Sensei Biotherapeutics, Inc. · NASDAQ:SNSE

Sensei Biotherapeutics — Investor Presentation (November 2023)

40 slides from Sensei Biotherapeutics's investor presentation, Nov 3, 2023

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

    Conditionally Active Antibodies for Immuno-oncology NOVEMBER 2023 | 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 Clinical Reach of Immuno-oncology Agents

    *Consists of cash, cash equivalents and marketable securities LEAD PROGRAM SNS-101, a conditionally active antibody targeting VISTA Initial Phase 1 data demonstrate well tolerated safety profile & potentially best-in-class pharmacokinetics (PK) TMAb PLATFORM Conditionally active antibodies designed

  4. Slide 4: Lack of Tumor Targeting is a Major Obstacle to IO Innovation

    Lack of Tumor Targeting is a Major Obstacle to IO 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

  5. Slide 5: TMAb Antibodies are Designed to Bind Selectively in the Tumor Microenvironment

    TMAb Antibodies are Designed to Bind Selectively in the Tumor Microenvironment Lack of peripheral target engagement can improve safety and pharmacokinetic parameters while focusing action to the tumor microenvironment

  6. Slide 6: 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

  7. Slide 7: SNS-101

    SNS-101

  8. Slide 8: 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 and is expressed extensively by myeloid cells SNS-101 targets immunosuppressive function mediated by PSGL-1 and oth

  9. Slide 9: Historical Challenges Targeting VISTA-Positive Myeloid Cells Resulted in Early Clinical Trial Termination

    Historical Challenges Targeting VISTA-Positive Myeloid Cells Resulted in Early Clinical Trial Termination JNJ-61610588 Human Plasma Concentration JNJ-61610588 (CI-8993) was the first anti-VISTA antibody to be studied in clinical trials in 2016 (NCT02671955) 1 Transient Cytokine Release Syndrome (CRS

  10. Slide 10: SNS-101 is a Differentiated, pH-Sensitive Antibody Designed to Overcome VISTA Challenges

    SNS-101 is a Differentiated, pH-Sensitive Antibody Designed to Overcome the Unique Challenges of VISTA Potential Best-in-Class Safety and PK Profile Supported by Initial Clinical Data No observed CRS or dose-limiting toxicity and no evidence of target-mediated drug disposition* Rapidly Enrolling Pha

  11. Slide 11: SNS-101 Phase 1/2 Study

    SNS-101 Phase 1/2 Study + As of October 3, 2023, enrollment complete in Cohort A4 (10.0 mg/kg), pending DLT assessment period ^ As of October 3, 2023, enrollment complete in Cohort B1 (3.0 mg/kg of SNS-101 + 350 mg of Libtayo), pending DLT assessment period RP2D = Recommended Phase 2 Dose MTD = Maxi

  12. Slide 12: SNS-101 Displayed Favorable Safety & Tolerability Profile

    SNS-101 Displayed Favorable Safety & Tolerability Profile DLT = Dose limiting toxicity CRS = Cytokine release syndrome TEAE – Treatment emergent adverse event SAE = Serious adverse event 0.3 mg/kg N=1 n (%) 1.0 mg/kg N=3 n (%) 3.0 mg/kg N=3 n (%) Total N=7 n (%) At least 1 TEAE 1 3 1 5 (71.4) At lea

  13. Slide 13: Cytokine Data Consistent with Lack of Observed CRS

    Cytokine Data Consistent with Lack of Observed CRS Cytokine analysis: Blood samples were taken pre-dose, 3 hours post-infusion and 6 hours post infusion at C1D1, and pre- and 3hr-post thereafter. Serum was assayed for indicated cytokines using a platform (MSD) that has been validated for clinical sa

  14. Slide 14: SNS-101 Clinical PK Data Show Linear Pharmacokinetics and Long Half-Life

    SNS-101 Clinical PK Data Show Linear Pharmacokinetics and Long Half-Life (Unlike Prior Anti-VISTA mAbs) Supports Every 3 Week Dosing Data from monotherapy dose escalation arm as of safety cut-off date of October 3, 2023

  15. Slide 15: Key SNS-101 Differentiators: Potential Best-in-Class Therapeutic

    Key SNS-101 Differentiators: Potential Best-in-Class Therapeutic 0.1 Dose (mg/kg) 0.3 3 10 1 JNJ-61610588 P1 DLT (CRS) SNS-101 current dose level+ ~33X 15 Dosing every 3 weeks vs. every 1 or 2 weeks for competitors Linear elimination kinetics vs. non-linear for competitors Safety Parameters On Track

  16. Slide 16: Single-agent Activity and Deepened Anti-tumor Responses to PD-1 Combo in Human VISTA KI Mice

    Single-agent Activity and Deepened Anti-tumor Responses to PD-1 Combo 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: SNS-101 Completed and Anticipated Clinical Milestones

    SNS-101 Completed and Anticipated Clinical Milestones May 2023: First patient dosed Sept 2023: First patient dosed in combination with Libtayo® Q4 2023: Initial monotherapy PK and safety data Q1 2024: Initial combination PK and safety data Q2 2024: Topline Phase 1 monotherapy data 2024: Topline comb

  19. Slide 19: VSIG-4

    VSIG-4

  20. Slide 20: 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-

  21. Slide 21: SNS-102 is a Highly pH-sensitive Antibody that Could Reverse T-cell Suppression

    SNS-102 is a Highly pH-sensitive Antibody that Could Reverse T-cell Suppression within the Tumor Microenvironment SNS-102 blocks the interaction of VSIG4 with its novel counter-receptor, which has been provisionally identified pH-Sensitive VSIG4 Parental Antibodies Selected for Further Optimization

  22. Slide 22: ENTPDase1 (CD39)

    ENTPDase1 (CD39 JI)

  23. Slide 23: ENTPDase1 (CD39) is the Rate Limiting Enzyme in Production of Immunosuppressive Adenosine

    ENTPDase1 (CD39) is the Rate Limiting Enzyme in the Production of Immunosuppressive Adenosine Primary function is conversion of extracellular ATP (eATP) to adenosine (ADO)​, which exerts immunosuppressive properties through binding to A2a/A2b receptors (ADA) Expressed on various immune cells in both

  24. Slide 24: Sensei Has Identified pH-sensitive ENTPDase1 (CD39) Antibodies

    Sensei Has Identified pH-sensitive ENTPDase1 (CD39) Antibodies Antibody Reference # Ratio of pH Selectivity (6.0 vs 7.4) 1 1 2 6 3 4 4 5 5 18 6 1 7 1 8 1 pH-Sensitive CD39 Parental Antibodies Selected for Further Optimization Development of a TMAb antibody has potential for improved safety and PK pr

  25. Slide 25: Summary

    Summary

  26. Slide 26: Completed and Anticipated Program Milestones

    SNS-101 (anti-VISTA) May 2023: First patient dosed Sept 2023: First patient dosed in combination with Libtayo® Q4 2023: Initial monotherapy PK and safety data Q1 2024: Initial combination PK and safety data Q2 2024: Topline Phase 1 monotherapy 2024: Topline combination data SNS-102 (anti-VSIG4) 2023

  27. Slide 27: Engineered Selectivity to Extend the Clinical Reach of Immuno-oncology Agents

    *Consists of cash, cash equivalents and marketable securities LEAD PROGRAM SNS-101, a conditionally active antibody targeting VISTA Initial Phase 1 data demonstrate well tolerated safety profile & potentially best-in-class pharmacokinetics (PK) TMAb PLATFORM Conditionally active antibodies designed

  28. Slide 28: Seasoned Leadership Team

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

  29. Slide 29: 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

  30. Slide 30: Appendix References

    Appendix References for Slide 20 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

  31. Slide 31: 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

  32. Slide 32: Partner / Collaborator Goal Description

    ​Partner / Collaborator Goal Description Clinical Supply Agreement Support 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 rights

  33. Slide 33: 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

  34. Slide 34: 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

  35. Slide 35: 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

  36. Slide 36: 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

  37. Slide 37: 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

  38. Slide 38: SNS-101 Is a Fully Differentiated Anti-VISTA Antibody

    KVA12123 (Kineta) SNS-101 Is a Fully Differentiated Anti-VISTA Antibody Phase 1 Phase 1 Phase 1 Phase 1 Phase 1 Preclinical Phase 1 (IgG1) (IgG1) (IgG1) (IgG4) (IgG1) Johnston et al., Nature 2019; Kineta website; Snyder et al, AACR Annual Meeting 2016; Pierre Fabre website; Hummingbird website; Thak

  39. Slide 39: 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

  40. Slide 40: Targeting VISTA and PD-1 Checkpoints 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

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