Molecular Templates is pioneering a new class of therapeutics known as engineered toxin bodies (ETBs), which represent a significant advancement in the field of immunotoxins. ETBs are designed to target specific receptors on tumor cells, enabling them to induce their own internalization and effectively destroy cancer cells that may be resistant to traditional treatment modalities. This innovative approach combines the specificity of antibodies with the potent cell-killing mechanism of a genetically engineered version of the Shiga-like Toxin A subunit (SLTA). The unique biology of ETBs allows for predictable pharmacokinetic and pharmacodynamic profiles, and they have demonstrated a favorable safety profile in clinical trials.

The company is actively developing a pipeline of ETBs targeting critical receptors in oncology, with candidates such as MT-6402 and MT-0169 currently in clinical trials. MT-6402 is a third-generation ETB that targets PD-L1 on solid tumors and incorporates antigen-seeding technology to enhance T-cell recognition of tumor cells. Meanwhile, MT-0169 is a second-generation ETB targeting CD38 in multiple myeloma, designed to minimize immunogenicity while effectively inducing cell death. Molecular Templates is committed to advancing these therapies through rigorous clinical development and has established a cGMP manufacturing facility to support their clinical trial needs.

United States

Molecular Templates is a clinical-stage biopharmaceutical company focused on the discovery and development of the next generation of immunotoxins called engineered toxin bodies (ETBs) which are a novel class of therapeutics with unique biology and a differentiated mechanism of action. ETBs are targeted, are designed to induce their own internalization, even against non-internalizing receptors, and destroy tumor cells that are resistant to other modalities. ETBs have been well-tolerated in the clinic to date and show predictable pharmacokinetic and pharmacodynamic effects.

Cancer

Molecular Templates

Solid tumor/s

MT-6402 is an ETB consisting 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 MTEM’s preclinical studies, MT-6402 was found to specifically bind and kill both tumor and immune PD-L1 expressing cells in a manner consistent with SLTA mediated cellular cytotoxicity through ribosomal inactivation, independent of checkpoint inhibition. Additionally, MT-6402 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. Third, 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.

MT-6402

MT-8421 was designed to target CTLA-4 in a wholly distinct manner from the current monoclonal antibody approaches. MT-8421 was designed to eliminate CTLA-4-expressing Tregs in the TME through a direct cell-kill mechanism independent of the effector cell presence that antibodies rely upon.
MT-8421 was also designed to avoid CTLA-4 blockade in the periphery, the major mechanism of antibody-mediated autoimmune toxicity.

MT-8421

Hematologic malignancies

MT-0169 is designed to destroy CD38+ tumor or immune cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and ER stress). In ex vivo cell kill assays, MT-0169 shows potency against plasma cells with IC50 activity in the picomolar or femtomolar range. Plasma cells are exceptionally sensitive to ER stress, making them uniquely susceptible to the MT-0169 mechanism of action. MT-0169 also shows potent activity against T-cells that express low levels of CD38. HLA-DR CD38+ T-cells have been implicated in many immune-mediated diseases.

MT-0169

Breast cancer

MT-5111 is a second generation engineered toxin body (ETB) consisting of a single-chain variable fragment (scFv) with an affinity for HER2, fused to the enzymatically active de-immunized Shiga-like toxin-A subunit (SLTA). MT-5111 specifically binds and kills HER2 expressing cells in a manner consistent with SLTA mediated cellular cytotoxicity.

MT-5111

Diffuse large B cell lymphoma

MT-3724, is a first generation ETB that targets CD20, a B-cell marker that is expressed in 90 percent of B-cell non-Hodgkin’s lymphoma (NHL).

MT-3724 with GEMOX (CD20) 

Extramedullary myeloma

Multiple myeloma

TAK-169 is a second generation engineered toxin body (ETB) that is a single-chain variable fragment (scFv) with an affinity for CD38, fused to the enzymatically active de-immunized Shiga-like toxin-A subunit (SLTA). TAK-169 specifically binds and kills CD38 expressing cells consistent with SLTA mediated cellular cytotoxicity. TAK-169 is being developed through a collaboration with Takeda Pharmaceuticals.

Molecular Templates

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