MT-6402

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

Completed

In-progress

Planning

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.