Denali Therapeutics Inc. · NASDAQ:DNLI

Denali Therapeutics — Technical Presentation (February 2026)

12 slides from Denali Therapeutics's technical presentation, February 2026

  1. Slide 1: Preliminary Results from Phase 1/2 Study of DNL126 in Children with MPS IIIA

    ©2026 Denali Therapeutics Inc. All rights reserved. Preliminary Results from Phase 1/2, First-in- Human, Open-Label Study of DNL126 in Children with Mucopolysaccharidosis IIIA (MPS IIIA) Elizabeth Jalazo, MD University of North Carolina, Chapel Hill, NC, USA

  2. Slide 2: MPS IIIA Pathogenesis, Biomarkers, and Clinical Manifestations

    ©2026 Denali Therapeutics Inc. All rights reserved. BACKGROUND MPS IIIA Pathogenesis, Biomarkers, and Clinical Manifestations TARGET PATHWAY CLINICAL Developmental delay and Genetic deficiency in SGSH Lysosomal dysfunction Neurodegeneration behavior problems, progressing to enzyme activity severe co

  3. Slide 3: Our Approach to Enzyme Replacement Therapy

    ©2026 Denali Therapeutics Inc. All rights reserved. BACKGROUND Our Approach to Enzyme Replacement Therapy THE BBB CHALLENGE DNL126 IV ADMINISTRATION AND BROAD BIODISTRIBUTION SGSH DNL126 (ETV:SGSH) TfR binding site TfR • The BBB is a major • DNL126 is designed to use the TfR to cross the BBB and • D

  4. Slide 4: DNL126 Phase 1/2 Study in Pediatric Participants with MPS IIIA

    ©2026 Denali Therapeutics Inc. All rights reserved. STUDY DESIGN DNL126 Phase 1/2 Study in Pediatric Participants with MPS IIIA • Study DNLI-I-0001 is a multicenter, open-label, 25-week study followed by an open-label extension period through 193 weeks (NCT06181136) in up to 26 pediatric participant

  5. Slide 5: All Cohorts: Participant Demographics and Characteristics

    ©2026 Denali Therapeutics Inc. All rights reserved. DEMOGRAPHICS AND CHARACTERISTICS All Cohorts: Participant Demographics and Characteristics Dose-finding cohorts Efficacy cohorts* Cohort A1 Cohort A2 Cohort A3 Cohort B1 All cohorts (n = 4) (n = 4) (n = 4) (n = 2) (n = 14) DNL126 treatment duration

  6. Slide 6: CNS Biomarkers: CSF Heparan Sulfate and GM3

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: BIOMARKERS Preliminary Data Phase 1 Dose-finding Cohorts (A1 and A2) CNS Biomarkers: CSF Heparan Sulfate and GM3 CSF HS CSF GM3 0 0 Percent change (GMR to BL [95% CI]) Percent change (GMR to BL [95% CI]) −25 −25 −50 −50 −75 −75 −100 −100 B

  7. Slide 7: Peripheral Measures: Urine HS and Liver Volume

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: BIOMARKERS Preliminary Data Phase 1 Dose-finding Cohorts (A1 and A2) Peripheral Measures: Urine HS and Liver Volume Urine HS Liver volume 0 2.0 Percent change (GMR to BL [95% CI]) Liver volume (mean multiples of 1.8 −25 normal and 95% CI)

  8. Slide 8: All Cohorts: Safety Overview

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: SAFETY All Cohorts: Safety Overview • All participants (n = 14) experienced a TEAE TEAEs reported in >30% of participants assessed by the investigator as related to the study intervention Preferred term All cohorts (n = 14) [n (%)] • The m

  9. Slide 9: All Cohorts: Infusion-related Reactions

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: SAFETY All Cohorts: Infusion-related Reactions Infusion-related Infusion related reactions by cohort and study week Cohort A1, N=4 Cohort A2, N=4 Cohort A3, N=4 Cohort B1, N=2 100 • IRR frequency and/or severity decreased after Week 25 in

  10. Slide 10: Conclusions

    ©2026 Denali Therapeutics Inc. All rights reserved. CONCLUSIONS Conclusions Preliminary results from dose-finding cohorts demonstrate that 49 weeks of DNL126 treatment resulted in substantial reductions in CSF and peripheral biomarkers, with some participants achieving normalization • CSF HS: 80% me

  11. Slide 11: Acknowledgements

    ©2026 Denali Therapeutics Inc. All rights reserved. Acknowledgements We give a special thank you to the participants and families who generously contributed through their participation We also thank our collaborators and the Denali Therapeutics team for the conduct of the study and data collection C

  12. Slide 12: Thank You

    ©2026 Denali Therapeutics Inc. All rights reserved. Thank You

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