Molecular Templates, Inc.

Technology

Next Generation Immunotoxins

ETBs are a proprietary biologic platform for designing and generating molecules with unique biologic properties for activity in cancer and other serious disease.

Combining the Specificity of an Antibody with the Potent Mechanism of Cell Destruction

ETBs utilize an antibody domain fused to a genetically engineered version of the Shiga-like Toxin A subunit (SLTA), a ribosome inactivating bacterial protein that can induce its own entry into a cell when proximal to the cell surface membrane, self-route to the cytosol, and enzymatically and irreversibly shut down protein synthesis via ribosome destruction resulting in cell death.

Our Differentiated Approach

A New ETB Scaffold for Rapid Screening and Scalable Production

Molecular Templates has created a new modular scaffold featuring the ability to induce targeted internalization, a differentiated mechanism of action, and a predictable PK and ADME profile. ETBs have been well-tolerated in clinical studies to date as monotherapy and in combination with standards of care. 

Continued De-Risking of the ETB Platform

1st Generation ETB:

MT-3724

Ribosome inactivation + forced internalization

MT-3724 is a 1st generation ETB that utilizes wild-type Shiga-like toxin A (SLTA) genetically fused to an scFv to CD20 designed to bind, induce internalization, and destroy CD20-expressing tumor cells through ribosomal inactivation. MT-3724 is the first clinical agent to show rapid and efficient internalization of CD20. In clinical studies, MT-3724 has shown monotherapy activity in heavily pre-treated patients and has been well-tolerated with no life-threatening toxicities observed to date. The dose-limiting toxicity with MT-3724 in the Phase 1 study was grade 2 capillary leak syndrome (CLS), a manifestation of innate immunity. Multiple Phase 2 studies are ongoing.

2nd Generation ETBs:

MT-5111

Ribosome inactivation + de-immunization

MT-5111 is a 2nd generation ETB technology that utilizes a genetically engineered de-immunized Shiga-like toxin A-subunit (SLTA) to reduce the potential for innate and adaptive immunogenicity. MT-5111 is designed to directly kill HER2-positive cells via ribosomal inactivation, a mechanism distinct from approved HER2 targeted agents. MT-5111 binds HER2 in the presence of trastuzumab and pertuzumab, creating the possibility of combining MT-5111 with other HER2 antibody-based agents. MT-5111 is 55 kDa, almost a third smaller than traditional antibody and antibody drug conjugate (ADC) therapies, and, because of its smaller size, may have superior tumor penetration. Dosing of MT-5111 in the Phase 1 study initiated in 4Q19.

2nd Generation ETBs:

 TAK-169

Ribosome inactivation + forced internalization + de-immunization

TAK-169 is a 2nd generation ETB that utilizes a genetically engineered de-immunized Shiga-like toxin A-subunit (SLTA) designed to reduce the potential for innate and adaptive immunogenicity. TAK-169 targets CD38, a poorly internalizing receptor expressed on myeloma cells. TAK-169 directly kills CD38-expressing tumor cells via ribosomal inactivation. Data in non-human primates suggest that TAK-169 can be dosed at higher doses than MT-3724 with a markedly reduced propensity of innate immune response compared with MT-3724. Preclinical data suggest that TAK-169 retains activity in the presence of daratumumab, an approved CD38 antibody. Dosing of TAK-169 Phase 1 study initiated in 1Q20.

3rd Generation ETB:

MT-6402

Ribosome inactivation + forced internalization + de-immunization + antigen-seeding

MT-6402 is a 3rd generation ETB that targets PD-L1, a poorly internalizing receptor expressed on various solid tumors. MT-6402 shares the de-immunized scaffold used with 2nd-generation ETBs and is further engineered to deliver a viral foreign class I peptide (antigen seeding) to alter the tumor immunophenotype. MT-6402 utilizes Antigen Seeding Technology and is designed to deliver a foreign class I viral antigen derived from cytomegalovirus (CMV) inside the tumor for presentation on the tumor cell surface in complex with MHC class I molecules. Pre-clinically, MTEM has shown that antigen seeding allows CMV-reactive T-cells to recognize and destroy tumor cells. T-cell response provides a mechanism of cell kill that is complementary to the ribosomal inactivation caused by the SLTA. An IND is expected to be filed for MT-6402 in 2H20.

Manufacturing Capabilities

Manufacturing Capabilities

Molecular Templates has built and operates a multi-product cGMP manufacturing facility in Austin, TX to supply clinical trial materials for internal and partnered ETB programs.

Posters

Posters

Learn more about our latest clinical developments.

View Posters