Sensei Biotherapeutics, Inc. · NASDAQ:SNSE

Sensei Biotherapeutics — Investor Presentation (August 2022)

26 slides from Sensei Biotherapeutics's investor presentation, Aug 31, 2022

  1. Slide 1: Next Generation Immuno-Oncology Medicines

    Next Generation Immuno-Oncology Medicines John K. Celebi, MBA President & Chief Executive Officer AUGUST 2022 | Nasdaq: SNSE Exhibit 99.2

  2. Slide 2: Disclaimer

    Disclaimer This presentation has been prepared by Sensei Biotherapeutics, Inc. (the “Company,” "we," "us") and is made for informational purposes only. The information set forth herein does not purport to be complete or to contain all of the information you may desire. Statements contained herein ar

  3. Slide 3: Positioned to Drive Value with Next Generation Product & Platform Development

    Positioned to Drive Value with Next Generation Product & Platform Development Two Platforms Generate Broad Pipeline Opportunities Current emphasis on pH-sensitive antibodies for improved selectivity TMAb™ ImmunoPhage™ Innovative Pipeline of Differentiated IO mAbs Lead program targets VISTA with IND

  4. Slide 4: Innovative Pipeline of IO Drugs with Broad Commercial Potential

    Innovative Pipeline of IO Drugs with Broad Commercial Potential Program (Target) Indication Discovery IND-enabling Phase 1 / 2 Clinical TMAb SNS-101 (VISTA) Solid Tumors SNS-102 (VSIG4) Solid Tumors SNS-103 (ENTPDase1/CD39) Solid Tumors ImmunoPhage SNS-401-NG (Multiple Tumor Antigens) Merkel Cell Ca

  5. Slide 5: The Modern-Day Challenge in Immuno-Oncology

    The Modern-Day Challenge in Immuno-Oncology No Survival Benefit 70% Survival Benefit 20-30% ~$30B ~$90B 2020 2026 Global PD-1/PD-L1 Market2 1. Gerber et al., Biochemical Pharmacology 2016 2. Market estimates from PD-1 and PDL-1 Inhibitors Market Size in 2021 – MarketWatch, 360 Research

  6. Slide 6: Two Major Types of Non-Responders to PD-1 Blockade

    Two Major Types of Non-Responders to PD-1 Blockade Green = T-cells Purple = tumor Non-Responders T-cells Absent T-cells Inactive or Outside Tumor Responders T-cells Inside Tumor Anti-PD-1 or PD-L1 Treatment Adapted from Van der Woulde-LL, et al, Trends in Cancer, 2017 Hot (inflamed) tumor Cold (excl

  7. Slide 7: The Challenge of Next Generation Checkpoint Blockade

    The Challenge of Next Generation Checkpoint Blockade Few new classes of checkpoint blocking antibodies approved since landmark approvals of CTLA-4 and PD-1 Antibodies blocking immune checkpoints are often limited by dose limiting toxicities that prevent maximal therapeutic outcomes Immune checkpoint

  8. Slide 8: pH-sensitive Antibodies Selectively Bind Their Targets in the Low-pH Tumor Microenvironment

    pH-sensitive Antibodies Selectively Bind Their Targets in the Low-pH Tumor Microenvironment Antibodies that bind at physiological pH may encounter a “sink” Prevents effective binding at the tumor and may lead to toxicity TMAb antibodies are expected to bypass tissue compartments other than the low-p

  9. Slide 9: VISTA: An Emerging Checkpoint Target on Myeloid Cells

    VISTA: An Emerging Checkpoint Target on Myeloid Cells Target Overview: B7 family ligand Extensive expression on myeloid cells1 correlating with poor survival rates across multiple cancers Novel development program with no approved therapies Large market opportunity Sensei’s Competitive Advantage: Ex

  10. Slide 10: Increased Understanding of VISTA as a Promising Target to Address the Needs of Patients with Cancer

    Increased Understanding of VISTA as a Promising Target to Address the Needs of Patients with Cancer

  11. Slide 11: VISTA Checkpoint is Activated at the Low pH of the Tumor Microenvironment

    VISTA Checkpoint is Activated at the Low pH of the Tumor Microenvironment VISTA’s extracellular domain is uniquely rich in histidines¹ Histidines are protonated at low pH enabling VISTA to distinguish the active (acidic pH) and inactive (neutral pH) PSGL-1 binding interface SNS-101 Has >600-Fold Sel

  12. Slide 12: No Significant Binding of SNS-101 to Monocytes, Neutrophils, NK Cells and T-cells

    No Significant Binding of SNS-101 to Monocytes, Neutrophils, NK Cells and T-cells in Whole blood at Physiological pH T-cells NK cells FOB 1.57 FOB 2.0 FOB 1.0 FOB 8.75 FOB 12.4 FOB 1.36 Monocytes FOB 9.9 FOB 13.5 FOB 1.4 FOB 2.2 FOB 2.5 FOB 1.0 Neutrophils CYNO HUMAN FOB 7.4 FOB 8.8 FOB 1.0 Clinical

  13. Slide 13: SNS-101 Induced Substantially Lower Cytokine Release in Whole-blood Assay

    SNS-101 Induced Substantially Lower Cytokine Release in Whole-blood Assay at Neutral pH Compared to pH-independent VISTA Antibody IFN-γ IL-8 TNF-α IL-6 IL-2 *** *** *** ** * ** ** ** ** ** ** ** ** ** ** Dose ranges: 1, 10, and 100 ug/ml #2

  14. Slide 14: SNS-101 Has Displayed a Favorable PK Profile in Preclinical Studies

    SNS-101 Has Displayed a Favorable PK Profile in Preclinical Studies No Significant TMDD in Human VISTA KI Mice or Single-dose Cyno Monkeys Pharmacokinetics of Single Dose 5 mg/kg SNS-101 in VISTA Knock-in Mice Demonstrated a long mean residence time in the blood, indicating a lack of significant tar

  15. Slide 15: SNS-101 Demonstrates Strong Combinatorial Activity with Anti-PD-1 in MC38 Model

    SNS-101 Demonstrates Strong Combinatorial Activity with Anti-PD-1 in MC38 Model in Human VISTA Knock-in Mice SNS-101-m2 0/10 PD-1 Mono 1/10 Combo 5/10 Isotype Control 0/10 *** ** ** ** p<0.01; *** p<0.001 Confidential

  16. Slide 16: SNS-101 Demonstrates Increased CD8 T-cells in Combination With Anti-PD-1

    SNS-101 Demonstrates Increased CD8 T-cells in Combination With Anti-PD-1 CTRL Anti-PD-1 1mg/kg 5mg/kg Anti-PD-1/SNS-101 3mg/kg 10mg/kg 30mg/kg Frequency of Live, CD45+ Population One-way ANOVA, Tukey Post-Hoc Analysis, * p<0.05; ** p<0.01, *** p<0.001, **** p<0.0001 with Anti-PD-1 with Anti-PD-1

  17. Slide 17: Key to Unlocking the Power of VISTA

    Key to Unlocking the Power of VISTA Block the pH-dependent binding of VISTA to PSGL-1 on T cells at low pH Selectively bind VISTA at low pH to avoid: target mediated drug disposition (TMDD) on-target/off-tumor side effects Utilize an Fc-competent IgG backbone to engage and activate FcƔR on tumor-inf

  18. Slide 18: SNS-101 Is a Differentiated Anti-VISTA Antibody

    SNS-101 VISTA.18 (BMS) KVA12.1 (Kineta) CI-8993; JNJ-61610588 (J&J/Curis) K01401-020; W0180 (Pierre Fabre) HMBD-002 (Hummingbird) Inhibit PSGL-1 Binding Yes Yes unknown Yes unknown No pH Sensitive Binding Yes Yes No No No No Fc Active Yes (IgG1) No (IgG4) Yes (IgG1) Yes (IgG1) N/A No (IgG4) Stage Pr

  19. Slide 19: VSIG4 is an Immunosuppressive Receptor Expressed on Tumor-associated Macrophages

    VSIG4 is an Immunosuppressive Receptor Expressed on Tumor-associated Macrophages B7 family related protein, also known as cRiG (complement receptor Immunoglobulin) Expressed primarily on macrophages, including tumor-associated macrophages (TAMs) and Kupffer cells VSIG-4 correlates with "M2" macropha

  20. Slide 20: Sensei Has Identified pH-sensitive VSIG4 Antibodies

    Sensei Has Identified pH-sensitive VSIG4 Antibodies pH-Sensitive VSIG4 Parental Antibodies Selected for Further Optimization Antibody Reference # Ratio of pH Selectivity (6.0 vs 7.4) Blockage of Immobilized VSIG4- T-cell Inhibition Blockage of Cellular VSIG4- T-cell Inhibition 1 1 + + 2 7 + + 3 1 +

  21. Slide 21: Cell Surface Expressed VSIG-4 Suppresses Primary Human T-cell Activation

    Cell Surface Expressed VSIG-4 Suppresses Primary Human T-cell Activation Zang et al. J Clin Invest. 2006;116(10):2590-2593 Day 4- Proliferation Cell Trace Violet Day 4 Cryopreserved PBMCs CD4+ T cell Purification Proliferation Cell Isolation Day 3 Activation-induced Expansion 3/3 Donors Responsive 1

  22. Slide 22: ENTPDase1 (CD39) is the Rate Limiting Enzyme in the Production of Immunosuppressive Adenosine

    ENTPDase1 (CD39) is the Rate Limiting Enzyme in the Production of Immunosuppressive Adenosine ATP AMP Adeno-sine Figure adapted from: Moesta et al, Nat Rev Immunol. 2020; 20 (12)​ Primary function is conversion of extracellular ATP / ADP to adenosine​, which exerts immunosuppressive properties throu

  23. Slide 23: Expected Program Milestones

    SNS-101 (anti-VISTA) 1H 2023: Multi-dose Non-Human Primate (NHP) PK & Toxicology data 1H 2023: IND filing SNS-102 (anti-VSIG4) 2023: Select product candidate / initiate IND-enabling studies SNS-103 (anti-ENTPDase1/CD39) 2023: Select product candidate Expected Program Milestones

  24. Slide 24: Proven Team With Deep Experience

    Proven Team With Deep Experience Patrick Gallagher Chief Business Officer Elisabeth Colunio VP, Human Resources Edward van der Horst, Ph.D. SVP, TMAb Antibodies John Celebi, MBA President and CEO Robert Pierce, M.D. Chief R&D Officer Erin Colgan Chief Financial Officer HansPeter Waldner,Ph.D. SVP, C

  25. Slide 25: HQ: D St, Unit , Boston, MA 02210 / MD: 1405 Research Blvd, Suite

    HQ: 451 D St, Unit 710 , Boston, MA 02210 / MD: 1405 Research Blvd, Suite 125, Rockville, MD 20850 senseibio.com

  26. Slide 26: Appendix References for Slide

    Appendix References for Slide 19 Zheng F, Devoogdt N, Sparkes A, Morias Y, Abels C, Stijlemans B, Lahoutte T, Muyldermans S, De Baetselier P, Schoonooghe S, Beschin A, Raes G. Monitoring liver macrophages using nanobodies targeting Vsig4: concanavalin A induced acute hepatitis as paradigm. Immunobio

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