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DENALI Denali Therapeutics Announces Positive Interim Data from Phase 1/2 Study with ETV : IDS ( DNL310 ) in Patients with the Lysosomal Storage Disease Hunter Syndrome ( MPS II ) July 25 , 2021 3:05 PM PDT • Rapid reduction and sustained normalization of heparan sulfate in CSF demonstrated robust and durable CNS activity with intravenous administration , and enhanced peripheral activity with reductions in urine and serum heparan sulfate after switching from standard - of - care idursulfase • Global Impression of Change scales data suggested clinical improvement in overall MPS II symptoms , cognitive abilities , behavior , and physical abilities • Exploratory biomarker data demonstrated reductions in CSF lysosomal lipid biomarkers that are consistent with improved lysosomal function ; and high variability in exploratory biomarker Nf - L was observed pre- and post - treatment • Safety profile with up to 43 weeks of dosing was consistent with standard of care enzyme replacement therapy with infusion - related reactions being the most frequently observed adverse events • Based on these data , Denali is accelerating efforts to initiate a pivotal Phase 2/3 study in 1H 2022 • Management will host a webinar for analysts and investors at 11:30 a.m. Eastern Time today SOUTH SAN FRANCISCO , Calif . , July 25 , 2021 ( GLOBE NEWSWIRE ) -- Denali Therapeutics Inc. ( NASDAQ : DNLI ) , a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood - brain barrier ( BBB ) for neurodegenerative diseases , today announced additional positive interim data from a Phase 1/2 study evaluating ETV : IDS ( DNL310 ) , an investigational brain - penetrant enzyme replacement therapy intended to treat both central nervous system ( CNS ) and peripheral manifestations of Hunter syndrome ( MPS II ) . The interim results being presented today at MPS 2021 , the 16th International Symposium on MPS and Related Diseases , include safety data up to Weeks 43 and 25 from Cohorts A and B , respectively , 6 - month biomarker data from Cohort A and up to 3 - month biomarker data from Cohort B. Denali Management will host a webinar today for analysts and investors beginning at approximately 11:30 a.m. Eastern Time . " The longer - term safety data and 6 - month biomarker data on DNL310 from Cohort A continue to demonstrate durability of effect with CNS impact , improved peripheral activity after switching from standard of care , and a safety profile consistent with standard of care enzyme replacement therapy , " said Carole Ho , M.D. , Denali's Chief Medical Officer . " We are also encouraged by initial indications of improved clinical symptoms and function reported by investigators and parents in all five patients enrolled in Cohort A. In addition , this is the first time we are sharing data from Cohort B , which is designed to inform dose selection , and exploratory biomarker data demonstrate activity of DNL310 across all dose regimens . Based on these data , we are accelerating our efforts to initiate a pivotal Phase 2/3 study of DNL310 in the first half of 2022 and to begin enrolling Cohort C in the Phase 1/2 study to further investigate clinical endpoints . " This interim analysis of the Phase 1/2 study included data on five patients enrolled in Cohort A and 12 patients enrolled in Cohort B. All patients have neuronopathic MPS II disease except for one patient with non - neuronopathic MPS II disease in Cohort B. The median age of patients is 6 years in both cohorts , with the youngest patients aged 5 and 2 in Cohorts A and B , respectively . All patients received weekly intravenous doses of DNL310 after switching from idursulfase enzyme replacement therapy on Day 1 of the study . Data being presented include safety data up to Weeks 43 and 25 from Cohorts A and B , respectively ; 6 - month and up to 3 - month biomarker data from Cohorts A and B , respectively ; and exploratory clinical Global Impression of Change data from Cohort A up to Week 24 . Results across Cohorts A and B showed that , following the switch from idursulfase to DNL310 , the levels of heparan sulfate in cerebrospinal fluid ( CSF ) normalized in all patients analyzed ( n = 15 ) , with rapid response observed in most patients ( n = 12 ) by Week 7 , which is consistent with crossing of the BBB by DNL310 and activity in tissues of the CNS . Rapid normalization of CSF heparan sulfate at low dose regimens suggest that BBB crossing with Denali's Transport Vehicle ( TV ) was robust and efficient . Furthermore , the observed decline in urine and serum heparan sulfate was consistent with improved peripheral activity with DNL310 . Exploratory clinical data suggest improved clinical symptoms and function for all five patients enrolled in Cohort A as reported by investigators and parents . Based on Global Impression of Change scales [ Clinician Global Impression of Change ( CGI - C ) and Parent Global Impression of Change ( PGI - C ) ] , which are standardized assessment scales used to measure change , the data showed clinical improvement in overall MPS II symptoms , cognitive abilities , behavior , and physical abilities . Exploratory lysosomal lipid data showed reductions , which are consistent with improved lysosomal function : 10 of 15 patients across Cohorts A and B had normal GM3 ganglioside levels , including patients on low dose regimens and with shorter duration of