Sensei Biotherapeutics, Inc. · NASDAQ:SNSE
Sensei Biotherapeutics — Technical Presentation (June 2023)
32 slides from Sensei Biotherapeutics's technical presentation, Jun 27, 2023
Slide 1: A New Vista for Cancer Care: Exploring SNS-101's Potential
June 27, 2023 A New Vista for Cancer Care: Exploring SNS-101’s Potential as a Transformative Treatment Option for Patients with Solid Tumors Sensei Presenters: John Celebi Chief Executive Officer Dr. Edward van der Horst Chief Scientific Officer Ron Weitzman Consulting Chief Medical Officer Guest Sp
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
Slide 3: Agenda
Agenda WELCOME John Celebi President & Chief Executive Officer, Sensei Biotherapeutics Improving treatment for patients with cancer James Gulley, M.D., Ph.D., F.A.C.P. Co-Director, Center for Immuno-Oncology, Clinical Director, National Cancer Institute, NIH SNS-101 PHASE 1/2 CLINICAL TRIAL OVERVIEW
Slide 4: 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
Slide 5: pH-sensitive Antibodies Have Potential to Selectively Bind Targets in 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
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
Slide 7: James L. Gulley: Immuno-Oncology Landscape
James L. Gulley, M.D., Ph.D., F.A.C.P. Co-Director, Center for Immuno-Oncology Clinical Director, National Cancer Institute, NIH Immuno-Oncology Landscape
Slide 8: Cancer Immunity Cyclical Evolution (E8)
Cancer Immunity Cyclical Evolution (E8) Expand 3 Engage 2 Expedition 4 Excursion 5 Establish ID 6 Enable 7 Emit antigen 1 Modified from Chen and Mellman, Immunity 2013
Slide 9: Cancer Immunity Cyclical Evolution (E8): Antigen spreading
Cancer Immunity Cyclical Evolution (E8): Antigen spreading
Slide 10: Importance of PD-1/PD-L1 blockade
Importance of PD-1/PD-L1 blockade NIH. News Headlines: https://ccr.cancer.gov/news/article/investigators-lead-first-human-trials-of-new-immunotherapy-drug (accessed August 2017)
Slide 11: PD-1/PD-L1 inhibition: rapid, deep, durable responses across tumors
Urothelial: avelumab Apolo AB et al. J Clin Oncol 2017 Urothelial: pembrolizumab Plimack ER P et al. Lancet Oncol 2017 HNSCC: pembrolizumab Seiwert TY et al. Lancet Oncol 2016 NSCLC (squamous only): nivolumab Rizvi NA et al. Lancet Oncol 2015 Urothelial: durvalumab Massard C et al. JCO 2016 Urotheli
Slide 12: Co-localization of inflammatory response and PDL1 expression
Co-localization of inflammatory response and PDL1 expression: TILs are being blocked at tumor site (Enable) Taube et al., Sci Trans Med 2012 IFN-γ upregulates PDL1 expression in vitro
Slide 13: What happens when there is little / no immune recognition
What happens when there is little / no immune recognition Strategies to enhance immune recognition include Generating new cells to recognize tumor ACT, vaccine, non-T-cell approaches etc. Expanding effector cells / bringing them to TIME Bi-specific Ab, cytokines etc. Addressing other negative aspect
Slide 14: Multi-layered immunosuppression
Multi-layered immunosuppression Lysis and apoptosis resistant tumor cells (e.g. SPI-6, IAPs) GcidiSrypoxic, ROS, peroxynitrite) isordered vasculature (e.g. FasL+, no ICAM) Lack of co-stimulation and antigen resentation (e.g. tolerogenic APCs) ‘Suppressive cytokines, (e.g. L-10., TGF-) Immunotherapy
Slide 15: Impact of targeting VISTA
Impact of targeting VISTA Hosseinkhani et al, Font. Immunol. 2021
Slide 16: Universal Strategy for Immunologically Cold Tumors?
Expand 3 Engage 2 Expedition 4 Excursion 5 Establish ID 6 Enable 7 Emit antigen 1 Universal Strategy for Immunologically Cold Tumors?
Slide 17: Examples of some combination approaches at NCI
Examples of some combination approaches at NCI QuEST (vaccine, IL-15, bintrafusp alfa) ESMO and AACR HPV Triple (vaccine, IL-12, bintrafusp alfa) ASCO BEST (HDACi, IL-12, bintrafusp alfa)
Slide 18: NCI's Center for Immuno-Oncology
NCI’s Center for Immuno-Oncology Formed in 2022 from parts of 3 groups Serves as a nidus for future immuno-Oncology growth at the CCR Has about 100 personnel Has CRADAs with 22 companies (pharma/biotech) Cooperative Research and Development Agreement Allows for novel/novel combinations from differen
Slide 19: CRADA with Sensei
CRADA with Sensei Executed Feb 2, 2023 Ongoing preclinical studies exploring combination approaches Led by Jeff Schlom Clinical trial NCI to act as clinical trial site for SNS-101 Scientific review (branch 6/28 then institute) à IRB
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 ** Currently screening patients in Cohort 2 (1.0 mg/kg) RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose Phase 1 Dose Escalation - Monotherapy: SNS-101 a
Slide 21: New VISTAs for our partnership
New VISTAs for our partnership Potential for novel / novel combination approaches in the clinic
Slide 22: SNS-101 Overview
Edward van der Horst, Ph.D. SNS-101 Overview
Slide 23: 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
Slide 24: 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
Slide 25: 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
Slide 26: 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
Slide 27: SNS-101 Responder Hypothesis
SNS-101 “Responder Hypothesis” Hypothesis Potential Clinical Direction Combination therapy with SNS-101 and approved anti-PD-(L)1 drugs can overcome adaptive resistance induced by CPI treatment Patients with hot tumors refractory to CPIs SNS-101 can unleash CPI response in immunologically active yet
Slide 28: Phase 1/2 Clinical Trial Biomarker Plan
Pharmacokinetics Is PK profile linear? Safety/Toxicology What are key toxicity issues related to SNS-101? Pharmacodynamics Does target engagement with protonated VISTA in the TME modulate directly and/or indirectly cellular activity? Patient Selection/Stratification What population is likely to expe
Slide 29: Anticipated SNS-101 Immuno-oncology Biomarkers
Anticipated SNS-101 Immuno-oncology Biomarkers Blood Serum PK/Safety PK & ADA Immunoassays SNS-101 exposure in blood Anti-SNS-101 antibody detection Blood Serum PBMCs Biomarker Immunoassays Flow cytometry Cytokine analysis Immunophenotyping Whole blood FFPE tissue (pre/on-treatment) Biomarker DNA se
Slide 30: Expected SNS-101 Program Milestones
Expected SNS-101 Program Milestones May 2023: First patient dosed In or before Q1 2024: Dose first patient in combination with Libtayo® 2024: Topline Phase 1 monotherapy data 2024: Initial Phase 1 combination data check
Slide 31: Question & Answer Session
Question & Answer Session € sensei BIO
Slide 32: A New Vista for Cancer Care: Exploring SNS-101's Potential
June 27, 2023 A New Vista for Cancer Care: Exploring SNS-101’s Potential as a Transformative Treatment Option for Patients with Solid Tumors Sensei Presenters: John Celebi Chief Executive Officer Dr. Edward van der Horst Chief Scientific Officer Ron Weitzman Consulting Chief Medical Officer Guest Sp
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