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].

Core Insights - Denali Therapeutics Inc. is set to present clinical and preclinical data from its Enzyme Transport Vehicle™ (ETV) programs at the 22nd Annual WORLDSymposium™ from February 2-6, 2026, showcasing the potential of ETV for delivering enzyme replacement therapies throughout the body, including the brain [1] Group 1: Clinical Data Presentations - Two oral presentations will cover follow-up data from the Phase 1/2 clinical study of tividenofusp alfa (DNL310) for Hunter syndrome (MPS II) and preliminary data from the ongoing Phase 1/2 study of DNL126 (ETV:SGSH) for Sanfilippo syndrome type A (MPS IIIA) [2][5] - The U.S. FDA is conducting a Priority Review of the Biologics License Application (BLA) for tividenofusp alfa, with a decision anticipated by April 5, 2026 [2] Group 2: Presentation Details - The platform presentations include a study on intravenous tividenofusp alfa for MPS II and preliminary results from the DNL126 study in children with MPS IIIA, both scheduled for February 5, 2026 [3] - Poster presentations will cover various topics, including a retrospective cohort study on unmet needs in Hunter syndrome, enhanced correction of skeletal muscle and brain pathology in a Pompe mouse model, and a case study involving a male sibling pair with MPS II [4][6] Group 3: Satellite Symposium - Denali will sponsor a satellite symposium titled "Transforming Patient Care in MPS II" on February 5, 2026, featuring expert speakers [7] Group 4: TransportVehicle™ Platform - Denali's TransportVehicle™ platform is designed to cross the blood-brain barrier, enabling the delivery of large therapeutic molecules, including antibodies and enzymes, to the brain, demonstrating significantly improved brain exposure compared to traditional methods [8] - The platform has been clinically validated, with five TV-enabled programs currently in clinical development [8] Group 5: Company Overview - Denali Therapeutics is a biotechnology company focused on developing biotherapeutics that can cross the blood-brain barrier, aiming to transform the lives of individuals with neurodegenerative and lysosomal storage diseases [9]

Core Insights - The biotech sector has experienced a resurgence after a decade of stagnation, attracting increased investor interest [1] - Growth in other economic sectors has resulted in elevated valuations for those sectors compared to the biotech sector [1] Industry Summary - Investors are focusing on top biotech names in the market, indicating a shift in investment strategy towards biotech [1] - The current market conditions suggest that biotech valuations may appear more attractive relative to other sectors [1]

Core Insights - Denali is focused on delivering biotherapeutics to the brain and has expanded its technology to target other regions of the body [2] - The company has seen significant maturation in both clinical and preclinical data, highlighting the effectiveness of using transferrin receptor technology for biotherapeutics [3] Company Overview - Denali was founded with the mission to develop biotherapeutics that can effectively access the brain [2] - The company is positioned in a competitive field, indicating a growing interest and activity in biotherapeutics targeting the central nervous system [3]

Denali Therapeutics FY Conference Summary Company Overview - **Company**: Denali Therapeutics (NasdaqGS:DNLI) - **Industry**: Biotechnology, focusing on biotherapeutics for neurological diseases Key Messages and Core Points 1. **Transport Vehicle Technology**: Denali emphasizes its transport vehicle technology as a validated and clinically proven platform for delivering biotherapeutics across the blood-brain barrier (BBB) [3][4][12] 2. **Market Potential**: The company anticipates capturing a market exceeding $1 billion with upcoming launches for treatments targeting rare diseases such as Hunter syndrome and Sanfilippo [3] 3. **Clinical Programs**: Denali is advancing multiple clinical programs, including: - TIVI for Hunter syndrome, with a BLA filing and a PDUFA date set for April 5, 2026 [16][33] - OTV MAPT and ATV A beta for Alzheimer's disease, with clinical studies expected to start soon [4][27] - DNL126 for Sanfilippo, aiming for accelerated approval by 2027 [18][44] Financial and Market Strategy 1. **Launch Strategy for TIVI**: The company plans a seamless transition for patients currently on standard care, focusing on engaging centers of excellence and ensuring payer coverage [34][38] 2. **Revenue Expectations**: Minimal revenues are expected in 2026 due to the nature of rare disease launches, with a significant increase anticipated in 2027 as coverage expands [37] 3. **Pricing Strategy**: Denali aims to price TIVI at a premium compared to current treatments, ensuring broad access and affordability for patients [38] Clinical Data and Safety 1. **TIVI Clinical Data**: Safety data shows a decline in infusion-related reactions over time, with normalization of biomarkers indicating efficacy in halting neurodegeneration [15][16] 2. **Sanfilippo Program**: The ongoing phase one-two study for DNL126 is designed to leverage learnings from TIVI, with a focus on CSF heparan sulfate as a surrogate biomarker [41][44] 3. **Alzheimer's Programs**: ATV-A shows promise in reducing amyloid-related imaging abnormalities (ARIA) and improving plaque reduction compared to standard treatments [23][25] Research and Development Focus 1. **Broad Portfolio**: Denali is expanding its portfolio to include treatments for lysosomal storage diseases and common neurodegenerative diseases, with a focus on both enzyme replacement and oligonucleotide therapies [6][22] 2. **Innovative Approaches**: The company is committed to advancing its transport vehicle technology to enhance drug delivery across the BBB and improve treatment outcomes [11][52] Competitive Landscape 1. **Market Position**: Denali acknowledges the competitive nature of the field but believes its unique technology and clinical validation position it favorably [2][3] 2. **Future Opportunities**: The company is exploring additional indications for its transport vehicle platform, prioritizing diseases with well-understood biology and significant unmet needs [52] Conclusion Denali Therapeutics is poised for significant growth with its innovative transport vehicle technology, targeting both rare diseases and common neurodegenerative conditions. The company is strategically positioned to launch its products, engage with the medical community, and ensure patient access while navigating the complexities of the biotechnology market.

Key Objectives & Platform - Denali aims to transform lives by delivering biotherapeutics to the whole body, including the brain[11] - The company's TransportVehicle (TV) platform enables systemic delivery of biologics to the brain and other hard-to-target tissues[12, 24] - Denali's TransportVehicle has demonstrated best-in-class properties for brain delivery, modularity, and safety[50] Near-Term Commercial Opportunities - Denali anticipates launching tividenofusp alfa (DNL310) in 2026 and DNL126 in 2027, establishing a commercial foundation for the Enzyme TransportVehicle (ETV) franchise[13] - Tividenofusp alfa has a PDUFA target action date of April 5, 2026, for accelerated approval[61, 81] - The ETV franchise targets lysosomal storage disorders (LSDs), with a combined market opportunity exceeding $1 billion for MPS II and MPS IIIA[13, 107] Pipeline & Milestones - Denali has a broad clinical-stage pipeline, including programs for Alzheimer's disease, with several near-term milestones expected[14] - The company anticipates an approval decision for tividenofusp alfa, ETV:SGSH Phase 1/2 data, and initiation of Phase 1 studies for OTV:MAPT, ATV:Abeta, and ETV:GAA in the first half of 2026[16] - Denali is developing the next generation of enzyme replacement therapies designed to treat brain and body manifestations of serious genetic diseases[61, 64] Financial Position - Denali has a strong financial foundation with approximately $873 million in cash and investments as of Q3 2025, plus $488 million from royalty financing and an equity capital raise in December 2025[146]

Core Insights - Denali Therapeutics Inc. (DNLI) has outlined its roadmap for 2026, focusing on investigational therapies for neurodegenerative diseases and lysosomal storage disorders, with an emphasis on the anticipated FDA approval and commercial launch of tividenofusp alfa for Hunter syndrome [1][9] Regulatory Developments - The company submitted a biologics license application (BLA) for tividenofusp alfa under the FDA's accelerated approval pathway, based on phase I/II study data [4] - The FDA extended the review timeline for the BLA to April 5, 2026, due to the submission of updated clinical pharmacology information, not related to efficacy or safety [5][6] Clinical Trials and Studies - Denali is conducting a phase II/III COMPASS study for tividenofusp alfa, with data expected to support global regulatory submissions [6] - The company is also evaluating DNL126 for Sanfilippo syndrome type A, with initial data set to be presented at the 2026 WORLDSymposium [7] - Ongoing studies include DNL593 for frontotemporal dementia in partnership with Takeda, and BIIB122 for early-stage Parkinson's disease in collaboration with Biogen, with readouts expected in 2026 [8][11] Financial Position - As of September 30, 2025, Denali held approximately $872.9 million in cash and marketable securities, and raised an additional $200 million through equity financing [14] - The company secured a royalty funding agreement worth up to $275 million based on future sales of tividenofusp alfa, providing necessary capital for regulatory activities and clinical trials [14] Future Outlook - The potential FDA approval of tividenofusp alfa in 2026 could transform Denali into a commercial-stage biotech, with positive data from ongoing studies likely to boost stock performance [15]