Denali Therapeutics announces new interim data from Phase 1/2 study of DNL310

Denali Therapeutics announced new interim data from the ongoing open-label, single-arm Phase 1/2 study of DNL310 in children with MPS II. DNL310 is an investigational enzyme replacement therapy designed to cross the BBB and address the behavioral, cognitive, and physical manifestations of MPS II. The interim data from the Phase 1/2 study of DNL310 were highlighted in an oral presentation at the Society for the Study of Inborn Errors of Metabolism Annual Symposium 2023 in Jerusalem, Israel. The interim Phase 1/2 data presented at SSIEM included new biomarker and safety data from additional participants receiving up to two years of treatment with DNL310 as well as previously presented clinical outcomes data for participants receiving one year of treatment. A summary of key results includes: Achievement of normal levels of CSF heparan sulfate, sustained over time, including in participants with high pre-existing anti-drug antibodies; Sustained normal levels of CSF lysosomal lipids in most participants consistent with improved lysosomal function; Robust reduction in serum neurofilament light, a marker of neuronal damage, reached statistical significance after 61 weeks and a 64% reduction after two years of treatment with DNL310; Improvements in mean cognitive Bayley Scales of Infant and Toddler Development III and Vineland Adaptive Behavior Scales II raw scores, and auditory brainstem response thresholds at week 49 of DNL310 treatment, suggest positive effects on cognition, adaptive behavior, and hearing; DNL310 continues to be generally well tolerated; the interim safety profile, clinical outcomes data, and biomarker effects, including normalization of CSF heparan sulfate and reduction in NfL, continue to support development of DNL310 in MPS II