1. Tividenofusp alfa showed significant improvement in key disease biomarkers. 2. FDA Priority Review for tividenofusp alfa BLA expected by April 5, 2026. 3. Treatment-related adverse events declined with continued use of tividenofusp alfa. 4. Tividenofusp alfa aims to treat both neurological and physical symptoms of MPS II. 5. Denali is committed to prepare for the potential launch of tividenofusp alfa.
FAQ
Why Very Bullish?
The positive clinical trial results and forthcoming FDA decision could significantly boost DNLI's stock price. Historically, FDA approvals have led to substantial price increases for biopharma stocks.
How important is it?
The article details significant clinical advancements and FDA reviews, marking critical milestones for DNLI.
Why Long Term?
Long-term price impact is expected due to ongoing development and expanding market opportunities for pivotal treatments.
Publication of Phase 1/2 Study Results for Denali Therapeutics' Tividenofusp Alfa (DNLI)
SOUTH SAN FRANCISCO, Calif., Dec. 30, 2025 (GLOBE NEWSWIRE) — Denali Therapeutics Inc. (Nasdaq: DNLI) has announced the publication of results from its open-label Phase 1/2 clinical trial of tividenofusp alfa (DNL310), an investigational enzyme replacement therapy (ERT) aimed at treating Hunter syndrome (mucopolysaccharidosis type II, or MPS II). The findings are set to be featured in the January 1, 2026 edition of The New England Journal of Medicine.
Key Findings on Tividenofusp Alfa
The Phase 1/2 study demonstrated significant reductions in key disease biomarkers, including:
- Reduction of heparan sulfate levels in cerebrospinal fluid by 91% from baseline at Week 24.
- Normalization of liver volume and improvements in adaptive behavior and cognition.
- Infusion-related reactions were the most common adverse events, which decreased with continued use.
The U.S. Food and Drug Administration (FDA) is currently conducting a Priority Review of the Biologics License Application (BLA) for tividenofusp alfa, with a decision expected by April 5, 2026.
Understanding Hunter Syndrome
MPS II is a life-threatening lysosomal storage disorder caused by a deficiency of the iduronate 2-sulfatase (IDS) enzyme, essential for breaking down glycosaminoglycans (GAGs). In patients with MPS II, GAGs accumulate in various tissues, leading to severe neurocognitive decline in approximately two-thirds of individuals. Current treatments do not effectively penetrate the blood-brain barrier, limiting their potential effectiveness on cognitive development and behavioral aspects of the disease.
Expert Commentary on Clinical Data
“There is an urgent need for new treatment options to address the full spectrum of Hunter syndrome,” stated Dr. Joseph Muenzer, lead investigator of the study. He emphasized the importance of addressing cognitive and motor deficits associated with the disease, highlighting that tividenofusp alfa showed promise in improving both central and peripheral biomarkers affected by MPS II.
Innovative Delivery Mechanism
Tividenofusp alfa utilizes Denali’s TransportVehicle™ platform, which is specifically engineered to cross the blood-brain barrier, thereby addressing neurological symptoms in addition to physical manifestations. Denali has received both Rare Pediatric Disease Designation and Breakthrough Therapy Designation from the FDA for this investigational therapy.
Clinical Results and Secondary Endpoints
The Phase 1/2 trial included 47 participants aged 0.3–13 years and focused on safety, tolerability, and the impact on key biomarkers. The following results were observed:
- At Week 24, 93% of participants had CSF heparan sulfate levels normalized.
- Urine heparan sulfate levels were reduced by 88% at Week 24, with 58% reaching normal levels.
- Serum neurofilament light chain levels, a marker of neuronal injury, decreased by 76% by Week 153.
These findings suggest potential for significant improvement in clinical outcomes for patients with MPS II, including normalization of liver volume and enhanced hearing thresholds.
Future Prospects for Tividenofusp Alfa
Dr. Peter Chin, Chief Medical Officer of Denali Therapeutics, expressed optimism regarding the potential of tividenofusp alfa to become the first FDA-approved ERT that treats both systemic and neurological symptoms of Hunter syndrome. The data reinforce the viability of Denali’s TransportVehicle™ as a platform that could revolutionize the delivery of therapeutic agents across various lysosomal storage disorders and neurodegenerative diseases.
Ongoing Clinical Studies
Denali is actively conducting the Phase 2/3 COMPASS study focusing on participants with MPS II across North America, South America, and Europe. This ongoing research aims to further validate tividenofusp alfa and support its approval process globally.