Takeda has decided to end its partnership with Denali Therapeutics, returning all rights to a dementia drug program back to the California-based biotech, according to an April 6 announcement. The decision follows more than eight years of collaboration between the two companies.
Denali said in a document filed with the Securities and Exchange Commission on April 3 that Takeda's decision "was driven by strategic considerations" and "is not related to efficacy or safety data." Takeda notified Denali of its choice on the same day, according to the filing.
The partnership began in January 2018 when Takeda provided $150 million upfront and agreed to potential milestone payments. Over time, both companies worked together on several projects, including DNL919—a TREM2 agonist for Alzheimer's disease—which faced challenges such as a clinical hold by the Food and Drug Administration in January 2022. Although that hold was later lifted, development was discontinued in August 2023 due to Phase 1 results indicating a "narrow therapeutic window."
In addition, Takeda had previously exercised an option in 2021 to co-develop DNL593, a protein replacement therapy designed for frontotemporal dementia that can cross the blood-brain barrier. On April 3, Denali announced it had regained full rights over DNL593. Chief Executive Officer Ryan Watts said in a press statement: “We are looking forward to advancing DNL593 independently,” adding that they “remain[s] confident” in its scientific rationale.
DNL593 aims to replace progranulin protein deficiencies seen in frontotemporal dementia patients—a deficiency leading to lysosomal defects and toxic buildup across tissues. The therapy is currently being evaluated in a Phase 1/2 study involving forty participants; so far no safety issues have been reported by Denali.
Looking ahead, Watts said Phase 1/2 data for DNL593 are expected before year-end. The news comes shortly after Denali secured approval from the FDA for Avlayah—its Hunter syndrome therapy—marking it as the first new treatment for this rare disease’s neurologic complications approved by regulators in nearly two decades.
