Denali Therapeutics Announces Presentations on DNL310 (ETV:IDS) Development Program in MPS II (Hunter Syndrome) at the Upcoming WORLDSymposium™

SOUTH SAN FRANCISCO, Calif., Feb. 01, 2022 (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 upcoming presentations from the DNL310 (ETV:IDS) clinical development program to be given at the 18^th Annual WORLDSymposium™, which will be held February 7-11, 2022, in San Diego, California, and virtually. DNL310 is an investigational brain-penetrant enzyme replacement therapy intended to treat both central nervous system (CNS) and peripheral manifestations of MPS II (Hunter syndrome).

An oral presentation will provide longer-term safety, biomarker (glycosaminoglycans and lysosomal lipids) and exploratory clinical data on Cohorts A and B from an ongoing Phase 1/2 clinical trial of DNL310 in MPS II. A poster presentation will provide details on a planned, potentially registrational Phase 2/3 clinical trial of DNL310 in MPS II. PDFs of the oral presentation and poster presentation will be posted on Denali’s corporate website under the Investor Events section on February 10^th and February 7^th, respectively. The presentation schedule at WORLDSymposium™ is as follows:

Title: Interim 49-week results of a phase 1/2 study of intravenous DNL310 (brain-penetrant enzyme replacement therapy) in MPS II
Session: Contemporary Forum Platform Presentations
Date: Thursday, February 10, 2022
Time: 8 a.m. Pacific Time
Presenter: Anna Bakardjiev, M.D.

Title: A blinded randomized phase 2/3 study of the efficacy and safety of intravenous DNL310 (brain-penetrant enzyme replacement therapy) in MPS II
Session: Contemporary Forum Poster Presentations
Date: Thursday, February 10, 2022
Time: 3:00 – 5:00 p.m. Pacific Time
Presenter: Jeff Harris, M.D., Ph.D.

Families interested in learning more about Denali’s efforts related to the discovery and development of therapeutics for the potential treatment of Hunter syndrome are invited to visit EngageHunter.com, the Denali Hunter syndrome community engagement website.

About DNL310 and Hunter Syndrome (MPS II)
Hunter syndrome (MPS II) is a rare neurodegenerative lysosomal storage disease caused by mutations in the gene that encodes for the enzyme iduronate-2-sulfatase (IDS). The resultant reduction or loss of IDS enzyme activity leads to accumulation of glycosaminoglycans, which causes lysosomal dysfunction and neurodegeneration as well as progressive damage to multiple organs including bone, cartilage, heart, and lung. Current standard of care enzyme replacement therapy only partially improves the peripheral manifestations of MPS II and does not address neuronopathic manifestations of the disease as it does not sufficiently cross the blood-brain barrier (BBB). DNL310 is an investigational fusion protein composed of IDS fused to Denali’s proprietary Enzyme Transport Vehicle (ETV), which is engineered to cross the BBB via receptor-mediated transcytosis into the brain. More information about the ongoing Phase 1/2 study of DNL310 in patients with Hunter syndrome can be found on ClinicalTrials.gov by following this link.

About Denali’s TV Platform
The blood-brain barrier (BBB) is essential in maintaining the brain’s microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for central nervous system (CNS) diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s Transport Vehicle (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules, such as antibodies, enzymes, proteins, and oligonucleotides, across the BBB after intravenous administration. The TV technology is based on engineered Fc fragments that bind to specific natural transport receptors, such as transferrin receptor, which are expressed at the BBB and deliver TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered using the TV 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.

About Denali Therapeutics 
Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com.  

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding Denali’s plans, timelines and expectations related to DNL310, the DNL310 ongoing Phase 1/2 study and expectations regarding enrollment in Cohort C, plans to accelerate efforts to initiate the planned Phase 2/3 in the first half of 2022, plans regarding other planned future studies, expectations regarding Denali’s TV technology platform, and the therapeutic potential of DNL310 and Denali’s TV platform. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: Denali’s business and operations caused directly or indirectly by the evolving COVID-19 pandemic; Denali’s early stages of clinical drug development; Denali’s and its partners’ ability to complete the development and, if approved, commercialization of DNL310; Denali’s and its partners’ ability to enroll patients in its ongoing and future clinical trials; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials; Denali’s dependence on successful development of the blood-brain barrier platform technology and TV-enabled product candidates; Denali’s and its partners’ ability to conduct or complete clinical trials on expected timelines; the potential for clinical trial results of DNL310 to differ from preclinical, preliminary or expected results; Denali’s ability to continue dose escalation in the Phase 1/2 study; whether DNL310 will cause any serious adverse events; whether DNL310 will impact downstream biomarkers of neurodegeneration; the possibility that early clinical biomarker studies will not translate to clinical benefit in late clinical studies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to DNL310; and the possibility that DNL310 may not receive regulatory approval as a treatment of Hunter syndrome necessary to be commercialized. In light of these risks, uncertainties and assumptions, the forward-looking statements in this press release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Information regarding additional risks and uncertainties may be found in Denali’s Annual and Quarterly Reports filed on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 26, 2021, and November 4, 2021, respectively, and Denali’s future reports to be filed with the SEC. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law.

Contact: 

Laura Hansen, Ph.D. 
Vice President, Investor Relations 
(650) 452-2747 
hansen@dnli.com