Approach

We aim to disable immunosuppressive signals within the tumor microenvironment while avoiding on-target, off-tumor activity.

Lack of selectivity has posed a significant challenge to expanding the range of immunotherapy options for patients. Checkpoints and other immunosuppressive signals are promising therapeutic targets, but widespread expression on tissues beyond the tumor microenvironment often leads to poor drug-like properties and narrow therapeutic windows that diminish efficacy and pose safety risks.

TMAb™ Platform

The TMAb Platform is designed to overcome this selectivity challenge by creating conditionally active antibodies that are intended to selectively activate within the low-pH tumor microenvironment.

Our Challenge

T cells are often present in the tumor microenvironment, but inactivated and limited to the periphery—making the tumor T cell-excluded and unlikely to trigger an immune response, or “cold.” Attempts to activate existing T cells must ensure sufficient drug delivery to the TME while avoiding on-target off-tumor effects in the periphery to inactivate primary or secondary immune checkpoints.

Our Strategy

The Tumor Microenvironment Activated Biologics platform (TMAb) discovers and develops antibodies that bind their targets only in the low-pH conditions characteristic of the tumor microenvironment. This strategy can also be designed around characteristics of the tumor microenvironment beyond low pH, such as redox potential and extracellular ATP concentration.

The Benefit

By preventing these unwanted interactions beyond the TME, TMAbs increase the amount of drug reaching the tumor and avoid triggering toxic side effects, including cytokine release syndrome.

The Result

This enables antibodies to reach their intended targets (immunosuppressive proteins on macrophages and other myeloid cells immediately surrounding the tumor) without interacting with corresponding targets in the bloodstream and other body compartments.

The Outcome

By blocking checkpoints and diminishing other sources of immunosuppression in the tumor microenvironment, TMAbs encourage T cell penetration and killing activity, turning these cold, T cell-excluded tumors hot.

Presentations

CICON 2023: Preclinical data for SNS-101

SNS-101, a clinical-stage pH-dependent and TME-selective anti-VISTA antibody with favorable pharmacokinetic and safety characteristics, promotes anti tumoral M1 macrophage polarization in PD-1 refractory settings

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