Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP
Tonix Pharmaceuticals — Technical Presentation (October 2025)
36 slides from Tonix Pharmaceuticals's technical presentation, Oct 2, 2025
Slide 1: TNX-1700 Gastric and Colorectal Cancers
TNX-1700 Gastric and Colorectal Cancers NASDAQ: TNXP Version PO6102 Oct 2, 2025 (Doc 1619) © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 2: Cautionary Note on Forward-Looking Statements
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 i
Slide 3: Table of Contents
Table of Contents IMMUNOLOGY PORTFOLIO 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 protei
Slide 4: TNX-1700: Targeting Gastric and Colorectal Cancer
TNX-1700: Targeting Gastric and Colorectal Cancer1 IMMUNOLOGY PORTFOLIO 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 People living with colorectal cancer in the US3 >140K People living
Slide 5: TNX-1700 (hTFF2-HSA): A Potential Treatment for Gastric and Colorectal Cancers
TNX-1700 (hTFF2-HSA): A Potential Treatment for Gastric and Colorectal Cancers IMMUNOLOGY PORTFOLIO 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
Slide 6: TNX-1700 (TFF2-HSA): Fighting GC and CRC by Targeting the Tumor Microenvironment
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 ❖Mechanism of Action ❖Target Validation • Partial agonist for the chemokine receptor CXCR4 • Human Gastric Cancer •
Slide 7: TNX-1700 (hTFF2-HSA) Fusion Protein: Tumor Microenvironment, MDSCs
TNX-1700 (hTFF2-HSA) Fusion Protein Tumor Microenvironment, MDSCs © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 8: Cancers Create Toxic, Immunosuppressive Tumor Microenvironments (TME)
Cancers Create Toxic, Immunosuppressive Tumor Microenvironments (TME) IMMUNOLOGY PORTFOLIO • Tumors are surrounded by Tumors Create a Toxic, Immunosuppressive Microenvironment1-3 endothelial and stroma cells, and invading immune cells, both Key innate and adaptive1,2 Healthy cell • Complex regulator
Slide 9: MDSCs Are a Major Treatment Target
MDSCs Are a Major Treatment Target IMMUNOLOGY PORTFOLIO • 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 cell
Slide 10: TFF2 Structure
TFF2 Structure Domains, CXCR4 Interaction, Cell Migration © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 11: TFF2 Contains Trefoil Domains, Each Containing Conserved Residues
TFF2 Contains 2 Trefoil Domains, Each Containing 5 Conserved Residues IMMUNOLOGY PORTFOLIO Domain 1 Domain 2 Crystal structure Rotate Rotate Space-filling model (side) Simplified view (top) 11 Carr M, et al. Biochemistry, 1994 91:2206-2210 © 2025 Tonix Pharmaceuticals Holding Corp. Carr et., PNAS (1
Slide 12: TFF2 Signals Through CXCR4
TFF2 Signals Through CXCR4 IMMUNOLOGY PORTFOLIO • 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
Slide 13: Chemokines Direct Immune Cell Production and Migration
Chemokines Direct Immune Cell Production and Migration IMMUNOLOGY PORTFOLIO • Immune cells constantly migrate from CXCR4 Signaling Directs Mobilization and Egress1-3 the blood into and out of lymphoid organs, processes known as homing Bone marrow Lymph nodes Spleen and egress1,2 • Homing and egress
Slide 14: TNX-1700 Protein Design
TNX-1700 Protein Design Albumin Fusion Proteins © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 15: Strategies for Half-Life Extension: Albumin Fusion
Strategies for Half-Life Extension: Albumin Fusion IMMUNOLOGY PORTFOLIO • 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
Slide 16: TNX-1700 (hTFF2-HSA) Fusion Protein: Structure, Preliminary Safety
TNX-1700 (hTFF2-HSA) Fusion Protein Structure, Preliminary Safety © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 17: TNX-1700 is a Fusion Protein of TFF2 and Human Serum Albumin; Preliminary Safety
TNX-1700 is a Fusion Protein of TFF2 and Human Serum Albumin (HSA) Preliminary Safety of TNX-1700 Fusion of TFF2 with HSA for half-life extension Mouse Toxicity Study Murine TNX-1700 generated for mouse studies No observable toxicity at efficacious dose Mice: C57BL/6; n=3/group Human Trefoil Factor
Slide 18: TNX-1700 (hTFF2-HSA) Fusion Protein: Target Validation, In Vitro
TNX-1700 (hTFF2-HSA) Fusion Protein Target Validation, In Vitro © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 19: Target Validation
Target Validation TFF2/TNX-1700 is a Partial CXCR4 Agonist Reduced Level of TFF2 Correlates with (and an Antagonist to SDF-1α) in vitro Elevated CXCR4+ PMN-MDSCs in GC % CXCR4+ in % PMN-MDSC TFF2 blocks SDF-1 Plasma TFF2 in PBMC PMN-MDSC Chemotaxis induced chemotaxis mSDF-1 TFF2, pg/mL mTNX-1700 %
Slide 20: Chemoprevention Studies: Murine AOM/DSS Model
TNX-1700 (hTFF2-HSA) Fusion Protein Chemoprevention Studies Murine AOM/DSS Model, Target Validation, In Vivo © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 21: Target Validation in vivo: Efficacy in the AOM/DSS CRC Induction Model
Target Validation in vivo: Efficacy in the AOM/DSS CRC Induction Model in C57BL/6 Mice Study Design Assessment AOM DSS Week 0 1 2 3 4 Study #2 16 20 Ad-TFF2-CTP-FLAG 2x/month Tumor Burden MDSC Number MDSC, % spleen Tumor number Study #1 • TFF2-Transgenic (Tg) • Wild-Type (WT) • TFF2-KO • N=6/group M
Slide 22: Therapeutic Studies: Synergy with PD-1 Blockade, Gastric Cancer
Therapeutic Studies Synergy with PD-1 Blockade Gastric Cancer (GC) ACKP, PC, Orthotopic Syngeneic Murine Models © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 23: mTNX-1700 Exhibits Synergy with anti-PD-1 mAb in Syngeneic Mouse Model of GC
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 IMMUNOLOGY PORTFOLIO CXCR4 partial agonism + checkpoint blockade has superior efficacy in mouse model ACKP Model mTNX-1700 + anti-PD-1 Tumor Inhibiti
Slide 24: Efficacy of mTNX-1700 on Tumor Growth in Multiple Syngeneic Murine Models
Efficacy of mTNX-1700 on Tumor Growth in Multiple Syngeneic Murine Models of Gastric Cancer (GC) and Colorectal Cancer (CRC) IMMUNOLOGY PORTFOLIO ACKP s.c. GC ACKP-Luc Orthotopic GC PC s.c. GC GC PC s.c. Vehicle Luminescence, p/sec/cm2/sr Anti-PD-1 Tumor Volume, mm3 AMD3100 Tumor Volume, mm3 AMD3100
Slide 25: mTNX-1700 Reduces PMN-MDSCs in the TME, Blood and Bone Marrow
The CXCR4 Partial Agonist mTNX-1700 Reduces PMN-MDSCs in the TME, Blood and Biogenesis in the Bone Marrow ACKP GC Model The CXCR4 full antagonist AMD3100 has the opposite effect Bone Marrow PMN Bone Marrow GMP Tumor PMN-MDSC Blood PMN-MDSC Cell number/femur, 107 % of Live Cells Vehicle % of CD45+ %
Slide 26: Therapeutic Studies: Synergy with PD-1 Blockade, Colorectal Cancer
Therapeutic Studies Synergy with PD-1 Blockade Colorectal Cancer (CRC) MC38 and CT26.wt Subcutaneous and CT26-Luc Orthotopic Syngeneic Murine Models © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 27: Inhibition of Tumor Growth in the MC38 CRC Model
Inhibition of Tumor Growth in the MC38 CRC Model IMMUNOLOGY PORTFOLIO **p<0.001 ****p<0.0001 27 Daugherty et al., AACR 2023 © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 28: Inhibition of Tumor Growth in the CT26.wt CRC Model
Inhibition of Tumor Growth in the CT26.wt CRC Model IMMUNOLOGY PORTFOLIO Days on Study 28 Daugherty et al., AACR 2023 © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 29: Inhibition of Tumor Growth in the CT26-Luc Orthotopic Tumor Model
Inhibition of Tumor Growth in the CT26-Luc Orthotopic Tumor Model IMMUNOLOGY PORTFOLIO Total Flux *p<0.001 * Study Day 29 Daugherty et al., SITC 2023 © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 30: Summary
Summary © 2025 Tonix Pharmaceuticals Holding Corp.
Slide 31: TNX-1700 Alters the TME by Activating Anti-Cancer CD8+ T Cells via Suppression of MDSCs
TNX-1700 Alters the TME by Activating Anti-Cancer CD8+ T Cells via Suppression of MDSCs Resulting in Reduction of Tumor Growth and Metastasis Tumor Formation TNX-1700 + Anti-PD-1 Key Stromal cell-derived factor-1 alpha (SDF-1α) Homeostasis Anti-programmed cell death-1 mAb (anti–PD-1) Myelopoiesis He
Slide 32: Conclusions
Conclusions IMMUNOLOGY PORTFOLIO • 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 th
Slide 33: Thank You / Appendix
THANK YOU APPENDIX © 2025 Tonix Pharmaceuticals Holding Corp. Holding Corp. © 2025 Tonix Pharmaceuticals
Slide 34: AACR Presentations
AACR Presentations IMMUNOLOGY PORTFOLIO 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,
Slide 35: AACR Presentations
AACR Presentations IMMUNOLOGY PORTFOLIO 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
Slide 36: Appendix
Appendix IMMUNOLOGY PORTFOLIO Qian et al., AACR 2023_Abstract #5088 Daugherty et al., AACR 2023 Abstract #704 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, Daughert
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