Denali's Enzyme Replacement Therapy Shows Encouraging Biomarker Effects In Early-Stage Hunter Syndrome Study

Denali Therapeutics Inc (NASDAQ: DNLI) has announced additional interim results from its ongoing Phase 1/2 study evaluating ETV:IDS (DNL310) as a potential brain-penetrant enzyme replacement therapy for Hunter syndrome (MPS II).
MPS II is a rare neurodegenerative lysosomal storage disorder caused by a mutation in the gene that encodes for the enzyme iduronate-2-sulfatase (IDS), thus accumulating GAGs, which causes lysosomal dysfunction and neurodegeneration as well as progressive damage to multiple organs.
Denali will present the data later today during a late-breaker session at WORLD Symposium.
The study included five patients whom all received three months of weekly intravenous doses of DNL310 after switching from idursulfase enzyme replacement therapy.
Normal levels of heparan sulfate, a glycosaminoglycan (GAG), in cerebrospinal fluid (CSF) that were seen after four weeks of dosing in 4/5 patients were sustained after three months of dosing (mean 85% reduction was observed across the cohort)
For the fifth patient, heparan sulfate levels were significantly reduced and approached normal levels (from 25% to 73% reduction from one to three months, respectively).
Reductions in downstream exploratory CSF biomarkers, GM3 and BMP, 39% and 15%, respectively, were observed after eight weeks of dosing with DNL310, consistent with an improvement in lysosomal function.
Reductions in urine heparan sulfate and dermatan sulfate following a switch from idursulfase, 76% and 82%, respectively, were observed after eight weeks of dosing.
DNL310 was generally well tolerated with no dose reductions, and all five patients continue in the study. The most frequent adverse events were mild or moderate infusion-related reactions in three of five patients.
Doses of DNL310 from 3 mg/kg to 30 mg/kg are generally well tolerated and provide flexibility for dose selection in clinical studies.
Price Action: DNLI stock is up 4.96% at $73 in the premarket trading on the last check Friday.