US-based biopharmaceutical company Denali Therapeutics Inc., (NASDAQ: DNLI) has announced in its Q2 2023 financial report that, in mutual agreement with development partner Takeda Pharmaceutical Co., Ltd (NYSE: TAK), the decision has been made to cease development of the Alzheimer’s drug candidate TAK-920/DNL919. This strategic decision was influenced by data from a Phase I trial and the rapidly evolving treatment landscape for Alzheimer’s disease.
Background on the Partnership and Drug Candidate
Contrasting with recently approved amyloid-targeted Alzheimer’s drugs, DNL919 is an Antibody Transport Vehicle (ATV)-enabled TREM2 agonist designed to enhance microglial function. The two companies initially partnered in 2018 to explore three different targets for neurodegenerative disorders and established a full collaboration on DNL919 in 2021.
Phase I Data and Decision Factors
According to sources, Phase I data demonstrated the molecule’s “robust target engagement and effects on microglial biomarkers”. However, safety signals indicated “moderate, reversible hematologic effects”, suggesting that the drug would likely have “a narrow therapeutic window for the Alzheimer’s disease patient population”, specific to the properties of DNL919 and TREM2 biology.
Refocusing Efforts on Backup Molecules and Combination Therapies
The two firms will continue their work in the field, redirecting efforts towards preclinical back-up molecules and exploring potential combination therapies. This shift comes in light of recent new drug approvals in Alzheimer’s disease, hinting at a possible future strategy involving an amyloid-targeted combination approach.-Fineline Info & Tech
