Tonix Pharmaceuticals Holding Corp. 8-K

Exhibit 99.02

Aims:Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are a potential therapeutic target in immune checkpoint cancer therapy, but MDSC-targeted therapies have yet been shown to improve survival. Trefoil factor family 2 (TFF2), a secreted anti-inflammatory peptide, can suppress MDSC expansion and activate tumor immunity in part through agonism of the CXCR4 receptor1-3. The aim of this study is to investigate whether a novel TFF2 –albumin fusion peptide (TFF2-MSA) can improve survival in anti-PD-1 treated syngeneic colorectal cancer (CRC) mouse models. Methods: Two syngeneic colon carcinoma mouse models were developed using cell lines grafted subcutaneously into mice. MC38 CRC cells were engrafted into C57BL/6 mice while CT26.wt CRC cells were implanted into BALB/C mice We generated a recombinant fusion protein, designated mTFF2-MSA, which contains murine TFF2 fused to murine serum albumin (MSA), for the purpose of increasing half-life and reducing dose frequency. Mice subsequently received either mTFF2-MSA or anti-PD-1 antibody (clone 29F.1A12) or both, and tumor volume, and survival were measured. At the endpoint, flow cytometry was performed to examine treatment-induced effects on immune profiles. Results: In the MC38 model, administration of mTFF2-MSA suppressed tumor growth (TGI 50%), the combination of mTFF2-MSA and anti-PD-1 had an additive effect and suppressed tumor growth dramatically (TGI 87%). The combination also exhibited a survival rate of 90% after 50 days, while vehicle and single mTFF2-MSA therapy were 20% and 50%, respectively. The percentage of exhausted CD8+ T cells was markedly reduced in the draining lymph node by the combination treatment, as measured by flow cytometry using antibodies against LAG3, TIM3 and PD-1. In the CT26.wt model, administration of mTFF2-MSA alone exhibited little effect, but the combination of anti-PD-1 and mTFF2-MSA showed a profound effect. In the CT26.wt model, administration of mTFF2-MSA suppressed tumor growth (TGI 16%), anti-PD-1 alone (TGI 40%) and the combination of mTFF2-MSA and anti-PD-1 (TGI 60%). Conclusion: Targeting MDSCs using mTFF2-MSA fusion protein synergizes well with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of colorectal cancer. In a separate abstract, additive effects between mTFF2-MSA and anti-PD-1 antibody were also demonstrated in a separate ACKP (Atp4b-Cre; Cdh1-/-; LSL-KrasG12D; Trp53-/-) gastric cancer model, suggesting combination therapy may also be applicable to gastric cancer. 704 MDSC-Targeted mTFF2-MSA (mTNX-1700*) Suppresses Tumor Growth and Increases Survival in Anti-PD-1 Treated MC38 and CT26.wt Murine Colorectal Cancer Models Bruce L. Daugherty1, Rebecca J. Boohaker2, Rebecca Johnstone2, Karr Stinson2, Jin Qian3, Timothy C. Wang3, Seth Lederman11Tonix Pharmaceuticals, Inc., Chatham, NJ,2Southern Research, Birmingham, AL,3Division of Digestive and Liver Diseases, Irving Cancer Research Center, Columbia University Medical Center, New York, NY Tumors Create a Toxic, Immunosuppressive Microenvironment (TME)  Tumors are surrounded by endothelial and stroma cells, and invading immune cells, both innate and adaptive4,5  Complex regulatory network supports tumor growth, enabling cancers to thrive by evading immune surveillance and destruction5,6  The TME sabotages tumor-killing cytotoxic CD8 T cells1  Myeloid-derived suppressor cells (MDSCs) interfere with anticancer immunity5.6  Levels of MDSCs tend to correlate with tumor stage, patient survival, and metastatic burden and may predict poor response to certain cancer treatments7  MDSCs represent a central mechanism of immunosuppression in cancer; targeting these cells could significantly improve our ability to fight cancer8,9  Therapeutic Strategies Include9:  Promoting differentiation of MDSCs to a non-immunosuppressive cell type  Blocking MDSC immunosuppressive functions  Inhibiting MDSC expansion  Eliminating MDSCs Time Post-Injection Concentration, μg/mL Murine TFF2 106 AA Murine Serum Albumin 584 AA Abstract MDSCs are a Major Therapeutic Target Fig 8: Immunophenotyping of the TME and the Lymph Nodes in the MC38 CRC Model Introduction Results Fig 1: mTFF2-MSA is a Novel Fusion Protein 1 2 SDS-PAGE 1) Reduced 2) Non-reduced Fig 2: Schematic of Syngeneic CRC Tumor Model Fig 3: PK Analysis of mTFF2-MSA in Mice Fig 6: Inhibition of Tumor Growth in the CT26.wt CRC Model Fig 5: Probability of Survival in the MC38 CRC Model Fig 4: Inhibition of Tumor Growth in the MC38 CRC Model Fig 7: Probability of Survival in the CT26.wt CRC Model Tumor Volume, mm3 Days on Study Dose Initiation **p<0.001 ****p<0.0001 Day 49 Vehicle mTFF2-MSA Anti-PD-1 mTFF2-MSA/Anti-PD1 Days on Study Day 25 *p<0.05 Percent Days Percent Days Conclusions  mTFF2-MSA (mTNX-1700) is a novel fusion protein and exhibits an extended half-life invivoin mice.  In the MC38 mouse model of colorectal cancer, mTFF2-MSA alone inhibited tumor growth by 50%, and is additive with anti-PD-1 by inhibiting tumor growth by 87%.  In the MC38 model, survival was 90% in the combination treated group after 50 days, with 40% exhibiting a complete response, while 20% survived in the untreated group.  In the MC38 model, the percentage of exhausted CD8+ T cells was markedly reduced in the draining lymph node by treatment with TFF2-MSA alone, and the combination treated group, as measured by flow cytometry using antibodies against LAG3, TIM3 and PD-1.  In the MC38 model, the percentage of total macrophages in the tumor microenvironment were markedly increased in the anti-PD-1 and the combination treated groups.  In the MC38 model, in animals with complete remission, comparison of exhaustion markers on CD8+ T cells, LAG3+ T cells are reduced in the draining lymphnodein the combination treated group, while suppression of PD-1+ T cells are observed in the axillary lymphnode.  In the CT26.wt mouse model of colorectal cancer, mTFF2-MSA alone inhibited tumor growth by 16%, and is additive with anti-PD-1 by inhibiting tumor growth by 60%.  In the CT26.wt model, survival was 60% in the combination treated group after 30 days, while 0% survived in the untreated group.  TNX-1700 is a novel mechanism for suppressing MDSCs and has the potential to synergize with other immuno-oncology drugs. References 1. DubeykovskayaZ, et al. JBC, 2009; 284:3650-366 2. DubeykovskayaZ, et al. Nature Comm. 2016;7:1-11 3. DubeykovskayaZ, et al. Cancer Gene Ther. 2019;26:48-57 4. Belli C, et al. Cancer Treat Rev.2018;65:22-32 5. Roma-Rodriguez C, et al. Int J Mol Sci.2019;20(4):840 6.Tsai M, et al. ISRN Biochem.2014:351959 7.Condamine T, et al. Annu Rev Med.2015;66:97-110 8.TuccitoA, et al. VirchowsArch. 2019;474(4):407-420 9.GabrilovitchDI, et al. Nat Rev Immunol.2009;9(3):162-174 TILs Draining LNs *TNX-1700 is an investigational new biologicand has not been approved for any indication AACR Annual Meeting, Orlando, FL, April 16, 2023 Vehicle mTFF2/MSA mTFF2/MSA/Anti-PD1 No treatmentmuTFF2-MSAAnti-PD1Combination 05101520 %CD11b+/F480-/Ly6Chi/CD206+nsnsns Total Macrophages M2 Macrophages TILs M2 φ Tumor Promotor Monocyte M1 φ Tumor Suppressor %CD8 PD-1 %CD8 LAG3 %CD8 TIM3 CD8 LAG3 CD8 TIM3 CD8 PD-1 *p<0.05 ****p<0.0001 LAG3 TIM3 PD1 LAG3 TIM3 PD1