Tonix Pharmaceuticals Holding Corp. · NASDAQ:TNXP

Tonix Pharmaceuticals — 2nd Richard Slayman Clinical Xenotransplantation Workshop (May 2026)

40 slides from Tonix Pharmaceuticals's conference presentation, May 17, 2026

  1. Slide 1: The History and Promise of α-CD154 Monoclonal Antibody Immunomodulation for Xeno-Transplantation

    The History and Promise of α-CD154 Monoclonal Antibody Immunomodulation for Xeno-Transplantation 2nd Richard Slayman Clinical Xenotransplantation Workshop May 17, 2026 PO6144 May 17, 2026 1661 © 2026 Tonix Pharmaceuticals Holding Corp.

  2. Slide 2: Conflict of Interest Requiring Disclosure

    Conflict of Interest Requiring Disclosure Name of Presenter: Seth Lederman, MD Conflict of interest requiring disclosure in relation to the presentation: 1. Research was funded by Tonix Pharmaceuticals, Inc. 2. Dr. Lederman is CEO of Tonix 2 © 2026 Tonix Pharmaceuticals Holding Corp.

  3. Slide 3: Cautionary Note on Forward-Looking Statements

    Cautionary Note on Forward-Looking Statements Certain statements in this presentation 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,” “e

  4. Slide 4: Introduction

    Introduction 4 © 2026 Tonix Pharmaceuticals Holding Corp.

  5. Slide 5: CD40L (also called CD154) was Identified in 1992 Mediates T-Helper Function

    CD40L (also called CD154) was Identified in 1992 Mediates “T-Helper” Function • Identified as “5c8 Antigen”1 • Monoclonal antibody 5c8 blocks helper function 5 1Lederman & al. J Exp Med. 1992 175(4):1091-1101. © 2026 Tonix Pharmaceuticals Holding Corp.

  6. Slide 6: CD40L is a Transiently Expressed 32 kD Surface Protein on a Subset of CD4+ T cells

    CD40L is a Transiently Expressed 32 kD Surface Protein on a Subset of CD4+ T cells • Transiently expressed on the surface of a subset of activated CD4+ T cells1 • Mediates T cell help • CD40L+ cells are: • T-helper cells (Th) • T-effector cells (T-eff) • 32 kD protein 6 1Lederman & al. J Exp Med. 19

  7. Slide 7: About CD40L

    About CD40L CD40L is a transiently expressed T cell surface molecule and is also called CD1541-4 ‒ Predominantly expressed by T cells and interacts with CD40 on B cells and macrophages Mediates T cell helper function1-4 ‒ Activates B cells for humoral (antibody-mediated) immune response (isotype swi

  8. Slide 8: α-CD40L Treatment is Treg Sparing and Tolerance is Partially Treg-Dependent

    α-CD40L Treatment is CD4+ Foxp3+ Treg Sparing and α-CD40L- induced Tolerance is at Least Partially Treg-Dependent CD4+ CD25+ Foxp3+ regulatory T cells (Treg) play roles in tolerance1-3 ‒ Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi were awarded the Nobel Prize in Physiology or Medicine 2025 for

  9. Slide 9: α-CD40L Effects on Humoral and Cellular Immunity Depend on Potency and Concentration

    α-CD40L Effects on Humoral and Cellular Immunity in Animal Models Are Dependent on Potency and Concentration Xeno- Potential indications: transplant • Sjögren’s syndrome rejection • Psoriatic arthritis • Multiple sclerosis Allo- transplant rejection Potential indication: Potency of mAb† • Prevention

  10. Slide 10: Structural Model of CD40/CD40L

    Structural Model of CD40/CD40L B cell Model is based on PDB ID: 3QD6 CD40 (gray, yellow, orange) CD40L soluble trimer (green, cyan, magenta) T cell 10 PDB=Protein Data Bank. An HJ. J Biol Chem. 2011;286(13):11226-11235. © 2026 Tonix Pharmaceuticals Holding Corp.

  11. Slide 11: CD40L and Humanized 5c8/Ruplizumab Fab Complex

    CD40L and Humanized 5c8/Ruplizumab Fab Complex Hu5c8 antibody CD40L Hu5c8 antibody CD40L CD40L Model based on PDB ID: 1I9R Hu5c8 antibody CD40L soluble trimer: green, cyan, yellow Hu5c8 antibody (Ruplizumab): blue, magenta 11 Karpusas M, et al. Structure. 2001;9(4):321-329. PDB=Protein Data Bank. ©

  12. Slide 12: CD40L Binds to CD11b to Promote Graft-Specific T-Cell Activation

    CD40L Binds to CD11b to Promote Graft-Specific T-Cell Activation Activated CD4+ T cell Activated APC • Blocking the interaction of CD40L and CD11b enhances B cell CD40 efficacy of α-CD40 treatment in prolonging allograft survival CD40 ‒ α-CD40 antibodies block CD40L CD40/CD40L binding but do CD11b n

  13. Slide 13: Engineering α-CD40L mAbs

    Engineering α-CD40L mAbs 13 © 2026 Tonix Pharmaceuticals Holding Corp.

  14. Slide 14: 3 Generations of α-CD40L Antibody Development

    3 Generations of α-CD40L Antibody (Ab) Development 2nd and 3rd Generations Engineered to Decrease the Risk of Thrombosis First-generation1-2 Second-generation3-12 Third-generation13 anti-CD40L mAbs anti-CD40L proteins anti-CD40L mAbs Ruplizumab Aglycosyl Dapirolizumab Letolizumab Dazodalibep TNX-150

  15. Slide 15: Third-Generation α-CD40L

    Third-Generation α-CD40L Engineered to decrease FcγRIIa binding 15 © 2026 Tonix Pharmaceuticals Holding Corp.

  16. Slide 16: 3rd Generation: Fc-modulated α-CD40L Abs

    3rd Generation: Fc-modulated α-CD40L Abs • Targeted amino acid substitutions to First-Generation Anti-CD40L Abs3 decrease FcR binding • First-generation anti-CD40L Ab Antigen-binding development was halted due to fragment (Fab) thromboembolic (TE) complications1,2 • TE complications were traced to F

  17. Slide 17: Generation of α-CD40L Variants to Decrease FcγRIIa Binding and Thrombosis Risk

    Generation of α-CD40L Variants to Decrease FcγRIIa (CD32A) Binding and Decrease Risk of Thrombosis Variant Fc mAb Hinge/CH2 CH3 TNX01 IgG1 N297Q CDKTHTCPPCPAPELLGGP QSTYR TNX02 IgG1 WT – G1 CDKTHTCPPCPAPELLGGP NSTYR TNX03 IgG1 N297G CDKTHTCPPCPAPELLGGP GSTYR TNX04 IgG1 C220S, C226S, C229S, SDKTHTSPP

  18. Slide 18: 3rd Generation: Fine-tuning α-CD40L Abs

    3rd Generation: Fine-turning α-CD40L Abs • Heavy chain IgG1 and IgG4 variants were grouped by mutation result Aglycosylation1 Disulfide Disruption Fc Modulated • Analyzed for: ‒ CD40L binding ‒ FcγR binding • Aglycosyl α-CD40L mAb was previously shown to lack activity in preventing TNX01 TNX04 TNX05

  19. Slide 19: TNX04 (α-CD40L Candidate) without Disulfide Bonds

    TNX04 (α-CD40L Candidate) without Disulfide Bonds • No H-L and H-H interchain disulfide bridges by posttranslational modifications • TNX04 heavy chains are expected to be in an equilibrium between monomers and a non-covalent dimer Ruplizumab Fab No disulfide bonds CH-CL (binding heavy and light chai

  20. Slide 20: TNX04 Monomers without Disulfide Bonds

    TNX04 Monomers without Disulfide Bonds Cell membrane Soluble CD40L 1. Each monomer Cell-associated CD40L binds one CD40L 3. Exposure molecule of hidden epitopes 2. Monomers are expected to bind soluble and TNX04 cell-associated CD40L Monomer Monomer Monomer with similar avidity Data on File. 20 © 20

  21. Slide 21: TNX05 (α-CD40L Candidate) Dimer with Disulfide Bonds

    TNX05 (α-CD40L Candidate) Dimer with Disulfide Bonds Cell membrane Cell-associated CD40L 1. Each dimer binds 2 CD40L molecules Ruplizumab full Fab TNX05 Disulfide bonds CH-CL (binding heavy and light chains) FcγR-modulated Disulfide bonds CH-CH (binding 2 heavy chains) 2. Dimers are Fc region expect

  22. Slide 22: Potential Differences: Dimers (TNX05) vs Monomers (TNX04)

    Potential Differences: Dimers (TNX05) vs Monomers (TNX04) TNX05 dimer preferentially binds surface CD40L Binding affinity of a dimer is ~monomer binding x monomer binding affinity (the square) TNX04 may bind surface or soluble CD40L as a monomer Binding affinity of a dimer is ~monomer binding affini

  23. Slide 23: Binding of α-CD40L mAb Variants to CD40L+ Jurkat D1.1 Cells by Flow Cytometry

    Binding of α-CD40L mAb Variants to CD40L+ Jurkat D1.1 Cells by Flow Cytometry Variant D1.1 Binding Kd (nM) TNX01 0.128 TNX02 0.162 TNX03 0.195 TNX04 0.261 TNX05 0.338 TNX06 0.285 TNX07 0.296 TNX08 0.293 TNX09 0.278 Anti-CD40L antibodies (TNX01–TNX05) bound with high affinity to CD40L+ TNX10 0.177 Ju

  24. Slide 24: Binding of α-CD40L mAb Variants to FcγRI by SPR

    Binding of α-CD40L mAb Variants to FcγRI (and other FcγRs) by Surface Plasmon Resonance (SPR) Binding, (Kd, µM) Variant Binding of anti-CD40L antibodies to CD40L was measured by surface plasmon resonance (SPR) to FcγRI, FcγRIIaH, FcγRIIbF, FcγRIIIaF, and FcγRIIIaV. All variants bound FcγRI with lowe

  25. Slide 25: Binding of α-CD40L mAb Variants to Fc Receptors by SPR

    Binding of α-CD40L mAb Variants to Fc Receptors by Surface Plasmon Resonance (SPR) Binding, (Kd, µM) Variant Binding of anti-CD40L antibodies was measured by surface plasmon resonance (SPR) to FcγRIIaH, FcγRIIbF, FcγRIIIaF, and FcγRIIIaV peptides. All variants bound FcγRIIaH with lower affinity than

  26. Slide 26: Binding of α-CD40L mAb Variants to FcRn and CD40L by SPR

    Binding of α-CD40L mAb Variants to FcRn and CD40L by Surface Plasmon Resonance (SPR) Variant FcRn CD40L TNX01 270 ±20 0.008 ±0.0005 TNX02 350 ±30 0.010 ±0.001 TNX03 310 ±90 0.013 ±0.001 TNX04 230 ±40 0.0095 ±0.001 TNX05 320 ±40 0.023 ±0.006 TNX06 300 ±20 - TNX07 340 ±30 - TNX08 340 ±40 - TNX09 280 ±

  27. Slide 27: TNX05 Renamed TNX-1500: Chosen for Clinical Development

    TNX05 Renamed TNX-1500: Chosen for Clinical Development Selectively Modified Anti-CD40L Ab • TNX-1500 is a new, third-generation Ab targeted to CD40L • Uses the full Fab from ruplizumab (hu5c8), Ruplizumab full Fab the first-generation anti-CD40L Ab most consistently effective at delaying allograft

  28. Slide 28: Immunomodulation in vivo Animal Results

    Immunomodulation in vivo Animal Results 28 © 2026 Tonix Pharmaceuticals Holding Corp.

  29. Slide 29: TNX-1500 Allo- Preclinical Data and Publications

    TNX-1500 Allo- Preclinical Data and Publications Two papers published in the August 2023 edition of the American Journal of Transplantation1,2 • No apparent loss of effector function with Fc-modified TNX-1500 mAb relative to hu5c8 Allo-kidney transplants in animals1 • TNX-1500 monotherapy consistent

  30. Slide 30: Non-Human Primate Kidney Xenograft Transplantation

    Non-Human Primate Kidney Xenograft Transplantation Dr. Tatsuo Kawai, Mass General Hospital TNX-1500 therapy is part of a regiment to prevent rejection in kidney xenograft transplants ‒ Goal of prolonged acceptance and function October 11, 2023 - Publication and news coverage in Nature ‒ Anand, R.P.,

  31. Slide 31: TNX-1500 as Immunomodulation in Heart Xenografts

    TNX-1500 as Immunomodulation in Heart Xenografts1 Dr. Richard Pierson, Mass General Hospital 31 1Chaban R, et al. J Heart Lung Transplant. 2024. 43(12):1932-1944. doi: 10.1016/j.healun.2024.07.022. © 2026 Tonix Pharmaceuticals Holding Corp.

  32. Slide 32: Phase 1 Topline Results

    Phase 1 Topline Results 32 © 2026 Tonix Pharmaceuticals Holding Corp.

  33. Slide 33: TNX-1500 Phase 1 Study Design

    TNX-1500 Phase 1 Study Design Goal: evaluate the safety, pharmacodynamics, and pharmacokinetics of TNX-1500 Enrolled (N=26) Cohort 1 Cohort 2 Cohort 3 3 mg/kg 10 mg/kg 30 mg/kg (N=4) (N=8) (N=8) Adverse events in active groups (n=7) Placebo n=2 Placebo n=2 Placebo n=2 Lost to follow-up (n=1, placebo

  34. Slide 34: TNX-1500 Phase 1 Methods

    TNX-1500 Phase 1 Methods Discharged Day -1 Day 2 Day 29 Screening Check-In Confinement Follow-Up 120/ET Up to 28 Included Visit Days 3 through 120 days Day 1 Day 2 Samples for anti-KLH Ab were obtained on Days 1 (pre-challenge), 8, 15, 29, 36, 50, 64, 78, and 120 3, 10, and 30 mg/kg Legend: Check-In

  35. Slide 35: TNX-1500 Phase 1 Topline Results: Safety

    TNX-1500 Phase 1 Topline Results Safety 3 mg/kg 10 mg/kg 30 mg/kg Placebo TEAEs 1 3 3 2 Serious AE 0 0 0 0 • TNX-1500 was generally well tolerated with a favorable safety profile in this study • The only treatment-emergent adverse event (TEAE) deemed possibly related to study drug was aphthous ulcer

  36. Slide 36: TNX-1500 Phase 1 Topline Results: Pharmacokinetics and Pharmacodynamics

    TNX-1500 Phase 1 Topline Results (Cont.) Pharmacokinetics and Pharmacodynamics Pharmacokinetics Pharmacodynamics Dose Mean (SD) half-life (t1/2) Mean % Inhibition of anti-KLH mg/kg in days antibody response KLH, Day 2 KLH, Day 29 challenge challenge 0 (placebo) - 0% 0% 3 19.6 (9.29) 100% 69%* 10 37.

  37. Slide 37: TNX-1500 Phase 1 Conclusions and Future Directions

    TNX-1500 Phase 1 Conclusions and Future Directions • Phase 1 completed; results support development for phase 2 trial (prevention of kidney transplant rejection) − Collaborations ongoing with Massachusetts General Hospital on allo-heart and -kidney transplantation in nonhuman primates • Engineered F

  38. Slide 38: Summary

    Summary • Calcineurin Inhibitors (CNIs) have enabled great success in transplantation by effectively preventing acute rejection; however, they also cause irreversible and progressive deterioration of kidney function in recipients of all types of solid organ transplants, which can be irreversible and

  39. Slide 39: Acknowledgments

    Acknowledgments Tonix Pharmaceuticals, Inc. Massachusetts General Hospital, University of Tennessee Harvard Medical School, Health Science Center, Boston, MA Memphis, TN Engineering/Biology Grace Lassiter Bruce Daugherty Ryo Otsuka Bernd Meibohm Seth Lederman Takayuki Hirose Ahmad Karadagi Modeling

  40. Slide 40: Thank You

    THANK YOU © 2026 Tonix Pharmaceuticals Holding Corp.

Tonix Pharmaceuticals Holding — 2nd Richard Slayman Clinical Xenotransplantation Workshop (May 2026) on 6ix