Molecular Templates today announced that they have convinced main shareholder Takeda to enter into a joint development of a CD38-targeted engineered toxin body (ETB). The collaboration combines Molecular Templates’ innovative Shiga-Like Toxin platform with Takeda’s epitope design skills. Molecular Templates is already testing a first generation drug candidate called MT-3724, which targets CD20, in the clinic but so far with mixed success. Looking at this year’s ASCO release, one of the main issues are side effects probably caused by innate immune reaction due to the activation of TLR4. That should not come as a surprise, given the bacterial origin of Shiga-Toxin. Molecular Template now seems to have overcome this immunogenicity well enough in order to convince Takeda to enter into collaboration.
Indeed, Molecular Templates’ approach has some intriguing properties. Like the toxin itself, the Shiga-Like toxin subunit of the engineered drug features a forced self-internalization mechanism. This means that the technology can be used to deliver a toxic payload via poorly internalizing domains like for example CD38, where conventional antibody drug conjugate approaches would fail. With MT-4019, Molecular Templates already has a CD38 targeting candidate in its pipeline but due to Takeda’s superior antibody design capabilities, it has now opted for the joint development project. One main advantage it seems is that Takeda’s antibody targets a different epitope of CD38 than Daratumumab, which of course will be a huge advantage when positioning the drug.
All in all, it seems that the collaboration with Takeda rubber stamps the whole ETB platform and given the versatility of the approach, more promising programs might follow from this innovative platform.