Gammadelta Therapeutics Ltd.

Takeda used its latest earnings to disclose that it had dropped a pair of phase 1-stage programs due to “strategic reasons.” \n Takeda has given up on an AstraZeneca-partnered neurological disorder program after the therapy flunked a phase 2 study.The Japanese pharma had been evaluating the alpha-synuclein antibody, called TAK-341 or MEDI1341, in a global study of 159 patients with multiple system atrophy (MSA), a rare condition that\'s caused by a loss of nerve cells in the brain. The midstage trial involved participants receiving intravenous infusions of TAK-341 or placebo every four weeksThe goal of the study was to demonstrate a benefit on the Modified Unified Multiple System Atrophy Rating Scale at Week 52, but Takeda revealed in its third-quarter earnings documents this morning that the study failed to hit its primary or secondary endpoints.This result “does not support further development in MSA,” Takeda concluded in its earnings document.The original agreement with AstraZeneca covered TAK-341’s development for both MSA and Parkinson’s disease, but Takeda’s updated pipeline doesn’t list any Parkinson’s programs. However, the alpha synuclein monoclonal antibody is still listed in AstraZeneca’s own phase 2 pipeline.Takeda also used its latest earnings to disclose that it had dropped a pair of phase 1-stage programs due to “strategic reasons.” They included GDX012, also called TAK-012-1501, an allogeneic gamma delta T-cell therapy the company gained from buying GammaDelta Therapeutics in 2021. Takeda had been evaluating TAK-012-1501 in a phase 1/2 study in patients with acute myeloid leukemia. But the asset’s future had already appeared hazy after Takeda announced earlier this year that the company was putting cell therapies on the back burner. More recently, Takeda unveiled a broader retreat from the cell therapy field.The final program being removed from Takeda’s pipeline plan is the development of danavorexton, also known as TAK-925, for narcolepsy. The orexin-2 receptor agonist remains in phase 2 development for respiratory conditions, but Takeda said it has discontinued the phase 1 work on the drug for narcolepsy “due to strategic considerations.”The decision comes almost exactly a year after the pharma stopped a phase 2 trial of danavorexton in post-anesthesia recovery for patients with obstructive sleep apnea who were at high-risk of developing respiratory complications because of slow enrollment.

Takeda said Thursday it has ended work on several early- and mid-stage drug candidates, adding that its second quarter sales took a hit from “generic erosion” and “unfavourable” exchange rates. The Japanese drugmaker nixed an AstraZeneca-partnered candidate for multiple system atrophy called TAK-341 after it missed the primary and secondary endpoints in a Phase 2 trial, according to a financial report . It also terminated two Phase 1 programs for narcolepsy (TAK-925) and acute myeloid leukemia (TAK-012), citing “strategic considerations.” Takeda obtained TAK-012 as part of its 2021 acquisition of GammaDelta Therapeutics. The cell therapy candidate was one of several programs impacted by Takeda’s broader decision to end all work on cell therapies earlier this month. Elsewhere, the company dropped a MASH asset called TAK-647 as part of a “portfolio prioritization.” The drug was originally developed by Pfizer, which licensed it out to Shire in 2016. Takeda then acquired Shire for $62 billion in 2019. Takeda has been trimming its pipeline as part of a multi-year rehaul designed in part to focus its resources on six late-stage programs that it believes could deliver billions of dollars in sales. These include its narcolepsy candidate, oxeporexton, which had a positive Phase 3 readout in September. The company has also been bulking out its late-stage pipeline through deals, licensing a Phase 3 ADC and a Phase 3-ready bispecific from Innovent for $1.2 billion upfront earlier this month. Meanwhile, Takeda’s Q2 revenues, from July to September, slid about 4% from the same time last year to JPY 2.2 trillion ($14.3 billion). The drop was largely due to weaker sales in the company’s neuroscience franchise, driven by generic competition for its ADHD medicine Vyvanse in the US. Vyvanse sales plummeted about 46% to $692.6 million, while its other ADHD drug Adderall XR declined 33% to $68.8 million. Takeda’s major depressive disorder treatment Trintellix was separately impacted by the redesign of Medicare Part D, with sales down 7% to $370.2 million.

Amidst slumping sales due to generic competition, Takeda cut back full-year expectations in its financial earnings report for the first half of 2025. Shares in the Japanese pharma, which also axed three clinical programmes from its portfolio, fell more than 8% on the New York Stock Exchange on Thursday."Our financial results for the first half of FY2025 were driven by year-over-year impact from generic erosion of Vyvanse, as anticipated," Chief Financial Officer Milano Furuta said. "In the second half, we expect this generic erosion impact to moderate and Growth and Launch Product growth to increase."Takeda reported JPY 106.6 billion ($691.7 million) in revenues for ADHD medication Vyvanse in the first half of the year, down 45.6% year-over-year at a constant exchange rate. The drug's sales seem to be falling faster than expected; the pharma previously projected that revenues would decline around 30% in 2025.In total, the company's revenues for the first half were JPY 2.2 trillion, a 6.9% drop from the same period last year. Takeda slightly moderated its full-year projections on Thursday, which "reflects impairment charges associated with strategic pipeline decisions taken in" the second quarter, CEO Christophe Weber said. The drugmaker recorded an impairment of JPY 58 billion when it discontinued all its cell therapy efforts earlier this month.The pharma now expects revenues of JPY 4.5 trillion, down from JPY 4.53 trillion; a net profit of JPY 153 billion, slightly below previous expectations of JPY 228 billion; and an operating profit of JPY 400 billion, down from JPY 475 billion.Pipeline cuts An asset caught in the crosshairs of Takeda's cell therapy retreat was one programme it confirmed Thursday as having been discontinued: GDX012 (TAK-012), an allogeneic variable delta 1 gamma-delta T-cell therapy gained through its acquisition of GammaDelta Therapeutics in 2021. It had been in Phase I testing for acute myeloid leukaemia. The pharma also cut a second Phase I asset, danavorexton (TAK-925), "due to strategic considerations." The intravenously delivered orexin 2 receptor agonist was once touted as a game-changer in narcolepsy, but seems to have been passed over in favour of oral candidate oveporexton (TAK-861) (see – ViewPoints: With oveporexton at the helm, Takeda’s orexin push gains steam).Takeda recently reported that oveporexton met all of its primary and secondary endpoints in a pair of Phase III studies, impressing physicians and experts alike (see – Physician Views Results: Strong prescriber interest suggests oveporexton could awaken orexin’s long-awaited potential and KOL Views Q&A: Takeda’s oveporexton is raising the bar for narcolepsy drugs, rival orexin agonists).While danavorexton's narcolepsy dreams have ended, the company noted that Phase II studies in respiratory conditions are still under way. The third programme to feel the axe was MEDI1341, also known as TAK-341. Takeda had teamed up with AstraZeneca in 2017 to co-develop the alpha-synuclein antibody in Parkinson's disease. The Japanese pharma was also studying the candidate in multiple system atrophy (MSA); however, it said in a pipeline update that "Phase II trial results did not meet primary and secondary endpoints, which does not support further development in MSA." ($1 = JPY 154.112)($1 = JPY 154.1)