Sensei Biotherapeutics : Company Presentation - Form 8-K

Training the Immune System to Fight Cancer John K. Celebi, MBA President & Chief Executive Officer JP Morgan Healthcare Conference January 10, 2022 NASDAQ: SNSE August © 2021 Sensei Biotherapeutics. All rights reserved.

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 of the date of this presentation unless stated otherwise, and neither the delivery of this presentation at any time, nor any sale of securities, shall under any circumstances create an implication that the information contained herein is correct as of any time after such date or that information will be updated or revised to reflect information that subsequently becomes available or changes occurring after the date hereof. This presentation contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This presentation also contains "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 that are based on our management's beliefs and assumptions and on information currently available to management. These forward-looking statements include, without limitation, statements regarding our industry, business strategy, plans, the preclinical and clinical development of our product candidates, and other financial and operating information. When used in this presentation, the words "may," "believes," "intends," "seeks," "anticipates," "plans," "estimates," "expects," "should," "assumes," "continues," "could," "will," "future" and the negative of these or similar terms and phrases are intended to identify forward-looking statements. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the development of therapeutic product candidates, such as preclinical discovery and development, conduct of clinical trials and related regulatory requirements, our reliance on third parties over which we may not always have full control, and other risk and uncertainties that are described in our Annual Report on Form 10-K filed with the SEC on March 30, 2021 and our other Periodic Reports filed with the SEC. Forward-looking statements represent our management's beliefs and assumptions only as of the date of this presentation and include all matters that are not historical facts. Our actual future results may be materially different from what we expect. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.

The Modern-Day Challenge in Immuno-Oncology Majority of patients don't respond to PD- Global PD-1/PD-L1 Market2 1/PD-L1 monotherapy1 2 1. . Market Gerber estimates et al., Biochemical from PD -Pharmacology 1 and PDL-1 Inhibitors 2016 Market Size in 2021 - MarketWatch, 360 Research

Two Major Types of Non-Responders to PD-1 Blockade Responders T-cells Inside Tumor Non-RespondersT-cells Inactive or T-cells Absent Outside Tumor Green = T-cells Purple = tumor Adapted from Van der Woulde-LL, et al, Trends in Cancer, 2017

Two Platforms to Unleash Anti-Cancer T-cell Activity TMAb™ (Tumor Microenvironment Activated Biologics) Platform Next-generation tumor activated mAbs Binding only in the low-pH tumor microenvironment Target checkpoints and/or other immune pathways Enable improved PK/PD and toxicity profiles 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 immunostimulatory nanobodies & cytokines

T-Cells Are Central to Our Approach and the Key to Unlocking Groundbreaking Clinical Activity Focus on novel immune checkpoints to UNLEASH anti-tumor T-cells Focus on multi-antigen approach to GENERATE anti-tumor T-cells

Positioned to Drive Value with Next Generation Product & Platform Development Two Platforms Pipeline Provide Opportunities Broad TMAb* ImmunoP Platform ™ Platfor manufacturing In-house GMP capabilities Strong Cash Position Ended 3Q 2021: $156.7M** Business Development **Consists *Tumor Microenvironment of cash, cash equivalents Activated biologics and mark

Pipeline Utilizing Pioneering ImmunoPhage Platform, TMAb Platform Program Phase 1 / 2 Indication Discovery IND-enabling (Target) Clinical SNS-101 Solid Tumors (VISTA) SNS-102 Solid Tumors (VSIG4) SNS-103 Solid Tumors (ENTPDase1/CD39) Merkel Cell Carcinoma Head and Neck Cancer SNS-401-NG (Multiple Tumor Lung Cancer Antigens) Melanoma Breast Cancer

TMAb (Tumor Microenvironment Activated biologics) Platform

pH-sensitive Antibodies Selectively Bind Their Targets in the Low-pH Tumor Microenvironment TMAb PLATFORM The tumor microenvironment of pH ~6 is lower than physiological pH of 7.4 Sensei's technology identifies pH-sensitive antibodies that bind only at the tumor 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

The Promise and Challenge of Immunotherapy Targeting Immunosuppressive myeloid cells is a promising strategy to overcome resistance to checkpoint Inhibitor therapy THE PROMISE Using the body's own immune system to attack cancer Capitalizing on immunological specificity and long-term memory Achieving durable cures with minimal toxicity THE CHALLENGE 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 2016

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 cells Excellent therapeutic combinability with CTLA-4 or PD-1/PD-L1 ICIs, especially in cold tumors2 VISTA expression correlates with poor survival rates across multiple cancers Novel development program with no approved therapies Sensei's Competitive Advantage: Extensive understanding of VISTA biology and differentiated candidate antibody 1 2 Lines Gao et et al al . .Nature Cancer medicine research vol vol . 23,5 . 74,7 (2017) (2014) VISTA is a Negative Regulator of T cell Function

Increased Understanding of VISTA as a Promising Target to Address the Needs of Patients with Cancer I IU H COMM U N I CA TIO N S VlSlA i) au inltibitory inuuune cht:ckpoint that is increased after !pUimum:1b therapy in patients With prostatt cancer

VISTA Checkpoint is Activated at the Low pH of the Tumor Microenvironment Antibodies that block protonated VISTA histidines interrupt PSGL-1 binding1 1. Johnston et al., Nature 2019 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

Key to Unlocking the Power of VISTA 1. Block the pH-dependent binding of VISTA to PSGL-1 on T cells at low pH 2. Selectively bind VISTA at low pH to avoid: target mediated drug disposition (TMDD) on-target/off-tumor side effects 3. Utilize an Fc-competent IgG backbone to engage and activate FcÆ"R on tumor-infiltrating myeloid cells

SNS-101 Inhibits Interaction of VISTA to its Receptor, PSGL-1, in CD4/CD8 T-Cells at Low pH 6.0 SNS-101: Fully human monoclonal antibody that selectively binds active (low pH) VISTA, but not inactive VISTA in the blood No significant binding to VISTA+ monocytes at pH 7.4 Potent inhibitor of PSGL-1 binding to VISTA Fc-competent framework to deliver positive "kick" to to help convert myeloid cells in the TME from an immunosuppressive to a proinflammatory state PSGL-1: VISTA Interaction on Primary T-cells at pH 6.0 IND-Enabling Studies are Underway for SNS-101 SITC 2021: Poster titled: Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti-tumor immunity

SNS-101 Has >600-Fold Selectivity for VISTApH6 Biophysical characterization demonstrates >600-fold selectivity for VISTA at pH 6.0 Picomolar binding at low pH No significant binding observed at physiological pH (7.4) pH 6.0 pH 7.4 132 Monovalent Affinity (KD) [nM] 0.218 (~No binding) SITC 2021: Poster titled: Antagonistic pH-selective VISTA antibody SNS-101 potentiates anti-PD-1/PD-L1-induced anti-tumor immunity

Proposed Mechanism of Action for SNS-101Fc-competent framework is required for optimal activity, but FcÆ"R engagement in the blood may result in untoward "off tumor" activation (i.e. CRS) Non-pH dependent pH-dependent

SNS-101 Is a Differentiated Anti-VISTA Antibody TMAb Platform K01401-020;SNS-101 VISTA.18 KVA12.1 CI-8993;JNJ-61610588HMBD-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 Active Yes (IgG1) No (IgG4) Yes (IgG1) Yes (IgG1) N/A No (IgG4) Stage Preclinical Preclinical Preclinical Phase I Phase I IND submission JNJ initiated Phase I study in 2016 Preclinical data 12 pts enrolled; initial dose presented at STIC 0.005 mg/kg Clinical Data / Ongoing IND-enabling studies N/A N/A Only patient treated at 0.3 Notes underway mg/kg experienced grade 3 CRS-associated encephalopathy; trial was halted Johnston et al, Nature, 2019; Kineta website; Snyder et al, AACR Annual Meeting 2016; Pierre Fabre website; Hummingbird website 19

VSIG4: A Novel Next Generation Checkpoint Modulating the Tumor Microenvironment Second TMAb program B7 family related protein Expressed on macrophages Inhibits T-cell activation Novel therapeutic combinability with existing IO drugs No approved therapies against VSIG4 Adapted from Zang et al., J Clin Invest. 2006

ImmunoPhage™ Platform

Bacteriophage Ubiquitous viruses that infect bacteria but not mammalian cells. Adept at activating the human immune system in multiple unique ways

Generating Strong Antibody and T-cell Responses Immuno Phage Platform Bacteriophage virus is engineered and manufactured with both antigen and immune stimulatory viral DNA The Immuno Phage™ bacteriophage is an icosahedron with a tail. This configuration can be viewed as an activating signal to the immune system

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. Phage taken up by antigen presenting cells Antigen cross presentation Positive co-stimulation Generation of Th1-biased immune response & cytokines

ImmunoPhage™ 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 Phortress™ library Personalized-yet off the shelf-medicines Pre-manufactured cost effectively-then combined based on genetic profile Gene therapy vehicle Phage containing self-replicating RNA Used to deliver payloads consisting of immunomodulatory proteins or nanobodies

SNS-401-NG: Building the First Custom Merkel Cell Polyoma Virus (MCPyV) ImmunoPhage SNS-401-NG Development Collaboration with University of Washington to build first custom Merkel Cell Carcinoma (MCC) vaccine cocktail consisting of Merkel Cell Polyoma Virus epitopes and other patient specific antigens MCC is a rare, aggressive neuroendocrine skin cancer 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 following definitive local treatment Integration of MCPyV is present in ~80% of U.S. cases In these cases, expression of a viral antigen (oncogenic T-antigen) appears to be a strictly required tumor driver Researchers at UW have mapped MCPyV epitopes and determined CD8 T-cell, CD4 T-cell, and B-cell epitopes that are antigenic in the context of MCPyV+ MCC tumors.

SNS-401-NG has Potential to be First Fully Customized, Yet Off-the-Shelf, Therapy SNS-401-NG Development in Merkle Cell Patients would receive a bespoke mixture of ImmunoPhage that included antigens from the MCPyV and a subset of TAA-expressing ImmunoPhage Immunophage expressing MCPyV+ MCPyV B- and T-cell antigens MCC tumors + Routine Tumor Immunophage expressing Biopsy Sequencing tumor associated antigens 1. Based on internal data Most MCC tumors contain multipleTAAs1 Common Tumor Antigens

Phortress: Proprietary Library of Personalized Vaccine Cocktails with Off-the-Shelf ImmunoPhage "Ingredients" 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

Personalized Immunotherapy Approach Could Accelerate Speed to Treatment High speed and low cost-of-goods of ImmunoPhage allows a broader array of antigens Personalized yet Off-the Shelf TAA Therapy Off-the-Shelf + Patient-specific Neoantigen Therapy Routine Tumor Personalized yet Neoantigen Neoantigen ImmunoPhage Biopsy Sequencing Off-the-shelf Prediction ImmunoPhage Injection Including ImmunoPhage Manufacturing Neoantigens Cocktail Assemble a Deliver neoantigen Engineer novel Tumor DNA personalized cocktail ImmunoPhage cocktail biopsy of tumor Identify additional tumor ImmunoPhages Tumor RNA from off-the-shelf TAA for administration and as input material specific neoantigens expressing distinct tumor Normal DNA ImmunoPhage for add neoantigen phages specific epitopes administration to bank for future use

Sensei's Vision to Capture Platform and Pipeline Value Feb 2021: IPO Invest in Advanced first Manufacturing and program into clinic Supply Chain Measured Absorb key Focus on Commercial investments in learnings and Platform Capabilities platform refine Innovation and and Pipeline technology New INDs Strength 2016 Research and Technology 2021 Pipeline and Product Candidates 2026

Proven Team With Deep Experience John Celebi, MBA President and CEO Robert Pierce, MD Chief R&D Officer Erin Colgan Chief Financial Officer Michael Boychyn, PhD VP, Technical Operations Elisabeth Colunio VP, Human Resources Edward van der Horst, PhD SVP, TMAb Antibodies auline Callinan, PhD P, Business perations and trategy Alice Drumheller P, Clinical Operations Jean Campbell, PhD VP, Biologics Discovery Bao Le VP, Regulatory

Expected Program Milestones SNS-101 (anti-VISTA) 1H 2023: IND filing 2022: Publish data demonstrating preclinical profile SNS-401-NG 2H 2022: Initiate IND-enabling studies SNS-102 (anti-VSIG4) 2023: Select product candidate SNS-103 (anti-ENTPDase1/CD39) 2023: Select product candidate

Training the Immune System to Fight Cancer John K. Celebi, MBA President & Chief Executive Officer JP Morgan Healthcare Conference January 10, 2022 NASDAQ: SNSE © 2021 Sensei Biotherapeutics. All rights reserved.