On June 17, Molecular Templates announced that the FDA has accepted the Investigational New Drug (IND) application for TAK-169, co-developed with Takeda, for the treatment of relapsed/refractory multiple myeloma.
TAK-169 is an engineered toxin body (ETB) therapeutic composed of a single-chain variable fragment (scFv) with affinity for CD38 fused to a genetically engineered Shiga-like toxin A subunit (SLTA, a ribosome-inactivating bacterial protein [RIP]). It specifically kills CD38-positive tumor cells through SLTA-mediated cytotoxicity. The irreversible inhibition of ribosomes induced by TAK-169, which leads to tumor cell death, occurs intracellularly. Consequently, this process alters the tumor microenvironment, such as by upregulating CD55/CD59. While such effects typically inhibit the antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) activities of antibody therapeutics, they do not affect the activity of TAK-169.
TAK-169 does not compete with daratumumab and other CD38 antibody drugs for the CD38 binding site, can overcome daratumumab resistance, and retains antitumor activity in the presence of daratumumab. Therefore, TAK-169 has the potential to be used in combination with approved CD38 antibody drugs.
Molecular’s proprietary Engineered Toxin Body (ETB) technology platform offers a novel targeted biotherapeutic approach, with multiple Phase I investigational drugs currently in development based on this platform, such as the HER2-targeted MT-5111.
Source: Molecular Templates official website
On September 19, 2018, Molecular Templates announced an agreement with Takeda to co-develop a CD38-targeted engineered toxin body therapeutic for the treatment of multiple myeloma, with TAK-169 as the core candidate drug. Under the terms of the agreement, Takeda will pay Molecular Templates a $30 million upfront payment. If Molecular Templates exercises its option to co-develop, it will be eligible for up to $632.5 million in subsequent development, regulatory, and commercialization milestone payments; if it does not exercise the option or withdraws from co-development, it will be eligible for up to $337.5 million in milestone payments. Takeda also agreed to pay royalties on sales of successfully launched products. Molecular Templates and Takeda will share development costs equally.