SNSE Sensei Biotherapeutics Inc

---

---

Conditionally Active Antibodies for Immuno-oncology Corporate Deck | June 2024 Exhibit 99.1

---

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 are made as of the date of this presentation unless stated otherwise, and the delivery of this presentation at any time shall not 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, expectations regarding the development and potential therapeutic benefits of our product candidates; the expected safety, pharmacokinetic and efficacy profile of our product candidates, including SNS-101; the expected timing of clinical data from our Phase 1/2 clinical trial of SNS-101; the expansion of the Phase 1 clinical trial to include additional patients with specific tumor types; and our belief that our existing cash and cash equivalents will be sufficient to fund our operations at least into the fourth quarter of 2025 and reach midway into Phase 2 clinical studies of SNS-101. When used in this presentation, the words and phrases "designed to," "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, including the risk of delay or cessation of any clinical trials of Sensei’s product candidates; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical trials and early results from the clinical trial of SNS-101, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Sensei’s product candidates, including SNS-101; our reliance on third parties over which we may not always have full control; risks regarding the accuracy of our estimates of expenses, capital requirements and needs for additional financing; and other risk and uncertainties that are described in our Quarterly Report on Form 10-Q filed with the SEC on May 9, 2024 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.

---

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 regulator of T-cell function and promising immune checkpoint target SNS-101 has demonstrated ability to overcome hurdles associated with drugging VISTA, including: a well-tolerated safety profile, potentially best-in-class PK, and initial signs of promising clinical activity Three additional early-stage drug candidates Cash runway into the fourth quarter of 2025, which is expected to fund operations midway into Phase 2 studies of SNS-101 Initial Phase 1 expansion data expected by year-end 2024

---

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)

---

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 (NSCLC) 214K 315K 1.15M Colorectal Cancer (CRC) VISTA’s Potential Commercial Impact The checkpoint market is large and growing fast1 Despite the widespread use of checkpoint inhibitors, only 20% of patients experience an objective response VISTA is implicated in numerous solid tumor types with large patient populations Indications such as CRC see little to no benefit from current treatment options Newly Diagnosed Patients Annually in 20262 ~2.6M new patients per year

---

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 poor PK & dose-limiting toxicities Conditionally active antibodies are selectively targeted to the tumor microenvironment, potentially providing: Little or no toxicity due to selective on-target/on-tumor action Lower & less frequent doses with tumor-specific binding Powerful activity selectively focused on the tumor microenvironment One new IO checkpoint inhibitor approved after the CTLA-4 and PD-1/PD-L1 group 2011 2014 2022 Lack of Tumor Targeting is a Major Obstacle in IO Innovation Ipilimumab (anti-CTLA-4) Pembrolizumab (anti-PD-1) Relatlimab (anti-LAG-3)

---

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 more frequent dosing due to poor pharmacokinetics Bolsters specific activities Unlocks previously undruggable immune targets Sensei’s technology identifies pH-sensitive antibodies designed to bind only at the tumor The tumor microenvironment of pH ~6 is lower than physiological pH of 7.4

---

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. *Sensei has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute. The goal of this collaborative effort is to further elucidate the role of VISTA in immune checkpoint resistance and expand the potential of SNS-101 as a combination therapy beyond anti-PD-1. 

---

SNS-101 (VISTA)

---

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 Increased expression on tissue infiltrating immune cells upon checkpoint therapy failure3 IS ACTIVATED IN A pH SENSITIVE MANNER T-cell proliferation & activation Extensive VISTA expression on off-tumor myeloid-lineage cells demands a conditionally active antibody approach VISTA has inherent pH sensitivity: its extracellular domain is uniquely rich in histidines4 Myeloid lineage cell or tumor cell (less common) 1 Wang et al, JEM, 2011 2 Deng et al, Cancer Immunonol Res 2019 3 Gao et al., Nat Med. 2017 4 Johnston et al., Nature 2019

---

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 light chain Human VISTA (shown in green and red) Human VISTA epitope for SNS-101 VISTA:SNS-101 co-crystal structure demonstrates SNS-101 encompasses VISTA's PSGL-1 epitope Selectivity for active VISTApH6 over VISTApH7.4 Blocks the key receptor regulating VISTA’s immunosuppressive activity Additional SNS-101 features IgG1 format Active Fc Thisted T. et al. Nature Communications 2024

---

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 Brown = SNS-101 Tumor (Acidic pH)

---

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 in clinical trials in 2016 (NCT02671955) 1 Transient Cytokine Release Syndrome (CRS) observed in several patients at 0.15 mg/kg Transient Grade 3 CRS-associated encephalopathy observed at 0.3 mg/kg, after which Janssen halted the study Challenging PK profile Non-linear PK, short t1/2 1 Curis, Inc., Corporate Presentation, Feb 2022

---

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 (PharmAbcine) CI-8993; JNJ-61610588 (J&J/Curis) K01401-020; WO180 (Pierre Fabre) KVA12123 (Kineta) VISTA.18 (BMS) Inhibit PSGL-1 Binding pH Sensitive Binding Fc Active Most Advanced Stage (IgG1) (IgG1) (IgG1) (IgG4) Phase 1 Phase 1 Phase 1 Phase 1 Phase 1 Preclinical Phase 1 (IgG1) (IgG4) (IgG1mut)

---

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-comer solid tumor population during dose escalation which included both "hot" and "cold" tumor histologies, allowing for efficient enrollment SECONDARY  Explore VISTA's role in both "cold" and "hot" tumor settings to allow for efficient enrollment and to explore signs of activity in both settings Identify RP2D Enroll selected patient populations to balance cold/hot tumor ratio Explore more discreet range of doses

---

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/kg + Libtayo* N=6 Cohort B3 15.0 mg/kg + Libtayo* N=6 CRC Basket (CRC, NSCLC, H&N, Melanoma) Monotherapy Dose Escalation SNS-101 (Q3W) Combination Dose Escalation SNS-101 + Libtayo* (Q3W) Phase 1 Dose Expansion ~ 50 to 70 patients Phase 1 Dose Escalation BOIN design in patients with advanced solid tumors ü ü ü ü Phase 1 Study Objectives Primary Safety, tolerability, MTD/RP2D Secondary  PK, immunogenicity & anti-tumor activity Phase 2 Single-arm, Simon two-stage minimax design SNS-101 (RP2D) +/- Libtayo (Q3W) Indications TBD Phase 2 Study Objectives Primary Anti-tumor activity Secondary Safety, tolerability, PK & immunogenicity  RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose CRC = colorectal cancer NSCLC = non small cell lung cancer H&N = head and neck cancer ü ü ü = cleared DLT assessment period Additional tumor types and doses may be considered for both the monotherapy & combination dose expansion ü ü Monotherapy 15 mg/kg Combination 3 mg/kg and 15 mg/kg + Libtayo

---

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 Therapy 0 0 Clinical Progression 0 1 * Related to disease progression, not related to SNS-101 (1 mg/kg dose level) # Patient discontinued due to immune mediated AEs of Grade 3 AST and ALT (10 mg/kg + cemi) Data as of 30April2024

---

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 Latino 14 (88) 14 (77) Hispanic or Latino 1 (6) 3 (17) Not reported 1 (6) 1 (6) Baseline ECOG, n (%) 0 6 (37) 4 (22) 1 10 (63) 14 (78) Majority of Patients had Tumor Type Typically Unresponsive to PD-1 Monotherapy Data as of 30April2024 SNS-101 Mono n=16 (%) SNS-101 Combo n=18 (%) Prior lines metastatic therapy Median 2 2.5 Min, Max 0,7 1,7 Prior PD-1/PDL-1 YES% % Yes 8 (50) 4 (22) Cancer Type, n (%) Responsive to PD-1 monotherapy (e.g. “hot” tumors) 3 (19) 2 (11) Head and Neck 2 0 Kidney 1 2 Typically Unresponsive to PD-1 monotherapy (e.g. “cold” tumors) 13 (81) 16 (89) MSS Colon 4 7 MSS Endometrial 0 1 Esophageal 1 0 Pancreatic 0 3 Sarcoma* 4 2 Other** 4 3 *Sarcoma: Leiomyosarcoma, Ewing Sarcoma, PEComa, Hemangiopericytoma (mono) and Leiomyosarcoma and Desmoplastic small round cell (combo) **Other Tumor Types:  Small cell lung carcinoma, Gallbladder, Adenocystic carcinoma maxillary sinus, and mediastinal carcinoma (mono) and Ovarian, Duodenal, granulosa cell tumor (germ cell) 85% of enrolled patients had tumors typically unresponsive to PD-1/PD-L1 therapy

---

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-papular at 3 mg/kg + cemi ^One patient experienced Grade 3 Diabetic Ketoacidosis at 3 mg/kg + cemi ^Two patients experienced elevated liver enzymes both at 10 mg/kg + cemi (one pt with Grade 3 ALT  and Grade 1 AST and one pt with Grade 3 AST and ALT which resulted in discontinuation from treatment) SNS-101 n=16 (%) SNS-101 + cemi  n=18 (%) At least 1 TEAE 13 (81) 14 (78) At least 1 SAE 1 (6) 8 (44) ≥Grade 3 TEAE 2 (13) 8 (44) At least 1 TEAE leading to discontinuation 1* (6) 1 (5) DLTs 0 0 AESI 1 (6) 5 (28) Immune-mediated^ 0 4 (22) CRS# 1 (6) 1 (6) Preferred Term SNS-101  Mono n=16 SNS-101 Combo n=18 Total n=34 Fatigue 0 5 5 Cough 3 1 4 Pleural effusion 1 2 3 Pyrexia 2 1 3 Rash maculopapular 1 2 3 Alanine aminotransferase increased 0 2 2 Anaemia 0 2 2 Aspartate aminotransferase increased 0 2 2 Blood bilirubin increased 0 2 2 Chills 1 1 2 COVID-19 1 1 2 Cytokine release syndrome 1 1 2 Dermatitis acneiform 2 0 2 Hypokalemia 1 1 2 Hypomagnesemia 1 1 2 Infusion related reaction 0 2 2 Lymphocyte count decreased 0 2 2 Nausea 0 2 2 Pruritis 0 2 2 Most Frequently Occurring AEs (≥ 2 Overall) Regardless of Causality Summary of Adverse Events Data as of 30April2024 No dose-limiting toxicities observed Majority of AEs were Grade 1 or 2 Two patients experienced Grade 1 CRS, suggesting that CRS is a class effect of VISTA-targeting antibodies

---

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 Syndrome (Chills and fever) Grade 1 C1D1 ~4 hours post SNS-101 Infusion 01-013 SNS-101 15.0 mg/kg + cemi Cytokine Release Syndrome  (Chills, no fever) Grade 1 C1D1 ~5 hours post SNS-101 Infusion 01-009 SNS-101 3.0 mg/kg + cemi Infusion-related reaction (Chills and flushing) Grade 2 C2D1 At the end of the SNS-101 Infusion 04-015 SNS-101 15.0 mg/kg + cemi Infusion-related reaction  (chest tightness, muscle aches, hypotension) Patient also reported grade 1 itching and flushing about 1 hour after C1D1 Grade 2 C2D1 ~6 minutes after start of SNS-101 infusion Data as of 30April2024 All CRS events have been low grade and manageable Demonstrates that SNS-101 has the potential to overcome a key hurdle that impeded development of first-generation VISTA mAbs

---

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 apparent effect on PK with combination  Some increase with repeat dosing, but no notable accumulation No significant immunogenicity detected in analysis of ADAs SNS-101 + cemiplimab Data as of 30April2024 SNS-101

---

No Significant Changes in Key Inflammatory Cytokines Data as of 30April2024

---

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 Indicate Potential SNS-101-Related Pharmacological Effect Data as of 30April2024

---

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 pembrolizumab-resistant HPV+ H&N pt had tumor regression of 17% at a dose level of 15.0 mg/kg; discontinued at Week 12 due to PD One pt with adenocystic carcinoma (maxillary sinus) continues on treatment with SD at 42+ weeks at a dose level of 1.0 mg/kg One pt with leiomyosarcoma (kidney) continues on treatment with SD at 24+ weeks at a dose level of 15.0 mg/kg Combination Dose Escalation 18 patients enrolled: 16 patients received both baseline and at least one follow-up scan. Patients of interest: One MSS endometrial pt at 3 mg/kg + cemi had a confirmed PR (59% decrease); ongoing 30+ weeks  One MSS colon pt at 3 mg/kg + cemi had tumor regression of 27%; discontinued at Week 18 due to PD One RCC pt at 10 mg/kg + cemi had tumor regression of 18%; discontinued due to immune-mediated toxicity Data as of 30April2024

---

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 sentinel lymph node dissection, Dec 2020 Paclitaxel/Carboplatin (adjuvant setting), Feb 2021 to Aug 2021 Anastrozole (metastatic setting), Aug 2023 to Sep 2023 Adverse Events Grade 3 diabetic ketoacidosis 4 days after Cycle 3 infusions, related to SNS-101 and cemiplimab, AESI (immune-mediated) and SAE (hospitalization) Patient recovered and maintained on Insulin and continued study therapy Tumor Assessments in Solitary Target Lesion 62 yo male with colon cancer; dx Jan 2017, ECOG 1 PD-1/PD-L1: Negative Prior Treatment/Surgery Received 7 prior lines of therapy in the metastatic setting with the last 3 therapies investigational Adverse Events Grade 2 dry skin, related to SNS-101, not related to cemiplimab Grade 2 rash maculo-popular, related to SNS-101 and cemiplimab, AESI (immune-mediated), resolved after treatment with prednisone Grade 2 pruritis, related to SNS-101 and cemiplimab Tumor Assessments 6-Week Scans: Stable Disease (19% decrease) 12-Week Scans: Stable Disease (27% decrease) 18-Week Scans: Progressive Disease (23% increase from nadir) I/O-naïve MSS Endometrial Cancer with PR 3.0 mg/kg SNS-101 + cemiplimab (Patient 01-005) I/O-naïve MSS Colon Cancer  3.0 mg/kg SNS-101 + cemiplimab (Patient 04-010) 6-Week SD (-0.6%) Baseline 12-Week PR (-34%) 18-Week (-45%) 24-Week PR (-52%) 30-Week PR (-59%) Data as of 30April2024 Microsatellite stable (MSS) colon and endometrial tumors are typically unresponsive to PD-1/PD-L1 single agent therapy

---

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 anti-tumor activity in a predominantly “cold” solid tumor patient population Well tolerated Potentially best-in-class PK Initial signs of encouraging clinical activity SNS-101 well positioned to be the first VISTA-targeted mAb to test the VISTA IO hypothesis

---

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, immunogenicity & anti-tumor activity RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose CRC = colorectal cancer NSCLC = non small cell lung cancer H&N = head and neck cancer Monotherapy 15 mg/kg  Combination 3 mg/kg and 15 mg/kg + cemiplimab* Patient enrollment advancing in dose expansion cohorts Exploring two dose levels in the combination cohort to further optimize study design for Phase 2 Expansion tumor types focused on a basket of “hot” tumors and one “cold” tumor, to rebalance between cold/hot given ~85% of patients in dose escalation had “cold” tumor types.  Additional tumor types and doses may be considered All patients with “hot” tumors will have received and failed a prior PD-1/PDL-1  Expansion phase expected to include ~50 to 70 patients Cash runway guidance unchanged (Q4 2025) Initial data from dose expansion expected in Q4 2024

---

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 data Initial Phase 1 dose expansion data - End of Phase 1 FDA meeting May 2023 September 2023 November 2023 May 2024 Q4 2024 February 2024 ü ü ü ü ü

---

SNS-102 (VSIG-4)

---

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 with immunosuppressive "M2" macrophage infiltration3 Inhibits T cell activation4 Promotes tumor growth based on data from a syngeneic Lewis lung carcinoma model in knockout mice5 VSIG4 is an Immunosuppressive Receptor with On-Target, Off-Tumor Challenges  doi: 10.1016/j.cell.2005.12.039. doi: 10.4049/jimmunol.2101109. doi: 10.4414/smw.2016.14301. doi: 10.1172/JCI25673. doi: 10.1038/labinvest.2014.73.

---

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 conditions pH 6.0 pH 7.4 0.7nm 410 nm (~No binding) Monovalent Affinity (KD) Ratio = 585

---

SNS-103 (ENTPDase1/CD39)

---

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 tumors and normal tissues Development of a TMAb antibody has potential for improved safety and PK profile compared to competitor CD39 mAbs

---

SNS-201 (VISTAxCD28)

---

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 activation to the tumor microenvironment, with no co-stimulation in the periphery CD28 is a major co-stimulatory pathway for T cells and a clinically validated therapeutic target for activating T cells in the tumor microenvironment

---

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 bispecific approach Avoids use of "tumor associated" antigens Anti-CD28 pH-Sensitive anti-VISTA Arm Cancer Cell or Myeloid Cell T Cell pH-sensitive arm confers tumor selective CD28 co-stimulation Can be used in “cis” (tumor cell) or in “trans” (myeloid or other immune infiltrate) CD28 agonist drives signal 2

---

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 backbone with silencing mutations abolishing Fc receptor interactions pH-sensitive VISTA binding to restrict CD28 activation to the TME Checkpoint release through anti-PD-1

---

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

---

*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-tolerated safety profile and potential best-in-class pharmacokinetic profile TMAb PLATFORM Conditionally active antibodies designed to widen therapeutic window and enable druggability of promising oncology targets EXPECTED MILESTONES Initial dose expansion data by end of 2024 Q4 2024: End of Phase 1 FDA Meeting FINANCIALS Ended Q1 2024: $58.1M* Cash runway into Q4 2025 Cash currently expected to reach midway into Phase 2 clinical studies for SNS-101

---

HQ: 1405 Research Blvd, Suite 125, Rockville, MD 20850  /  MA: 22 Boston Wharf Rd, 7th floor, Boston, MA 02210 senseibio.com

---

SNS-101 Duration of Treatment Data as of 30April2024

---

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 clinical trial Sensei to fund planned clinical trial Regeneron to provide Libtayo® Sensei maintains global development and commercial rights to SNS-101 Cooperative Research & Development Agreement Further elucidate role of VISTA in immune checkpoint resistance and expand potential of SNS-101 as a combination therapy beyond anti-PD-1 Sensei collaborating with NCI Center for Immuno-Oncology Co-Directors, Jeffrey Schlom, Ph.D., and James Gulley, M.D., Ph.D. Preclinical studies will assess SNS-101 mechanism of action in combination with therapies beyond anti-PD-1 Research Collaboration Further study the mechanism of SNS-101's anti-tumor activity Sensei collaborating with laboratory of immuno-oncology KOL, Robert Schreiber, Ph.D. Preclinical studies will include identification of SNS-101 response biomarkers   

---

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 given every 2w for all efficacy endpoints, while maintaining a similar safety profile. 2018: FDA approves Ultomiris® (ravulizumab, ALXN1210) 2020: Ultomiris sales = $1.08 billion  Revulizumab utilized histidine insertions into the CDR regions (VH_Y27H, VH_S57H) and Fc substitutions (M428L, N434S) of eculizumab Soliris® (eculizumab), an anti-C5 monoclonal antibody (mAb), was considered standard of care for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome, but had a short half-life as a result of extensive TMDD. Engineering eculizumab using histidine substitutions resulted in a pH-sensitive mAb with markedly improved half-life. Sheridan et al, PLOS One, April 2018 (https://doi.org/10.1371/journal.pone.0195909) Lee et al, Blood, (doi:10.1182/blood-2018-09-876136) Sales figures: https://media.alexion.com/news-releases/news-release-details/alexion-reports-fourth-quarter-and-full-year-2020-results Antibody Engineering of Solaris Led to pH Sensitivity and Half-Life Improvements

---

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

---

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 Anti-PD-1

---

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 Hummingbird HMBD-002 Preclinical PK Linear Non-linear 1. Hummingbird SITC 2022; 2. Kineta Corporate Presentation; 3. Abcine, SITC 2022; 4. Curis, SITC 2022 *Each graph differs by time course based on data presented Clinical mAb #1 10 mg/kg

---

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

---

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

---

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 significant target-mediated drug disposition (TMDD) and clearance in non-malignant tissues SNS-101 displayed linear elimination kinetics unlike a pH-independent anti-VISTA mAb, which demonstrated TMDD and rapid clearance Pharmacokinetics of Single Dose SNS-101 in Cyno monkeys Clinical mAb #1 10 mg/kg

---

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 subset of M2-type cells SNS-101 targets suppressive signaling in the myeloid compartment, and in combination with anti-PD-1 may help shift the balance of macrophage polarization toward an anti-tumor M1 phenotype

v3.24.1.1.u2

Document and Entity Information	Jun. 03, 2024
Document And Entity Information [Line Items]
Amendment Flag	false
Entity Central Index Key	0001829802
Document Type	8-K
Document Period End Date	Jun. 03, 2024
Entity Registrant Name	Sensei Biotherapeutics, Inc.
Entity Incorporation State Country Code	DE
Entity File Number	001-39980
Entity Tax Identification Number	83-1863385
Entity Address, Address Line One	1405 Research Blvd
Entity Address, Address Line Two	Suite 125
Entity Address, City or Town	Rockville
Entity Address, State or Province	MD
Entity Address, Postal Zip Code	20850
City Area Code	(240)
Local Phone Number	243-8000
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Entity Emerging Growth Company	true
Entity Ex Transition Period	false
Common Stock [Member]
Document And Entity Information [Line Items]
Security 12b Title	Common Stock
Trading Symbol	SNSE
Security Exchange Name	NASDAQ
Series A Preferred Stock [Member]
Document And Entity Information [Line Items]
Security 12b Title	Series A Preferred Stock Purchase Rights
Security Exchange Name	NASDAQ

---