Denali Therapeutics Announces New Interim Data from Phase 1/2 Study of DNL310 (ETV

IDS) in MPS II (Hunter Syndrome) at SSIEM 2023 - Seite 3

About DNL310

DNL310 is an investigational fusion protein composed of IDS fused to Denali’s proprietary Enzyme Transport Vehicle (ETV), which is engineered to cross the blood-brain barrier via receptor-mediated transcytosis into the brain. Preclinical studies demonstrate that DNL310 delivers IDS to lysosomes, where it is needed to break down GAGs. DNL310 is engineered for broad delivery of IDS into cells and tissues throughout the body, including the brain, with the goal of addressing the behavioral, cognitive, and physical manifestations of MPS II. In March 2021, the U.S. Food and Drug Administration granted Fast Track designation to DNL310 for the treatment of patients with MPS II. In May 2022, the European Medicines Agency granted DNL310 Priority Medicines designation. DNL310 is an investigational product candidate and has not been approved by any Health Authority.

About the Phase 2/3 COMPASS study

Based on supportive clinical and preclinical data to date, Denali is conducting the Phase 2/3 COMPASS study, which is expected to enroll 54 participants with MPS II with and without neuronopathic disease. The participants will be randomized 2:1 to receive either DNL310 or idursulfase, respectively. Cohort A will include children ages 2 to 6 with neuronopathic disease; cohort B will include children ages 6 to 17 without neuronopathic disease.

The Phase 2/3 COMPASS study is being conducted globally in North America, South America, and Europe. Upon completion of the ongoing Phase 1/2 study, and together with data from the global COMPASS study, this combined data package is intended to support registration. More information about the COMPASS study can be found here.

About Denali’s Transport Vehicle Platform

The blood-brain barrier is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the blood-brain barrier has posed significant challenges to drug development for central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s Transport Vehicle platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes, proteins, and oligonucleotides across the blood-brain barrier after intravenous administration. The Transport Vehicle technology is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptors, which are expressed at the blood-brain barrier and deliver the Transport Vehicle and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered with the Transport Vehicle technology demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates.