Sensei Biotherapeutics (SNSE) Study Update summary

Scientific rationale and drug design

• Solnerstotug is a monoclonal antibody targeting VISTA, an immune checkpoint protein involved in tumor immunosuppression, with pH-dependent binding to minimize off-tumor effects.

• VISTA is broadly expressed in solid tumors, often more than PD-1/PD-L1, making it a promising target for patients with high unmet needs.

• Solnerstotug was engineered to avoid the toxicity and poor pharmacokinetics seen in earlier VISTA-targeted therapies by binding selectively in acidic tumor environments.

• Preclinical and early clinical data show a differentiated safety and pharmacokinetic profile, supporting further development.

Study design and patient population

• Phase 1/2 dose expansion trial evaluated solnerstotug as monotherapy and with cemiplimab in PD-(L)1 resistant and non-responsive tumors.

• 60 patients enrolled: 40 with "hot" tumors (e.g., NSCLC, melanoma, MCC, MSI-H CRC) and 20 with "cold" MSS CRC.

• "Hot" tumor patients received solnerstotug plus cemiplimab; MSS CRC patients received either monotherapy or combination.

• Most "hot" tumor patients had a median age of 70, ECOG 0-1, and a median of two prior therapies; 90% had failed prior PD-1/PD-L1 therapy.

Efficacy results

• 14% ORR and 62% DCR among 21 evaluable PD-(L)1 resistant "hot" tumor patients, nearly triple historical rechallenge rates.

• Durable responses included one complete response in MCC, two partial responses (one MCC, one MSI-H CRC), all ongoing at 12–42+ weeks.

• Several patients experienced meaningful tumor shrinkage after failing prior PD-1/PD-L1 therapy, including two with Merkel cell carcinoma (one with a 100% response, another with 45% reduction).

• Six patients with stable disease remain on treatment past 12+ weeks, with tumor reductions up to 17%.

• No responses observed in MSS CRC ("cold" tumor) cohort.