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Takeda drops cancer candidates, axing immunocytokine and CAR-Ts amid shifting treatment landscape

Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday, when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline.

Under CEO Christophe Weber, Takeda has worked to establish itself as a leader in oncology. But, as the executive said on a quarterly results call with investors, the company has “had some wins … [and] some setbacks.” The results brought news of more setbacks, with Takeda using the update to reveal it has dropped a clutch of cancer candidates led by modakafusp alfa.

Formerly known as TAK-573, modakafusp alfa consists of two interferon alpha-2b molecules fused to an anti-CD38 monoclonal antibody. The idea was to activate innate and adaptive immune cells, while also directly stopping the proliferation of multiple myeloma cells, through targeted interferon signaling.

Takeda began a phase 1/2a Darzalex combination trial one year ago, adding to the slate of studies run in support of the immunocytokine, but has now pulled the plug on the program. Andrew Plump, M.D., Ph.D., president of R&D at Takeda, explained the decision on the conference call with investors. 

“This is a strategic decision based on a number of factors, including the existing data set, the rapidly evolving multiple myeloma treatment landscape and the long development timelines,” the R&D chief said. 

Takeda pushed modakafusp alfa out of the door as part of a pipeline clear out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, the GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy.

While Takeda axed a clutch of cancer candidates, Plump said the company “remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.” The R&D chief highlighted the SUMO inhibitor subasumstat, a pair of STING agonists and two T-cell engagers from the Maverick Therapeutics acquisition as candidates to watch. 

Plump also cited the appointment of PK Morrow, who joined Takeda from CRISPR Therapeutics last month, as a boost for the oncology unit. Morrow became head of the oncology therapeutic area unit at Takeda having previously worked as chief medical officer of CRISPR and held various roles at Amgen.

Takeda’s pipeline cull also affected assets outside of oncology. The drugmaker removed three phase 2 drug candidates, namely the rare disease asset TAK-611—which flunked a trial last year—the Parkinson’s disease prospect TAK-071 and the depression molecule TAK-041. In phase 1, Takeda axed treatments for Alzheimer’s disease and nausea, as well as a Zika vaccine candidate.

Amid the changes, Takeda grew its R&D spend by 7.3%, although Chief Financial Officer Costa Saroukos said that “does reflect some phasing” and the company is still aiming for a mid-single-digit increase over the full year. Saroukos made the comment on what looks set to be his last quarterly results conference call as CFO of Takeda. 

Milano Furuta, president of Takeda’s Japan pharma business unit, is preparing to take over as CFO in April. Saroukos is leaving because “after 20 years working abroad, I’m ready to move back to Australia to be closer to my family,” the outgoing CFO told investors.

https://www.fiercebiotech.com/biotech/takeda-drops-cancer-candidates-axing-immunocytokine-and-car-ts-amid-shifting-treatment

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