Denali Therapeutics Reports Positive Three-Month Data from Phase 1/2 Study with ETV

IDS (DNL310) in Patients with Hunter Syndrome (MPS II)

• Sustained normalization and further decreased levels of CSF glycosaminoglycan heparan sulfate, a key CNS disease biomarker, observed after three months of intravenous dosing
  
  
• Reductions in exploratory CSF biomarkers consistent with improved lysosomal function 
  
  
• Reductions in levels of urine glycosaminoglycans following a switch from idursulfase support potential for improved peripheral effects relative to standard of care
  
  
• Generally well tolerated with safety profile consistent with other enzyme replacement therapies; most frequently observed adverse events of mild or moderate infusion-related reactions 
  
  
• Management will host a webinar for analysts at 8:00 a.m. Eastern Time today 
  

SOUTH SAN FRANCISCO, Calif., Feb. 12, 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 results from the ongoing Phase 1/2 study evaluating ETV:IDS (DNL310) as a potential brain-penetrant enzyme replacement therapy for treating both central nervous system (CNS) and peripheral manifestations of Hunter syndrome (MPS II). The data will be presented later today during a late-breaker session at WORLDSymposium. Denali management will host an analyst webinar today beginning at 8:00 a.m. Eastern Time to discuss both interim clinical and new preclinical data that will be presented at the conference.  

An interim analysis included data on a total of five patients enrolled in Cohort A in the Phase 1/2 study, who all received three months of weekly intravenous doses of DNL310 after switching from idursulfase enzyme replacement therapy on Day 1 of the study. Key results included:

• Normal levels of heparan sulfate, a glycosaminoglycan (GAG), in cerebrospinal fluid (CSF) that were seen after four weeks of dosing in four of five patients were sustained after three months of dosing (mean 85% reduction across Cohort A; p<0.001); heparan sulfate levels were further significantly reduced and approached normal levels in the fifth patient (from 25% to 73% reduction from one to three months, respectively).
• Reductions in downstream exploratory CSF biomarkers, GM3 and BMP (lysosomal lipids), of 39% and 15%, respectively, were observed after eight weeks of dosing with DNL310, consistent with improvement in lysosomal function.
• Reductions in urine heparan sulfate and dermatan sulfate following a switch from idursulfase, of 76% and 82%, respectively, were observed after eight weeks of dosing of DNL310, supporting potential for improved peripheral effects relative to standard of care.
• DNL310 was generally well tolerated with no dose reductions and all five patients continue in the study. The most frequently observed adverse events were mild or moderate infusion-related reactions in three of five patients, which is consistent with other enzyme replacement therapies (ERTs).  
• Based on three-month clinical data, doses of DNL310 from 3 mg/kg to 30 mg/kg are generally well tolerated and provide flexibility for dose selection in clinical studies.