• START is a pilot program newly launched jointly by the FDA CDER and CBER divisions to further accelerate the development of novel drug and biological products for rare diseases
  
  
• DNL126 was selected as one of three CDER-regulated products based on eligibility criteria including the potential for clinical benefit for a rare neurodegenerative disease and the drug sponsor’s ability to advance development towards a marketing application
  
  
• Participation in START is expected to facilitate and accelerate development of DNL126 through more rapid and ad hoc communication with FDA review staff

 Denali Therapeutics Inc., a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative and lysosomal storage diseases, today announced that the U.S. Food and Drug Administration (FDA) has selected DNL126 for participation in the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program. DNL126 is an investigational enzyme replacement therapy designed to cross the BBB for the potential treatment of MPS IIIA (Sanfilippo syndrome type A).

The FDA announced the START Pilot Program on September 29, 2023, with the stated purpose to further accelerate the pace of development of novel drug and biological products that are intended to address an unmet medical need as a treatment for a rare disease. Selected participants of the START Pilot Program are provided opportunities to obtain frequent advice and engage in more rapid ad hoc communication with FDA review staff to address product-specific development issues. The START pilot and metrics are milestone driven and agreed upon by the FDA and sponsor. Initial selection for START planned to include up to six eligible programs (three each) from the FDA’s Center for Biologics Evaluation and Research's (CBER) Office of Therapeutic Products and Center for Drug Evaluation and Research's (CDER) Office of New Drugs.¹

“We are thrilled to be selected by the FDA for participation in START and see this as another important opportunity to work together to solve challenges unique to rare disease drug development,” said Carole Ho, M.D., Chief Medical Officer of Denali. “It is an exciting time to be part of the collective effort of making new treatments available to individuals and families living with rare diseases. We look forward to continued collaboration with CDER to determine the most efficient development path for DNL126 in MPS IIIA, a devastating and progressive disease for which treatments are urgently needed.”

Denali is conducting a Phase 1/2 study of DNL126 for children with MPS IIIA, which has generated high interest from the MPS IIIA community for whom there are no approved treatment options. As a selected START participant, Denali anticipates the increased level of engagement will facilitate alignment on the most efficient development path to ultimately support a marketing application for DNL126 in MPS IIIA.

Denali is also developing tividenofusp alfa (DNL310) as a potential treatment for people living with MPS II (Hunter syndrome) and expects to complete enrollment of the Phase 2/3 COMPASS study this year. Given the advanced development stage of the program, Denali did not apply to START for tividenofusp alfa. The FDA granted Fast Track designation to tividenofusp alfa, which also facilitates increased communication and engagement with the FDA specific to this program.