Sensei Biotherapeutics (SNSE) Study Update summary

Study background and rationale

• SNS-101 is a conditionally active, pH-sensitive antibody targeting VISTA, an immune checkpoint primarily expressed on myeloid cells and implicated in resistance to current therapies.

• Previous VISTA antibodies failed due to severe CRS and poor pharmacokinetics, prompting the design of a tumor-selective, conditionally active antibody.

• SNS-101 binds VISTA only at acidic pH, focusing activity within tumors and avoiding peripheral toxicity.

• Preclinical data showed SNS-101 accumulates in tumors and avoids binding in the periphery at neutral pH.

• The TMAb platform’s pH-sensitive approach is validated by commercial precedents, such as Ultomiris, which improved half-life and safety via similar engineering.

Study design and patient population

• Phase I/II trial included monotherapy and combination (with cemiplimab) dose escalation arms for solid tumors.

• 16 patients received monotherapy, 18 received combination; most had cold tumors unresponsive to PD-1 inhibitors.

• Patients were heavily pretreated, with 2–2.5 prior lines of therapy on average.

• Dose expansion phase will enroll 50–70 patients, focusing on both hot and cold tumor types.

• Only a minority had hot tumors; most had cold tumors, including MSS colorectal and endometrial cancers.

Safety and tolerability

• SNS-101 was well tolerated as monotherapy and in combination, with no dose-limiting toxicities observed.

• Most adverse events were grade 1 or 2; mild, manageable CRS or infusion reactions occurred at the highest dose.

• Infusion-related reactions and CRS events were low grade and manageable, with no need for steroids or tocilizumab.

• No significant immunogenicity detected; no prophylaxis was used for CRS.

• SNS-101 is the first VISTA-targeting mAb to avoid dose-limiting CRS at relevant doses, overcoming toxicity and PK issues seen with earlier VISTA antibodies.