US-based biopharmaceutical firm Denali Therapeutics has started dosing patients with its investigational drug DNL747 in a Phase Ib clinical trial for the treatment of Alzheimer’s disease.
DNL747 is designed to target the receptor-interacting serine / threonine-protein kinase 1 (RIPK1) protein, which is associated with signalling in the TNF receptor pathway that controls inflammation and cell death in tissues.
Denali is developing various RIPK1-targeting molecules in collaboration with Sanofi, including DNL747 for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis.
The randomised, double-blind, placebo-controlled, cross over Phase Ib trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics of oral DNL747 doses in up to 26 patients over 28 days.
The trial will also evaluate target and pathway engagement biomarkers in the cerebrospinal fluid (CSF) and blood.
Primary outcome measures of the study are the proportion of patients with treatment-emergent adverse events (AEs) and serious adverse events (SAEs), clinically significant neurological examination abnormalities, and laboratory test abnormalities.
Results from the trial are expected in the fourth quarter of this year.
Denali Therapeutics chief medical officer Carole Ho said: “We are excited to advance DNL747 in a second neurodegeneration indication based on Phase I healthy volunteer data regarding DNL747’s safety profile, CNS penetration, and target engagement, at the studied doses.
“Similar to our previously announced Phase Ib study in ALS, the primary purpose of this Phase Ib study is to gain additional safety and biomarker data in patients with Alzheimer’s disease to support dose selection.”
The company commenced dosing in the 28-day, randomised, double blind, placebo controlled Phase Ib trial of DNL747 for ALS in January this year.