Denali announces data, expansion of BBB-crossing enzyme replacement therapy

Denali Therapeutics announced new data presentations highlighting the broad potential of its BBB-crossing enzyme replacement therapies in development for the treatment of mucopolysaccharidoses. New clinical data on tividenofusp alfa in MPS II and mouse model data on DNL126 in MPS IIIA are being presented this week at the 20th Annual WORLDSymposium in San Diego, California. In addition, new data on somatic outcomes from the same study of tividenofusp alfa will be presented for the first time by Barbara Burton, M.D., Professor of Pediatrics, Genetics, Genomics and Metabolism at Feinberg School of Medicine in Chicago. The Phase 1/2 results demonstrate normalization of enlarged liver and spleen volumes and maintenance of normal growth compared to healthy boys in almost all participants. New two-year peripheral biomarker data demonstrate high magnitude and sustained reduction of urine heparan sulfate and dermatan sulfate, including in participants who switched from standard-of-care enzyme replacement therapy to tividenofusp alfa, suggesting enhanced peripheral activity. Tividenofusp alfa treatment continued to be generally well tolerated. New MPS IIIA mouse model data on DNL126 will also be presented at the conference showing improvements in lysosomal and microglial morphology, neurodegeneration, and cognitive function. Treatment with DNL126 resulted in lowered heparan sulfate accumulation in the brain and in cerebrospinal fluid and improved cognitive function in adult MPS IIIA mice. A correlation between the levels of heparan sulfate and cognitive behavioral performance was observed. Denali also announced that dosing has begun in the Phase 1/2 study of DNL126 for the potential treatment of MPS IIIA.