Pipeline

About the program

Solnerstotug is a conditionally active, human monoclonal IgG1 antibody designed to block the VISTA checkpoint, which acts as a suppressor of T cells by binding the receptor PSGL-1. Sensei Bio has initiated a Phase 1/2 clinical trial to evaluate Solnerstotug as both a monotherapy and in combination with cemiplimab in patients with advanced solid tumors.

Selectivity advantage

VISTA is widely expressed by immune cells throughout the body. Non-selective therapeutic approaches have led to unwanted inflammatory reactions such as cytokine release syndrome. Non-selective therapeutics have also been prone to target-mediated drug disposition, in which off-tumor cells absorb the bulk of a drug before it can reach the tumor. Solnerstotug was designed to address these problems by binding only under low-pH conditions, such as those found in the tumor microenvironment.

About the program

Sensei’s SNS-102 is a conditionally active, monoclonal antibody targeting VSIG4, a B7 family-related protein that is often overexpressed on macrophages within the tumor microenvironment and is a potent inhibitor of T cell activity.

Selectivity advantage

VSIG4 is also expressed by macrophages in non-malignant tissues, such as the liver and peritoneal cavity. We believe that a tumor-selective VSIG4-blocking monoclonal antibody may have potent anti-tumor effects while minimizing on-target, off-tumor toxicities and poor pharmacokinetics.

About the program

Sensei’s SNS-103 is a conditionally active, monoclonal antibody targeting ENTPDase1 (CD39), an enzyme commonly upregulated by tumors and involved in the conversion of ATP into immunosuppressive adenosine in the tumor microenvironment.

Selectivity advantage

ENTPDase1 is also expressed by immune and vascular cells in non-malignant tissues, such as the liver and pancreas. Non-selective targeting of ENTPDase1 may pose a risk of inflammatory conditions like thrombosis, atherosclerosis or metabolic dysregulation. We believe that a tumor-selective blocking monoclonal antibody may have potent anti-tumor effects while avoiding on-target, off-tumor toxicities and poor pharmacokinetics.

About the program

SNS-201 is designed to conditionally activate CD28 under low pH conditions, such as those found in the tumor microenvironment, resulting in T cell activation in the tumor while minimizing off-tumor toxicity. It is a bispecific format with monovalent CD28 engagement and bivalent pH-selective VISTA binding for efficient engagement at low pH.

Selectivity advantage

CD28 is a major costimulatory pathway for T-cells. While CD28 agonism has shown some clinical promise, human testing has been stymied by dose-limiting toxicities that result from systemic activation of CD28. We believe that a bispecific antibody incorporating both a CD28 agonist arm and a pH-sensitive anti-VISTA arm will allow us to conditionally activate CD28 under low pH conditions, such as those found in the tumor microenvironment, leading to T cell activation in the tumor while minimizing off-tumor toxicity.