On November 3, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported initial data from the monotherapy dose-escalation portion of its Phase 1/2 clinical trial for SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, NOV 3, 2023, View Source [SID1234636900]). The data, to be presented in a late-breaker poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting, suggest a potential best-in-class safety and pharmacokinetic profile among VISTA blocking antibodies and the potential to overcome long-standing pharmacological challenges encountered by first generation approaches to blocking VISTA.

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"We are pleased to report favorable clinical data for SNS-101, a pioneering VISTA-blocking antibody that provides validation of our conditionally active approach. The data support that this highly innovative antibody is well tolerated across dose levels tested to date, shows linear, dose-dependent pharmacokinetics predicted preclinically to elicit immune-mediated anti-tumor activity, and a cytokine profile consistent with an absence of cytokine release syndrome," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "Data from this clinical study to date provides important initial evidence that SNS-101 can provide clinically meaningful and mechanistic differentiation from first generation anti-VISTA approaches, as indicated by SNS-101 dose levels that are at least 10 times higher than the first clinical study of a competitor VISTA antibody that was prematurely halted due to cytokine release syndrome and poor pharmacokinetics. We believe this represents a foundational clinical achievement in the pursuit of a transformational VISTA-blocking antibody, and we look forward to building on this success with additional data readouts, including efficacy analysis, expected next year."

The multi-center Phase 1/2 clinical trial is a dose escalation study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in patients with advanced solid tumors.

Summary of reported data (as of the October 3, 2023 cutoff date):

A total of 13 patients were enrolled in the study.
In the monotherapy dose escalation arm, ten patients were enrolled across four dosing cohorts receiving SNS-101 treatment at 0.3, 1, 3, or 10 mg/kg.
In the combination arm, three patients were enrolled at the first dose level of 3.0 mg/kg of SNS-101 plus 350 mg of Libtayo (cemiplimab).
Safety, cytokine expression and pharmacokinetic data were presented for seven patients from the first three monotherapy cohorts, all of which have cleared the dose-limiting toxicity assessment period.
A total of 11 adverse events (including one serious adverse event not considered related to SNS-101) was reported in five patients, with no dose-limiting toxicities observed. Only one adverse event (Grade 2 dermatitis acneiform) was considered related to SNS-101.
There were no instances of cytokine release syndrome and no significant changes in key inflammatory cytokines over time, consistent with preclinical studies.
Pharmacokinetic data demonstrate dose-proportional exposure consistent with lack of target mediated drug disposition, no notable accumulation with repeat dosing, and linear elimination kinetics of SNS-101, in concordance with preclinical data.
"Too many patients remain underserved by existing immunotherapies. SNS-101 highlights the potential of targeting VISTA through an innovative concept, thoughtful approach and a well-executed study as Sensei has done," said Shiraj Sen, M.D., Ph.D., a medical oncologist at NEXT Oncology and investigator on the Phase 1/2 SNS-101 clinical trial. "I’m encouraged by the patient experience so far in the SNS-101 trial, including a potentially best-in-class safety profile and an every-three-week dosing schedule that helps alleviate the logistical burden imposed on patients by agents requiring more frequent administration due to their unfavorable PK profiles."

Sensei expects to report initial safety and pharmacokinetic combination data in Q1 2024, with topline monotherapy data in Q2 2024, and topline combination data in 2024.

Presentation at SITC (Free SITC Whitepaper):

Title: A phase 1/2 study of safety, tolerability and pharmacokinetics of SNS-101, a pH-sensitive anti-VISTA mAb, as monotherapy and in combination with cemiplimab in patients with advanced solid tumors
Presentation type: Poster (late breaking abstract)
Abstract Number: 1532
Date and time: Saturday, November 4, 2023, at 9 a.m. PT – 8:30 p.m. PT
Location: Exhibit Halls A and B1 – San Diego Convention Center
Lead authors: Shiraj Sen, M.D., Ph.D. and F. Donelson Smith, Ph.D.

A copy of the presentation materials will be added to the "Events & Presentations" section of the Company’s Investor Relations website at www.senseibio.com.