Denali Therapeutics Publishes Hunter Syndrome Therapy Trial Results
Written by Emily J. Thompson, Senior Investment Analyst
Updated: Dec 30 2025
0mins
Should l Buy DNLI?
Denali Therapeutics announced the publication of results from the open-label Phase 1/2 clinical trial of its investigational, next-generation enzyme replacement therapy, tividenofusp alfa, for the treatment of Hunter syndrome in the January 1, 2026 issue of The New England Journal of Medicine. The U.S. Food and Drug Administration is conducting a Priority Review of the Biologics License Application for tividenofusp alfa, which is supported by these data and for which Denali is seeking accelerated approval. A decision by the FDA on the tividenofusp alfa BLA is expected by April 5, 2026. Tividenofusp alfa is composed of IDS fused to Denali's TransportVehicle platform and is engineered to cross the blood-brain barrier, aiming to treat neurological manifestations of MPS II in addition to physical symptoms. The FDA has granted Rare Pediatric Disease Designation and Breakthrough Therapy Designation to tividenofusp alfa. The primary objective of the Phase 1/2 study was safety and tolerability, and secondary objectives evaluated central nervous system and peripheral effects of tividenofusp alfa by measuring the GAG heparan sulfate in cerebrospinal fluid and urine, adaptive behavior and liver volume. The study evaluated treatment in 47 ERT-naive and previously treated study participants, ranging from less severe to severe disease variants. Safety and tolerability data were consistent with previously reported results from this Phase 1/2 trial. The most common treatment-related adverse events were infusion-related reactions, which decreased in incidence with continued use. Results from key secondary endpoints are: Mean CSF levels of HS, the primary substrate found in high levels in the brain of individuals with MPS II, were reduced from baseline by 91% at Week 24 and maintained through Week 153. At Week 24, 93% of study participants reached levels within the range of children without MPS II. Mean urine HS levels were reduced by 88% from baseline at Week 24 and maintained through Week 153. At Week 24, 58% of participants reached levels in the range of children without MPS II. Serum neurofilament light chain levels, a well-established biomarker of neuronal injury and an exploratory endpoint of the study, were reduced by 21% from baseline at Week 49. At Week 153, NfL was reduced by 76%, and 85% of participants reached levels within the range of children without MPS II. Clinical results included normalization in liver volume after 24 weeks, improvement in hearing thresholds across tested frequencies, and skill gains in most participants on measures of adaptive behavior and cognition.
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Analyst Views on DNLI
Wall Street analysts forecast DNLI stock price to rise over the next 12 months. According to Wall Street analysts, the average 1-year price target for DNLI is 32.36 USD with a low forecast of 25.00 USD and a high forecast of 40.00 USD. However, analyst price targets are subjective and often lag stock prices, so investors should focus on the objective reasons behind analyst rating changes, which better reflect the company's fundamentals.
13 Analyst Rating
13 Buy
0 Hold
0 Sell
Strong Buy
Current: 21.280
Low
25.00
Averages
32.36
High
40.00
Current: 21.280
Low
25.00
Averages
32.36
High
40.00
About DNLI
Denali Therapeutics Inc. is a biopharmaceutical company. The Company is focused on developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. It has developed a technology, called the TransportVehicle (TV), to address the BBB challenge. Its advanced TV-enabled program is tividenofusp alfa (DNL310, ETV:IDS) for the potential treatment of mucopolysaccharidosis II (MPS II or Hunter syndrome). Its TV-enabled clinical development portfolio also includes DNL126 (ETV:SGSH) for MPS IIIA (Sanfilippo syndrome) and DNL593 (PTV:PGRN) for frontotemporal dementia-granulin (FTD-GRN). Its small-molecule clinical development portfolio includes BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson’s disease; and DNL343 (small molecule eIF2B activator) for amyotrophic lateral sclerosis (ALS). It is also exploring programs in oncology, inflammation, and other diseases.
About the author
Emily J. Thompson
Emily J. Thompson, a Chartered Financial Analyst (CFA) with 12 years in investment research, graduated with honors from the Wharton School. Specializing in industrial and technology stocks, she provides in-depth analysis for Intellectia’s earnings and market brief reports.
Denali Therapeutics Advances in Hunter Syndrome Treatment
- Clinical Trial Update: Denali Therapeutics reported significant biomarker reductions in its Phase 1/2 trial for Hunter syndrome (MPS II), with tividenofusp alfa (DNL310) achieving an 80% mean reduction in cerebrospinal fluid heparan sulfate, indicating its potential to address the full disease spectrum.
- Launch Readiness: The company is preparing for the April 5, 2026 PDUFA date, with plans to submit a Biologics License Application (BLA), which would provide much-needed treatment options for patients with Hunter syndrome.
- Sanfilippo Syndrome Research: Preliminary data from the Phase 1/2 study of DNL126 (ETV:SGSH) in Sanfilippo syndrome showed an 83% mean reduction in cerebrospinal fluid heparan sulfate among 20 participants, offering new hope for treatment in a field lacking effective therapies.
- Pompe Disease Clinical Design: Denali presented the Phase 1 clinical study design for DNL952 (ETV:GAA) in Pompe disease, aimed at evaluating safety and tolerability across different dosing regimens, highlighting the therapeutic potential for muscle and nervous system manifestations.
See More
Denali Therapeutics Presents Clinical Data at WORLDSymposium 2026
- Clinical Data Presentation: Denali Therapeutics will showcase clinical and preclinical data from its Enzyme Transport Vehicle (ETV) programs at the 2026 WORLDSymposium, highlighting the potential for delivering enzyme replacement therapies throughout the body, including the brain.
- FDA Priority Review: The Biologics License Application for DNL310 (for Hunter syndrome) is under FDA Priority Review, with a decision expected by April 5, 2026, which could expedite its market entry.
- Multiple Oral Presentations: Two oral presentations will discuss clinical study data for DNL310 and DNL126 (for Sanfilippo syndrome type A), demonstrating the company's progress in rare disease research.
- Poster Presentation Content: Denali will also present several posters, including a health outcomes analysis for MPS II patients and the study design for DNL952 (for Pompe disease), further solidifying its leadership in rare disease treatments.
See More
Denali Therapeutics (DNLI) Offers Covered Call with 2.60% Potential Return
- Covered Call Strategy: Investors can buy DNLI shares at $17.30 and sell a $17.50 call option at $0.25, committing to sell at expiration for a potential total return of 2.60%, enhancing overall investment yield.
- Expiration Risk: With the strike price approximately 1% above the current stock price, there is a 42% chance the call option will expire worthless, allowing investors to retain both their shares and the premium collected, further boosting returns.
- Yield Boost Effect: Should the call option expire worthless, investors could see an additional 1.45% return, annualized to 6.07%, referred to as YieldBoost, providing an attractive opportunity for enhanced earnings.
- Volatility Insights: The call option has an implied volatility of 67%, while the actual trailing twelve-month volatility stands at 61%, indicating market expectations for DNLI's price fluctuations, which investors should monitor for informed decision-making.
See More
Denali Therapeutics Advances Tividenofusp Alfa with FDA Priority Review for Hunter Syndrome
- Clinical Trial Results: Denali Therapeutics' tividenofusp alfa demonstrated a 91% reduction in heparan sulfate levels in cerebrospinal fluid among 47 participants, indicating significant potential for improving neurocognitive function in Hunter syndrome patients.
- FDA Review Progress: The Biologics License Application for tividenofusp alfa is under FDA Priority Review, with a decision expected by April 5, 2026, which will provide urgently needed treatment options for patients.
- Treatment Safety: The most common adverse events in the clinical trial were infusion-related reactions, which significantly decreased in incidence with continued use, demonstrating the therapy's good tolerability.
- Market Outlook: As the first enzyme replacement therapy designed to cross the blood-brain barrier, tividenofusp alfa could transform the treatment landscape for Hunter syndrome, addressing the urgent market demand for new therapies.
See More
Denali Therapeutics Advances Tividenofusp Alfa with Promising Phase 1/2 Results for Hunter Syndrome
- Clinical Trial Results: Denali Therapeutics' tividenofusp alfa demonstrated a 91% reduction in cerebrospinal fluid glycosaminoglycan levels in 47 participants, indicating significant potential in treating Hunter syndrome and possibly improving cognitive and behavioral outcomes for patients.
- FDA Priority Review: The Biologics License Application for tividenofusp alfa is under FDA Priority Review, with a decision expected by April 5, 2026, paving the way for market introduction and addressing the urgent needs of Hunter syndrome patients.
- Safety and Tolerability: The most common adverse events were infusion-related reactions, which significantly decreased with continued treatment, demonstrating good tolerability and laying the groundwork for broader application in clinical settings.
- Innovative Platform: Tividenofusp alfa utilizes Denali's TransportVehicle™ platform designed to cross the blood-brain barrier, representing a new direction in biotherapeutic development that could transform the treatment landscape for Hunter syndrome.
See More
Denali Therapeutics Prices Public Offering at $200 Million
- Offering Size: Denali Therapeutics announced a public offering of 9,142,857 shares at $17.50 per share, expecting to raise approximately $200 million, which will significantly bolster its funding for research and operations.
- Pre-Funded Warrants: The offering includes pre-funded warrants allowing certain investors to purchase 2,285,714 shares at $17.49 each, enhancing investor engagement and participation in the capital raise.
- Underwriter Selection: The offering is managed by Goldman Sachs, J.P. Morgan, Morgan Stanley, and Jefferies, reflecting strong market confidence in Denali and providing robust promotional capabilities for the company.
- Future Outlook: Denali expects to close the offering on December 11, 2025, subject to customary closing conditions, with proceeds aimed at advancing its biotherapeutics designed to cross the blood-brain barrier, thereby strengthening its market position in neurodegenerative diseases.
See More
Denali Therapeutics Advances in Hunter Syndrome Treatment
- Clinical Trial Update: Denali Therapeutics reported significant biomarker reductions in its Phase 1/2 trial for Hunter syndrome (MPS II), with tividenofusp alfa (DNL310) achieving an 80% mean reduction in cerebrospinal fluid heparan sulfate, indicating its potential to address the full disease spectrum.
- Launch Readiness: The company is preparing for the April 5, 2026 PDUFA date, with plans to submit a Biologics License Application (BLA), which would provide much-needed treatment options for patients with Hunter syndrome.
- Sanfilippo Syndrome Research: Preliminary data from the Phase 1/2 study of DNL126 (ETV:SGSH) in Sanfilippo syndrome showed an 83% mean reduction in cerebrospinal fluid heparan sulfate among 20 participants, offering new hope for treatment in a field lacking effective therapies.
- Pompe Disease Clinical Design: Denali presented the Phase 1 clinical study design for DNL952 (ETV:GAA) in Pompe disease, aimed at evaluating safety and tolerability across different dosing regimens, highlighting the therapeutic potential for muscle and nervous system manifestations.
See More
Denali Therapeutics Presents Clinical Data at WORLDSymposium 2026
- Clinical Data Presentation: Denali Therapeutics will showcase clinical and preclinical data from its Enzyme Transport Vehicle (ETV) programs at the 2026 WORLDSymposium, highlighting the potential for delivering enzyme replacement therapies throughout the body, including the brain.
- FDA Priority Review: The Biologics License Application for DNL310 (for Hunter syndrome) is under FDA Priority Review, with a decision expected by April 5, 2026, which could expedite its market entry.
- Multiple Oral Presentations: Two oral presentations will discuss clinical study data for DNL310 and DNL126 (for Sanfilippo syndrome type A), demonstrating the company's progress in rare disease research.
- Poster Presentation Content: Denali will also present several posters, including a health outcomes analysis for MPS II patients and the study design for DNL952 (for Pompe disease), further solidifying its leadership in rare disease treatments.
See More
Denali Therapeutics (DNLI) Offers Covered Call with 2.60% Potential Return
- Covered Call Strategy: Investors can buy DNLI shares at $17.30 and sell a $17.50 call option at $0.25, committing to sell at expiration for a potential total return of 2.60%, enhancing overall investment yield.
- Expiration Risk: With the strike price approximately 1% above the current stock price, there is a 42% chance the call option will expire worthless, allowing investors to retain both their shares and the premium collected, further boosting returns.
- Yield Boost Effect: Should the call option expire worthless, investors could see an additional 1.45% return, annualized to 6.07%, referred to as YieldBoost, providing an attractive opportunity for enhanced earnings.
- Volatility Insights: The call option has an implied volatility of 67%, while the actual trailing twelve-month volatility stands at 61%, indicating market expectations for DNLI's price fluctuations, which investors should monitor for informed decision-making.
See More
Denali Therapeutics Advances Tividenofusp Alfa with FDA Priority Review for Hunter Syndrome
- Clinical Trial Results: Denali Therapeutics' tividenofusp alfa demonstrated a 91% reduction in heparan sulfate levels in cerebrospinal fluid among 47 participants, indicating significant potential for improving neurocognitive function in Hunter syndrome patients.
- FDA Review Progress: The Biologics License Application for tividenofusp alfa is under FDA Priority Review, with a decision expected by April 5, 2026, which will provide urgently needed treatment options for patients.
- Treatment Safety: The most common adverse events in the clinical trial were infusion-related reactions, which significantly decreased in incidence with continued use, demonstrating the therapy's good tolerability.
- Market Outlook: As the first enzyme replacement therapy designed to cross the blood-brain barrier, tividenofusp alfa could transform the treatment landscape for Hunter syndrome, addressing the urgent market demand for new therapies.
See More
Denali Therapeutics Advances Tividenofusp Alfa with Promising Phase 1/2 Results for Hunter Syndrome
- Clinical Trial Results: Denali Therapeutics' tividenofusp alfa demonstrated a 91% reduction in cerebrospinal fluid glycosaminoglycan levels in 47 participants, indicating significant potential in treating Hunter syndrome and possibly improving cognitive and behavioral outcomes for patients.
- FDA Priority Review: The Biologics License Application for tividenofusp alfa is under FDA Priority Review, with a decision expected by April 5, 2026, paving the way for market introduction and addressing the urgent needs of Hunter syndrome patients.
- Safety and Tolerability: The most common adverse events were infusion-related reactions, which significantly decreased with continued treatment, demonstrating good tolerability and laying the groundwork for broader application in clinical settings.
- Innovative Platform: Tividenofusp alfa utilizes Denali's TransportVehicle™ platform designed to cross the blood-brain barrier, representing a new direction in biotherapeutic development that could transform the treatment landscape for Hunter syndrome.
See More
Denali Therapeutics Prices Public Offering at $200 Million
- Offering Size: Denali Therapeutics announced a public offering of 9,142,857 shares at $17.50 per share, expecting to raise approximately $200 million, which will significantly bolster its funding for research and operations.
- Pre-Funded Warrants: The offering includes pre-funded warrants allowing certain investors to purchase 2,285,714 shares at $17.49 each, enhancing investor engagement and participation in the capital raise.
- Underwriter Selection: The offering is managed by Goldman Sachs, J.P. Morgan, Morgan Stanley, and Jefferies, reflecting strong market confidence in Denali and providing robust promotional capabilities for the company.
- Future Outlook: Denali expects to close the offering on December 11, 2025, subject to customary closing conditions, with proceeds aimed at advancing its biotherapeutics designed to cross the blood-brain barrier, thereby strengthening its market position in neurodegenerative diseases.
See More
