Sensei Biotherapeutics, Inc. · NASDAQ:SNSE

Sensei Biotherapeutics — Investor Presentation (April 2023)

34 slides from Sensei Biotherapeutics's investor presentation, Apr 20, 2023

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

    Conditionally Active Antibodies for Immuno-oncology APRIL 2023 | Nasdaq: SNSE Exhibit 99.1

  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 Clinical Reach of Immuno-oncology Agents

    Engineered Selectivity to Extend the Clinical 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 2022: $107.1M* Cash runway into 2H 2025 OUR STRATEGY Conditionally active

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

    Innovative Pipeline of IO Drugs with Broad Commercial Potential *Sensei has entered into a clinical supply agreement with Regeneron supporting the planned evaluation of SNS-101 in combination with Regeneron’s anti-PD-1 therapy Libtayo® (cemiplimab) in a Phase 1/2 clinical trial in solid tumors. *Sen

  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 Tumor Targeting is a Major Obstacle to CI Innovation

    Lack of Tumor Targeting 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

  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: Commercially Validated Precedent for pH-sensitive Approach

    Commercially Validated Precedent for pH-sensitive Approach Soliris (Eculizumab) KD pH 7.4 (nM) 0.03 KD pH 6.0 (nM) 0.6 t½ (d) 3.9 Ultomiris (Ravulizumab, ALXN1210) 0.49 22 13.4 Due to its longer half-life (13.4 d vs 3.9 d), ravulizumab given every 8 weeks achieved noninferiority compared with eculiz

  9. Slide 9: SNS-101

    SNS-101

  10. Slide 10: VISTA is a Potent T cell Checkpoint Extensively Expressed on Myeloid Cells

    VISTA is 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 Immunosuppressive function believed to be mediated by PSGL-1 receptor T-cell proliferation & activation Extensive V

  11. Slide 11: 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 0.218​ 132​ (~No binding) Additional SNS-101 features IgG1 format Active Fc Monovalent Affinity (KD) [nM]​ SNS-101 strongly inhibits the VISTA:PSGL-1 interaction and all other potential binding partners at pH 6.0 in vitr

  12. Slide 12: 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

  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 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 Non-human Primates 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 signifi

  15. Slide 15: PK Sink Continues to be an Issue with Non-pH-Sensitive VISTA programs

    PK Sink Continues to be an Issue with Non-pH-Sensitive VISTA programs* SNS-101 is designed to overcome elimination kinetics and half-life related to PK sink observed in non-pH-sensitive VISTA programs Curis CI-8993 Plasma Concentration Kineta KVA12123 Cyno PK Abcine PMC-309 Serum Conc Cyno Hummingbi

  16. Slide 16: SNS-101 Drove Single-agent Activity and Deepened Anti-tumor Responses to PD-1

    SNS-101 Drove Single-agent Activity and Deepened Anti-tumor Responses to PD-1 in Human VISTA KI Mice ** ** MC38-7r (Anti-mPD-1 insensitive MC38 clone) *** ** ** * P<0.05; ** P<0.01; *** P<0.001 MC38

  17. Slide 17: SNS-101 Increased CD8 T-cells in Combination With Anti-PD-1 in MC38 Tumors

    SNS-101 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-PD-1 with Ant

  18. Slide 18: Targeting VISTA and PD-1 Checkpoints in the TME Promotes Anti-tumoral M1 Macrophage Polarization

    Targeting VISTA and PD-1 Checkpoints in the TME Promotes Anti-tumoral M1 Macrophage Polarization M1 macrophages are anti-tumorigenic through secretion of pro-inflammatory cytokines and chemokines, and driving of Th1 CD4+ T cell responses M2 macrophages are immunosuppressive; pro-tumor TAMs are a sub

  19. Slide 19: SNS-101 Re-sensitized Anti-PD-1 Insensitive Sarcoma Tumors in Human VISTA Knock-in Mice

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

  20. Slide 20: SNS-101 Phase 1/2 Study

    SNS-101 Phase 1/2 Study * Safety Monitoring Committee (SMC) to determine initiation of combination arm based on emerging clinical data RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose Phase 1 Dose Escalation - Monotherapy: SNS-101 alone Phase 1 Dose Escalation – Combination: SNS-101 + Li

  21. Slide 21: Partner / Collaborator

    ​Partner / Collaborator Goal Description Clinical Supply Agreement Supports evaluation of SNS-101 in combination with Libtayo® (cemiplimab) in planned Phase 1/2 clinical trial Sensei to fund planned clinical trial Regeneron to provide Libtayo® Sensei maintains global development and commercial right

  22. Slide 22: SNS-101 Is a Fully Differentiated Anti-VISTA Antibody

    SNS-101 Is a Fully Differentiated Anti-VISTA Antibody Phase 1 Phase 1 Phase 1 Phase 1 Phase 1 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 al, J o

  23. Slide 23: VSIG-4

    VSIG-4

  24. Slide 24: VSIG4 is an Immunosuppressive Receptor with On-Target, Off-Tumor Challenges

    VSIG4 is an Immunosuppressive Receptor with On-Target, Off-Tumor Challenges 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 cells1-2 Appears to drive significant target-

  25. Slide 25: 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 +

  26. Slide 26: Tumor Micro-Environment: ENTPDase1 (CD39)

    TUMOR MICRO-ENVIRONMENT ENTPDase1 (CD39)

  27. Slide 27: 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 (eATP)

  28. Slide 28: Sensei Has Identified pH-sensitive ENTPDase1 (CD39) Antibodies

    Sensei Has Identified pH-sensitive ENTPDase1 (CD39) Antibodies Program milestones to date: Identified 8 parental antibodies for further optimization Identified pH-sensitive parental antibodies for lead optimization Plan to select lead product candidate in 2023 Antibody Reference # Ratio of pH Select

  29. Slide 29: Summary

    Summary

  30. Slide 30: Expected Program Milestones

    SNS-101 (anti-VISTA) Mid-year 2023: First patient first dose 2024: Topline Phase 1 monotherapy data 2024: Initial Phase 1 combination data SNS-102 (anti-VSIG4) 2023: Select product candidate SNS-103 (anti-ENTPDase1/CD39) 2023: Select product candidate Expected Program Milestones TMAb Platform Advanc

  31. Slide 31: Engineered Selectivity to Extend the Clinical Reach of Immuno-oncology Agents

    Engineered Selectivity to Extend the Clinical 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 2022: $107.1M* Cash runway into 2H 2025 OUR STRATEGY Conditionally active

  32. Slide 32: Seasoned Leadership Team

    Seasoned Leadership Team John Celebi, MBA President and CEO Patrick Gallagher Chief Business Officer Christopher Gerry, J.D. VP, General Counsel Erin Colgan Chief Financial Officer Edward van der Horst, Ph.D. Chief Scientific Officer

  33. Slide 33: HQ: 1405 Research Blvd, Suite 125, Rockville, MD 20850 / MA: 22 Boston Wharf

    HQ: 1405 Research Blvd, Suite 125, Rockville, MD 20850 / MA: 22 Boston Wharf Rd, 7th floor, Boston, MA 02210 senseibio.com

  34. Slide 34: Appendix References

    Appendix References for Slide 24 Helmy KY, Katschke KJ Jr, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van Lookeren Campagne M. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell. 2006 Mar 10;124(5):915-27. doi: 10.1016/j.cell.2005

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