The annual JP Morgan HealthCare conference is the time many biotech companies use to announce pipeline development, and Denali Therapeutics used its speaking time to make a noteworthy conference: Partner Takeda Pharmaceuticals exercise its option Co-development of an Alzheimer’s disease drug candidate that is undergoing first-in-human trials. But the day after the announcement, the FDA informed the company that its application to continue the study was on hold.
Denali disclose Clinical trial on Thursday. The company didn’t provide additional details, and it probably doesn’t have any. The notice was emailed Wednesday night, according to South San Francisco-based Denali, which said a formal letter would be sent within 30 days.
When clinical pauses occur, they are usually caused by patient injury or by risks observed while the study is being conducted. However, the FDA can also suspend investigational new drug applications that are still under review. This step may mean that the agency has some questions or wants more details about some aspect of the clinical trial program. The FDA can have many problems with therapies that cross the blood-brain barrier to deliver therapeutic payloads.
Denali refers to its drug-delivery technology as a “vehicle,” or TV. TV drugs work by binding to certain receptors in brain capillaries, using them to transport therapeutic drug cargoes across protective barriers and into the brain. Carriers containing these drugs can be antibodies, enzymes, proteins or oligonucleotides. The FDA, which has encountered Denali’s technology before, has approved the company to begin clinical trials for Hunter syndrome, an enzyme deficiency. Hunter syndrome drug DNL310 is an enzymatic TV currently being evaluated in a Phase 1/2 study.
Denali’s partnership with Takeda began in 2018. Denali granted the Japanese pharmaceutical giant an option to participate in the development and potential commercialization of drugs that use the biotech’s blood-brain barrier delivery technology to treat neurodegenerative diseases. In addition to the $40 million upfront payment, Denali will receive up to $75 million in total milestone payments for the three projects covered by the agreement.Two months ago, Takeda exercise It could choose one, a drug candidate in development for frontotemporal dementia. The announcement during JPM was for DNL919, a drug that penetrates the brain to treat Alzheimer’s disease.
DNL919, an antibody drug, is the most advanced antibody TV program in Denali’s pipeline. The biotech company designed the drug to activate TREM2, a protein that plays a role in the growth and development of several immune cells in the central nervous system. The drug’s goal is to normalize the function of a specific type of immune cell: microglia. TREM2 mutations are associated with an increased risk of Alzheimer’s disease. By modulating TREM2 signaling, Denali’s drug aims to normalize the function of microglia, which in turn may have implications for Alzheimer’s.
In mouse studies, Denali reported that its TREM2-targeted antibody, TV, showed higher brain uptake and effects on microglia compared to TREM2 antibodies. At JPMorgan, Denali executives said they hope to begin phase one testing in the first half of the year and report safety and biomarker data in the second half. The clinical hold makes that timeline uncertain.
Denali is not the only biotech company developing TREM2-targeting antibodies for neurodegenerative diseases. The biotech lags behind its neighbor south of San Francisco, Alector, which has entered Phase 2 testing for Alzheimer’s disease in partnership with AbbVie. at the same time, Vigil Neuroscience raises $98M from IPO last week, cash will go to prepaid clinics Antibody therapy for the rare disease adult-onset leukoencephalopathy with axonal spheroids and pigmented glial cells. Vigil licensed the TREM2 target asset from Amgen.
Photos by Flickr users Dominic Guzzo through Creative Commons license
