Full Dose Expansion Data for Solnerstotug in PD-(L)1 Resistant Tumors

Full Dose Expansion Data for Solnerstotug in PD-(L)1 Resistant Tumors

October 20, 2025

Presenters:

Dr. Kyriakos Papadopoulos

Co-Director of Clinical Research START, San Antonio Principal Investigator for Ph1 trial of Solnerstotug

John Celebi

Chief Executive Officer

Ron Weitzman

Chief Medical Officer

Solnerstotug is a Potential First-in-Class VISTA Targeting Mab Designed to Improve Therapeutic Index

Solnerstotug bound to VISTA

Tumor cells

Solnerstotug unbound

Periphery

Targets VISTA:

• An immune checkpoint protein and B7 family member that drives immunosuppression analogous to PD-1/PD-L1

• Unique and extensive expression pattern, found on tumors and

  myeloid-lineage cells

• Plays a key role in both primary (innate) and secondary (acquired) resistance to checkpoint blockade

  Solnerstotug MOA:

• Inhibits VISTA:PSGL-1 interaction selectively within the acidic TME

• Drives anti-tumor activity by reversing immunosuppression

Solnerstotug is a pioneering approach designed to overcome the toxicity and PK issues of 1st-generation VISTA-targeted antibodies

Gao et al. Nat Med. 2017

Kakavand et al. Mod Pathol. 2017

Thisted et al. Nat Commun 15, 2917 (2024)

MOA = mechanism of action 3

TME = tumor micoenvironment

PSGL-1 = P-selectin glycoprotein ligand-1

The Broad VISTA Commercial Opportunity PD-(L)1 Targeted Therapies Are One of the Largest Classes of Drugs Across All Therapeutic Areas VISTA Has the Most Prevalent Expression Across Cancer Indications Among Immune Checkpoints

Sales of Top 5 PD-(L)1 Targeted Therapies

Keytruda Opdivo Tecentriq Imfinzi Libtayo

$37

$0

$3

$4

$43

$1

$4

$4

$1

$5

$4

$9

$9

$8

$21

$25

$29

$B

$49

2022 2023 2024

Sources:

AstraZeneca press releases February 8, 2024 and February 6, 2025

BMS press releases February 2, 2023, February 2, 2024, and February 6, 2025

Merck press releases February 1, 2024 and February 4, 2025

Regeneron press releases February 3, 2023 and February 4, 2025

Roche press releases February 1, 2023, January 31, 2024, and January 29, 2025

Nishizaki, D. et al. ESMO Open, Volume 9, Issue 4, 102942,

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The Challenge of Targeting VISTA

Competitors Halted Development of VISTA Antibodies as a Result of Toxicities and Poor PK

• 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

• Transient Grade 3 CRS-associated encephalopathy observed at 0.3 mg/kg, leading to termination of the study after treating 12 patients

Key issues likely driven by extensive off-tumor expression of VISTA

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1 Curis, Inc., Corporate Presentation, Feb 2022

Solnerstotug Binds VISTA Selectively at the Tumor

Periphery (Neutral pH) = No Binding

Solnerstotug has no detectable binding in peripheral or normal tissues

Control Pierre Fabre

JNJ

Solnerstotug

Tumor (Acidic pH) = Binding

Solnerstotug rapidly accumulates in the tumor

Isotype control

6h post-dosing

Solnerstotug

6h post-dosing

Blue = tumor

Brown = Solnerstotug

Solnerstotug minimizes off-tumor binding, providing potential for an improved toxicity and PK profile

SITC 2022 Annual Meeting, Poster Presentation #856, "SNS-101, a highly pH-selective VISTA:PSGL-1 inhibitory

antibody, potentiates anti-PD-1 sensitivity, expands memory T-cells and enhances tumor infiltration of CD8 T-cells" 6

Monotherapy Dose Escalation Solnerstotug (Q3W)

Combination Dose Escalation Solnerstotug + Cemiplimab (Q3W)

Given prior history of VISTA antibodies, Sensei prioritized establishing:

1. Lack of severe CRS

2. Acceptable PK

3. Dosing at pharmacologically

relevant levels

Solnerstotug Phase 1 Dose Escalation Study

✓

Cohort A5 15 mg/kg N=6

✓

Cohort B3

15 mg/kg

+ cemiplimab N=6

✓

Cohort A3 3 mg/kg N=3

Cohort A4 10 mg/kg N=3

✓

Cohort B2 10 mg/kg + cemiplimab N=6

✓

Cohort B1

3 mg/kg

+ cemiplimab N=6

✓

✓

Cohort A2 1 mg/kg N=3

Cohort A1

0.3 mg/kg

N=1

✓

RP2D = Recommended Phase 2 Dose MTD = Maximum Tolerated Dose

Q3W = dosing once every three weeks Dose of Cemiplmab (Libtayo) is 350 mg BOIN = Bayesian Optimal INterval

✓ = cleared DLT assessment period 8

Well-tolerated

Commercially acceptable and potentially best-in-class PK profile

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

First and only agent to be dosed at pharmacologically relevant levels

Forward focus on patients with "hot" tumors more likely to respond to immunotherapy

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