Takeda has shot down candidates acquired in its $525 million Maverick Therapeutics takeover, blowing a hole in its oncology R&D pipeline in the process. The two terminations, coupled to the removal of a third asset, halved (PDF) the number of cancer candidates in Takeda’s phase 1 and 2 pipeline.
Japan-based Takeda began working with Maverick in 2017, when it invested $125 million for an exclusive option to buy the T-cell engager specialist. The “build-to-buy” alliance came to fruition in 2021. Takeda agreed to pay up to $525 million to buy Maverick, bagging drug candidates for treating solid tumors that express EGFR or B7-H3.
The company axed the EGFR and B7-H3 programs from its pipeline Thursday in its fourth-quarter financials update. Takeda took 27.8 billion Japanese yen ($192 million) in charges in relation to the terminations, causing its impairment losses on intangible assets associated with products to come in almost twice as high as expected. A Takeda spokesperson provided a statement on the terminations.
"We continue to make data-driven decisions to maintain focus on our most promising pipeline programs. These decisions allow us to pivot resources and rapidly advance development of our six late-stage programs," the spokesperson said.
TAK-186, a T-cell engager designed to bind to EGFR, was the more advanced of the two drug candidates. The bispecific was in the phase 2 portion of a phase 1/2 solid tumor trial when Takeda pulled the plug. Takeda began the trial in 2021. The company stopped enrolling patients, more than 160 subjects short of its target, earlier this year.
TAK-280, a T-cell engager designed to bind to B7-H3, entered the clinic in 2022. Takeda stopped enrolling patients in the trial, again well short of its target, earlier this year. Like TAK-186, TAK-280 used Maverick’s prodrug technology to restrict activation to the tumor microenvironment.
Takeda axed another solid tumor candidate, the STING agonist dazostinag, from its phase 2 pipeline. The small molecule entered the clinic in 2020 and got as far as the phase 2 portion of a trial that was testing it in combination with Merck & Co.’s blockbuster oncology drug Keytruda before Takeda deemed it surplus to requirements.
The three removals halved the size of Takeda’s phase 1 and 2 oncology pipeline. Takeda’s phase 2 cancer pipeline now consists of elritercept, an activin inhibitor it paid $200 million for in December, and life cycle management work on mirvetuximab. The company has one candidate, the acute myeloid leukemia cell therapy TAK-012 in phase 1, but its pullback from the modality has raised questions about the program.
Takeda also removed trials of danavorexton, zamaglutenase and TAK-653 from its phase 2 pipeline. The company stopped a phase 2 trial of danavorexton, an orexin-2 receptor agonist also known as TAK-925, in certain patients in post-anesthesia care units in October over slow enrollment. Takeda has removed a phase 2 post-anesthesia recovery trial from its pipeline.
Zamaglutenase, also known as TAK-062, is a celiac disease prospect that Takeda acquired in its $330 million PvP Biologics buyout in 2020. Takeda completed a phase 2 trial of zamaglutenase late last year. The company, which has gone after the condition from multiple angles, still has two celiac disease drug candidates in phase 2 development.
Finally, Takeda removed TAK-007 and TAK-500 from its phase 1 pipeline. STING agonist TAK-500 quietly vanished from the Takeda’s consolidated pipeline earlier in its financial year but was only listed among the removed trials in the latest update. TAK-007 is a CD19-targeted CAR-NK therapy that Takeda stopped developing in B-cell malignancies last year before briefly exploring its use in autoimmune indications.