Ann: Appendix 4C and Quarterly Update, page-33

Hi all,

Another seemingly failure for a MND treatment. Denali collaboration with Takeda. Takeda paid at least $150 million up front.

January 2022, the FDA placed a clinical hold on Denali’s investigational new drug application for DNL919 in the U.S., pending clarification of questions regarding the preclinical toxicology, clinical trial protocol, informed consent form, and investigator brochure (press release, SEC disclosure).

In July 2022, Denali began a Phase 1 study in the Netherlands, to assess safety, tolerability, pharmacokinetics, and target engagement after single ascending doses of DNL919 in 80 healthy participants.

On August 8, 2023, Denali announced that the company and Takeda had stopped development of DNL919 (press release).

According to the release, DNL919 altered multiple microglial biomarkers, such as CSF1R, SPP1, IL1RA, IP10, MIP1b, MCP-1, indicating target engagement. It caused no serious adverse events, but did trigger moderate, reversible hematological changes at the highest dose tested.

A news report cited Denali executives who said the antibody caused anemia.

Kpax