DNL622

DNL622 (ETV:IDUA) is an investigational fusion protein drug candidate developed by Denali Therapeutics. It is designed as an enzyme replacement therapy for mucopolysaccharidosis type I (MPS I), a rare lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase (IDUA). DNL622 utilizes Denali’s proprietary Enzyme Transport Vehicle (ETV) technology to deliver recombinant alpha-L-iduronidase across the blood-brain barrier and into the central nervous system as well as peripheral tissues. The goal is to degrade accumulated heparan sulfate and dermatan sulfate in lysosomes, thereby addressing both neurological and systemic manifestations of MPS I. As of early 2025, DNL622 is in IND-enabling preclinical development[1][2].