Sensei Biotherapeutics, Inc. · NASDAQ:SNSE
Sensei Biotherapeutics — Technical Presentation (November 2021)
37 slides from Sensei Biotherapeutics's technical presentation, Nov 16, 2021
Slide 1: VISTA Science Symposium
Exhibit 99.1 VISTA Science Symposium November 16, 2021 Sensei Presenters: Guest Speaker: John Celebi Prof. Robert Schreiber Chief Executive Officer Andrew M. Bursky and Jane M. Bursky Distinguished Professor of Pathology and Immunology, Professor of Molecular Microbiology and co-leader of the tumor
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 are m
Slide 3: Agenda
AGENDA Speaker Topics John Celebi • Welcome/TMAb Mission President & CEO Professor, Robert Schreiber, Ph.D. • VISTA biology Washington University School of Medicine Sensei IOAB member Robert Pierce, M.D. • SNS-101 preclinical data Chief Scientific Officer highlights from SITC Edward van der Horst, P
Slide 4: Our TMAb Platform Mission
Our TMAb (Tumor Microenvironment Activated biologics) Platform Mission Leverage unique features of the tumor microenvironment to selectively activate biologics that unleash clinically meaningful anti-cancer immune responses 4
Slide 5: The Modern-Day Challenge in Immuno-Oncology
The Modern-Day Challenge in Immuno-Oncology Majority of patients don’t respond to PD- 2 Global PD-1/PD-L1 Market 1 1/PD-L1 monotherapy 2026 2020 Survival Benefit 20-30% No Survival ~$90B ~$30B Benefit 70% 1. Gerber et al., Biochemical Pharmacology 2016 2. Market estimates from PD-1 and PDL-1 Inhibit
Slide 6: Two Major Types of Non-Responders to PD-1 Blockade
Two Major Types of Non-Responders to PD-1 Blockade Responders Non-Responders T-cells Inactive or T-cells Inside Tumor T-cells Absent Outside Tumor Green = T-cells Purple = tumor 6 Adapted from Van der Woulde-LL, et al, Trends in Cancer, 2017
Slide 7: Two Platforms to Unleash Anti-Cancer T-cell Activity
Two Platforms to Unleash Anti-Cancer T-cell Activity TODAY’S DISCUSSION TMAb™ (Tumor ImmunoPhage™ Platform Microenvironment Activated Biologics) Platform • Powerfully self-adjuvanted nanoparticle vaccine that drive • Next-generation tumor activated tumor-specific T cell mAbs responses
Slide 8: VISTA Target Overview
VISTA (V-domain Ig suppressor of T cell activation) Target Overview: • Established immune checkpoint target to overcome checkpoint resistance • Large market opportunity • Extensive expression on normal myeloid cells Low pH tumor Sensei’s Competitive Advantage: microenvironment Leverage extensive und
Slide 9: Leveraging a Team with Decades of Experience
Leveraging a Team with Decades of Experience 9
Slide 10: Dr. Schreiber: VISTA Biology
Dr. Schreiber VISTA Biology VISTA (B7-H5) is recognized an important immune checkpoint and B7 family member that is expressed on myeloid cells, a hub of immunosuppressive activity, and is activated via binding to its receptor on T-cells (PSGL-1) at sub-physiologic pH
Slide 11: The Promise and Challenge of Immunotherapy
The Promise and Challenge of Immunotherapy Targeting Immunosuppressive myeloid cells is a promising strategy to overcome resistance to checkpoint Inhibitor therapy THE PROMISE THE CHALLENGE • Using the body’s own immune system to • 70-80% of patients do not achieve increased 1 attack cancer survival
Slide 12: VISTA Has Emerged as an Important Checkpoint Regulator Target
VISTA Has Emerged as an Important Checkpoint Regulator Target Gao. J., et al Yuan, L., et.al
Slide 13: High Circulating Myeloid Cells and Lower Overall Survival
Patients with High Circulating Myeloid Cells Have Shown Lower Overall Survival When Treated with Checkpoint Blockade Ipilimumab-treated Melanoma Patients Nivolumab-treated Melanoma Patients MDSC ≤ 12.65 MDSC low MDSC > 12.65 MDSC high Kitano et al., Cancer Immunol Res. 2012 13 Weber et al., Cancer I
Slide 14: VISTA may be a Compensatory Pathway Following Checkpoint Therapy
VISTA may be a Compensatory Pathway Following Checkpoint Therapy Can targeting VISTA augment T-cell checkpoint blockade in refractory tumors? VISTA Increases on Prostate Tumor Cell Prostate Tumor Cell Infiltrates Increase Infiltrates Following Ipilumimab Treatment Following Ipilumimab Treatment Gao
Slide 15: VISTA Expression Increases in PBMC Subsets of NSCLC Patients
VISTA Expression Increases in PBMC Subsets of Patients with Non-Small Cell Lung Cancer (NSCLC) 15 Cairns B et al, AACR Annual Meeting 2016.
Slide 16: VISTA Blockade Synergizes With PD-1/L-1 Pathway Inhibition
VISTA Blockade Synergizes With PD-1/L-1 Pathway Inhibition CT26 Syngeneic Tumor Model Liu J. et al. PNAS 2015 16
Slide 17: VISTA is An Emerging Target on Myeloid Cells
VISTA is An Emerging Target on Myeloid Cells and Key Resistance Mechanism for PD-1/PD-L1 Blockade • VISTA is a B7 family (e.g., same protein VISTA is a Negative Regulator of T cell family as PD-L1) ligand expressed on Function at Low pH myeloid cells, a hub of immunosuppressive 1 activity T-cell • V
Slide 18: VISTA is an Emerging Target: Tumor pH Mechanism
VISTA is an Emerging Target on Myeloid Cells and Key Resistance Mechanism for PD-1/PD-L1 Blockade • Tumors are typically lower in pH than Tumors are typically lower in pH than normal tissues normal tissues • At low pH, key amino acids in VISTA become protonated, changing its Tumor pH ~6-6.5 charge,
Slide 19: The Binding of VISTA to PSGL-1 is pH Dependent
The Binding of VISTA to PSGL-1 is pH Dependent Active VISTA Inactive VISTA 19 Adapted from Gao et al. Nature medicine vol. 23,5 (2017)
Slide 20: VISTA has been difficult to drug due to its unique biology
Dr. Schreiber VISTA has been difficult to drug due to its unique biology
Slide 21: VISTA is Expressed at High Levels on Human Monocytes and Neutrophils
VISTA is Expressed at High Levels on Human Monocytes and Neutrophils Flow Cytometry Analysis of VISTA Expression on Normal Human Peripheral Immune Cells 21 Snyder et al, 2016 AACR Annual Meeting, Oral Presentation
Slide 22: High VISTA Expression Results in Sub-Optimal PK
High VISTA Expression on Monocytes and Neutrophils Results in Sub-Optimal PK and may Decrease the Therapeutic Window Case Study + • Antibodies binding VISTA cells CI-8993 Clinical Ongoing Clinical Study (e.g. monocytes) at physiological • Phase 1 Dose Escalation Study pH result in rapid elimination
Slide 23: The VISTA Checkpoint is Only ON Under Low pH Conditions
The VISTA Checkpoint Itself is Only ON Under Low pH Conditions 1 Antibodies that block VISTA histidines H153, H154 and H155 interrupt PSGL-1 binding VISTA’s extracellular domain is uniquely 1 rich in histidines PSGL-1 Histidines are protonated at low pH enabling VISTA to distinguish the active (acid
Slide 24: Engagement of FcγR May be Required for Optimal Activity
Engagement of FcƔR may be Required for Optimal Activity of Anti-VISTA Monoclonal Antibodies JNJ-61610588 VSTB140 Fc competent IgG1 Fc silent IgG2���� 24 Snyder et al., AACR Annual Meeting 2016
Slide 25: Summary: Reasons Why VISTA Has Been Difficult to Drug
Summary Reasons Why VISTA Has Been Difficult to Drug Historically • VISTA is expressed at high levels on monocytes and neutrophils • For non-pH-dependent blocking antibodies, high expression on monocytes and neutrophils results in a sub-optimal PK due to target-mediated clearance and may decrease th
Slide 26: SITC 2021: SNS-101 Preclinical Data Poster Presentation
Dr. Rob Pierce SITC 2021: SNS-101 Preclinical Data Poster Presentation
Slide 27: pH-sensitive Antibodies Bind in the Low pH Tumor Microenvironment
pH-sensitive Antibodies Primarily Bind Their Antibodies in the Low pH Tumor Microenvironment TMAb Platform The tumor microenvironment of pH ̴ 6.0 is lower than Sensei’s technology identifies pH-sensitive antibodies physiological pH of 7.4 that bind primarily at the tumor pH 7.4 • Antibodies that bin
Slide 28: SNS-101 Inhibited VISTA/PSGL-1 Interaction in T-Cells at Low pH
SNS-101 Inhibited Interaction of VISTA to its Receptor, PSGL-1, in CD4/CD8 T-Cells at Low pH 6.0 PSGL-1: VISTA Interaction on primary T-cells at pH 6.0 T-cell PE PSGL-1 VISTA-Bio SA 28 SITC 2021: Poster titled: Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti
Slide 29: SNS-101 Identified Based on Stringent Cell-Based Assay
SNS-101 Identified Based on Stringent Cell-Based Assay Candidate profile: no significant binding at pH 7.4 pH6.0 29
Slide 30: SNS-101 Has >600-Fold Selectivity for VISTA
pH6 SNS-101 Has >600-Fold Selectivity for VISTA • Biophysical characterization demonstrates pH 6.0 pH 7.4 >600-fold selectivity for VISTA at pH 6.0 132 • Picomolar binding at low pH Monovalent Affinity (K ) [nM] 0.218 (~No D binding) • No significant binding observed at physiological pH (7.4) pH7
Slide 31: SNS-101 Does Not Significantly Bind to VISTA Monocytes at pH 7.4
+ SNS-101 Does Not Significantly Bind to VISTA Monocytes at pH 7.4 • VISTA+ monocytes are one of the main causes of TMDD • Non-pH sensitive VISTA mAbs bind to monocytes at pH 7.4 thus allowing TMDD and have potential for on-target/off-tumor toxicity VISTA Copy Number: Kasumi-3: 70,202 CD14+ Monocyte
Slide 32: Proposed Mechanism of Action for SNS-101
Proposed Mechanism of Action for SNS-101 Fc-competent framework is required for optimal activity, but FcƔR engagement in the blood may result in untoward “off tumor” activation (i.e. CRS) Non-pH dependent pH-dependent Monocyte Macrophage Blood Monocyte Peripheral Sink and Activation No Activation CR
Slide 33: High-bar In Vivo Screening Test of SNS-101 Activity
‘High-bar’ In Vivo Screening Test of SNS-101 Activity 1-week Administration Black Line (IgG Control human & ratl) Antibodies were administered I.P. 2/wk for 1 week Blue Line (IgG Control human & rat anti-mPD-1) at 40 mg/kg total (20 mg/kg each) Red Line (rat anti-mPD-1 & anti-VISTA) 33 SITC 2021: P
Slide 34: SNS-101 Is a Differentiated Anti-VISTA Antibody
SNS-101 Is a Differentiated Anti-VISTA Antibody TMAb Platform K01401-020; SNS-101 VISTA.18 KVA12.1 CI-8993; JNJ-61610588 HMBD-002 W0180 (BMS) (Kineta) (J&J/Curis) (Hummingbird) (Pierre Fabre) Inhibit PSGL-1 Yes Yes unknown Yes unknown unknown Binding pH Sensitive Yes Yes No No No No Binding Fc Activ
Slide 35: Key to Unlocking the Power of VISTA
Key to Unlocking the Power of VISTA 1. Block VISTA’s interaction with PSGL-1 at pH 6 within the tumor microenvironment 2. Selectively bind VISTA at low pH to avoid: • target mediated drug disposition • on-target/off-tumor side effects 3. Design an Fc-competent IgG engaging with FcƔR on tumor- infilt
Slide 36: Question & Answer Session
Question & Answer Session em HERAPEUTICS,
Slide 37: VISTA Science Symposium
VISTA Science Symposium November 16, 2021 Sensei Presenters: Guest Speaker: John Celebi Prof. Robert Schreiber Chief Executive Officer Andrew M. Bursky and Jane M. Bursky Distinguished Professor of Pathology and Immunology, Professor of Molecular Microbiology and co-leader of the tumor Dr. Robert Pi
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