Sensei Biotherapeutics, Inc. · NASDAQ:SNSE

Sensei Biotherapeutics — Investor Presentation (January 2024)

42 slides from Sensei Biotherapeutics's investor presentation, Jan 4, 2024

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

    Conditionally Active Antibodies for Immuno-oncology Corporate Deck | January 2024 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: Company Highlights

    Company Highlights Sensei Bio’s proprietary platform is designed to harness the unique acidic tumor microenvironment to widen the therapeutic window and enable druggability of promising oncology targets SNS-101, the company’s lead asset, targets VISTA, a critical negative regulator of T-cell functio

  4. Slide 4: Leadership Team with History of Antibody Oncology Success

    Leadership Team with History of Antibody Oncology Success Erin Colgan Chief Financial Officer John Celebi, MBA President and CEO Christopher Gerry, J.D. VP, General Counsel Edward van der Horst, Ph.D. Chief Scientific Officer Stephanie Krebs, M.S., MBA Chief Business Officer Ron Weitzman, M.D. Chief

  5. Slide 5: 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% The Modern-Day Challenge in Immuno-Oncology (IO) 1. Gerber et al., Biochemical Pharmacology 2016 2. Market estimates from PD-1 and PDL-1 I

  6. Slide 6: Lack of Tumor Targeting is a Major Obstacle in 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 higher & more frequent dosing Suboptimal activity due to poo

  7. Slide 7: The TMAb Platform: pH-sensitive Antibodies

    The TMAb Platform: pH-sensitive Antibodies Selectively Bind to Targets in the Low-pH Tumor Microenvironment Exploits the tumor microenvironment using pH-selective properties Intended to alleviate undesirable PK/PD properties: Dose-limiting toxicities due to on-target/off-tumor binding Higher and mor

  8. Slide 8: 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

  9. Slide 9: SNS-101 (VISTA)

    SNS-101 (VISTA)

  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 Cells VISTA is a B7 family member that inhibits T cell activation1 Immunosuppressive function believed to be mediated by PSGL-1 receptor Upregulated on immune suppressive myeloid-derived suppressor cells (MDSCs) via hypoxia2 Increa

  11. Slide 11: SNS-101: Selectively Targets VISTA via a pH-sensitive Antibody

    SNS-101: Selectively Targets VISTA via a pH-sensitive Antibody pH 6.0 pH 7.4 0.218 ​nM 132​ nM (~No binding) Additional SNS-101 features IgG1 format Active Fc Monovalent Affinity (KD)​ SNS-101 strongly inhibits the VISTA:PSGL-1 interaction and all other potential binding partners at pH 6.0 in vitro

  12. Slide 12: Competitors Halted Development of VISTA Antibodies

    Competitors Halted Development of VISTA Antibodies as a Result of Severe Toxicities From Non-Tumor Activity & Poor PK Dose-limiting toxicity Grade 3 CRS-associated encephalopathy JNJ-61610588 Human Plasma Concentration JNJ-61610588 (CI-8993) was the first anti-VISTA antibody to be studied in clinica

  13. Slide 13: SNS-101 is Designed to Overcome VISTA's Unique Challenges

    SNS-101 is Designed to Overcome VISTA’s Unique Challenges 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 through 3 mg/kg monotherapy* Enrolling Phase 1/2 Clinical Trial Mul

  14. Slide 14: SNS-101 is Unique and Differentiated From Its Peers

    SNS-101 is Unique and Differentiated From Its Peers Johnston et al., Nature 2019; Kineta website; Snyder et al, AACR Annual Meeting 2016; Pierre Fabre website; Hummingbird website; Thakkar et al, J of Immunother Cancer, 2022; PharmAbcine website KVA12123 (Kineta) Phase 1 Phase 1 Phase 1 Phase 1 Phas

  15. Slide 15: SNS-101 Phase 1/2 Study

    SNS-101 Phase 1/2 Study * Libtayo 350 mg + As of January 2, 2024, cleared Cohort A5 (15.0 mg/kg) ^ As of January 2, 2024, Cohort B2 (10.0 mg/kg of SNS-101 + Libtayo) enrolled, pending DLT assessment period RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose Cohort A1 0.3 mg/kg N=1 Cohort B1

  16. Slide 16: SNS-101 Displayed Favorable Safety & Tolerability Profile Through 3 mg/kg

    SNS-101 Displayed Favorable Safety & Tolerability Profile Through 3 mg/kg Monotherapy 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

  17. Slide 17: Monotherapy Data Consistent with Lack of Observed Cytokine Release Syndrome

    Monotherapy Data Consistent with Lack of Observed Cytokine Release Syndrome Through 3.0 mg/kg 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 (M

  18. Slide 18: SNS-101 Monotherapy Data Show Linear Pharmacokinetics and Long Half-Life

    SNS-101 Monotherapy Data Show Linear Pharmacokinetics and Long Half-Life in Stark Contrast to Prior Anti-VISTA mAbs Supports Every 3 Week Dosing Data from monotherapy dose escalation arm as of cut-off date of October 3, 2023

  19. Slide 19: Key SNS-101 Differentiators: Potential Best-in-Class

    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+ ~50X 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

  20. Slide 20: Completed and Anticipated SNS-101 Clinical Milestones

    Completed and Anticipated SNS-101 Clinical Milestones First patient dosed with SNS-101 First patient dosed in combination with Libtayo® Initial monotherapy dose escalation PK & safety data Initial combination dose escalation PK & safety data Topline Phase 1 monotherapy dose escalation data Topline P

  21. Slide 21: SNS-102 (VSIG-4)

    SNS-102 (VSIG-4)

  22. Slide 22: VSIG4 is an Immunosuppressive Receptor with On-Target, Off-Tumor Challenges

    A B Tissue macrophages (Kupffer cells) in the liver Tumor-associated macrophages in tumors & stroma (inset) In the liver, VSIG-4 … Is expressed on Kupffer cells1-2 Appears to drive significant target-mediated drug disposition (TMDD) and clearance In the tumor microenvironment, VSIG-4 … Correlates wi

  23. Slide 23: SNS-102 is a pH-sensitive Antibody Designed to Reverse T-cell Suppression

    SNS-102 is a pH-sensitive Antibody Designed With the Goal of Reversing T-cell Suppression within the Tumor Microenvironment SNS-102 blocks the interaction of VSIG4 with its novel counter-receptor, which has been provisionally identified SNS-102 is 585-fold more selective for VSIG4 at low pH conditio

  24. Slide 24: SNS-103 (ENTPD1/CD39)

    ¢ 1S.103 (ENTP| ICD39) SNS-103 (ENTP! /CD39)

  25. Slide 25: ENTPDase1 (CD39) is the Rate Limiting Enzyme in Adenosine Production

    ENTPDase1 (CD39) is the Rate Limiting Enzyme in the Production of Immunosuppressive Adenosine The primary function of ENTPDase 1 is conversion of extracellular ATP to adenosine, which exerts immunosuppressive properties through binding to A2a/A2b receptors Expressed on various immune cells in both t

  26. Slide 26: SNS-201 (VISTAxCD28)

    SNS-201 (VISTAxCD28)

  27. Slide 27: Overcoming Toxicity Challenges Associated with Targeting CD28

    Overcoming Toxicity Challenges Associated with Targeting CD28 Targeting CD28 has shown clinical evidence of efficacy, but has been limited by dose-limiting toxicities resulting from systemic CD28 activation The Challenge Sensei’s Solution Leverage TMAb approach to potentially restrict CD28 activatio

  28. Slide 28: Bispecific TMAb Approach Can Generate T Cell Co-Stimulation Selectively Within the TME

    Bispecific TMAb Approach Can Generate T Cell Co-Stimulation Selectively Within the TME Co-Stimulatory VISTAxCD28 Bispecific Powerful co-stimulatory “signal 2” selectively within the TME Potential for little or no toxicity due to selective targeting No linkers or masks A single, off-the-shelf bispeci

  29. Slide 29: SNS-201 Provides Potential for Profound Anti-Tumor Activity

    SNS-201 Provides Potential for Profound Anti-Tumor Activity By Selectively Co-Stimulating T Cells SNS-201 (VISTAxCD28) Bispecific format with monovalent CD28 engagement Bivalent pH-selective VISTA binding for efficient engagement at low pH with cells displaying moderate VISTA copy numbers​ IgG1 back

  30. Slide 30: In Vivo Study Shows Prototype Bispecific CD28xVISTA Induces Tumor Growth Inhibition

    In Vivo Study Shows Prototype Bispecific CD28xVISTA Induces Significant Tumor Growth Inhibition in Combo with anti-mPD-1​ NS = not significant *** = P<0.001 ** = P<0.01

  31. Slide 31: Engineered Selectivity to Extend the Clinical Reach of IO Agents

    *Consists of cash, cash equivalents and marketable securities Engineered Selectivity to Extend the Clinical Reach of IO Agents LEAD PROGRAM SNS-101, a conditionally active antibody targeting VISTA Initial Phase 1 data demonstrate well tolerated safety profile & potentially best-in-class pharmacokine

  32. Slide 32: 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

  33. Slide 33: Key Partnerships Supporting SNS-101's Clinical Development

    Key Partnerships Supporting SNS-101’s Clinical Development Potential opportunities for combination therapy and biomarker identification ​Partner / Collaborator Goal Description Clinical Supply Agreement Support evaluation of SNS-101 in combination with Libtayo® (cemiplimab) in planned Phase 1/2 clin

  34. Slide 34: 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 (13.4d vs 3.9d), ravulizumab given every 8w achieved noninferiority compared with eculizumab gi

  35. Slide 35: Single-agent Activity and Deepened Anti-tumor Responses to PD-1 Combo

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

  36. Slide 36: SNS-101 Increased CD8 T-cells in Combination With Anti-PD-1

    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

  37. Slide 37: 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

  38. Slide 38: SNS-101 Re-sensitized Anti-PD-1 Insensitive Sarcoma Tumors

    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

  39. Slide 39: SNS-101 Induced 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

  40. Slide 40: SNS-101 Has Displayed a Favorable Single-dose PK Profile Preclinically

    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

  41. Slide 41: 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

  42. Slide 42: 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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