Sensei Biotherapeutics, Inc. · NASDAQ:SNSE
Sensei Biotherapeutics — Corporate Update (October 2025)
45 slides from Sensei Biotherapeutics's corporate update, Oct 17, 2025
Slide 1: Conditionally Active Immuno-oncology Therapeutics
Conditionally Active Immuno-oncology Therapeutics October 2025 Exhibit 99.2
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: Solnerstotug is a Potential First-in-Class VISTA Targeting Mab
Solnerstotug is a Potential First-in-Class VISTA Targeting Mab Designed to Improve Therapeutic Index Tumor cells Periphery Solnerstotug bound to VISTA Solnerstotug unbound Targets VISTA: An immune checkpoint protein and B7 family member that drives immunosuppression analogous to PD-1/PD-L1 Unique an
Slide 4: The Broad VISTA Commercial Opportunity
The Broad VISTA Commercial Opportunity Nishizaki, D. et al. ESMO Open, Volume 9, Issue 4, 102942, VISTA Has the Most Prevalent Expression Across Cancer Indications Among Immune Checkpoints 32.3% (166/514) Sources: AstraZeneca press releases February 8, 2024 and February 6, 2025 BMS press releases Fe
Slide 5: The Challenge of Targeting VISTA
Dose-limiting toxicity Grade 3 CRS-associated encephalopathy The Challenge of Targeting VISTA JNJ-61610588 Human Plasma Concentration J&J ran the first clinical trial for a VISTA antibody in 2016 (NCT02671955)1 Transient Cytokine Release Syndrome (CRS) observed in several patients at 0.15 mg/kg Tran
Slide 6: Solnerstotug Binds VISTA Selectively at the Tumor
Solnerstotug Binds VISTA Selectively at the Tumor Pierre Fabre JNJ Solnerstotug Control Periphery (Neutral pH) = No Binding Solnerstotug has no detectable binding in peripheral or normal tissues Solnerstotug rapidly accumulates in the tumor Solnerstotug 6h post-dosing Isotype control 6h post-dosing
Slide 7: Solnerstotug Dose Escalation Data
Solnerstotug Dose Escalation Data
Slide 8: Solnerstotug Phase 1 Dose Escalation Study
Solnerstotug Phase 1 Dose Escalation Study Cohort A1 0.3 mg/kg N=1 Cohort B1 3 mg/kg + cemiplimab N=6 Cohort A2 1 mg/kg N=3 Cohort A3 3 mg/kg N=3 Cohort A4 10 mg/kg N=3 Cohort A5 15 mg/kg N=6 Cohort B2 10 mg/kg + cemiplimab N=6 Cohort B3 15 mg/kg + cemiplimab N=6 Monotherapy Dose Escalation Solnerst
Slide 9: Phase 1 Dose Escalation Data Affirms Solnerstotug's MOA
Phase 1 Dose Escalation Data Affirms Solnerstotug’s MOA and Focused Patient Population in Dose Expansion Solnerstotug positioned to be the first VISTA-targeted mAb to test the VISTA IO hypothesis Well-tolerated Commercially acceptable and potentially best-in-class PK profile First and only agent to
Slide 10: Solnerstotug Dose Expansion Data
Solnerstotug Dose Expansion Data
Slide 11: Dose Expansion Cohort Designed to Explore Efficacy in "Hot" Tumor Population
Dose Expansion Cohort Designed to Explore Efficacy in "Hot" Tumor Population * Libtayo (cemiplimab) 350 mg "Hot" tumors: Responsive to PD-1 monotherapy "Cold" tumors: Unresponsive to PD-1 monotherapy MSS CRC “Cold” N=10 MSS CRC “Cold” N=10 Phase 1 Dose Expansion N=64 Phase 1 Study Objectives Primary
Slide 12: Patient Disposition
Patient Disposition Solnerstotug + Cemiplimab N = 44 (%) Enrolled 44 Dose Received 3 mg/kg 15 mg/kg 18 (41) 26 (59) Treatment Ongoing 11 (25) Discontinued 33 (75) Reason for Discontinuation Progressive Disease 22 (50) Adverse Event 1 (2) Withdrew Consent 2 (5) Death 2 (5)* Clinical Progression 5 (11
Slide 13: Patient Demographics in Dose Expansion
Patient Demographics in Dose Expansion Patient Characteristic Solnerstotug + Cemiplimab N, (%) Female, N (%) 13 (30) Age, median (min, max) 68 (28, 87) Baseline ECOG, N (%) 0 16 (36) 1 28 (64) Prior lines metastatic tx, median (min, max) 2 (0, 7) Prior PD-1/PD-L1, N (%)* 41 (93) Prior PD-1/PD-L1 pre
Slide 14: Most Frequent Treatment-Emergent Adverse Events in Dose Expansion
Most Frequent Treatment-Emergent Adverse Events in Dose Expansion Solnerstotug (3 or 15 mg/kg) + Cemiplimab Adverse Events With >10% Frequency All Grades n=44 (%) Grade 3/4 n=44 (%) Fatigue 10 (22.7) 1 (2.3) Hypomagnesaemia 10 (22.7) 0 (0) Nausea 9 (20.5) 1 (2.3) Dehydration 9 (20.5) 0 (0) Vomiting
Slide 15: Pharmacokinetic Data Support Q3W (or Greater) Dosing
Pharmacokinetic Data Support Q3W (or Greater) Dosing Detectable in blood for thousands of hours (e.g., weeks) Supports Q3W dosing in humans No apparent effect on PK with combination Some increase with repeat dosing, but no notable accumulation Data as of April 2025 15 mg/kg Solnerstotug + Cemiplimab
Slide 16: Swimmers Plot: Durable Disease Control
Swimmers Plot: Durable Disease Control Data as of September 8, 2025 10/41 (24%) patients with prior PD-(L)1 therapy remain on treatment Overall 6-month PFS = 37% CRC = microsatellite high colorectal cancer NSCLC = non small cell lung cancer H&N = head and neck cancer MCC = Merkel cell carcinoma Mel
Slide 17: Waterfall: Multiple Responses and Disease Control in a PD-(L)1-Resistant Population
Excludes 6 patients who discontinued and were unevaluable prior to first scan Data as of September 8, 2025 Waterfall: Multiple Responses and Disease Control in a PD-(L)1-Resistant Population CRC = microsatellite high colorectal cancer NSCLC = non small cell lung cancer H&N = head and neck cancer MCC
Slide 18: Responder Detail
Responder Detail Data as of September 8, 2025 Pre-Study On Study Histology Most Recent CPI Best Response on Prior CPI Best Response on Study (%) Onset of Best Response Duration of Response Merkel Cell Carcinoma Avelumab (adjuvant) NA CR (-100%) Week 18 54 Weeks + MSI-High CRC Pembrolizumab Complete
Slide 19: 6-month PFS Compares Favorably to Benchmarks
6-month PFS Compares Favorably to Benchmarks and Suggests Potential Phase 2 Dose 15 mg/kg Solnerstotug + Cemiplimab 3 mg/kg Solnerstotug + Cemiplimab PFS-6 (15 mg/kg) = 50% PFS-6 (3 mg/kg) = 24% Regimen Patient Population 6-Month PFS (%) Tolerability Solnerstotug (15 mg/kg) + Cemiplimab PD-(L)1-refr
Slide 20: Responder Case Studies
Responder Case Studies Prior therapies include multiple PD-1 inhibitors (pembrolizumab, nivolumab + ipilimumab, then nivolumab alone), with best response of stable disease Achieved partial response at week 12 (-45%), which was sustained through week 36 before disease progression Patient was PD-(L)1
Slide 21: Higher Dose Associated With More Sustained CD8+ TEM and TEMRA Modulation
Higher Dose Solnerstotug + Cemiplimab Associated With More Sustained CD8+ TEM and TEMRA Modulation in Patients With Disease Control Flow data tracking CD8+ memory T-cells in the blood of treated patients changed over time – particularly the TEM and TEMRA subsets: CD8⁺ TEM cells are antigen-experienc
Slide 22: Phase 1 Conclusions
Phase 1 Conclusions Solnerstotug/cemiplimab combination therapy demonstrates clinical activity in a PD-(L)1 resistant population of solid tumors: Durable clinical responses observed with a pattern of late onset response seen in 4 out of 5 patients Encouraging overall rate of PFS-6 of 37% Data sugges
Slide 23: Phase 2 Planning Rationale and Assumptions
Rooted in key observations made with solnerstotug/cemiplimab combination in PD-(L)1 responsive cohort: Impressive/encouraging rates (PFS-6) of durable disease control over a broad range of solid tumor types Most of the objective responses are observed in the “hottest” of tumor types (Merkel Cell and
Slide 24: Potential Phase 2 Study Designs
Potential Phase 2 Study Designs Randomized Study in Large Indication Single Arm Study in Niche Indication Combination* (15 mg/kg solnerstotug + anti-PD-1) Merkel Cell Carcinoma (PD-1 refractory) N= 20 (expand to 100 if ORR ≥ 30%) Phase 2 Study Objectives Primary Overall Response Rate Secondary Progr
Slide 25: Solnerstotug Clinical Milestones
Solnerstotug Clinical Milestones Initial combination dose escalation PK & safety data First patient dosed with solnerstotug Initial monotherapy dose escalation PK & safety data Topline Phase 1 monotherapy & combination dose escalation data Nov 2023 May 2024 May 2023 Feb 2024 Mar 2025 Phase 2 studies
Slide 26: Appendix
Appendix ¢ sensei BIO
Slide 27: Evaluable "Hot" Tumor Patients on Combination Therapy: Responders
*Did not receive prior PD-(L)1 Abbreviations: H&N = Head and Neck Squamous Cell Carcinoma, Eso = Esophageal Cancer, CRC = Microsatellite High Colorectal Cancer, MCC = Merkel Cell Carcinoma Data as of September 8, 2025 Evaluable “Hot” Tumor Patients on Combination Therapy Responders (n=6) Solnerstotu
Slide 28: Merkel Cell Carcinoma Patient (03-009) Complete Response
85 yo male with Merkel Cell Carcinoma of skin (right nasal sidewall) Diagnosed June 2022 TMB 91, MSS. ATR, BLM, RB1 TP53 RASA1, CDKN1B and ARID1B K1250fs Prior treatment: 20Oct2022 to 18Jan2024: Avelumab (Bavencio) with Signatera of 553 MTM/ml, best response stable disease, stopped due to progressio
Slide 29: MSI-High CRC Patient (01-031) Partial Response
51 yo male with MSI High CRC (adenocarcinoma of the transverse colon) Diagnosed 18Nov2019 RAS (wild type); NRAS (wild type); BRAF(wild type); MSI-High; MMR- Deficient; MSH2 (S77fs) Prior anti-cancer treatment Dec 2019 to Feb 2020: FOLFOX + Avastin, best response progression Feb 2020 to Apr 2024: Pem
Slide 30: Merkel Cell Carcinoma Patient (01-046) Partial Response
58 yo female with Metastatic Merkel Cell Carcinoma Diagnosed 2Dec2022 TMB 15.16 mut/Mb KMT2D, DPTOR, EPHA5, CREBBP+ Hx of follicular lymphoma (received chemo followed by Zydelig maintenance until 2021, remission) Prior Treatment: March 2023 to July 2023: Pembrolizumab (adjuvant setting), best respon
Slide 31: Head & Neck Squamous Cell Carcinoma Patient (07-007) Partial Response
64 yo male with H&N Squamous Cell Carcinoma Diagnosed November 2016. Prior Treatment: 05Jun2018 to 19Jul2018 Cisplatin with RT (Aduvant Setting).Best response is Non-evaluable. Completed treatment course. 28Sep2018 to 16Aug2022 anti-Ox40+41BB + Avelumab. Best response is partial response, stopped du
Slide 32: Head & Neck Squamous Cell Carcinoma Patient (07-002) Durable Stable Disease
73 yo male with Neck squamous cell carcinoma Diagnosed 20June 2020 Positive PD1/PDL1 screening TMB 7muts/mb, MSS stable, ARID1A Prior Treatment/Surgery: Jul2020 to Aug 2020: Carboplatin + Paclitaxel (neoadjuvant setting), best response progression, completed treatment course Sep 2020 to Nov 2020: Ci
Slide 33: Renal Cell Carcinoma Patient (04-024) Stable Disease
Renal Cell Carcinoma Patient (04-024) Stable Disease Accompanied by Tumor Regression 3 mg/kg solnerstotug + cemiplimab 59 yo male with Renal Cell Carcinoma Diagnosed 26November2014 Prior Treatment/Surgery: 2014: Right nephrectomy Dec 2020 to Feb 2022: Pembrolizumab and Axitinib, best response PR, st
Slide 34: Esophageal Adenocarcinoma Patient (03-015) Partial Response
Esophageal Adenocarcinoma Patient (03-015) Partial Response 15 mg/kg solnerstotug + cemiplimab 53 yo male with Esophageal invasive moderately differentiated Adenocarcinoma Diagnosed 25Sep2020 (GEJ, T3N0. Chemo-radiation then surgery. Relapse August 2021 with left acetabular bone met) Prior Treatment
Slide 35: Non-Small Cell Lung Cancer (01-029) Partial Response
Non-Small Cell Lung Cancer (01-029) Partial Response 15.0 mg/kg solnerstotug + cemiplimab 81 yo male with Lung Adenocarcinoma (malignant neoplasm of lower lobe, left broncus or lung) Diagnosed 2011. TPS (PD-L1) < 5% TMB is 1 Mut/Mb, no MSI high. Med HX: 2009 prostate cancer (treated with XRT), 2011
Slide 36: MSI-high Intrahepatic Cholangiocarcinoma Patient (01-048) Stable Disease
75 yo Male with MSI-High Cholangiocarcinoma Diagnosed 11Apr2019 MSI-high, TP53, EGFR, IDH2, GNAQ, PIK3CA Hx Prior Treatment: May 2019 to Apr 2021: Pembrolizumab, Best response was CR with residual CT-lesions. Completed treatment per protocol Oct 2023 to Jan 2025: Pembrolizumab, Best response SD, sto
Slide 37: Renal Cell Carcinoma Patient (04-025) Stable Disease
76 yo male with Renal Clear Cell Carcinoma Diagnosed 19Jul2021 PDL-1 negative 2021, Left radical nephrectomy Prior Treatment: Dec 2022 to Mar 2023: Nivolumab + Cabozantinib, best response SD, stopped due to Toxicity/Adverse Event Cabozantinib continued through Jul 2023 until progression. Nov 2023 to
Slide 38: MSI-High Colorectal Carcinoma Patient (01-049) Stable Disease
56 yo male with MSI-high Colon Adenocarcinoma Diagnosed 5Mar2021 MSI-HighATM, PDGFRA, BRCA2, MSH2, CTNNB1, PBRM1, CDH1, Hx of Melanoma, Lynch syndrome Prior Treatment: May 2021 to Aug 2024: Pembrolizumab, Best response was SD, reason for stopping is unknown. Oct 2024 to Dec 2024: Nivolumab + Ipilimu
Slide 39: Head and Neck Squamous Cell Carcinoma Patient (08-004) Stable Disease
73 yo male with oropharynx squamous cell carcinoma Diagnosed 06Sep2022 Positive PD1/PDL1 screening Prior Treatment/Surgery: Oct2022 to Dec2022: Carboplatin + Paclitaxel + Pembrolizumab, best response PR, completed treatment Jan2023 to Feb2023: Cisplatin, best response SD, completed treatment May2024
Slide 40: MSI-High Colorectal Carcinoma Patient (01-050) Stable Disease
MSI-High Colorectal Carcinoma Patient (01-050) Stable Disease 3 mg/kg Solnerstotug + Cemiplimab 66 yo male with Cecum Adenocarcinoma Diagnosed 17Apr2023 TMB 49 mut/Mb MSI-high,ERBB3, PIK3CA, PTEN Positive, PDL-1 Negative APC, ARID2, ASXL1, B2M, BCL9, CDKN2A, CIC, FBXW7, MSH6, MUTYH, PPP2RIA, PRKDC,
Slide 41: Renal Cell Carcinoma Patient (03-011) Stable Disease
59 yo male with metastatic Renal Clear Cell Carcinoma (malignant neoplasm of left kidney, except renal pelvis) Diagnosed 8Mar2017 Evidence of a PTEN deletion in his tumor MSI-high not detected Prior Treatment/Surgery: Apr 2018 to Feb 2019: Pembro + Lenvatinib, best response SD, stopped due to progre
Slide 42: Hepatocellular Patient (01-038) Durable SD
Hepatocellular Patient (01-038) Durable SD with Tumor Kinetics and AFP Consistent with Pseudo-Progression 15 mg/kg Solnerstotug + Cemiplimab 67 yo male with hepatocellular carcinoma Diagnosed 2017 RAD51C; ATM; TP53; CTNNB1 Prior Treatment/Surgery: 2017 and 2018: Chemoembolization x 2, Radiofrequency
Slide 43: NSCLC Patient (01-035) Durable Stable Disease
78 yo male with squamous cell carcinoma of the lung Diagnosed 26Oct 2021 PD-1/PD-L1 positive, PD-L1 80% GNAS (R201C), TP53(Y126N), CCDKN2A (E33), TB53 (c.920-2del), ARID1A(P697fs), TMB-17.72 mut/mb Prior Treatment/Radiation Nov 2021: Paclitaxel + Carboplatin + Pembrolizumab in the metastatic setting
Slide 44: Participating Sites
Participating Sites Investigator Site Dr. Shiraj Sen, MD, PhD NEXT Oncology Dallas, Irving, Texas 75039 Dr. Steven Powell, MD Sanford Cancer Center, Sioux Falls, South Dakota 57104 Dr. Kyriakos Papadopoulos, MD South Texas Accelerated Research Therapeutics (START) San Antonio, San Antonio, Texas 782
Slide 45: MD: 1405 Research Blvd, Suite 125, Rockville, MD 20850 / MA: 451 D Street,
MD: 1405 Research Blvd, Suite 125, Rockville, MD 20850 / MA: 451 D Street, Suite 906, Boston, MA 02210 senseibio.com
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