Molecular Templates, Inc.


Delivering Dual Mechanisms of Action to Directly Target Tumors Expressing PD-L1

MT-6402 is a third generation engineered toxin body (ETB) that consists of a single chain variable fragment (scFv) with affinity for PD-L1, fused to the enzymatically active de-immunized Shiga-like toxin-A subunit (SLTA) and a class I antigen derived from the human cytomegalovirus (HCMV) pp65 protein. MT-6402 was designed to induce potent anti-tumor effects via PD-L1 targeting through multiple mechanisms that may overcome the limitations of the PD-L1 antibodies.

In preclinical studies, MT-6402 specifically binds and kills both tumor and immune PD-L1 expressing cells in a manner consistent with SLTA mediated cellular cytotoxicity through ribosomal inactivation, independent of checkpoint inhibition.

MT-6402 also alters the immunophenotype of targeted cells by delivering foreign class I antigen from CMV for presentation in complex with MHC class I, which may provoke a CMV-specific immune response against the targeted cells. MT-6402 may rehabilitate the tumor microenvironment (TME) and allow for immune recognition of tumors by destroying PD-L1-expressing immune cells in the TME through ribosomal inactivation.

Program Partner Indication (Target) Preclinical Phase 1 Phase 2 Phase 3 Next Stage
MT-6402 Multiple - solid tumors (PD-L1)
Preclinical Phase complete
Phase 1 Phase in progress
Phase 2 Phase not started
Phase 3 Phase not started

Key Benefits

A Promising ETB Targeting PD-L1

  • MT-6402’s dual mechanisms of action include enzymatic destruction of ribosomes and Antigen Seeding Technology whereby MT-6402 delivers a viral class I antigen payload derived from CMV (pp65) into the targeted tumor to change the immunophenotype of the tumor to be targeted by antigen-specific T-cells.  
  • MT-6402’s antigen seeding CMV pp65 payload covers the largest MHC haplotype in the United States.
  • Further engineered to reduce or eliminate the propensity for innate immunity.

Clinical Overview

The IND for MT-6402 was accepted in January 2021. A Phase I study of MT-6402 in checkpoint inhibitor relapsed/refractory patients initiated in July 2021.