TNX-1500 for Prevention of Kidney Transplant Rejection and Autoimmune Disorders: 2nd Richard Slayman Clinical Xenotransplantation Workshop Presentation

Published: 2026-05-18 09:54:09 ET TNXP

Published on 05/18/2026 at 09:54 am EDT

2nd Richard Slayman Clinical Xenotransplantation Workshop

May 17, 2026

PO6144 May 17, 2026 1661

Conflict of Interest Requiring Disclosure

Conflict of interest requiring disclosure in relation to the presentation:

Research was funded by Tonix Pharmaceuticals, Inc.

Dr. Lederman is CEO of Tonix

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," "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 successfully launch and commercialize TONMYA® and any of our approved products; risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; 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, 2025, as filed with the Securities and Exchange Commission (the "SEC") on March 12, 2026, 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.

CD40L (also called CD154) was Identified in 1992

Mediates "T-Helper" Function

Identified as "5c8 Antigen"1

Monoclonal antibody 5c8 blocks helper function

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

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 switching)

Activates macrophages and dendritic cells

Provides T cell help to activated CD8+ T cells

linked hyper-IgM syndrome is caused by a defective CD40L gene5-6

Lack T helper function with only IgM serum antibodies but no IgG or IgE

If maintained on gamma globulin, patients are otherwise healthy

Member of the TNFα superfamily4

TNFα, RANKL, TL1a and CD30L are other family members that are drug targets

α-TNFα, and α-RANKL approved (e.g., Humira® for RA and Prolia® for osteoporosis)

α-CD40L mAb prevent rejection of allo-transplants

Humanized (Hu) 5c8 as monotherapy prevents rejection in non-human primates (NHPs)7,8

Primatized (Pr) 5c8 controls antibody-mediated rejection in highly sensitized NHPs9

1Lederman S, et al. J Exp Med. 1992;175(4):1091-1101. 2Lederman S, et al. J Immunol. 1992;149(12):3817-3826. 3Lederman S, et al. J Immunol. 1994;152(5):2163-2171. 4Covey LR, et al. Mol Immunol. 1994;31(6):471-484

6Callard RE, et al. J Immunol. 1994;153(7):3295-3306.

7Kirk AD, et al. Nat Med. 1999. (6):686-93. 7

8Pierson RN 3rd, et al. Transplantation. 1999 68(11):1800-5.

9Anwar IJ, et al. Sci Transl Med. 2025. 17(779):eadn8130.

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 peripheral immune tolerance

Tregs are generally unable to express CD40L

α-CD40L treatment induces, preserves and expands CD4+ CD25+ Foxp3+ Tregs4-10

In transplantation models, α-CD40L is repeatedly linked to higher frequencies or preserved pools of CD4⁺Foxp3⁺ Tregs

α-CD40L-induced experimental graft tolerance is Treg-dependent consistent with Tregs being spared and functionally competent

α-CD40L treatment induces/preserves Tregs whereas CTLA4-Ig treatment decreases Tregs7

α-CD40L treatment induces/preserves Tregs to a greater extent than α-CD11b10

α-CD40L synergizes with CAR-Tregs to enforce infectious tolerance in a heart-allograft model11

1 Brunkow ME, et al. Nat Genet. 2001 27(1):68-73.

2 Ramsdell F. Immunity. 2003 19(2):165-8

3 Sakaguchi S. J Clin Invest. 2003 112(9):1310-2.

4 Pinelli DF, Ford ML. Immunotherapy. 2015;7(4):399-410.

5 Muckenhuber M, et al. Front Immunol. 2022 13:969633.

6 Haribhai D, et al. Am J Transplant. 2011; 11(9):1815-1824.

7 Kim et al., Am J Transplant 2017. 17(5):1182-1192

8 Pinelli et al., Am. J. Transplant. 2013. 13(11):3021-30

9 Ferrer et al., PNAS 2011. 108(51):20701-6.

10 Liu et al., Am J Transplant. 2024. 24(8):1369-1381. 8

11 Durgam SS, et al. JCI Insight 2025. 8;10(7):e188624.

α-CD40L Effects on Humoral and Cellular Immunity in Animal Models Are Dependent on Potency and Concentration

Potential indications:

Sjögren's syndrome

Psoriatic arthritis

Multiple sclerosis

Xeno-transplant rejection

Potential indication:

Prevention of genetically engineered pig donor-organ transplant rejection

Potency of mAb†

Allo-transplant rejection

Potential indications:

Allergy

Atopic dermatitis

IgE production

IgG production

Cell-mediated autoimmunity

Potential indication:

Potential indications:

Myasthenia gravis

Systemic lupus erythematosus

Prevention of human-donor organ transplant rejection

Concentration* (dose x half-life)

*Concentration is dependent on dose and half-life.

†Potency depends on binding affinity and other factors, eg, neutralization of CD40L trimers. 9

IgE=immunoglobulin E; IgG=immunoglobulin G; mAb=monoclonal antibody.

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

PDB=Protein Data Bank.

An HJ. J Biol Chem. 2011;286(13):11226-11235.

CD40L and Humanized 5c8/Ruplizumab Fab Complex

Hu5c8 antibody

CD40L

Hu5c8 antibody

CD40L

Hu5c8 antibody

Model based on PDB ID: 1I9R

CD40L soluble trimer: green, cyan, yellow

Hu5c8 antibody (Ruplizumab): blue, magenta

PDB=Protein Data Bank.

Karpusas M, et al. Structure. 2001;9(4):321-329.

CD40L Binds to CD11b to Promote Graft-Specific T-Cell Activation

Activated CD4+ T cell

Activated APC

CD40

B cell

CD40

CD40L

CD11b

Anti-CD40

CD11b

CD40

Anti-CD40L

Activated endothelial cell

Blocking the interaction of CD40L and CD11b enhances efficacy of α-CD40 treatment in prolonging allograft survival

- α-CD40 antibodies block CD40/CD40L binding but do not affect CD11b/CD40L binding

α-CD40L antibodies offer the advantage of blocking interactions of CD40L with both CD40 and CD11b

Liu D, et al. Am J Transplant. 2020;20(8):2216-2225.

3 Generations of α-CD40L Antibody (Ab) Development

2nd and 3rd Generations Engineered to Decrease the Risk of Thrombosis

Third-generation13 anti-CD40L mAbs

TNX-1500

Second-generation3-12 anti-CD40L proteins

Aglycosyl Dapirolizumab Letolizumab Dazodalibep Ruplizumab

First-generation1-2 anti-CD40L mAbs

Ruplizumab "Humanized 5c8 IgG1"

1Pierson RN 3rd, et al. Transplantation. 1999 68(11):1800-5.

2Mirabet M, et al. Mol Immunol. 2008;45(4):937-944.

3Saxena A, et al. Front Immunol. 2016;7:580.

4Xie JH, et al. J Immunol. 2014;192(9):4083-4092.

5Ferrant JL, et al. Int Immunol. 2004;16(11):1583-1594. 6Daley SR, et al. Am J Transplant. 2008;8(11):2265-2271. 7Shock A, et al. Arthritis Res Ther. 2015;17(1):234.

mAb=monoclonal antibody.

8Tocoian A, et al. Lupus. 2015;24(10):1045-1056.

9Kim SC, et al. Am J Transplant. 2017;17(5):1182-1192. 10Pinelli DF, et al. Am J Transplant. 2013;13(11):3021-3030. 11ClinicalTrials.gov identifier: NCT02273960. Updated July 16, 2019. Accessed August 20, 2025. https://clinicaltrials.gov/ct2/show/results/NCT02273960?view=results

12ClinicalTrials.gov identifier: NCT03605927. Updated June 5, 2025. Accessed August 20, 2025. https://clinicaltrials.gov/ct2/show/NCT03605927

13Data on File. 14

3rd Generation: Fc-modulated α-CD40L Abs

First-Generation Anti-CD40L Abs3

Antigen-binding fragment (Fab)

FcγR-binding region

Fc region

Interaction of the FcγR-binding region with platelets leads to stabilization of platelet aggregates that can cause TE complications.1,2

Targeted amino acid substitutions to decrease FcR binding

First-generation anti-CD40L Ab development was halted due to thromboembolic (TE) complications1,2

TE complications were traced to interactions between the fragment crystallizable (Fc) gamma receptor (FcγR)-binding region and platelets3

FcRγIIa was linked to the platelet activation effect4

Some Fc function is required for the treatment effect5

1Koyama I, et al. Transplantation. 2004 77(3):460-2. 2Mirabet M, et al. Mol Immunol. 2008;45(4):937-944. 3Shock A, et al. Arthritis Res Ther. 2015;17(1):234.

4Robles-Carrillo L, et al. J. Immunol. 2010 185(3):1577-1583. 16

5Monk NJ, et al. Nat Med. 2003 9(10):1275-80.

Generation of α-CD40L Variants to Decrease FcγRIIa (CD32A) Binding and Decrease Risk of Thrombosis

Variant

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, P238S

SDKTHTSPPSPAPELLGGS

NSTYR

TNX05

IgG4

S228P, L235A

ESKYGPPCPPCPAPEFAGGP

NSTYR

TNX06

IgG4

WT - G4

ESKYGPPCPSCPAPEFLGGP

NSTYR

TNX07

IgG4

S228P

ESKYGPPCPPCPAPEFLGGP

NSTYR

TNX08

IgG4

S228P, L235E

ESKYGPPCPPCPAPEFEGGP

NSTYR

TNX09

IgG4

S228P, F234A, L235A

ESKYGPPCPPCPAPEAAGGP

NSTYR

TNX10

IgG1

L234A, L235A

CDKTHTCPPCPAPEAAGGP

NSTYR

TNX11

IgG1

C226S, C229S, P238S

CDKTHTSPPSPAPELLGGS

NSTYR

TNX12

IgG1

C229S, P238S

CDKTHTCPPSPAPELLGGS

NSTYR

TNX13

IgG1

C226S, P238S

CDKTHTSPPCPAPELLGGS

NSTYR

IgG=immunoglobulin G; mAb=monoclonal antibody.

Data on File.

3rd Generation: Fine-turning α-CD40L Abs

Aglycosylation1

Disulfide Disruption

Fc Modulated

TNX01

TNX03

TNX04

TNX11 TNX12 TNX13

TNX05

TNX07 TNX08 TNX09 TNX10

Heavy chain IgG1 and IgG4 variants were grouped by mutation result

Analyzed for:

CD40L binding

FcγR binding

Aglycosyl α-CD40L mAb was previously shown to lack activity in preventing transplant rejection, so were studied as controls1

Thrombosis potential for α-CD40L mAbs was conferred to mice by expression of human FcγRIIa2

1Ferrant JL, et al. Int Immunol. 2004;16(11):1583-1594. 18

2Robles-Carrillo L, et al. Journal of Immunology. 2010 185(3):1577-1583.

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

FcγR-modulated

Fc region

No disulfide bonds CH-CL (binding heavy and light chains)

No disulfide bonds CH-CH (binding 2 heavy chains)

Monomer Dimer

TNX04 Monomers without Disulfide Bonds

Soluble CD40L

Each monomer binds one CD40L

molecule

Cell-associated CD40L

Cell membrane

3. Exposure of hidden epitopes

Monomers are expected to bind

soluble and

cell-associated CD40L with similar avidity

Monomer

TNX04

Monomer Monomer

Disclaimer

Tonix Pharmaceuticals Holding Corp. published this content on May 17, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 18, 2026 at 13:53 UTC.