Benzinga | Feb 12, 2021 08:54AM EST

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.