Sensei Biotherapeutics, Inc. · NASDAQ:SNSE

Sensei Biotherapeutics — Investor Presentation (November 2022)

31 slides from Sensei Biotherapeutics's investor presentation, Nov 8, 2022

  1. Slide 1: Conditionally Active Antibodies for Immuno-oncology

    Conditionally Active Antibodies for Immuno-oncology NOVEMBER 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: Engineered Selectivity to Extend the Reach of Immuno-oncology Agents

    Engineered Selectivity to Extend the Reach of Immuno-oncology Agents THE CHALLENGE Systemically delivered I/O drugs often fail in the clinic due to on-target/off-tumor effects (TMDD, CRS) OUR FINANCIAL POSITION Ended 3Q 2022: $116.6M* Cash runway into Q1 2025 OUR STRATEGY Conditionally active antibo

  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 SNS-101 (VISTA) SNS-102 (VSIG4) SNS-103 (ENTPDase1/CD39) Solid Tumors Solid Tumors Solid Tumors

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

    The Modern-Day Challenge in Immuno-Oncology The PD-1/PD-L1 market is big and growing fast1 PD-1/PD-L1 monotherapy does not benefit 70% of patients2 2020 2026 Survival Benefit 20-30% No Survival Benefit 70% 1. Gerber et al., Biochemical Pharmacology 2016 2. Market estimates from PD-1 and PDL-1 Inhibi

  6. Slide 6: Lack of Selectivity is a Major Obstacle to CI Innovation

    Lack of Selectivity is a Major Obstacle to CI Innovation Industry Problem Sensei’s Solution Conventional antibodies target immune checkpoints that are highly expressed in normal tissues, resulting in: Dose-limiting toxicities due to on-target/off-tumor action Pharmacological sink effect requires hig

  7. Slide 7: pH-sensitive Antibodies Have Potential to Selectively Bind Their Targets in the Low-pH Tumor Microenvironment

    pH-sensitive Antibodies Have Potential to Selectively Bind Their Targets in the Low-pH Tumor Microenvironment Exploits the tumor microenvironment using pH-selective properties Intended to alleviate undesirable properties: Dose-limiting toxicities due to on-target/off-tumor binding Higher and more fr

  8. Slide 8: SNS-101

    SNS-101

  9. Slide 9: VISTA: A Potent T cell Checkpoint Extensively Expressed on Myeloid Cells

    VISTA: A Potent T cell Checkpoint Extensively Expressed on Myeloid Cells1 1. Lines et al. Cancer research vol. 74,7 (2014) VISTA is a B7 family member that suppresses T cell function T-cell proliferation & activation

  10. Slide 10: The VISTA:PSGL-1 Interaction is Selective for low pH

    The VISTA:PSGL-1 Interaction is Selective for low pH Data are based on in vitro assay.

  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 1. Johnston et al., Nature 2019 VISTA extracellular domain is uniquely rich in histidines¹ Protonated VISTA histidines are required for PSGL-1 binding1

  12. Slide 12: SNS-101: Selectively Targeting VISTA with a pH-sensitive Antibody

    SNS-101: Selectively Targeting VISTA with a pH-sensitive Antibody pH 6.0 pH 7.4 Monovalent Affinity (KD) [nM]​ 0.218​ 132​ (~No binding) Key features Selectivity for Active VISTApH6 over VISTApH7.4 Designed to block VISTA’s interaction with PSGL-1 and all other T-cell receptors at pH 6.0 IgG1 format

  13. Slide 13: SNS-101 Is a Fully Differentiated Anti-VISTA Antibody

    SNS-101 Is a Fully Differentiated Anti-VISTA Antibody Preclinical Phase 1 Phase 1 Phase 1 Preclinical Preclinical Preclinical (IgG1) (IgG1) (IgG1) (IgG4) (IgG1) Johnston et al., Nature 2019; Kineta website; Snyder et al, AACR Annual Meeting 2016; Pierre Fabre website; Hummingbird website; Thakkar et

  14. Slide 14: SNS-101 Strongly Inhibits the VISTA:PSGL-1 Interaction at pH 6.0

    SNS-101 Strongly Inhibits the VISTA:PSGL-1 Interaction And All Other Potential Binding Partners at pH 6.0 in In Vitro Assay Receptor IC50 [nM] PSGL-1 7 VSIG3 6 VSIG8 6 Syndecan-2 6 LRIG1 6

  15. Slide 15: No Significant Binding of SNS-101 to Monocytes, Neutrophils, NK Cells and T-cells in Whole Blood

    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

  16. Slide 16: 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

  17. Slide 17: SNS-101 Has Displayed a Favorable Single-dose PK Profile in Preclinical Studies

    SNS-101 Has Displayed a Favorable Single-dose PK Profile in Preclinical Studies - No Significant TMDD in Human VISTA KI Mice or 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 t

  18. Slide 18: SNS-101 Demonstrated Strong Combinatorial Activity with Anti-PD-1 in MC38 Model

    SNS-101 Demonstrated Strong Combinatorial Activity with Anti-PD-1 in MC38 Model in Human VISTA Knock-in Mice SNS-101 0/10 PD-1 Mono 1/10 Combo 5/10 Isotype Control 0/10 *** ** ** * P<0.05; ** P<0.01; *** P<0.001 *

  19. Slide 19: SNS-101 Demonstrated Increased CD8 T-cells in Combination With Anti-PD-1

    SNS-101 Demonstrated Increased CD8 T-cells in Combination With Anti-PD-1 in MC38 Tumors In Vivo 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-

  20. Slide 20: SNS-101 Re-sensitized Anti-PD-1 Insensitive Sarcomas Tumors in 1956 Model

    SNS-101 Re-sensitized Anti-PD-1 Insensitive Sarcomas Tumors in 1956 Model in Human VISTA Knock-in Mice 5/8 CR 1/8 CR * p<0.05

  21. Slide 21: Preliminary SNS-101 Phase 1/2 Study Schematic

    Preliminary SNS-101 Phase 1/2 Study Schematic 2 Phase 1 Dose Escalation Monotherapy Projected Scheme * Phase 2 Cohort Expansion *** *** Tumor types, indication and samples size to be determined based on findings from dose-escalation phase and emerging scientific data; cohorts may run concurrently. P

  22. Slide 22: VSIG-4

    VSIG-4

  23. Slide 23: VSIG4 is an Immunosuppressive Receptor Expressed On- and Off-tumor

    VSIG4 is an Immunosuppressive Receptor Expressed On- and Off-tumor See references in Appendix A B Tissue macrophages (Kupffer cells) in liver Tumor-associated macrophages in tumor and stroma (inset) In the liver, VSIG-4 … Is expressed on Kupffer cells Appears to drive significant target-mediated dru

  24. Slide 24: 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 +

  25. Slide 25: ENTPDase1 (CD39)

    ENTPDase1 (CD39)

  26. Slide 26: 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 Figure adapted from: Moesta et al, Nat Rev Immunol. 2020; 20 (12)​ Hypoxia/cell damage ATP AMP Adeno-sine Blocking CD39 leads to: Immune Activation Primary function is conversion of extracellular ATP / ADP

  27. Slide 27: 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 SNS-103 (anti-ENTPDase1/CD39) 2023: Select product candidate Expected Program Milestones

  28. Slide 28: Engineered Selectivity to Extend the Reach of Immuno-oncology Agents

    Engineered Selectivity to Extend the Reach of Immuno-oncology Agents THE CHALLENGE Systemically delivered I/O drugs often fail in the clinic due to on-target/off-tumor effects (TMDD, CRS) OUR FINANCIAL POSITION Ended 3Q 2022: $116.6M* Cash runway into Q1 2025 OUR STRATEGY Conditionally active antibo

  29. Slide 29: Proven Team With Deep Experience

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

  30. Slide 30: 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

  31. Slide 31: Appendix References

    Appendix References for Slide 23 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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