Back to the drawing board for Molecular Templates

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Takeda’s decision to give up on the Molecular Templates-originated TAK-169 makes sense given the competitive nature of the molecule’s target, CD38, but it will raise doubts over the junior partner’s approach. This technology revolves around so-called engineered toxin bodies (ETBs), which comprise toxic payloads fused to antibody-derived binding domains, resulting in smaller and possibly more tumour penetrative constructs than typical antibody-drug conjugates. This seems an attractive proposition, but unfortunately ETBs have yet to deliver a knockout blow clinically, and Takeda’s move follows months of stalling: TAK-169 was to have delivered efficacy data last year, but its trial has only enrolled four subjects. Molecular Templates stock fell 24% yesterday as the group also switched its focus to second-generation ETBs; MT-3724, a first-gen ETB that had been put on clinical hold after a treatment-related death, has now been discontinued. It will not help sentiment that TAK-169 is a second-generation construct, and that one of the four subjects treated with it experienced dose-limiting, grade 2 myocarditis. The patient had had multiple pre-existing cardiac risk factors, so this could well be unrelated to TAK-169, but the overwhelming question for investors is whether the ETB approach is quite ready for prime time.

Molecular Templates' R&D pipeline
Project Target ETB type Features Status
MT-3724 CD20 1st gen Wild-type toxin + targeting ScFv domain Discontinued after ph2 was put on clinical hold
MT-5111 Her2 2nd gen Engineered toxin + targeting ScFv domain Ph2 starting May 2021
TAK-169 CD38 2nd gen Engineered toxin + targeting ScFv domain Ph1; Takeda handed back rights
MT-6402 PD-L1 3rd gen Engineered toxin + targeting ScFv domain + antigen seeding Ph1 starting May 2021
TBD CTLA-4 2nd gen* Engineered toxin + targeting ScFv domain 1 of 5 constructs to start clinical trials in 2021
TBD CS1 2nd gen* Engineered toxin + targeting ScFv domain Preclinical
TBD CD45 2nd gen* Engineered toxin + targeting ScFv domain Preclinical
TBD CD20 2nd or 3rd gen TBD Preclinical
Source: company filings. Note: *according to preclinical posters. ETB=engineered toxin body.

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