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

IDS (DNL310) in Patients with Hunter Syndrome (MPS II) - Seite 2

“We are encouraged by these new Phase 1/2 data, which continue to support the overall safety profile and biomarker effects of DNL310 as an investigational treatment in Hunter syndrome,” said Carole Ho, M.D., Denali’s Chief Medical Officer. “Importantly, at dose levels resulting in robust and durable biomarker response, DNL310 appears generally well tolerated and consistent with standard of care ERT. We are pleased to observe that early biomarker effects initially seen after four weeks of treatment with DNL310 were sustained after three months of dosing. We are also encouraged by the findings related to exploratory lipid biomarkers which indicate, for the first time, improvement in lysosomal function. Taken together, these data support our previously announced decision to expand and advance clinical studies with DNL310 as a potential treatment for both body and brain in patients with Hunter syndrome.” 

Denali also presented preclinical research at WORLDSymposium on a mouse model of Hunter syndrome showing that ETV:IDS treatment reduces CSF GAGs and that these reductions are correlated with GAG reductions in the brain. Furthermore, reduction in CSF GAG levels was associated with subsequent improvements in lysosomal function, neurodegeneration biomarkers, neurobehavioral outcomes and correction of skeletal disease manifestations in the mouse model.

“The magnitude and durability of biomarker response and tolerability seen with DNL310 provide strong support for the potential application of our Transport Vehicle (TV) technology to deliver enzymes and other therapeutic modalities to the brain,” said Ryan Watts, Ph.D., Denali’s Chief Executive Officer. “Compared to other investigational BBB transport technologies, we have engineered specific molecular properties into our TV technology for better brain uptake and biodistribution of the therapeutic cargo to relevant cell types. The DNL310 Phase 1/2 results also support the potential for systemic administration of TV-enabled therapeutics to address peripheral disease. Taken together, these data increase our confidence that DNL310 may ultimately prove to be an impactful therapy for Hunter syndrome patients and their families and that we can apply our TV technology more broadly to defeat degeneration and address other diseases with brain manifestations.”