Key Takeaways DNLI reported a Q4 loss of $0.73 per share, beating estimates but wider year over year.Denali Therapeutics' BLA for tividenofusp alfa faces April 5, 2026, FDA action date after major amendment.DNLI ended 2025 with $966.2M in cash as it advances DNL126 and other partnered programs.Denali Therapeutics (DNLI) reported a fourth-quarter 2025 loss of 73 cents per share, narrower than the Zacks Consensus Estimate of a loss of 75 cents. The company reported a loss of 67 cents in the year-ago quarter.T ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 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) Delaware 46-3872213 (State o ...

Exhibit 99.1 Denali Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Business Highlights SOUTH SAN FRANCISCO, Calif., – February 26, 2026 – Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided business highlights. Fourth Quarter 2025 and Recent Program Updates CLINICAL PROGRAMS Tividenofusp alfa (DNL310; ETV:IDS) for Hunter syndrome (mucopolysaccharidosis type II [MPS II]) Denali has es ...

Tividenofusp alfa (DNL310; ETV:IDS) launch readiness established ahead of April 5, 2026 Prescription Drug User Fee Act (PDUFA) target action date for Hunter syndromeDNL126 (ETV:SGSH) Phase 1/2 preliminary data presented at 2026 WORLDSymposium™, supporting plans to pursue an accelerated approval path in Sanfilippo syndrome type AStart-up activities underway for DNL628 (OTV:MAPT) Phase 1b study for Alzheimer's disease and DNL952 (ETV:GAA) Phase 1 study for late-onset Pompe diseaseTransportVehicle™ platform an ...

Core Insights - Denali is focused on delivering biotherapeutics to the entire body, including the brain, for individuals with serious diseases [2][3] Group 1: Company Overview - Denali was founded to harness the potential of biotherapeutics for comprehensive treatment [2] - The company is presenting highlights of its enzyme transport vehicle technology at the WORLDSymposium in San Diego [1] Group 2: Technology Introduction - Denali has engineered the binding of the Transferrin receptor into its TransportVehicle [2]

Denali Therapeutics Update Summary Company Overview - **Company**: Denali Therapeutics (NasdaqGS:DNLI) - **Focus**: Development of biotherapeutics targeting serious diseases, particularly those affecting the brain and body Key Points from the Call Enzyme Transport Vehicle Technology - Denali has engineered a binding mechanism using transferrin receptor to cross the blood-brain barrier, allowing for systemic delivery of therapeutics [2][3] - The company has three main franchises: Enzyme Transport Vehicle, Oligo Transport Vehicle, and Antibody Transport Vehicle [2] Clinical Programs and Data - **Tividenofusp alfa (TIVI)**: - Focused on treating Hunter syndrome, with a phase 1/2 study showing an 80% mean reduction in CSF heparan sulfate and significant biomarker improvements [4][10] - Anticipated BLA filing and potential accelerated approval in 2027 based on interim data [4][22] - Long-term follow-up data showed sustained reductions in biomarkers and improvements in cognitive and behavioral outcomes [10][15] - **DNL126**: - Designed for MPS IIIA, with preliminary data showing an 80% reduction in CSF heparan sulfate after 49 weeks [22] - Safety profile consistent with established enzyme replacement therapies, with no serious adverse events reported [20][22] - Ongoing evaluation for potential accelerated approval based on biomarker data [22] - **DNL952**: - Investigational therapy for Pompe disease, showing enhanced delivery of GAA to muscle and nervous system [23][24] - Preclinical data indicated significant reductions in glycogen accumulation in muscle and nervous system tissues [26] Safety and Efficacy - Safety profiles for both TIVI and DNL126 were generally manageable, with infusion-related reactions being the most common adverse events [20][22] - The efficacy of TIVI was highlighted by improvements in hearing thresholds and cognitive skills across different age groups [10][15] Future Directions - Denali is preparing for the launch of TIVI, with a PDUFA date set for April 5, 2027 [4] - The company is also exploring the potential for breakthrough designation for TIVI based on the promising data [38] - Ongoing discussions with the FDA regarding trial designs and potential accelerated approvals for both TIVI and DNL126 [80] Market Context - Denali's therapies address significant unmet medical needs in rare diseases, particularly those with neurological manifestations, positioning the company favorably in the biopharmaceutical landscape [16][22] Additional Insights - The data presented at the WORLD Symposium emphasized the potential of Denali's therapies to not only stabilize but also improve patient outcomes over time, particularly in younger populations [10][15] - The company is actively engaging with regulatory bodies to ensure the timely advancement of its clinical programs [80] This summary encapsulates the critical aspects of Denali Therapeutics' recent developments, focusing on their innovative therapeutic approaches and the promising data emerging from their clinical trials.

February 5, 2026 Analyst Call This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements do not relate strictly to historical or current facts and they may be accompanied by such words as "anticipate," "believe," "could," "estimate," "expected," "forecast," "intend," "may," "plan," "potential," "possible," "future," "will" and other words and terms of similar meaning. All statements other than statements ...

Core Insights - Denali Therapeutics Inc. presented data on its Enzyme TransportVehicle™ (ETV) platform at the 22nd Annual WORLDSymposium™, showcasing its potential for delivering enzyme replacement therapies (ERT) for Hunter syndrome, Sanfilippo syndrome type A, and Pompe disease [1][2] Denali Therapeutics Overview - Denali is focused on developing biotherapeutics that can cross the blood-brain barrier using its proprietary TransportVehicle™ platform, aiming to address neurodegenerative and lysosomal storage diseases [19] Hunter Syndrome (MPS II) - Tividenofusp alfa (DNL310) showed significant reductions in cerebrospinal fluid heparan sulfate and urine heparan sulfate, with improvements in clinical endpoints maintained through Week 201 [3][6] - The Biologics License Application (BLA) for tividenofusp alfa is under Priority Review by the FDA, with a decision expected by April 5, 2026 [3][6] - A case study of two siblings with non-neuronopathic MPS II supports the therapy's potential to address the full disease spectrum [4] Sanfilippo Syndrome Type A (MPS IIIA) - DNL126 (ETV:SGSH) is fully enrolled in a Phase 1/2 study, showing an 80% mean reduction in cerebrospinal fluid heparan sulfate and an 83% reduction in urine heparan sulfate at Week 49 [5][8] - The FDA has indicated that cerebrospinal fluid heparan sulfate may serve as a surrogate endpoint for accelerated approval, with a BLA submission expected in 2027 [8][15] Pompe Disease - DNL952 (ETV:GAA) is in a Phase 1 clinical study designed to evaluate its safety and efficacy in late-onset Pompe disease, with preclinical data showing improved glycogen reduction compared to second-generation ERTs [9][17] - The study will assess various dose regimens and includes treatment-naïve patients [9] Regulatory and Developmental Progress - Denali is collaborating with regulatory authorities to advance its ETV platform and is preparing for the commercial launch of tividenofusp alfa [2][6] - The company is also planning a global Phase 3 confirmatory study for DNL126 [8][15]

Core Insights - The fourth-quarter 2025 reporting cycle for the Medical sector is commencing, with major firms expected to release earnings results in the coming weeks, primarily in the pharma/biotech and medical device segments [1] - Johnson & Johnson's strong performance has set a positive tone, while Roche faced challenges due to unfavorable foreign-exchange impacts, particularly from a weak U.S. dollar [1] - Sanofi reported mixed results, beating earnings estimates but slightly missing sales expectations [1] Earnings Trends - As of January 28, 11.7% of Medical sector companies, representing 26% of the sector's market capitalization, have reported quarterly earnings, with 42.9% beating both earnings and revenue estimates [2] - Year-over-year earnings decreased by 15.5%, while revenues increased by 10.3% [2] - Overall, fourth-quarter earnings for the Medical sector are expected to decrease by 2.4%, while sales are projected to rise by 8.7% compared to the previous year [3] Company Highlights - **Zoetis (ZTS)**: Expected to report earnings on February 12, with a consensus estimate of $1.40 per share and revenues of $2.37 billion. The company has an Earnings ESP of +0.84% and a Zacks Rank of 3. Recent performance has been driven by strong demand for companion animal products, although sales of certain monoclonal antibody products may have declined [7][8] - **Pacira BioSciences (PCRX)**: Anticipated to report earnings soon, with a consensus estimate of 85 cents per share and revenues of $196.99 million. The company has an Earnings ESP of +7.38% and a Zacks Rank of 2. Revenue growth is expected from its pain-management product, Exparel, and other products [9][10] - **Apellis Pharmaceuticals (APLS)**: Expected to report earnings soon, with a consensus estimate of a loss of 41 cents per share and revenues of $194.37 million. The company has an Earnings ESP of +4.52% and a Zacks Rank of 3. Revenue growth is likely driven by its geographic atrophy drug, Syfovre [11][12] - **Acadia Pharmaceuticals (ACAD)**: Set to report earnings soon, with a consensus estimate of 12 cents per share and revenues of $292.64 million. The company has an Earnings ESP of +14.92% and a Zacks Rank of 3. Revenue growth is expected from its lead drug, Nuplazid, and its second product, Daybue [13][14] - **Denali Therapeutics (DNLI)**: Expected to report a loss of 75 cents per share and revenues of $18.47 million. The company has an Earnings ESP of +6.11% and a Zacks Rank of 3. Revenue expectations are based on collaboration revenues, with updates on pipeline programs anticipated [15][16]

Core Viewpoint - Denali Therapeutics Inc. is set to showcase its Enzyme TransportVehicle™ (ETV) programs at the 22nd Annual WORLDSymposium™, highlighting the potential of ETV in delivering enzyme replacement therapies throughout the body, including the brain [1]. Company Overview - Denali Therapeutics Inc. is a biotechnology company focused on developing biotherapeutics that can cross the blood-brain barrier using its proprietary TransportVehicle™ platform [2]. - The company has a clinically validated delivery platform and a diverse portfolio of therapeutic candidates at various stages of development, aiming to provide effective treatments for neurodegenerative diseases, lysosomal storage disorders, and other serious conditions [2].