The U.S. Food and Drug Administration extended on Monday Denali Therapeutics Inc.’s (NASDAQ:DNLI) review timeline of the Biologics License Application (BLA), seeking accelerated approval of tividenofusp alfa for the treatment of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. • DNLI is in negative territory. Track the latest developments here.The Prescription Drug User Fee Act (PDUFA) target date has been extended from Jan. 5, 2026, to April 5, 2026.Also Read: Denali Therapeutics Ends ...

Key Takeaways The FDA extended review of Denali's tividenofusp alfa BLA for Hunter syndrome treatment.The timeline moved from Jan. 5 to April 5, 2026, after Denali submitted new pharmacology data.The extension isn't tied to safety or efficacy, and no extra data was requested by the FDA.Denali Therapeutics Inc. (DNLI) announced that the FDA has extended its review timeline of the Biologics License Application (“BLA”) for pipeline candidate, tividenofusp alfa.The BLA is seeking accelerated approval of tividen ...

SOUTH SAN FRANCISCO, Calif., Oct. 13, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today announced that the U.S. Food and Drug Administration (FDA) has extended its review timeline of the Biologics License Application (BLA) seeking accelerated approval of tividenofusp alfa for the treatment of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome. The Prescription Drug User Fee Act (PDUFA) target date has been extended from January 5, 2026, to April 5, 2026. The extension ...

Core Insights - Denali Therapeutics reported a second-quarter 2025 loss of $0.72 per share, which was narrower than the Zacks Consensus Estimate of a loss of $0.74, but wider than the loss of $0.59 in the same quarter last year [1][8] - The company did not generate any collaboration revenues in the reported quarter, missing the Zacks Consensus Estimate of $25 million [2] - Year-to-date, shares of Denali have declined by 31.7%, while the industry has only seen a 0.6% decline [2] Financial Performance - Research and development expenses increased by 12.4% to $102.7 million, primarily due to higher spending on multiple preclinical programs and increased costs for consultants and general facilities [4] - General and administrative expenses rose by 28% to $32.3 million, driven by preparations for the potential launch of tividenofusp alfa [4] - As of June 30, 2025, the company had cash, cash equivalents, and marketable securities totaling approximately $977.4 million [5] Pipeline Developments - The FDA accepted Denali's biologics license application (BLA) for tividenofusp alfa for priority review, with a target action date set for January 5, 2026 [6][8] - The BLA seeks accelerated approval based on data from a phase I/II study in individuals with Hunter syndrome, with previous designations from the FDA including Breakthrough Therapy and Fast Track [7] - Denali is also advancing DNL126 for Sanfilippo syndrome type A, with alignment from the FDA on using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval [10] Ongoing Studies - Data from the ongoing phase I/II study of DNL126 shows a significant reduction in cerebrospinal fluid heparan sulfate levels, supporting continued development [11] - Denali is conducting a phase I/II study of DNL593 for frontotemporal dementia, in collaboration with Takeda [12] - The company is also evaluating BIIB122/DNL151 in partnership with Biogen for Parkinson's disease, with a global phase IIb study fully enrolled [13][14] Future Plans - Denali plans to submit regulatory applications for one to two TV-enabled programs each year over the next three years across its various franchises [15] - The most advanced programs include DNL952 for Pompe disease and DNL111 for Parkinson's/Gaucher disease, among others [15] Overall Assessment - Denali's recent pipeline progress is viewed positively, with potential approval of tividenofusp alfa expected to significantly boost the company [16] - The strong cash position is seen as a positive factor for funding ongoing programs [16]

Core Insights - Denali Therapeutics reported financial results for Q2 2025, highlighting significant advancements in its clinical programs and financial performance [1][12]. Clinical Programs - The FDA accepted Denali's Biologics License Application (BLA) for tividenofusp alfa for Hunter syndrome, with a PDUFA target action date of January 5, 2026, indicating a potential accelerated approval path [3][8]. - DNL126 for Sanfilippo syndrome type A has reached alignment with the FDA on using cerebrospinal fluid heparan sulfate as a surrogate endpoint for accelerated approval, with ongoing Phase 1/2 study data showing significant reductions in CSF HS [4][8]. - Denali is collaborating with Takeda on DNL593 for frontotemporal dementia, with a Phase 1/2 study currently in progress [5]. - The company is co-developing BIIB122 with Biogen for Parkinson's disease, with the Phase 2b LUMA study completed enrollment and results expected in 2026 [6]. Financial Performance - Denali reported a net loss of $124.1 million for Q2 2025, compared to a net loss of $99.0 million in Q2 2024 [12][19]. - Research and development expenses increased to $102.7 million in Q2 2025 from $91.4 million in Q2 2024, driven by external R&D expenses and personnel-related costs [13][19]. - General and administrative expenses rose to $32.3 million in Q2 2025 from $25.2 million in Q2 2024, primarily due to preparations for the potential commercial launch of tividenofusp alfa [14][19]. - As of June 30, 2025, Denali had approximately $977.4 million in cash, cash equivalents, and marketable securities [14]. Research and Development Pipeline - Denali plans to submit regulatory applications for one to two additional TV-enabled programs each year over the next three years, with advanced programs including DNL952 for Pompe disease and DNL111 for Parkinson's/Gaucher disease [9]. - Preclinical research on the ATV:Abeta program for Alzheimer's disease was published, demonstrating improved brain distribution and reduced ARIA risk compared to conventional treatments [10].

Core Insights - Denali Therapeutics, Inc. (DNLI) has received FDA acceptance for its biologics license application (BLA) for tividenofusp alfa, aimed at treating Hunter syndrome, with a target action date set for January 5, 2026 [1][7] - The acceptance of the BLA marks a significant step for DNLI towards becoming a commercial-stage biotech company, especially as its shares have declined by 30.1% year to date [2] Drug Development and Clinical Trials - Tividenofusp alfa has received Breakthrough Therapy Designation from the FDA for Hunter syndrome, a rare genetic disorder caused by a deficiency in the iduronate 2-sulfatase (IDS) enzyme [3] - The drug is designed to cross the blood-brain barrier, addressing both cognitive and physical symptoms of MPS II, unlike traditional enzyme replacement therapies [4] - The BLA submission is supported by data from a phase I/II study involving 47 participants, and an ongoing phase II/III COMPASS study is expected to provide pivotal data for global regulatory filings [5] Pipeline and Collaborations - Denali is also evaluating DNL126 for Sanfilippo syndrome type A and has engaged in discussions with the FDA for an accelerated development path [9] - Another candidate, DNL593, is being co-developed with Takeda for frontotemporal dementia, with an ongoing phase I/II study [10] - Denali and Biogen are jointly developing a LRRK2 inhibitor for Parkinson's disease, with a global phase IIb study fully enrolled and results expected in 2026 [11] - Denali is also conducting a phase IIa study for LRRK2-associated Parkinson's disease and evaluating DNL343 for amyotrophic lateral sclerosis (ALS), although a primary endpoint was not met in a recent trial [12] - The company has multiple early-stage clinical and preclinical programs and maintains a sound cash position to fund ongoing initiatives [13]

Core Insights - Denali Therapeutics Inc. announced that the FDA has accepted the Biologics License Application (BLA) for tividenofusp alfa, seeking accelerated approval for the treatment of Hunter syndrome, with a target action date of January 5, 2026 [1][7]. Company Overview - Denali Therapeutics is a biotechnology company focused on developing therapies that can cross the blood-brain barrier (BBB) for neurodegenerative and lysosomal storage diseases [9]. - The company utilizes a proprietary TransportVehicle™ platform designed to deliver large therapeutic molecules across the BBB, enhancing drug efficacy [8]. Product Details - Tividenofusp alfa is an investigational enzyme replacement therapy designed to address both neurological and physical symptoms of Hunter syndrome by delivering the iduronate 2-sulfatase (IDS) enzyme into the brain and body [2][4]. - The therapy has received Fast Track and Breakthrough Therapy designations from the FDA, as well as Priority Medicines designation from the European Medicines Agency [4]. Clinical Studies - The BLA submission is supported by data from a Phase 1/2 study involving 47 participants with Hunter syndrome [3]. - Denali is conducting an ongoing Phase 2/3 COMPASS study to support global regulatory approvals, with participants randomized to receive either tividenofusp alfa or idursulfase [5]. Disease Context - Hunter syndrome (MPS II) is a rare genetic disorder caused by a deficiency in the IDS enzyme, leading to the accumulation of glycosaminoglycans and resulting in cognitive decline, behavioral issues, and physical complications [6]. - Current therapies do not effectively address neurological symptoms due to their inability to cross the BBB, highlighting the unmet need for new treatments [6].

Company Strategy & Priorities - Denali is preparing for the potential launch of tividenofusp alfa for MPS II (Hunter syndrome), aiming for a late 2025 or early 2026 U S launch [13, 32, 68] - The company is focused on expanding its Enzyme TransportVehicle (ETV) franchise to realize the platform's potential for lysosomal storage diseases [13] - Denali is advancing its TransportVehicle (TV) portfolio programs for neurodegeneration and other indications [13] Technology & Pipeline - Denali's TransportVehicle (TV) platform is designed to optimize brain delivery, with over 350 patents and applications, and more than 10 programs [16, 18] - The company's OTV:MAPT program demonstrates sustained brain tau knockdown for over 15 weeks following four IV doses [96] - Denali expects to file 1-2 INDs (Investigational New Drug applications) per year over the next 3 years across its TV franchises [90] Clinical Data & Market Opportunity - Tividenofusp alfa Phase 1/2 data in MPS II shows robust reduction in CSF HS and serum NfL, with the majority of participants reaching the normal range by Week 104 [44] - The company estimates a total addressable market of approximately 2,000 patients worldwide for MPS II [72] - Denali is developing a broad ETV franchise targeting lysosomal storage diseases, with approximately 30,000 people affected worldwide, two-thirds of whom have CNS manifestations [38, 76]

Core Viewpoint - Denali Therapeutics reported a wider-than-expected loss in Q1 2025, primarily due to increased operating expenses, and did not generate collaboration revenues during the quarter [1][2]. Financial Performance - The company reported a loss of 78 cents per share, compared to the Zacks Consensus Estimate of a loss of 71 cents and a loss of 68 cents in the same quarter last year [1]. - Research and development expenses rose by 8.6% to $116.3 million, driven by increased spending on clinical and preclinical programs [5]. - General and administrative expenses increased by 16.4% to $29.4 million, attributed to activities related to the submission of a biologics license application for tividenofusp alfa [6]. - As of May 31, 2025, the company had approximately $1.05 billion in cash, cash equivalents, and marketable securities [6]. Pipeline Developments - Denali completed the submission of a biologics license application for tividenofusp alfa under the FDA's accelerated approval pathway, based on phase I/II study data for Hunter syndrome [7]. - The FDA granted Breakthrough Therapy Designation for tividenofusp alfa in January 2025 [8]. - Denali is conducting a global phase II/III COMPASS study to support regulatory approvals for tividenofusp alfa [8]. - The company is evaluating DNL126 for Sanfilippo syndrome type A and has had productive discussions with the FDA regarding its accelerated development [9]. - Denali is collaborating with Takeda on DNL593 for frontotemporal dementia and is conducting a phase I/II study [10]. - Denali and Biogen are jointly evaluating BIIB122/DNL151 for Parkinson's disease, with the LUMA study fully enrolled [11]. - The company is also conducting the phase IIa BEACON study for LRRK2-associated Parkinson's disease and evaluating DNL343 in a phase II/III study for ALS [12]. - Denali's partner Sanofi discontinued the development of SAR443820/DNL788 for ALS due to unmet primary endpoints in the phase II study [14]. Market Performance - Shares of Denali Therapeutics have declined by 31.4% year-to-date, while the industry has seen a smaller decline of 2.2% [4]. Overall Assessment - The progress in Denali's pipeline is viewed as encouraging, with potential approval of tividenofusp alfa expected to significantly benefit the company [15].

Core Insights - Denali Therapeutics has completed the Biologics License Application (BLA) submission for tividenofusp alfa, marking a significant milestone in its development as a late-stage commercial organization focused on treating Hunter syndrome [2][3] - The company is preparing for the commercial launch of tividenofusp alfa, expected in late 2025 or early 2026, which would be the first FDA-approved enzyme replacement therapy designed to cross the blood-brain barrier [2][3] - Denali's clinical pipeline includes ongoing programs for Sanfilippo syndrome Type A and frontotemporal dementia, with collaborations with the FDA and Takeda, respectively [4][5] Financial Performance - For Q1 2025, Denali reported a net loss of $133.0 million, an increase from a net loss of $101.8 million in Q1 2024 [10] - Research and development expenses rose to $116.2 million in Q1 2025 from $107.0 million in Q1 2024, primarily due to increased spending on clinical and preclinical programs [11] - General and administrative expenses increased to $29.4 million in Q1 2025 from $25.2 million in Q1 2024, driven by activities related to the BLA submission for tividenofusp alfa [14] Clinical Program Updates - The BLA submission for tividenofusp alfa is based on data from a Phase 1/2 study involving 47 participants, with the FDA's review process now initiated [3] - Denali is conducting a global Phase 2/3 COMPASS study to support regulatory approvals for tividenofusp alfa [3] - The company is also advancing DNL126 for Sanfilippo syndrome Type A, with ongoing discussions with the FDA for an accelerated development path [4] Corporate Developments - Denali has launched a clinical biomanufacturing facility in Salt Lake City, enhancing its manufacturing capabilities and supply chain control [9] - The company is actively participating in several upcoming investor conferences to engage with stakeholders and present its developments [13]