Key Takeaways Denali posted a Q3 loss of $0.74 per share, wider than last year's $0.63 loss. FDA extended tividenofusp alfa's approval decision to April 2026 after a major amendment.DNLI advanced programs for Sanfilippo, Alzheimer, Parkinson and Pompe diseases.Denali Therapeutics (DNLI) reported a third-quarter 2025 loss of 74 cents per share, narrower than the Zacks Consensus Estimate of a loss of 76 cents. The company reported a loss of 63 cents in the year-ago quarter.The loss per share widened year over ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38311 Denali Therapeutics Inc. (Exact name of registrant as specified in its charter) (State or other jur ...

Exhibit 99.1 Denali Therapeutics Reports Third Quarter 2025 Financial Results and Business Highlights SOUTH SAN FRANCISCO, Calif., – November 6, 2025 – Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the third quarter ended September 30, 2025, and provided business highlights. "Momentum is building across Denali as we prepare for the anticipated launch of tividenofusp alfa with an experienced and focused commercial team in place," said Ryan Watts, Ph.D., Chief Executive Officer ...

Tividenofusp alfa BLA review process for accelerated approval for MPS II continues with productive engagement with the FDA; commercial launch preparations on trackDNL126 Phase 1/2 study enrollment completed, supporting an accelerated approval path in MPS IIIATwo new regulatory applications submitted to initiate clinical studies with DNL628 (OTV:MAPT) for Alzheimer’s disease and DNL952 (ETV:GAA) for Pompe diseaseTim Van Hauwermeiren, CEO of argenx, to join Denali's Board of DirectorsCarole Ho, M.D., Chief Me ...

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 ...

Core Insights - Denali Therapeutics Inc. (DNLI) announced that the FDA has extended the review timeline for its Biologics License Application (BLA) for tividenofusp alfa, a treatment for mucopolysaccharidosis type II (MPS II) [1][3][7] - The new target date for the BLA review is now April 5, 2026, pushed back from January 5, 2026, due to the submission of updated clinical pharmacology information [3][7] - The extension is classified as a major amendment and is not related to the drug's efficacy, safety, or biomarkers [3][4][7] Company Performance - Denali's stock experienced a decline of 26.5% year to date, contrasting with the industry average gain of 9.2% [2] Drug Development Details - Tividenofusp alfa is designed to deliver the iduronate 2-sulfatase (IDS) enzyme to address symptoms of Hunter syndrome [4][5] - The FDA has previously granted Fast Track and Breakthrough Therapy designations to tividenofusp alfa, and the European Medicines Agency has given it Priority Medicines designation [8] Other Pipeline Candidates - Denali is also developing DNL126 for Sanfilippo syndrome type A (MPS IIIA), with the FDA considering cerebrospinal fluid heparan sulfate as a potential surrogate endpoint for accelerated approval [9] - Another candidate, TAK-594/DNL593, is in collaboration with Takeda for treating frontotemporal dementia (FTD) [10] - Denali and Biogen are jointly evaluating BIIB122/DNL151 for Parkinson's disease, with a global phase IIb study currently ongoing [11][12] Market Position - Denali currently holds a Zacks Rank 3 (Hold), while competitors Amicus Therapeutics and CorMedix have higher rankings of 1 (Strong Buy) and 2 (Buy) respectively [13]

Core Points - Denali Therapeutics Inc. announced an extension of the FDA review timeline for the Biologics License Application (BLA) for tividenofusp alfa from January 5, 2026, to April 5, 2026 [1][2] - The extension is due to Denali's submission of updated clinical pharmacology information, classified as a Major Amendment, and does not relate to efficacy, safety, or biomarkers [2] - Denali is preparing for the potential approval and commercial launch of tividenofusp alfa, emphasizing the urgency to deliver this therapy to the MPS community [3] Product Information - Tividenofusp alfa (DNL310) is designed to deliver the iduronate 2-sulfatase (IDS) enzyme to address symptoms of Hunter syndrome, including behavioral, cognitive, and physical symptoms [4] - The FDA has granted Fast Track and Breakthrough Therapy designations to tividenofusp alfa, and the European Medicines Agency has granted Priority Medicines designation [4] - The Phase 2/3 COMPASS study is currently enrolling participants in North America, South America, and Europe to support global approval [5] Disease Background - Hunter syndrome (MPS II) is a rare genetic lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency of the IDS enzyme [6] - Symptoms include developmental delays, cognitive decline, and physical complications, with current therapies not addressing neurological symptoms due to their inability to cross the blood-brain barrier [6] - There is a significant unmet need for therapies that can address both central nervous system and peripheral manifestations of Hunter syndrome [6] Company Overview - Denali Therapeutics is focused on developing therapies that can cross the blood-brain barrier for neurodegenerative and lysosomal storage diseases [7] - The company employs a rigorous approach to assess genetically validated targets and develop treatments guided by biomarkers [7]

Core Viewpoint - Denali Therapeutics Inc. has shown a positive stock performance, gaining approximately 16.2% since the last earnings report, outperforming the S&P 500, but questions remain about the sustainability of this trend leading up to the next earnings release [1] Financial Performance - Denali reported a second-quarter 2025 loss of 72 cents per share, which was narrower than the Zacks Consensus Estimate of a loss of 74 cents, but worse than the loss of 59 cents in the same quarter last year [2] - The company did not generate any collaboration revenues in the reported quarter, despite a Zacks Consensus Estimate for revenues set at $25 million [3] - Research and development expenses increased by 12.4% to $102.7 million, primarily due to heightened spending on multiple preclinical programs, while general and administrative expenses rose by 28% to $32.3 million due to preparations for a potential product launch [4] Cash Position - As of June 30, 2025, Denali 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 tividenofuspalfa for priority review, with a target action date set for January 5, 2026 [6] - The BLA seeks accelerated approval based on data from a phase I/II study for Hunter syndrome, with tividenofuspalfa having received multiple designations from the FDA [7] - Denali is preparing for the commercial launch of tividenofuspalfa and is conducting a phase II/III COMPASS study to support global regulatory submissions [8] Additional Pipeline Candidates - Denali is evaluating DNL126 for Sanfilippo syndrome type A and has aligned with the FDA on using cerebrospinal fluid heparan sulfate as a potential surrogate endpoint for accelerated approval [9] - Data from an ongoing phase I/II study for DNL126 shows significant reductions in CSF HS and a favorable safety profile [10] - Denali is also collaborating with Takeda on DNL593 for frontotemporal dementia and with Biogen on BIIB122/DNL151 for Parkinson's disease [12][13] Future Outlook - Denali plans to submit regulatory applications for one to two TV-enabled programs each year over the next three years across various therapeutic franchises [14] - Estimates for Denali's stock have been trending upward, with a Zacks Rank of 3 (Hold), indicating expectations for an in-line return in the coming months [15][17] Industry Comparison - Denali operates within the Zacks Medical - Biomedical and Genetics industry, where another player, MannKind, has seen a 50.6% increase in stock price over the past month [18] - MannKind reported revenues of $76.53 million, reflecting a year-over-year increase of 5.7%, but is expected to post a significant decline in earnings for the current quarter [19]

Denali Therapeutics Conference Call Summary Company Overview - Denali Therapeutics focuses on crossing the blood-brain barrier and addressing neurodegeneration, particularly in diseases like Hunter syndrome and Alzheimer's [3][4][5] Key Points Industry and Company Focus - Denali is advancing its transport vehicle (TV) technology, which allows for the delivery of therapeutic agents across the blood-brain barrier [3][4] - The company is targeting various diseases, including Hunter syndrome, Alzheimer's, and Parkinson's, using its TV technology [4][5] Hunter Syndrome - Hunter syndrome is a monogenic disease with an existing enzyme replacement therapy, idursulfase, which does not effectively treat neurological symptoms due to its inability to cross the blood-brain barrier [8][9] - Denali's lead asset, tividenofusp alfa (formerly DNL310), aims to provide a more effective treatment by addressing both peripheral and central nervous system symptoms [7][15] - Clinical data shows significant normalization of heparan sulfate levels in cerebrospinal fluid and urine, indicating the effectiveness of the TV technology [10][12] Clinical Data and Efficacy - In a Phase 1/2 study, 90% of patients showed a reduction in cerebrospinal fluid heparan sulfate levels, with improvements in cognitive and behavioral symptoms [12][13] - The company is preparing for a Biologics License Application (BLA) submission, with a PDUFA date set for January 2026 [16][19] Strategic Commercial Approach - Denali is focusing on engaging with centers of excellence and patient services to facilitate the transition from standard care to its new therapy [17][18] - The company has a field team in place to support the launch and patient engagement efforts [17] Regulatory Engagement - Denali has maintained active communication with the FDA, receiving consistent feedback and support for its accelerated approval pathways [19][20][21] Sanfilippo Syndrome Program - Denali is also developing a program for Sanfilippo syndrome, which differs from Hunter syndrome primarily in its neurological focus and lack of a standard of care [22][23] - The company plans to leverage its experience from Hunter syndrome to inform the development of the Sanfilippo program [23] Future Pipeline and Expansion - Denali aims to file one to two Investigational New Drug (IND) applications per year, expanding its portfolio to include various therapeutic modalities [32][34] - The company is exploring treatments for other lysosomal storage diseases and neurodegenerative conditions, including Parkinson's and Alzheimer's [34][36] Collaborations and Partnerships - Denali has partnerships with Biogen for the LRRK2 program and with Sanofi for the RIPK1 program, focusing on Parkinson's disease and other indications [41][44] Conclusion - Denali is positioned for significant growth with its innovative therapies targeting the blood-brain barrier, with multiple programs in the pipeline and a strong focus on regulatory engagement and commercial strategy [45][46]

Company Overview - Denali Therapeutics focuses on developing a platform to cross the blood-brain barrier, enabling the delivery of large molecules such as enzymes, antibodies, and oligonucleotides into the brain [3][4] - The company was founded approximately 10 years ago during a period when many firms were exiting the neurodegeneration space [3] Development Timeline - The first five years were dedicated to inventing the platform, while the subsequent five years were spent proving its efficacy in treating Hunter syndrome [4] - Denali aims to expand its therapeutic offerings based on initial discoveries and proof of concept achieved with blood-brain barrier-enabled therapeutics over the next five years [4] Industry Context - The current period is described as an exciting time for both Denali and the broader biotech sector, indicating a potential resurgence in interest and investment in neurodegenerative treatments [3]