Sensei Biotherapeutics, Inc. · NASDAQ:SNSE
Sensei Biotherapeutics — Investor Presentation (June 2024)
50 slides from Sensei Biotherapeutics's investor presentation, Jun 3, 2024
Slide 1: Conditionally Active Antibodies for Immuno-oncology
Conditionally Active Antibodies for Immuno-oncology Corporate Deck | June 2024 Exhibit 99.1
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: Company Highlights
Company Highlights Sensei Bio’s proprietary platform is designed to harness conditional activation of antibodies to widen the therapeutic window and enable druggability of promising oncology targets SNS-101, the company's lead asset, is in a Phase 1b study and targets VISTA, a critical negative regu
Slide 4: Seasoned Leadership Team
Seasoned Leadership Team John Celebi, MBA President and CEO Edward van der Horst, Ph.D. Chief Scientific Officer Stephanie Krebs, M.S., MBA Chief Business Officer Christopher Gerry, J.D. SVP, General Counsel Ron Weitzman, M.D. Chief Medical Officer (part-time)
Slide 5: Large Commercial Opportunity for Immuno-Oncology Drugs
Large Commercial Opportunity for Immuno-Oncology Drugs Market opportunity estimates for PD-1, PDL-1 & anti-CTLA-4 Inhibitors – TD Cowen’s Guide to Immuno-oncology GlobalData; Incident cases diagnosed in 8MM 2026 (US, UK, Japan, China, France, Germany, Italy, Spain) 960K Non-Small Cell Lung Cancer (N
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
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
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
Slide 9: SNS-101 (VISTA)
SNS-101 (VISTA)
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
Slide 11: SNS-101 is a pH-sensitive Antibody Selective for VISTA
SNS-101 is a pH-sensitive Antibody Selective for VISTA pH 6.0 pH 7.4 0.218 nM 132 nM (~No binding) Monovalent Affinity (KD) SNS-101 potently inhibits the VISTA:PSGL-1 interaction and all other potential binding partners at pH 6.0 in vitro IC50 = 7nm 2.59 Å Resolution SNS-101 heavy chain SNS-101 l
Slide 12: SNS-101 Designed to Bind VISTA at the Tumor but Not in the Periphery
SNS-101 Designed to Bind VISTA at the Tumor but Not in the Periphery Pierre Fabre JNJ SNS-101 Control Periphery (Neutral pH) SNS-101 has no detectable binding in peripheral or normal tissues SNS-101 rapidly accumulates in the tumor SNS-101 6h post-dosing Isotype control 6h post-dosing Blue = tumor B
Slide 13: Competitors Halted Development of VISTA Antibodies
Competitors Halted Development of VISTA Antibodies as a Result of Severe Toxicities From Off-Tumor On-Target 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
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 SNS-101 Sensei Bio HMBD-002 (Hummingbird) PMC-309 (Pha
Slide 15: Early Development Plan is in Alignment with Corporate Objectives
Early Development Plan is in Alignment with Corporate Objectives Corporate Objectives Impact on Study Design PRIMARY Rapidly confirm conditionally active MOA through: Lack of severe CRS Absence of TMDD Reach doses several folds higher than doses where prior anti-VISTA mAbs experienced DLT Enroll all
Slide 16: SNS-101 Phase 1/2 Study
SNS-101 Phase 1/2 Study * Libtayo 350 mg Patient enrollment has started for the monotherapy & combination expansion cohorts Cohort A1 0.3 mg/kg N=1 Cohort B1 3.0 mg/kg + Libtayo* N=6 Cohort A2 1.0 mg/kg N=3 Cohort A3 3.0 mg/kg N=3 Cohort A4 10.0 mg/kg N=3 Cohort A5 15.0 mg/kg N=6 Cohort B2 10.0 mg/k
Slide 17: Patient Disposition
Patient Disposition Monotherapy Combination SNS-101 n=16 (%) SNS-101 + cemi n=18 (%) Enrolled 16 (100.0) 18 (100.0) Treatment Ongoing 2 (13) 2 (11) Discontinued 14 (88) 16 (89) Progressive Disease 13 13 Adverse Event 0 1# Withdrew Consent 0 1 Death Regardless of Causality 1* 0 Death Related to Study
Slide 18: Patient Demographics and Baseline Characteristics
SNS-101 Mono n=16 (%) SNS-101 Combo n=18 (%) Gender, n (%) Male 12 (75) 11 (61) Female 4 (25) 7 (39) Age, years Median 61.5 62 Min, Max 35, 79 33, 81 Race, n (%) Asian 1 (6) 1 (6) Black or African American 0 2 (11) Not Reported 1 (6) 1 (6) White 14 (88) 14 (77) Ethnicity, n (%) Not Hispanic or Latin
Slide 19: SNS-101 Was Well Tolerated as Monotherapy and in Combination with Cemiplimab
SNS-101 Was Well Tolerated as Monotherapy and in Combination with Cemiplimab *One patient experienced an SAE, Grade 5 bronchial obstruction, that resulted in death; not related to SNS-101, but to disease progression #Two patients experienced Grade 1 CRS ^One patient experienced Grade 2 rash maculo-p
Slide 20: SNS-101 Has Only Been Associated with Mild IRR/CRS-like Adverse Events
SNS-101 Has Only Been Associated with Mild IRR/CRS-like Adverse Events (Unlike First Generation VISTA Antibodies) Subject Number Dose Level Adverse Event Preferred Term (Event description) Severity (Grade) Time of Onset relative to start of Infusion 01-010 SNS-101 15.0 mg/kg Cytokine Release Syndrom
Slide 21: Pharmacokinetic Data Show Linear Elimination Kinetics with Long Half-Life
Pharmacokinetic Data Show Linear Elimination Kinetics with Long Half-Life * Cemiplimab administered on Cycle 1 Day 2; co-administration thereafter Dose proportional exposure through 5 dose levels of SNS-101 (0.3 to 15.0 mg/kg) Consistent with lack of TMDD and supports Q3W dosing in humans No apparen
Slide 22: No Significant Changes in Key Inflammatory Cytokines
No Significant Changes in Key Inflammatory Cytokines Data as of 30April2024
Slide 23: Dose-dependent Changes in Specific T-cell Populations
Naïve Central Memory Effector Memory Effector Memory RA+ CCR7+ CD45RA+ CD27+ TCM CCR7+ CD45RA- TEM CCR7- CD45RA- TEMRA CCR7- CD45RA+ Peripheral homing Effector function Lymphoid homing Self-renewal capacity Quiescent Antigen-inexperienced Dose-dependent Changes in Specific T-cell Populations Indicat
Slide 24: SNS-101 Has Shown Early Signs of Clinical Activity
SNS-101 Alone or in Combination with Cemiplimab Has Shown Early Signs of Clinical Activity Monotherapy Dose Escalation 16 patients enrolled: 15 patients received both baseline and at least one follow-up scan 7 patients achieved stable disease as best overall response Patients of interest: One pembro
Slide 25: Two Examples of Patients with MSS Solid Tumors and Objective Tumor Regression
Two Examples of Patients with MSS Solid Tumors and Objective Tumor Regression 68 yo female with endometrial carcinoma, dx Dec 2020, ECOG 0 ER/PR positive, HER negative; PD-1/PD-L1: Not tested Prior Treatment/Surgery Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy, and additional
Slide 26: SNS-101 ASCO 2024 Summary
SNS-101 ASCO 2024 Summary SNS-101 is a conditionally active VISTA targeting mAb that has demonstrated promising early clinical data consistent with its mechanism of action, including: First VISTA-targeting mAb without dose-limiting CRS at pharmacologically relevant dose levels Initial signals of ant
Slide 27: SNS-101 Next Steps
SNS-101 Next Steps * cemiplimab 350 mg "Hot" tumors: Responsive to PD-1 monotherapy "Cold" tumors: Unresponsive to PD-1 monotherapy CRC Basket (CRC, NSCLC, H&N, Melanoma) Phase 1 Dose Expansion ~ 50 to 70 patients Phase 1 Study Objectives Primary Safety, tolerability, MTD/RP2D Secondary PK, immunoge
Slide 28: 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 & combination dose escalation
Slide 29: SNS-102 (VSIG-4)
SNS-102 (VSIG-4)
Slide 30: 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
Slide 31: SNS-102 is a pH-sensitive Antibody
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
Slide 32: SNS-103 (ENTPD1/CD39)
¢ 1S.103 (ENTP| ICD39) SNS-103 (ENTP! /CD39)
Slide 33: ENTPDase1 (CD39) is the Rate Limiting Enzyme in Production of Adenosine
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
Slide 34: SNS-201 (VISTAxCD28)
SNS-201 (VISTAxCD28)
Slide 35: 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
Slide 36: 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
Slide 37: 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
Slide 38: 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
Slide 39: 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 Clinical data demonstrated initial signs of promising clinical activity in multiple tumor types, a well
Slide 40: 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
Slide 41: SNS-101 Duration of Treatment
SNS-101 Duration of Treatment Data as of 30April2024
Slide 42: 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
Slide 43: 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
Slide 44: 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
Slide 45: 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
Slide 46: 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
Slide 47: 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
Slide 48: SNS-101 Induced Substantially 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
Slide 49: 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 50: Targeting VISTA and PD-1 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
Sensei Biotherapeutics — Investor Presentation (June 2024) on 6ix