Denali Therapeutics announced that the FDA had placed a clinical hold on the IND application for DNL919 and would receive an official clinical hold letter from the agency in about 30 days.
South San Francisco-based Denali Therapeutics announced that the U.S. Food and Drug Administration had placed a clinical hold on the Investigational New Drug (IND) application for DNL919 (ATV:TREM2). Denali indicated that they would receive an official clinical hold letter from the agency in about 30 days.
On Monday, at the JP Morgan Healthcare Conference, Denali had reported that the IND for DNL919 had been submitted and had hopes of initiating a Phase I trial in the first half of 2022. It also announced that Takeda had exercised its option in December 2021 to co-develop and co-commercialize the drug for the treatment of Alzheimer’s disease.
DNL919 is an Antibody Transport Vehicle (ATV) engineered to activate TREM2 and improve microglial function. TREM2 is a receptor expressed on microglia, which are immune cells of the brain. Genetic mutations in TREM2 that result in loss of function are strongly linked with an increased risk for Alzheimer’s disease. Animal studies have shown enhanced brain uptake with DNL919 compared to a non-ATV TREM2 antibody, as well as improved pharmacodynamic response.
In late November, Takeda has also exercised an option to co-develop and co-commercialize another of Denali’s drugs, DNL593 (PTV:PGRN), an investigational, brain-penetrant progranulin replacement therapy for frontotemporal dementia-granulin (IFTD-GRN). The two companies inked a collaboration deal in January 2018, with Takeda receiving an option for three programs.
“We are excited to advance our collaboration with Takeda on the development of DNL593 as a potential treatment for people with FTD-GRN,” said Ryan Watts, Denali’s Chief Executive Officer, in a November statement. “Pending acceptance of regulatory submissions, DNL593 will be the sixth therapeutic candidate from our broad pipeline, and our second Transport Vehicle (TV)-enabled molecule, in clinical development. This progress underscores the potential of our TV platform technology, which is designed to enable and enhance delivery of biologic therapeutics to the brain for the treatment of neurodegenerative diseases.”
In addition to today’s news about DNL919 and the update on Takeda, Denali reported a broad update at JPM on its pipeline. This includes DNL310 (ETV:IDS), a Phase II/III trial for MPS II (Hunter syndrome), which is expected to start in the first half of this year; BIIB122/DNL151 (LRRK2 inhibitor), which is partnered with Biogen on for Parkinson’s disease. Phase I and Ib trials of the drug have demonstrated robust target and pathway engagement.
Other programs include SAR443820/DNL788 and SAR443122/DNL758 (RIPK1 inhibitors). They are collaborating with Sanofi on developing these drugs for neurogenerative and peripheral inflammatory diseases. Sanofi is initiating a Phase II HIMALAYA trial in amyotrophic lateral sclerosis (ALS) of SAR443820, while Denali is leading preclinical studies of SAR443820 for Alzheimer’s disease. Sanofi is also initiating a Phase II trial of SAR443820 in multiple sclerosis. Sanofi will also evaluate SAR443122 for cutaneous lupus erythematosus (CLE) and start a Phase II trial of the drug in ulcerative colitis.
“We are looking forward to a high impact year in 2022, having accomplished several clinical and regulatory milestones in 2021 as well as further validation of our TV platform for delivery of biotherapeutics to the brain,” stated Watts at JPM. “We are well positioned to deliver in 2022 with our dedicated team, our BBB-crossing platforms and our diversified portfolio of Denali owned and strategically partnered assets. We continue to build our clinical manufacturing and commercial capabilities as well as expand our global footprint.”
