Denali Therapeutics Inc. · NASDAQ:DNLI
Denali Therapeutics — Q2 2026 Earnings Presentation
34 slides from Denali Therapeutics's earnings presentation, Aug 6, 2026
Slide 1: Transforming Life: 2Q 2026 Financial Results
1 August 6 | 2Q 2026 Financial Results Transforming Life
Slide 2: Forward-Looking Statements
2 Forward-Looking Statements 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 “anticipa
Slide 3: Agenda and Speakers
3 Agenda and Speakers AG END A Opening Remarks – Ryan Watts, Ph.D., CEO Ryan Watts, Ph.D. Alexander Schuth, M.D. Commercial Update – Katie Peng, CCO Chief Executive Officer Chief Operating and Financial Officer Pipeline Highlights – Ryan Watts, Ph.D., CEO Financials – Alexander Schuth, M.D., COO/CFO
Slide 4: CEO Opening Remarks
CEO Opening Remarks Ryan Watts, Ph.D., CEO
Slide 5: Our Purpose: Transforming Life for People with Serious Diseases
5 Our Purpose: Transforming Life for People with Serious Diseases We bring the power of biotherapeutics to the whole body, including the brain. Rare Genetic Diseases Common Neurodegenerative Diseases Hunter (MPS II) / Sanfilippo (MPS IIIA) / Alzheimer’s disease / Parkinson’s disease FTD-GRN / Pompe
Slide 6: Addressing the Challenge of Delivering Therapy to the Brain
6 Addressing the Challenge of Delivering Therapy to the Brain The TransportVehicle (TV) is engineered to deliver efficacious concentrations of biotherapeutics across the blood-brain barrier via receptor-mediated transcytosis Blood Brain Enzyme + TransportVehicle Blood-Brain Barrier Transferrin Recep
Slide 7: Now Approved in the U.S.
JENALI ©2026 Denali Therapeutics Inc. 7 Now Approved in the U.S. AVLAYAH tividenotusp alfa-eknm AVLAYAH™ (tividenofusp alfa-eknm), an enzyme replacement therapy, received accelerated approval from the U.S. Food and Drug Administration for the treatment of neurologic manifestations of Hunter syndrome
Slide 8: A Powerful Combination: Product, Pipeline, Platform, Capital
8 A Powerful Combination: Product, Pipeline, Platform, Capital Commercial Broad Validated a TV Operational & Product Pipeline Platform Financial Scale First FDA-approved 7 clinical programs from Leading BBB technology and Fully integrated capabilities product designed to cross the rare diseases to t
Slide 9: 2Q 2026 Highlights: A Transformative Quarter for Denali
9 2Q 2026 Highlights: A Transformative Quarter for Denali Commercial Pipeline Financials Alzheimer’s Positioned Disease to Deliver $3.6 Million DNL628 (OTV:MAPT) & ~$1.1 Billion net product revenue in first DNL921 (ATV:Abeta) pro forma1 cash, cash full commercial quarter initiated clinical developme
Slide 10: Commercial Update
Commercial Update Katie Peng, Chief Commercial Officer
Slide 11: Setting a New Bar for the Treatment of MPS II
11 Setting a New Bar for the Treatment of MPS II The first FDA-approved enzyme replacement therapy (ERT) to cross the blood-brain barrier to reach the brain in addition to the body 9 out of 10 9 out of 10 individuals had normal levels* of CSF HS after individuals had normal levels* of uGAGs 6 months
Slide 12: AVLAYAH is Approved in the U.S. for ~375 Eligible Patients
12 AVLAYAH is Approved in the U.S. for ~375 Eligible Patients Global MPS II Population U.S. MPS II Population ~2,000 Current Eligible MPS II Patients Worldwide Currently Receiving ERT ~500 Population2 Treatment for Hunter ~25% Prevalent Patients ~375 Syndrome in Addressable Markets1 Located in U.S.
Slide 13: Strong Momentum with AVLAYAH Launch
13 Strong Momentum with AVLAYAH Launch 2026: Building the Foundation Across Key Stakeholders for Revenue Acceleration Reach Switch Access Coverage Achieve broad patient Activate and maintain Support seamless Drive fast coverage reach through community- switch to AVLAYAH access for patients aligned t
Slide 14: Healthcare Organization (HCO) Engagement
©2026 Denali Therapeutics Inc. 14 Healthcare Organization (HCO) Engagement High awareness and motivating data translated into broad launch engagement across targeted treating HCOs P RE-LAUNC H P RE-LAUNC H LAUNC H HCP Awareness Data Motivation Launch Reach Prior to Launch >80%Physicians1 aware 90% V
Slide 15: Patients and Caregivers are Aware of AVLAYAH
15 Patients and Caregivers are Aware of AVLAYAH Patient & Family Webinars Media Coverage 3 Launch Webinars Focused on Clinical Data and Patient Access REACHING 100+ >25% Families of Eligible Patient Pool This treatment is important to us — ...the chance to start treatment feels they have a chance no
Slide 16: Positive Experience with Denali and AVLAYAH
16 Positive Experience with Denali and AVLAYAH For the first time, it felt like Adam's world was opening up. We began to see changes in his speech The Denali team is doing a and mobility that meant so much to our family. While fantastic job navigating the his previous treatment helped his body, we a
Slide 17: Exceptional Progress on Payer Coverage in the First Quarter After Launch
17 Exceptional Progress on Payer Coverage in the First Quarter After Launch, Exceeding Rare Disease Launch Analogs1 • Motivated and Commercial Medicaid committed HCPs pushing through payer appeals 14 • Payer approvals across Commercial and State Medicaid >50% Programs list AVLAYAH as covered Medicai
Slide 18: AVLAYAH U.S. Launch Dynamics
18 AVLAYAH U.S. Launch Dynamics 2026: Building the Foundation To Become the Standard of Care for MPS II Pediatric Patients * Commercial ~$10M Projected $3.6M 2Q 2026 Net Revenue >50% Lives 3Q 2026 Net Covered to $12M Revenue 2026 2027 2028+ Activation & Access Adoption Growth & Broad Access & Patien
Slide 19: Building the ETV Franchise Portfolio for Lysosomal Storage Diseases
19 Building the ETV Franchise Portfolio for Lysosomal Storage Diseases Zafinofusp alfa PTV:PGRN ETV:GAA ETV:GCase ETV:IDUA Delivering the (DNL126) (DNL593) (DNL952) (DNL111) (DNL622) Next-Generation of TransportVehicle- Enabled ERT • Addressing neurologic and MPS II MPS IIIA FTD-GRN Pompe Parkinson’
Slide 20: Pipeline Highlights
Pipeline Highlights Ryan Watts, Ph.D., CEO
Slide 21: On Track to Deliver Denali's D3X3 Goals Over 2026-2028
21 On Track to Deliver Denali’s D3X3 Goals Over 2026-2028 2 Growing Brands • AVLAYAH • zafinofusp alfa Deliver 5 Clinical Proofs of Concept Develop Alzheimer’s Disease D3 • DNL628 (OTV:MAPT) • DNL921 (ATV:Abeta) Pompe Disease 4-6 • DNL952 (ETV:GAA) New Clinical FTD-GRN Programs • Continued leadershi
Slide 22: DNL593 (PTV:PGRN) PGRN Replacement for FTD-GRN
22 DNL593 (PTV:PGRN) PGRN Replacement for FTD-GRN DNL593 Phase 1/2 Clinical Study Study Population Study Plan Goals & Objectives Enrollm ent Completed • Part A: Healthy • Part A: Safety, PK volunteers aged • Parts B & C: ≥18 to ≤55 years SAD Cohort A LAMP2 • Part B: GRN mutation – Safety, PK, PD bio
Slide 23: Transformative Time for Alzheimer's Disease
23 Transformative Time for Alzheimer’s Disease New Opportunities for Success in Neurodegeneration Blood-Brain Biology Biomarkers Barrier New insights into the Enabling early diagnosis, Validated technologies to underlying, multifaceted monitoring of progression and address key challenge for biology
Slide 24: The Next Advances in AD May Depend on Better Brain Delivery
24 The Next Advances in AD May Depend on Better Brain Delivery Amyloid-beta TransportVehicle (TV) Opportunity Amyloid plaque • Plaque clearance clinically validated • Current limitations DNL921 DNL628 (ATV:Abeta) (OTV:MAPT) – Modest efficacy – ARIA safety risk Potential best-in-class Potential first
Slide 25: ATV:Abeta Reduces ARIA Due to TfR-Mediated Capillary Delivery
25 ATV:Abeta Reduces ARIA Due to TfR-Mediated Capillary Delivery to Brain in Mouse Model of AD Incidence of MRI Lesions1 Route of Entry into Brain2 5xFAD; TfRmu/hu KI; QW IP Anti-Abeta (5-10 mg/kg) Conventional # of Mice with ARIA Event Anti-Abeta 100 m Artery / Arteriole Zone ATV:Abeta (5-10 mg/kg
Slide 26: DNL921 Optimized for Robust Brain Delivery, Safety & Stability
26 DNL921 Optimized for Robust Brain Delivery, Safety & Stability DNL921 (ATV:Abeta) Fusion Molecules1 Effector Molecule Architecture Epitope Function Abeta Binding TV 1 2 3 Control Control IgG N/A Full DNL921 TV- TfR in Fc Apical Conditional Molecule #1 C-term TfR Protease Full cisLALA Molecule #2
Slide 27: OTV Enhances Biodistribution of ASO Evenly Across Brain Regions
27 OTV Enhances Biodistribution of ASO Evenly Across Brain Regions Limited biodistribution Widespread biodistribution with intrathecal ASO with intravenous OTV:ASO Spinal Spinal Cord Cord ASO Immunofluorescence hemibrain coronal section Cervical Lumbar Cervical Lumbar Adapted from Barker et al. Scie
Slide 28: DNL628 Displays Robust and Sustained Knockdown in Mice Expressing Human Tau
28 DNL628 Displays Robust and Sustained Knockdown in Mice Expressing Human DNL628 Tau TimecourseininhTau DNL628Knockdown KnockdownTimecourse hTauxxhTfR hTfRmice mice DNL628 DNL628Knockdown Knockdown DNLI-24-23 Timecourse Timecourse ininhTau hTauxxhTfR hTfRmice mice DNLI-24-23and andDNLI-23-202 DNLI-
Slide 29: Initial Clinical Data from Both AD Programs Expected in 2027
29 Initial Clinical Data from Both AD Programs Expected in 2027 DNL921 Phase 1/1b DNL628 Phase 1b Clinical Study Clinical Study Phase 1b • Phase 1/1b study is ongoing • Phase 1b study ongoing • Safety and clinical proof-of-concept data in 2027 • Clinical biomarker data expected in 1H 2027
Slide 30: Financial Update
Financial Update Alexander Schuth, M.D., COO/CFO
Slide 31: Our Broad Therapeutic Portfolio
31 Our Broad Therapeutic Portfolio Lysosomal Storage Disorders Common Neurodegenerative Diseases Molecule Indication Stage Molecule Indication Stage tividenofusp alfa-eknm FDA Approved DNL151 MPS II PD Phase 2a (LRRK2) (ETV:IDS) Phase 2/3 LRRK2 Inhibitor zafinofusp alfa DNL628 MPS IIIA Phase 1/2 AD
Slide 32: Capital to Execute
32 Capital to Execute Strong Financial Key Capital Allocation Priorities Foundation Invest Strategically • Successful launches of AVLAYAH and potentially zafinofusp alfa $940M • Focused R&D investments to accelerate and expand pipeline Cash and investments as of Q2 2026 Drive Capital Efficiency $195
Slide 33: Q2 2026 Financial Summary
33 Q2 2026 Financial Summary Three Months Ended Three Months Ended $ in millions June 30, 2026 June 30, 2025 AVLAYAH Net Product Revenue $3.6 $– Total Revenue 3.6 – Cost of Goods Sold 0.1 – R&D Expense 97.0 102.7 SG&A 36.3 32.3 Amortization of Intangible Asset 0.7 – Total Operating Expense 134.1 135
Slide 34: Q&A
JENALI J Q&A