Denali Therapeutics Inc (NASDAQ:DNLI) provided an update on Phase 1b trial findings involving its RIPK1 small molecule inhibitor used to target ALS and Alzheimer’s disease.
Delani has been running the RIPK1 program in partnership with Sanofi SA (NASDAQ:SNY). RIPK1 is a threonine-protein kinase 1 that is a vital signaling protein within the TNF receptor pathway, which regulates cell death and inflammation in body tissues. The major update that the company was releasing on June 6 focuses on data collected from 31 patients involved in the Phase 1b studies. The data was collected over a period of 29 days.
“Together with our partner Sanofi, we have decided to pause clinical studies with DNL747 and focus our efforts on accelerating development of DNL788, which we believe has superior drug properties and a more rapid path toward proof-of-concept clinical studies in patients in multiple neurological indications,” stated Denali CEO Ryan Watts.
The data collected from the study indicates that DNL747 was well tolerated and safe in the dose that was administered to the patients. Patients did not show any significant adverse effects related to the treatment. The study’s findings also indicate that the researchers achieved the 80% target engagement in pRIPK1 median inhibition.
The toxicity findings from a parallel toxicity study introduced some challenges.
Denali and Sanofi also conducted parallel studies to determine chronic toxicity, through which they administered doses of DNL747 in cynomolgus monkeys. The findings from the toxicity study showed that there were notable adverse effects at doses higher than those administered in pre-clinical studies. The adverse effects were dependent on the administered dosage and the duration of the dosage.
The toxicity findings mean that the researchers will not pursue a dosage increase to achieve more target inhibition. It also means that Denali will have to spend additional time conducting clinical studies to determine the long-term safety and efficacy of the treatment in patients.
Despite the drawback of the toxicity findings, Carole Ho, Denali’s Chief Medical Officer, stated that the recent study’s DNL747 biomarkers have produced encouraging results. The findings are an important step forward for research that will help patients suffering from ALS and Alzheimer’s disease in the future. The findings from the RIPK1 indicate that the research is still on the right track.