– SNS-101, a highly pH-selective antibody to VISTA, demonstrated anti-tumor effects and promising pharmacokinetic properties in preclinical studies –

– Characterization of endogenous expression patterns, and identification of novel T-cell receptors, of VSIG4 enables advancement of SNS-102 program –

BOSTON, MA, USA I November 10, 2022 I Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, today presented preclinical data for SNS-101, a conditionally active VISTA-blocking antibody, as well as characterization of VSIG4, an immune checkpoint targeted by Sensei’s discovery-stage SNS-102 program, at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting.

“The data presented at SITC add to the growing body of evidence that our TMAb™ platform is a potentially powerful approach for unlocking previously undruggable immune targets. With the advancement of SNS-101, we have a highly pH-selective antibody to VISTA, which is designed to be conditionally active within the tumor microenvironment,” said Robert Pierce, M.D., Chief R&D Officer at Sensei. “We have also made exciting progress in our SNS-102 program, with the functional characterization and identification of novel T-cell receptors that may play a role in VSIG4-mediated immunosuppression. We look forward to advancing both programs with an upcoming IND filing for SNS-101 and identification of a lead anti-VSIG4 antibody in 2023.”

Presentation Highlights:

Poster presentation titled, “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”

Summary: Sensei has developed SNS-101, a conditionally active, human monoclonal IgG1 antibody specific for the protonated, active form of VISTA, which in preclinical studies has demonstrated the ability to disrupt the immunosuppressive VISTA:PSGL-1 interaction, avoid target-mediated drug disposition (TMDD) and mitigate potential cytokine release syndrome (CRS).

  • SNS-101 did not bind to human or non-human primates (NHP) VISTA+ monocytes, neutrophils and natural killer cells in blood or other normal tissue compartments.
  • SNS-101 induced significant expansion of naïve CD8 T-cells and memory CD4 and CD8 T-cells in vivo without activation or depletion of monocytes.
  • SNS-101 exhibited linear elimination kinetics in non-human primates, overcoming TMDD-induced pharmacokinetic limitations observed with other anti-VISTA antibodies.
  • In an MC-38 syngeneic tumor model, SNS-101 demonstrated significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies and a dose-dependent increase in CD8+ T-cells.
  • IND filing for SNS-101 is anticipated in the first half of 2023.

Poster presentation titled, “Functional characterization of the inhibitory activity and identification of novel T-cell receptors for the tumor-associated macrophage receptor VSIG4”

Summary: Sensei characterized endogenous expression patterns of VSIG4 in polarized macrophage populations and showed a robust VSIG4-mediated suppression of primary human T-cells. Additionally, a ligand receptor capture-trifunctional chemoproteomic (LRC-TriCEPS)-based proteomics strategy identified receptors on primary human T-cells that interact with recombinant VSIG4 protein.

  • Primary monocytes were purified from peripheral blood mononuclear cells and differentiated into macrophages. Multiplexed droplet digital PCR analysis revealed a robust induction of gene expression of VSIG4 following multiple immunosuppressive stimulations.
  • Development of multiple functional assays demonstrated VSIG4-mediated suppression of primary human CD4 T-cells.
  • Through the LRC-TriCEPS proteomics screen, a set of potentially novel T cell receptor candidates that interact with VSIG4 were identified.
  • A Cas9/CRISPR-based target gene knockdown methodology will be implemented for validation of VSIG4-interacting T-cell receptor candidates.
  • An initial set of pH-selective anti-VSIG4 antibodies have been identified and further optimization is ongoing to identify a lead antibody.

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.

About Sensei Biotherapeutics
Sensei Biotherapeutics (NASDAQ: SNSE) is an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients. Through its TMAb™ (Tumor Microenvironment Activated biologics) platform, Sensei develops conditionally active therapeutics designed to disable checkpoints and other immunosuppressive signals selectively in the tumor microenvironment to unleash T cells against tumors. Sensei’s lead investigational candidate is SNS-101, a conditionally active antibody designed to block the V-domain Ig suppressor of T cell activation (VISTA) checkpoint selectively within the low pH tumor microenvironment, where VISTA acts as a suppressor of T cells by binding the receptor PSGL-1. The company is also developing SNS-102, a conditional binding monoclonal antibody targeting V-Set and Immunoglobulin Domain Containing 4 (VSIG-4), as well as SNS-103, also a conditionally active monoclonal antibody targeting ecto-nucleoside triphosphate diphosphohydrolase-1 (ENTPDase1), also known as CD39. For more information, please visit www.senseibio.com, and follow the company on Twitter @SenseiBio and LinkedIn.