+ % of CD45+ % of CD45+ Cell number/femur, 107 Cell number/femur, 107 ns, non-significant; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 N=5/group N=3/group N=3/group N=6/groupN=6/group
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. Therapeutic Studies Synergy with PD-1 Blockade Colorectal Cancer (CRC) MC38 and CT26.wt Subcutaneous and CT26-Luc Orthotopic Syngeneic Murine Models
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© 2025 Tonix Pharmaceuticals Holding Corp. 27 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Inhibition of Tumor Growth in the MC38 CRC Model Daugherty et al., AACR 2023 **p<0.001 ****p<0.0001
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© 2025 Tonix Pharmaceuticals Holding Corp. 28 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Inhibition of Tumor Growth in the CT26.wt CRC Model Days on Study Daugherty et al., AACR 2023
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© 2025 Tonix Pharmaceuticals Holding Corp. 29 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Inhibition of Tumor Growth in the CT26-Luc Orthotopic Tumor Model Total Flux Study Day * *p<0.001 Daugherty et al., SITC 2023
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. Summary
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. TNX-1700 Alters the TME by Activating Anti-Cancer CD8+ T Cells via Suppression of MDSCs Resulting in Reduction of Tumor Growth and Metastasis Egress Mobilization Bone marrow Metastasis site Primary tumor Key Stromal cell-derived factor-1 alpha (SDF-1α) Anti-programmed cell death-1 mAb (anti–PD-1) TNX-1700 CXCR4 Hematopoietic stem cell Developing neutrophil Developing monocyte Developing B cell Immature myeloid cell Myeloid-derived suppressor cell (MDSC) Tumor cell Cytotoxic CD8+ T cell Neutrophil Primary tumor Homeostasis Tumor Formation TNX-1700 + Anti-PD-1 SDF-1α CXCR4 TNX-1700 Anti-PD-1 CAR cell Metastasis site Myelopoiesis Hematopoiesis Bone marrow Bone marrow
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© 2025 Tonix Pharmaceuticals Holding Corp. 32 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Conclusions • TFF2 is a naturally occurring anti-inflammatory peptide that is a key part of the inflammatory reflex. • TFF2 is a partial agonist for CXCR4, suppresses the proliferation and expansion of myeloid progenitors, thus reducing MDSCs. • Overexpression of TFF2, either through transgenic or adenoviral expression, reduces the development of colorectal cancer (CRC) following AOM/DSS treatment. mTNX- 1700 synergizes with anti-PD-1 blockade to increase survival and eradicate gastric cancer (GC) in advanced orthotopic and metastatic models. • mTFF2-MSA (mTNX-1700) peptide synergizes with PD1 blockade therapy to reduce tumor size and increase survival in CRC syngeneic subcutaneous and orthotopic mouse models. • mTNX-1700 reduces the production of MDSC and promotes a T-cell rich microenvironment, inducing a 50-fold increase in intratumor CD8+ T cells.
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© 2025 Tonix Pharmaceuticals Holding Corp. © 2025 Tonix Pharmaceuticals Holding Corp. THANK YOU APPENDIX
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© 2025 Tonix Pharmaceuticals Holding Corp. 34 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO AACR Presentations Presentation #1 Title: MDSC-targeted TFF2-MSA suppresses tumor growth and increases survival in anti-PD-1 treated MC38 and CT26.wt murine colorectal cancer models Authors: Bruce L. Daugherty1, Rebecca J. Boohaker2, Rebecca Johnstone2, Karr Stinson2, Jin Qian3, Timothy C. Wang3, Seth Lederman1 Tonix Pharmaceuticals, Inc., 26 Main Street, Suite 101, Chatham, NJ 07928 Southern Research, 2000 9th Ave S, Birmingham, AL 35205 Division of Digestive and Liver Diseases, Irving Cancer Research Center, Columbia University Medical Center, New York, NY 10032, USA Topic: Oncolytic Viruses, Anticancer Vaccines, and Other Immunomodulatory Therapies Location: Orange County Convention Center, Orlando, Fla. Section: 24, #704 Date: Sunday, April 16, 2023 Time: 1:30 p.m. – 5:00 p.m. ET Abstract: Click here Presentation #2 Title: MDSC-targeted TFF2-MSA synergizes with PD-1 blockade therapy in diffuse-type gastric cancer Authors: Jin Qian1, Sandra Ryeom1, Bruce Daugherty2, Seth Lederman2, Timothy C. Wang2. Division of Digestive and Liver Diseases, Irving Cancer Research Center, Columbia University Medical Center, New York, NY 10032, USA Tonix Pharmaceuticals, Inc., 26 Main Street, Suite 101, Chatham, NJ 07928 Title: Combination Immunotherapies 1 Location: Orange County Convention Center, Orlando, Fla. Section: 21, #5088 Date: Tuesday, April 18, 2023 Time: 1:30 p.m. – 5:00 p.m. ET Abstract: Click here
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© 2025 Tonix Pharmaceuticals Holding Corp. 35 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO AACR Presentations Presentation #3 Title: A CXCR4 partial agonist TFF2-MSA improves anti-PD-1 immunotherapy in advanced gastric cancer by selectively targeting PMN-MDSC Authors: Jin Qian1, Chenkai Ma2, Quin T. Waterbury1, Christine S. Moon1, Xiaofei Zhi1, Feijing Wu1, Ruhong Tu1, Biyun Zheng1, Hiroki Kobayashi1, Leah B. Zamechek1, Ryan H. Moy1, Arnold Han1, Bruce Daugherty3, Seth Lederman3, Timothy C. Wang1 1Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY ,2Integrated Diagnostic, Human Health, Health and Biosecurity, CSIRO, Westmead, Australia,3Tonix Pharmaceuticals, Inc., Chatham, NJ Topic: Immune Targets and Therapies Location: San Diego Convention Center, San Diego, CA. Session: MS.IM01.02 Date: Monday, April 8, 2024 Time: 3:20 p.m. – 3:35 p.m. PT Abstract: Click Here
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© 2025 Tonix Pharmaceuticals Holding Corp. 36 © 2025 Tonix Pharmaceuticals Holding Corp. IMMUNOLOGY PORTFOLIO Appendix Daugherty et al., AACR 2023 Abstract #704 Qian et al., AACR 2023_Abstract #5088 Qian J, Ma C, Waterbury QT, Zhi X, Moon CS, Tu R, Kobayashi H, Wu F, Zheng B, Zeng Y, Zheng H, Ochiai Y, White RA, Harle DW, LaBella JS, Zamechek LB, ZhongMing Hu L, Moy RH, Han AS, Daugherty BL, Lederman S, Wang TC. A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis. Cancer Cell. 2025 Aug 11;43(8):1512- 1529.e11. doi: 10.1016/j.ccell.2025.06.006. Epub 2025 Jun 26. PMID: 40578360; PMCID: PMC12233206. A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis - PubMed