- Phase 1 healthy volunteer study of DNL747 meets all endpoints, including CSF exposure levels, RIPK1 inhibition, and pathway engagement, at doses that were safe and well tolerated
- Data from the Phase 1 healthy volunteer study of DNL747 will be presented at Denali’s upcoming R&D Day on December 10, 2018
- Denali and partner Sanofi plan to evaluate DNL747 in clinical studies for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)
SOUTH SAN FRANCISCO, CA, USA I November 19, 2018 I Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates for neurodegenerative diseases, today announced positive results from its Phase 1 healthy volunteer study of DNL747, a brain penetrant small molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). RIPK1 is a critical signaling protein in the tumor necrosis factor receptor pathway and is a regulator of inflammation and cell death in tissues throughout the body.
In a randomized, double blind, placebo-controlled, oral dose study in 56 healthy subjects who received either single or multiple ascending doses or placebo, DNL747 achieved its safety, pharmacokinetic, and pharmacodynamic objectives. DNL747 was generally well tolerated with no serious adverse events at doses that achieved high levels of brain exposure and robust target engagement as measured by a blood-based biomarker of RIPK1 activity.
Denali recently announced a broad collaboration with Sanofi on the development of multiple RIPK1 inhibitor molecules, including DNL747, to study their potential to treat a range of neurological and systemic inflammatory diseases.
“The data generated in this study provides a solid foundation for rational dose selection for future clinical trials. We are excited that we are able to achieve near complete inhibition of RIPK1 activity at doses that are well tolerated in healthy subjects. We look forward to working with our partner Sanofi to initiate patient studies in Alzheimer’s disease, ALS, and MS shortly,” said Carole Ho, M.D., Chief Medical Officer.
In addition to DNL747, Sanofi and Denali are pursuing several other compounds, including DNL758, a RIPK1 inhibitor acting peripherally without meaningful blood-brain barrier penetration, for systemic inflammatory diseases. Sanofi intends to initiate clinical trials with DNL758 in 2019.
Clinical data from the Phase 1 study with DNL747 will be presented at Denali’s R&D Day which will take place on December 10, 2018 in New York City. The R&D Day will also include updates on Denali’s LRRK2 program, pipeline and its blood-brain barrier platform. A live webcast will be available on the company’s website at www.denalitherapeutics.com.
About Denali
Denali is a biopharmaceutical company developing a broad portfolio of therapeutic candidates for neurodegenerative diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the blood-brain barrier and guiding development with biomarker monitoring to demonstrate target engagement and select patients. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com.
SOURCE: Denali Therapeutics
Post Views: 95
- Phase 1 healthy volunteer study of DNL747 meets all endpoints, including CSF exposure levels, RIPK1 inhibition, and pathway engagement, at doses that were safe and well tolerated
- Data from the Phase 1 healthy volunteer study of DNL747 will be presented at Denali’s upcoming R&D Day on December 10, 2018
- Denali and partner Sanofi plan to evaluate DNL747 in clinical studies for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)
SOUTH SAN FRANCISCO, CA, USA I November 19, 2018 I Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates for neurodegenerative diseases, today announced positive results from its Phase 1 healthy volunteer study of DNL747, a brain penetrant small molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). RIPK1 is a critical signaling protein in the tumor necrosis factor receptor pathway and is a regulator of inflammation and cell death in tissues throughout the body.
In a randomized, double blind, placebo-controlled, oral dose study in 56 healthy subjects who received either single or multiple ascending doses or placebo, DNL747 achieved its safety, pharmacokinetic, and pharmacodynamic objectives. DNL747 was generally well tolerated with no serious adverse events at doses that achieved high levels of brain exposure and robust target engagement as measured by a blood-based biomarker of RIPK1 activity.
Denali recently announced a broad collaboration with Sanofi on the development of multiple RIPK1 inhibitor molecules, including DNL747, to study their potential to treat a range of neurological and systemic inflammatory diseases.
“The data generated in this study provides a solid foundation for rational dose selection for future clinical trials. We are excited that we are able to achieve near complete inhibition of RIPK1 activity at doses that are well tolerated in healthy subjects. We look forward to working with our partner Sanofi to initiate patient studies in Alzheimer’s disease, ALS, and MS shortly,” said Carole Ho, M.D., Chief Medical Officer.
In addition to DNL747, Sanofi and Denali are pursuing several other compounds, including DNL758, a RIPK1 inhibitor acting peripherally without meaningful blood-brain barrier penetration, for systemic inflammatory diseases. Sanofi intends to initiate clinical trials with DNL758 in 2019.
Clinical data from the Phase 1 study with DNL747 will be presented at Denali’s R&D Day which will take place on December 10, 2018 in New York City. The R&D Day will also include updates on Denali’s LRRK2 program, pipeline and its blood-brain barrier platform. A live webcast will be available on the company’s website at www.denalitherapeutics.com.
About Denali
Denali is a biopharmaceutical company developing a broad portfolio of therapeutic candidates for neurodegenerative diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the blood-brain barrier and guiding development with biomarker monitoring to demonstrate target engagement and select patients. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com.
SOURCE: Denali Therapeutics
Post Views: 95
