Denali Therapeutics Announces Achievement of RIPK1 Milestone for Phase 2 Clinical Trial Initiation in Multiple Sclerosis by Sanofi
- Category: Small Molecules
- Published on Thursday, 26 January 2023 11:03
- Hits: 3452
- Partner Sanofi has commenced dosing in a Phase 2 clinical trial of SAR443820 (DNL788) in individuals with multiple sclerosis
- Denali to receive a milestone payment of $25 million from Sanofi for Phase 2 clinical trial initiation
- Development of RIPK1 inhibitor program continues in a broad range of central nervous system and peripheral inflammatory conditions
SOUTH SAN FRANCISCO, CA, USA I January 25, 2023 I Denali Therapeutics Inc. (Nasdaq: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier for the treatment of neurodegenerative diseases and lysosomal storage diseases, today announced that its partner Sanofi has commenced dosing in a Phase 2 study of SAR443820 (DNL788) in individuals with multiple sclerosis. SAR443820 is a central nervous system (CNS)-penetrant investigational small molecule inhibitor of RIPK1.
“Multiple sclerosis is a chronic and disabling, inflammation-mediated neurodegenerative disease with limited treatment options that target disease progression1,” said Nazem Atassi, M.D., Global Head of Early Neurology Development at Sanofi. “RIPK1 inhibition with SAR443820 is a novel therapeutic approach that may reduce inflammation and cell death associated with disease progression in multiple sclerosis. SAR443820 has demonstrated robust target engagement and CNS penetration at doses that were generally well tolerated in Phase 1 studies in healthy volunteers, and we are eager to learn more from this Phase 2 study of SAR443820 in multiple sclerosis as we strive to bring innovative therapies to people with unmet medical needs.”
“Following the initiation of the Phase 2 HIMALAYA study in ALS with SAR443820 last year by Sanofi, this Phase 2 study in multiple sclerosis marks another important milestone for our RIPK1 program,” said Carole Ho, M.D., Chief Medical Officer at Denali. “We look forward to collaborating with Sanofi as we aim to make a meaningful difference for individuals living with neurodegenerative diseases by delivering novel treatment options.”
About SAR443820 and Sanofi RIPK1 Inhibitor Collaboration
In 2018, Denali and Sanofi entered into a broad partnership for the global development and commercialization of CNS-penetrant and peripherally restricted RIPK1 inhibitors. RIPK1 is a critical signaling protein in a canonical inflammatory and cell death pathway. Increased RIPK1 activity in the brain drives neuroinflammation and cell necroptosis and contributes to neurodegeneration. RIPK1 inhibition has been shown to have beneficial effects in preclinical models of amyotrophic lateral sclerosis (ALS), multiple sclerosis, Alzheimer's disease, and other diseases.
SAR443820 is a CNS-penetrant RIPK1 inhibitor and was discovered by Denali scientists. Sanofi leads Phase 1 and Phase 2 development of SAR443820 for ALS and multiple sclerosis and leads co-development of SAR443820 with Denali in Phase 3 clinical trials for ALS, multiple sclerosis and Alzheimer’s disease. Sanofi completed a Phase 1 trial of SAR443820 in healthy volunteers in which robust target engagement was demonstrated at doses that were generally well tolerated. Based on these results, Sanofi initiated the HIMALAYA global Phase 2 study of SAR443820 in ALS in 2022, with an anticipated enrollment of approximately 260 participants.
Under the collaboration agreement, Denali will receive a milestone payment of $25 million from Sanofi for initiation of the Phase 2 study with SAR443820 in multiple sclerosis. Denali is entitled to receive additional development and regulatory milestone payments. Denali will share profits and losses equally with Sanofi for CNS-penetrant products sold in the United States and China, and Denali is entitled to receive royalties on net sales for CNS-penetrant products sold outside of the United States and China.
Sanofi is also conducting two Phase 2 clinical studies with another RIPK1 inhibitor, SAR443122 (eclitasertib; DNL758), in cutaneous lupus erythematosus and ulcerative colitis. SAR443122 (eclitasertib) is a peripherally restricted RIPK1 inhibitor and was discovered by Denali scientists. Sanofi is responsible for the development and commercialization of SAR443122 (eclitasertib) and covers all costs related to the program. Denali is entitled to receive development, regulatory and sales milestone payments and royalties on product sales.
SAR443820 and SAR443122 (eclitasertib) are investigational therapeutics that have not been approved by any regulatory authority for any commercial use.
About Denali Therapeutics
Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier for neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the blood-brain barrier and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com.
SOURCE: Denali Therapeutics