Sensei Biotherapeutics (SNSE) Oppenheimer 35th Annual Healthcare Life Sciences Conference (Virtual) 2025 summary

Key milestones and program overview

• Lead program solnerstotug is a conditionally active antibody targeting VISTA, now in dose expansion after completing dose escalation, with a major milestone expected in Q2.

• Solnerstotug leverages pH sensitivity to selectively bind VISTA in acidic tumor environments, aiming to overcome toxicity and PK issues seen in prior VISTA-targeting antibodies.

• Cash runway extends into Q2 2026, sufficient to complete phase one clinical trials.

• VISTA is widely expressed in myeloid cells and tumors, offering significant commercial potential and combinability with PD-1 therapies.

• Previous VISTA-targeting efforts by competitors failed due to dose-limiting toxicity and poor PK, which solnerstotug aims to address.

Clinical data and study design

• Dose escalation included 16 monotherapy and 18 combination patients, showing solnerstotug was well tolerated with no dose-limiting toxicities and mostly mild adverse events.

• The antibody demonstrated a long half-life, supporting a once-every-three-week dosing regimen.

• Efficacy in cold tumors was limited, but encouraging responses were observed in hot tumors, including partial responses and significant tumor shrinkage.

• Dose expansion focuses on hot tumors (about 50 of 60 patients) and a smaller cohort of cold tumors, with a special interest in microsatellite stable colorectal cancer.

• The study is exploring both monotherapy and combination arms, with the combination arm targeting patients with prior PD-1 exposure.

Competitive landscape and scientific rationale

• Solnerstotug is one of the few VISTA antibodies with pH sensitivity, PSGL-1 inhibition, and an active FC, with only one other preclinical competitor (BMS) sharing this profile.

• Conditional activity, especially pH-dependent binding, is seen as a next-generation approach in antibody development, offering improved selectivity and safety.

• The tumor microenvironment's acidic pH is widespread, driven by rapid tumor proliferation, making pH-sensitive targeting broadly applicable.

• VISTA acts as a checkpoint primarily in low pH environments, suggesting potential for other similar targets.