Sensei Biotherapeutics, Inc. · NASDAQ:SNSE
Sensei Biotherapeutics — World Vaccine Congress 2022
24 slides from Sensei Biotherapeutics's conference presentation, Apr 20, 2022
Slide 1: SNS-101, A Unique Tumor-selective Anti-VISTA Monoclonal Antibody
Robert Pierce, MD World Vaccine Congress 2022 Washington, DC SNS-101, A Unique Tumor-selective Anti-VISTA Monoclonal Antibody with a Novel Mechanism of Action
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: The Therapeutic Problem: PD-1/PD-L1 Non-Response
The Therapeutic Problem: PD-1/PD-L1 Non-Response Anti-PD-1 or PD-L1 More Likely to Respond Less Likely to Respond Treatment T-cells T-cells Inside Tumor T-cells Absent Outside Tumor Green = T-cells Purple = tumor Adapted from Van der Woulde-LL, et al, Trends in Cancer, 2017
Slide 4: Two Platforms to Unleash Anti-Cancer T-cell Activity
Two Platforms to Unleash Anti-Cancer T-cell Activity TMAb™ (Tumor ImmunoPhage™ Platform Microenvironment Activated Biologics) Platform • Powerfully self-adjuvanted nanoparticle vaccine can drive • Next-generation tumor activated B cell and T cell responses mAbs • Multi-antigen vaccine enables • Bind
Slide 5: VISTA: A Promising but Difficult Target on Myeloid Cells
VISTA: A Promising but Difficult Target on Myeloid Cells VISTA is a Negative Regulator of T cell Function • VISTA (aka B7-H5; PD-1H) is B7 family ligand wi homology to PD-L1 • VISTA suppresses T cell activation1 • Expressed on myeloid cells including macropha and neutrophils; NK cells and T-regs2 •
Slide 6: VISTA Negatively Regulates CD4 and CD8 T Cell Responses
VISTA Negatively Regulates CD4 and CD8 T Cell Responses VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses Li Wang,1 Rotem Rubinstein,4,5 Janet L. Lines,1 Anna Wasiuk,1 Cory Ahonen,1 Yanxia Guo,1 Li-Fan Lu,1 David Godek,1 Yan Wang,1 Roy A. Fava,3 Andras Fiser,4,5 S
Slide 7: Anti-VISTA mAb Treatment Leads to Tumor Growth Inhibition in Syngeneic Mouse Models
Anti-VISTA mAb Treatment Leads to Tumor Growth Inhibition in Multiple Syngeneic Mouse Tumor Models WT Mice Bearing MB49 Murine Bladder Carcinom a VISTA Expression on Myeloid Cells in Tumor-Bearing Mice Control-Ig ) 2 (10 mg/kg) (mm Isotype Spleen p-value = 0.001 control size Ascites Tumor 13F3 Anti-
Slide 8: PD-1/VISTA Double Knock-out Mice Have Increased Antigen-specific T cell Responses
PD-1/VISTA Double Knock-out Mice Have Increased Antigen-specific T cell Responses Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murineT-cell responses Jun Liua,b, Ying Yuana,1,a, Wenna Chena, Juan Putrac, Arief A. Suriawinatac, Austin D. Schenkd, Halli E. Millera, Indira Guleriae
Slide 9: Combination of VISTA Inhibition and PD-1 Blockade Yields Synergistic Anti-tumor Responses
Combination of VISTA Inhibition and PD-1 Blockade Yields Synergistic Anti-tumor Responses Mice Bearing CT26 Tumors Combination) 2 Control-Ig (n=8) (mm Anti-VISTA mAb (n=8) Survival size Anti-PD-L1 Anti-PD-L1 mAb (n=8) Anti-VISTA Tumor Combo (n=8) Percent Control-Ig Time (Days) Time (Days) Liu J. et
Slide 10: Anti-VISTA mAb Binding on Myeloid Cells Results in Target-mediated Drug Disposition
Anti-VISTA mAb Binding on Myeloid Cells in Blood Results in Significant Target-mediated Drug Disposition (TMDD) Mouse Pharmacokinetics of Anti-VISTA Antibodies (BMS) at 5 mg/kg Antibodies binding VISTA+ cells Week 1 Week 2 (e.g . monocytes) at physiological pH are eliminated from circulation No targ
Slide 11: VISTA Binding to PSGL-1 is pH-dependent
VISTA Binding to PSGL-1 is pH-dependent Due to a Unique Histidine-rich Extracellular Binding Domain Antibodies that block protonated VISTA VISTA’s extracellular histidines interrupt PSGL-1 binding1 domain is uniquely rich in histidines¹ Histidines are protonated at low pH enabling VISTA to the activ
Slide 12: Strongest Interaction between Candidate VISTA Binding Partners is VISTA/PSGL-1 at Low pH
Strongest Interaction between Candidate VISTA Binding Partners is VISTA/PSGL-1 at Low pH 3 VSIG3 pH 6.0 pH 7.4 VSIG8 PSGL-1 Syndecan-2 OD450 2 LRIG1 Mean 1 0 5 . 5 1 2 4 8 125. 2 0 0625 . 0 . 0 0 VISTA (μg/ml) VISTA binds specifically to PSGL-1 and Syndecan-2 in a pH-dependent manner VSIG-3, VSIG-8
Slide 13: Active Protonated VISTA Binds the T cell Checkpoint PSGL-1 in the Tumor Microenvironment
Active “Protonated” VISTA Binds the T cell Checkpoint PSGL-1 in the Tumor Microenvironment “Active” VISTA Protonated “Inactive” VISTA Unprotonated Adapted from Yuan-L, Trends Immunol, 2021 Mar;42(3):209-227
Slide 14: pH-dependent mAb Binding to VISTA May Mitigate On-Target/Off-tumor Reactivity
pH-dependent mAb Binding to VISTA May Mitigate On-Target/Off-tumor Reactivity Low pH- pH Non-selective Binder selective Binder • Blocks VISTA/PSGL-1 • Blocks checkpoint VISTA/PSGL-1 • Active Fc  myeloid checkpoint activation • IgG1 Fc  myeloid • TMDD  low tumor Tumor activation drug exposur
Slide 15: Critical Design Features for SNS-101
Critical Design Features for SNS-101 1. Block the critical checkpoint (pH-dependent binding of VISTA to PSGL-1 on T cells) 2. Selectively bind “active”/protonated VISTA at low pH to avoid: • target mediated drug disposition (TMDD) • on-target/off-tumor side effects 3. Utilize an Fc-competent IgG (e.
Slide 16: SNS-101 Inhibits VISTA/PSGL-1 Interaction
SNS-101 Inhibits VISTA/PSGL-1 Interaction CTRL-lgG SNS-101 CTRL-lgG SNS101 SITC 2021: Poster titled: Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti-tumor immunity PSGL-1: VISTA interaction on Primary T-cells at pH 6.0
Slide 17: SNS-101 Has >600-Fold Selectivity for VISTA at pH 6.0
SNS-101 Has >600-Fold Selectivity for VISTApH6 >600-fold selectivity for VISTA at pH 6.0 Subnanomolar binding at low pH physiological No significant pH binding (7.4) observed at pH 6.0 pH 7.4 132 Monovalent Affinity (KD) [nmol] 0.218 (~No binding) pH-dependent pH-independent SNS-101 “benchmark” “ben
Slide 18: No Significant Binding of SNS-101 to Blood Cells at Physiological pH
No Significant Binding of SNS-101 to Monocytes, Neutrophils, NK Cells and T-cells in Whole blood at Physiological pH CYNO HUMAN Monocytes Neutrophils NK cells T-cells CRTL PF JNJ SNS101 CRTL PF JNJ SNS101
Slide 19: SNS-101 Displays Favorable PK Profile
SNS-101 Displays Favorable PK Profile No significant TMDD in human VISTA KI mice Pharmacokinetics of Single Dose 5 mg/kg SNS-101 in VISTA Knock-in Mice Week 1 Week 2 Week 3 Week 4 Ø Tumor bearing mice have a favorable PK profile Ø Non-tumor bearing mice demonstrate no TMDD VISTA KI mice No Target WT
Slide 20: MC38 Syngeneic Tumor Model Confirms Combinatorial Activity of SNS-101
MC38 Syngeneic Tumor Model in huVISTA Knock-in Mice Confirms Combinatorial Activity of SNS-101 SNS-101* in Combination with Anti-mouse PD-1 Tumor Growth Inhibition Survival *SNS-101 was grafted on to a mouse IgG2a framework to decrease anti-drug antibody production Anti-PD-1 + SNS-101 (5/10) Anti-PD
Slide 21: Preclinical Development Summary
Manufacturing of SNS-101 is ongoing • No “developability” issues to date • Cell line has demonstrated great productivity/quality (~ 9 grams/liter and low % aggregates) IND-enabling studies have been initiated • Single-dose mouse and non-human primate PK • Optimized preclinical efficacy models in huV
Slide 22: Preliminary PSGL-1/VISTA Proximity Assay on HNSCC Tumor Samples
Preliminary PSGL-1/VISTA Proximity Assay on HNSCC Tumor Samples Low Proximity High Proximity H&N (HN483a) Core C6,R7 H&N (HN483a) Core C5,R4
Slide 23: Beyond VISTA: Tumor Microenvironment Activated Biologics (TMAbs)
Beyond VISTA: Tumor Microenvironment Activated Biologics (TMAbs) The tumor microenvironment of pH ~6 is lower than physiological pH of 7.4 Sensei’s technology identifies antibodies that selectively bind in the distinct biochemical milieu of the tumor, for example, sub-physiologic pH Antibodies that
Slide 24: Sensei Biotherapeutics Collaborators and Acknowledgements
Sensei Biotherapeutics Collaborators TMAb Fred Hutchinson Cancer Research Center Edward van der Horst Kimberly Smythe Thomas Thisted Cecilia Yeung Yuliya Kleschenko Brandon Seaton Zuzana Biesova Kanam Malhotra Adimab Arnab Mukherjee Anokhi Cifuentes Nadthakarn Boland Nels Nielson Translational Medic