Sensei Biotherapeutics, Inc. · NASDAQ:SNSE
Sensei Biotherapeutics — Investor Presentation (December 2021)
34 slides from Sensei Biotherapeutics's investor presentation, Dec 6, 2021
Slide 1: Training the Immune System to Fight Cancer
August 4, 2021 Training the Immune System to Fight Cancer December 6, 2021 Exhibit 99.1
Slide 2: This presentation has been prepared by Sensei Biotherapeutics, Inc. (the “Company,” "we," "us") and
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 made as o
Slide 3: The Modern-Day Challenge in Immuno-Oncology
Gerber et al., Biochemical Pharmacology 2016 Market estimates from PD-1 and PDL-1 Inhibitors Market Size in 2021 – MarketWatch, 360 Research The Modern-Day Challenge in Immuno-Oncology Majority of patients don’t respond to PD-1/PD-L1 monotherapy1 Global PD-1/PD-L1 Market2 ~$30B ~$90B 2020 2026
Slide 4: Two Major Types of Non-Responders to PD-1 Blockade
Adapted from Van der Woulde-LL, et al, Trends in Cancer, 2017 Two Major Types of Non-Responders to PD-1 Blockade Green = T-cells Purple = tumor Non-Responders T-cells Absent T-cells Inactive or Outside Tumor Responders T-cells Inside Tumor
Slide 5: Two Platforms to Unleash Anti-Cancer T-cell Activity
Generate anti-tumor T-cells Unleash anti-tumor T-cells ImmunoPhage™ Platform Powerfully self-adjuvanted nanoparticle vaccine can drive B cell and T cell responses Multi-antigen vaccine enables personalized approach from “off-the-shelf” components Targets APCs Enhanced through addition of immunostimu
Slide 6: T-Cells Are Central to Our Approach
T cell APC Peptide TCR HLA T cell Immune Checkpoint Focus on multi-antigen approach for HLA-mediated immunotherapy to GENERATE anti-tumor T-cells ImmunoPhage™ TMAb Target Cell Focus on novel immune checkpoints to UNLEASH anti-tumor T-cells T-Cells Are Central to Our Approach and the Key to Unlocking
Slide 7: Positioned to Drive Value with Next Generation Product & Platform Development
Two Platforms Provide Broad Pipeline Opportunities TMAb* Platform ImmunoPhage™ Platform *Tumor Microenvironment Activated biologics **Consists of cash, cash equivalents and marketable securities In-house GMP manufacturing capabilities Business Development Strong Cash Position Ended 3Q 2021: $156.7M*
Slide 8: Pipeline Utilizing Pioneering ImmunoPhage Platform, TMAb Platform
Pipeline Utilizing Pioneering ImmunoPhage Platform, TMAb Platform Program (Target) Indication Discovery IND-enabling Phase 1 / 2 Clinical TMAb SNS-101 (VISTA) Solid Tumors SNS-VSIG4 Solid Tumors ImmunoPhage SNS-401-NG (Multiple Tumor Antigens) Merkel Cell Carcinoma Head and Neck Cancer Lung Cancer M
Slide 9: TMAb (Tumor Microenvironment Activated biologics) Platform
TMAb (Tumor Microenvironment Activated biologics) Platform
Slide 10: pH-sensitive Antibodies Only Bind Their Targets in the Low-pH Tumor Microenvironment
Antibodies that bind at physiological pH may encounter a “sink” Prevents effective binding at the tumor and may lead to toxicity TMAb antibodies bypass tissue compartments other than the low-pH tumor microenvironment Potential for improved safety and clinical activity profile pH 7.4 pH 7.4 pH 7.4 pH
Slide 11: The Promise and Challenge of Immunotherapy
70-80% of patients do not achieve increased survival with CPI monotherapy1 The immunosuppressive tumor microenvironment (TME) influences response to immune checkpoint blockade Innate immune cells such as myeloid cells are a key driver of immunosuppressive TME 1 Gerber, et al Biochemical Pharmacology
Slide 12: VISTA: An Emerging Checkpoint Target on Myeloid Cells
1 Lines et al. Cancer research vol. 74,7 (2014) 2 Gao et al. Nature medicine vol. 23,5 (2017) VISTA: An Emerging Checkpoint Target on Myeloid Cells Target Overview: Large market opportunity B7 family ligand Extensive expression on myeloid cells1 Inhibition of VISTA may lead to activation of myeloid
Slide 13: Increased Understanding of VISTA as a Promising Target
Increased Understanding of VISTA as a Promising Target to Address the Needs of Patients with Cancer
Slide 14: VISTA Checkpoint is Activated at the Low pH of the Tumor Microenvironment
VISTA’s extracellular domain is uniquely rich in histidines¹ Histidines are protonated at low pH enabling VISTA to distinguish the active (acidic pH) and inactive (neutral pH) PSGL-1 binding interface 1. Johnston et al., Nature 2019 VISTA Checkpoint is Activated at the Low pH of the Tumor Microenvir
Slide 15: Key to Unlocking the Power of VISTA: SNS-101
Block VISTA’s interaction with PSGL-1 at pH 6 within the tumor microenvironment Selectively bind VISTA at low pH to avoid: target mediated drug disposition on-target/off-tumor side effects Design an Fc-competent IgG engaging with FcƔR on tumor-infiltrating myeloid cells Key to Unlocking the Power of
Slide 16: SNS-101 Inhibited Interaction of VISTA to PSGL-1 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-Bio PE T-cell SA PSGL-1: VISTA Interaction on primary T-cells at pH 6.0 CD4 T-cells CD8 T-cells SITC 2021: Poster titled: Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD
Slide 17: SNS-101 Has >600-Fold Selectivity for VISTA at pH 6.0
R [RU] [Vista] – 7.5 nmol – 0.2 nmol SNS-101 Has >600-Fold Selectivity for VISTApH6 ka = 4.59E+06 M-1s-1 Kd = 1.00E-03 s-1 KD = 2.18E-10 M SNS-101 ka = 7.11E+05 M-1s-1 Kd = 1.78E-04 s-1 KD = 2.5E-10 M SNS-101 [Vista] – 15 nmol – 0.2 nmol [Vista] – 7.5 nmol – 0.2 nmol [Vista] – 15 nmol – 0.2 nmol R [
Slide 18: 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 Blood Tumor Monocyte VISTA Non-pH sensitive mAb FcƔR SNS-101 Peripheral Sink and A
Slide 19: SNS-101 Is a Differentiated Anti-VISTA Antibody
TMAb Platform Johnston et al, Nature, 2019; Kineta website; Snyder et al, AACR Annual Meeting 2016; Pierre Fabre website; Hummingbird website SNS-101 Is a Differentiated Anti-VISTA Antibody SNS-101 VISTA.18 (BMS) KVA12.1 (Kineta) CI-8993; JNJ-61610588 (J&J/Curis) K01401-020; W0180 (Pierre Fabre) HMB
Slide 20: VSIG4: A Novel Next Generation Checkpoint
Second TMAb program B7 family related protein Expressed on macrophages Inhibits T-cell activation Novel therapeutic combinability with existing IO drugs Adapted from Zang et al., J Clin Invest. 2006 VSIG4: A Novel Next Generation Checkpoint Modulating the Tumor Microenvironment No approved therapies
Slide 21: ImmunoPhage Platform
ImmunoPhage™ Platform
Slide 22: Bacteriophage
Ubiquitous viruses that infect bacteria but not mammalian cells. Adept at activating the human immune system in multiple unique ways Bacteriophage
Slide 23: ImmunoPhage Platform Generating Strong Antibody and T-cell Responses
ImmunoPhage Platform Generating Strong Antibody and T-cell Responses Bacteriophage virus is engineered and manufactured with both antigen and immune stimulatory viral DNA Viral DNA (self-adjuvant) Target antigen The ImmunoPhage™ bacteriophage is an icosahedron with a tail. This configuration can be
Slide 24: Generating Strong Antibody and T-cell Responses
Generating Strong Antibody and T-cell Responses ImmunoPhages are taken-up by APCs and deliver three critical signals required to drive activation of T cells. Antigen cross presentation Positive co-stimulation Generation of Th1-biased immune response & cytokines CD28 CD80 T cell receptor Antigen T- C
Slide 25: A Multi-Pronged Approach to Address the Complexities of Cancer
Our ImmunoPhages can mount a multi-modal attack on cancer, combining the benefits of a traditional vaccine with localized gene therapy Targeted therapeutic vaccine MHC-mediated immunity Bacteriophage have natural tropism for APCs Can be further targeted to APCs with non-antigen capsid modifications
Slide 26: SNS-401-NG: Building the First Custom MCPyV ImmunoPhage
33-46% disease-specific mortality 2,500 cases/yr with disease-specific mortality approaching 50% Vaccine combination therapy in adjuvant or neoadjuvant is attractive and feasible PD-1/PD-L1 refractory MCC remains unmet medical need with aggressive clinical course ~40% MCC patients recur <24 months f
Slide 27: Activation and Maturation of Dendritic Cells
Critical signals of dendritic cell activation show dose-dependent increases when cells are exposed to increasing amounts of ImmunoPhages Mechanism of Action: Activation and Maturation of Dendritic Cells Dose-response of engineered lambda phage on human skin-derived DC cultures Signal: Dendritic cell
Slide 28: SNS-401-NG Development in Merkel Cell
SNS-401-NG Development in Merkle Cell 1. Based on internal data SNS-401-NG has Potential to be First Fully Customized, Yet Off-the-Shelf, Therapy Common Tumor Antigens + MCPyV+ MCC tumors Immunophage expressing MCPyV B- and T-cell antigens Routine Biopsy Tumor Sequencing Immunophage expressing tumor
Slide 29: Phortress: Proprietary Library of Personalized Vaccine Cocktails
These “cocktails” are defined by the disease or patient genetics Combinations are customized to cover multiple epitopes, protein domains or targets Each ImmunoPhage is pre-manufactured to target a discrete antigen Phortress: Proprietary Library of Personalized Vaccine Cocktails with Off-the-Shelf Im
Slide 30: Personalized Immunotherapy Approach Could Accelerate Speed to Treatment
Neoantigen Prediction Neoantigen ImmunoPhage Manufacturing ImmunoPhage Injection Including Neoantigens Deliver neoantigen ImmunoPhage cocktail for administration and add neoantigen phages to bank for future use Identify additional tumor specific neoantigens Engineer novel ImmunoPhages expressing dis
Slide 31: Sensei's Vision to Capture Platform and Pipeline Value
Sensei’s Vision to Capture Platform and Pipeline Value 2016 Measured investments in platform Advanced first program into clinic Absorb key learnings and refine technology 2021 Feb 2021: IPO 2026 Focus on Platform Innovation and New INDs Invest in Manufacturing and Supply Chain Commercial Capabilitie
Slide 32: Proven Team With Deep Experience
Proven Team With Deep Experience John Celebi, MBA Pauline Jean President and CEO Michael Callinan, PhD Campbell, PhD VP, Business Tt : Boychyn, PhD a VP, Biologics X4 Ea ov SVP, CMC Qperations and Discovery y ANE . trategy i % @® ARQULE ote Elisabeth Alice Colunio Drumheller Bao Le & VP. Human VP. C
Slide 33: Upcoming Expected Program Milestones
Upcoming Expected Program Milestones SNS-101 (anti-VISTA) YE 2021: Present preclinical data at 36th Annual SITC Conference Select lead candidate Initiate IND-enabling studies underway SNS-401-NG 2H 2022: Initiate IND-enabling studies SNS-VSIG4 2023: Select product candidate
Slide 34: Training the Immune System to Fight Cancer
August 4, 2021 Training the Immune System to Fight Cancer December 6, 2021
Sensei Biotherapeutics — Investor Presentation (December 2021) on 6ix