Denali Therapeutics Inc. · NASDAQ:DNLI

Denali Therapeutics — Technical Presentation (February 2026)

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

  1. Slide 1: Phase 1/2 Study of Intravenous Tividenofusp Alfa for Mucopolysaccharidosis Type II

    ©2026 Denali Therapeutics Inc. All rights reserved. Phase 1/2 Study of Intravenous Tividenofusp Alfa for Mucopolysaccharidosis Type II Professor Joseph Muenzer, MD, PhD University of North Carolina School of Medicine, Chapel Hill, NC, USA

  2. Slide 2: Developing a Therapy for MPS II (Hunter Syndrome)

    ©2026 Denali Therapeutics Inc. All rights reserved. BACKGROUND DEVELOPING A THERAPY FOR MPS II (HUNTER SYNDROME) Tividenofusp alfa (DNL310) is an investigational IDS fusion protein engineered for CNS and peripheral delivery to address cognitive, behavioral, and somatic disease control in MPS II with

  3. Slide 3: Tividenofusp Alfa Phase 1/2 Study in Pediatric Participants with MPS II

    ©2026 Denali Therapeutics Inc. All rights reserved. STUDY DESIGN TIVIDENOFUSP ALFA PHASE 1/2 STUDY IN PEDIATRIC PARTICIPANTS WITH MPS II • Study DNLI-E-0002 is an international, open-label, 24-week study with safety and open-label extension periods (NCT04251026) – Data are presented from the clinica

  4. Slide 4: Participant Enrollment and Disposition

    ©2026 Denali Therapeutics Inc. All rights reserved. DISPOSITION PARTICIPANT ENROLLMENT AND DISPOSITION 3 Failed screeninga 50 Underwent screening Exposure summary n = 47 Median: 134 weeks 47 Were allocated to Minimum: 19 weeks treatment screening Maximum: 243 weeks 1 Discontinued 47 Entered the 24-w

  5. Slide 5: Baseline Characteristics

    ©2026 Denali Therapeutics Inc. All rights reserved. PARTICIPANT CHARACTERISTICS BASELINE CHARACTERISTICS All (cohorts A–E) All (cohorts A–E) Characteristic Characteristic n = 47 n = 47 Mean (SD) 5.5 (3.1) MPS II phenotype, Neuronopathic 44 (93.6) Age, years Median (min, max) 5.0 (0.3, 12.6) n (%) No

  6. Slide 6: CNS and Peripheral Biomarkers: CSF and Urine HS

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: BIOMARKERS CNS AND PERIPHERAL BIOMARKERS: CSF AND URINE HS CSF HS Urine HS Percent change (GMR to BL [95% CI]) 0 0 Percent change (GMR to BL [95% CI]) −25 −25 −50 −50 −75 −75 BL 24 49 104 153 201 BL 7 13 21 49 104 129 153 177 201 Visit (we

  7. Slide 7: CNS Biomarkers: Serum NfL

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: BIOMARKERS CNS BIOMARKERS: SERUM NfL Serum NfL 30 (GMR to BL [95% CI]) 0 Percent change −30 −60 −90 BL 7 13 24 37 49 61 73 85 97 104 117 129 141 153 165 177 189 201 Visit (week) n 47 45 42 28 21 13 Participants below ULN (n/N), % 19.1 24.4

  8. Slide 8: Hearing Threshold

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: CLINICAL HEARING THRESHOLD Mean CFB in pure tone average by ABR (eHL) and audiometry (HL) Pure tone average 0 CFB in dB, Visit n P value CFB (mean and 95% CI, dB) adjusted mean (95% CI) −5 W24 27 −9.4 (−13.7, −5.0) < 0.0001 −10 W49 28 −10.

  9. Slide 9: Liver Volume: MRI (Cohorts C, D, and E)

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: CLINICAL LIVER VOLUME: MRI (COHORTS C, D, AND E) Liver volume (multiples of normal) 1.4 Liver volume (mean multiples of 1.3 Liver volume (proportion below ULN) b normal and 95% CI) 1.2 1.1 Percent [proportion (n/N)]c below the ULNb Populat

  10. Slide 10: Adaptive Behavior

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: CLINICAL ADAPTIVE BEHAVIOR Vineland-3 ABRS-8 All < 2 years CFB (mean and 95% CI) 200 ≥ 2 to < 4 years ≥ 4 years 100 0 BL 13 24 37 49 61 73 85 104 117 129 141 153 165 177 189 201 213 Visit (week) n 46 26 44 38 41 37 34 33 29 28 25 23 22 19

  11. Slide 11: Cognition

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: CLINICAL COGNITION BSID-III cognitive raw score All 40 < 2 years CFB (mean and 95% CI) ≥ 2 to < 4 years 30 ≥ 4 years 20 10 0 −10 BL 13 24 37 49 61 73 104 129 153 177 201 Visit (week) n 39 13 33 9 31 5 23 20 19 16 13 6 < 2 years 5 5 5 5 4 4

  12. Slide 12: Safety Overview

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: SAFETY SAFETY OVERVIEW Most frequently reported TEAEs • Long-term exposure (median ~2.5 years) demonstrated a stable All cohorts (n = 47) safety profile with no new safety signals since the primary Preferred term n (%) of participants anal

  13. Slide 13: IRRs

    ©2026 Denali Therapeutics Inc. All rights reserved. RESULTS: SAFETY IRRs Proportion of participants with at least one IRR during each 4-week interval, categorized by severitya IRR severity Mild Moderate Severe 75 at least one IRR (%) Participants with 50 25 0 Weeks • In total, 41 participants (87%)

  14. Slide 14: Conclusions

    ©2026 Denali Therapeutics Inc. All rights reserved. CONCLUSIONS CONCLUSIONS Treatment with tividenofusp alfa led to substantial reductions from baseline in CNS and peripheral biomarkers of disease • The majority of participants achieved normalization of CSF and urine HS, and serum NfL • Reduction an

  15. Slide 15: Acknowledgments

    ©2026 Denali Therapeutics Inc. All rights reserved. ACKNOWLEDGMENTS We would like to give a special thank you to the participants and families who generously contributed through their participation in this study sponsored by Denali Therapeutics Inc. We also thank the study principal investigators, c

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