Subasumstat

Dive Brief:Takeda plans to simplify how its workforce is organized, cut spending and slim down its drug pipeline in a restructuring aimed at improving its profit margin over the next several years.The Japanese pharmaceutical company revealed its plans alongside earnings for the 2023 fiscal year, which showed a sharp decline in operating profit compared to the prior year. Patents protecting some of Takedas top-selling and high-margin drugs, like the ADHD medication Vyvanse, have recently expired, putting pressure on the companys finances.Takeda estimates it will incur about $900 million in restructuring costs during the coming fiscal year, which runs from April to March. The company aims to to improve its core operating profit margin by 1% to 2.5% each year from 2025 on, targeting an eventual range in the low-to-mid 30%.Dive Insight:Takeda has good company in restructuring its business, joining other large pharmas like Bristol Myers Squibb, Bayer, Sanofi and Novartis that have recently cut back on spending, laid off staff or reprioritized their research.In Takedas case, the company is pruning an array of early-stage drug programs to focus investment on late-stage assets it expects to become large sellers, like an inflammatory disease drug it acquired from Nimbus Therapeutics.As we look ahead to FY2024, we anticipate having up to six programs in Phase 3 development, said Takeda CEO Christophe Weber, in a company statement. Advancing these promising therapies through late-stage development while moderately increasing our biopharma R&D investment is requiring rigorous prioritization, efficiencies and organizational agility.Among the drugs affected by Takedas prioritization are three mid-stage cancer therapies: modakafusp alfa, subasumstat and the cell therapy TAK-007. Development of the latter drug in blood cancers will be shuttered, and work instead shift to autoimmune conditions a pivot that many companies involved in cell therapy are now making.In all, 18 drug programs have now been cut from Phase 1 or Phase 2 testing, although some, like TAK-007, will continue to be developed in other indications. That's up from 11 programs listed in a February presentation as removed from those stages.Alongside the R&D prioritization, Takeda plans to invest further in what it terms data, digital and technology, and cut back on external spending in areas like supply chain and third-party vendors.The company said it would share further details and timing of specific actions in due course.As we work to bring these initiatives to fruition, difficult choices will be required and some employees will be impacted as a result, Takeda said in a statement emailed to BioPharma Dive. However, we do not have a specific number to share, as the changes being made will look different across Takeda and will be phased according to unique business needs and country requirements.While loss of exclusivity for drugs like Vyvanse has hurt Takeda, the company anticipates it will have limited exposure to such risks moving forward, at least until the early 2030s. As a result, it expects to be able to return to revenue and profit growth from the 2025 fiscal year onward.Editors note: This story has been updated with comment from Takeda. '

Takeda’s pipeline cull affected assets outside of oncology. 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, 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.