Wave Life Sciences Ltd. · NASDAQ:WVE

Wave Life Sciences — 2024 EHDN Plenary Meeting & Enroll-HD Congress

16 slides from Wave Life Sciences's conference presentation, Sep 13, 2024

  1. Slide 1: Results from SELECT-HD: allele-selective mHTT-lowering approach in Huntington's Disease

    Results from SELECT-HD: An allele-selective mutant huntingtin-lowering approach in Huntington’s Disease Jane Atkins, PhD SVP, HD Global Program Lead September 13, 2024 1 Presented at 2024 EHDN Plenary Meeting & Enroll-HD Congress

  2. Slide 2: Forward-looking statements

    Forward-looking statements This document contains forward-looking statements. All statements other than statements of historical facts contained in this document, including statements regarding possible or assumed future results of operations, preclinical and clinical studies, business strategies, r

  3. Slide 3: Disclosures

    Disclosures • Jane Atkins in an employee of Wave Life Sciences 3

  4. Slide 4: Results from SELECT-HD

    Results from SELECT-HD WVE-003* exceeded our predefined criteria for ≥30% CSF mHTT lowering Confirmed WVE-003’s allele-selective, wild-type HTT sparing mechanism of action 30 mg Q8W regimen had a safe and tolerable profile First demonstrated association between mHTT lowering and slowing of caudate a

  5. Slide 5: WVE-003: First-in-class allele-selective, mHTT lowering oligonucleotide

    WVE-003: First-in-class investigational allele-selective, mHTT lowering oligonucleotide WVE-003 suppresses mHTT protein expression Recruit by promoting degradation of the transcript RNase H SNP3 mHTT transcript Expanded CAG repeat mHTT allele ‘003 Transcript degradation Reduced mHTT protein wtHTT tr

  6. Slide 6: Adaptive Ph1b/2a randomized, placebo controlled trial designed to assess WVE-003 in HD

    : Adaptive Ph1b/2a randomized, placebo controlled, double-blind clinical trial designed to rapidly assess WVE-003 in HD Key eligibility criteria Single-ascending dose phase Multidose phase Key objectives • CAG >36 30, 60, 90 mg single doses & 30 mg Q8W & follow-up • Safety and tolerability follow-up

  7. Slide 7: Baseline characteristics were generally balanced across cohorts

    Baseline characteristics were generally balanced across cohorts Single Dose Multidose Placebo 30 mg 60 mg 90 mg Placebo 30 mg Category (N=16) (N=13) (N=10) (N=8) (N=7) (N=16) Age at diagnosis (years), mean 38.81 42.31 39.60 45.25 37.43 41.88 Sex, n (%) Male 10 (62.5) 7 (53.8) 7 (70.0) 5 (62.5) 5 (71

  8. Slide 8: Multidose safety: 30 mg WVE-003 was generally safe and well tolerated

    Multidose safety: 30 mg WVE-003 was generally safe and well tolerated Safety Summary WVE-003 • 30 mg WVE-003: all AEs mild or moderate in intensity Category Placebo 30 mg n=7 (%) [# events] n=16 (%) [#events] • AEs balanced across cohorts Patients with at least one TEAE 7 (100) [25] 13 ( 81.3) [53]

  9. Slide 9: Multiple doses of WVE-003 demonstrated selective, potent, durable reduction of mHTT

    Multiple doses of WVE-003 demonstrated selective, potent, and durable reduction of mHTT Poster J005 CSF mHTT protein levels CSF wtHTT protein levels Geometric Mean Ratio to Baseline +/- SE 2.00 Geometric Mean Ratio to Baseline +/- SE 2.00 Placebo WVE-003 30 mg 1.75 1.75 46% mHTT mHTT Protein (fM) wt

  10. Slide 10: Some CSF NfL elevations observed

    Some CSF NfL elevations observed CSF NfL 4.75 (fold change from baseline) 4.00 3.25 CSF NfL 2.50 Placebo range (5%-95%) 1.75 1.00 0.25 1 29 57 85 113 141 169 197 Day CSF NfL changes not correlated with severity or number of AEs, change in caudate volume 10 Gray box represents 5-95% range for CSF NfL

  11. Slide 11: Disconnect in NfL changes between plasma and CSF

    There was a disconnect in NfL changes between plasma and CSF Plasma NfL 2.5 (Geometric mean ratio to baseline – 95% CI) Placebo WVE-003 30 mg 2.0 Plasma NfL (pg/mL) 1.5 ** 1.0 0.5 0 -0.5 1 29 57 85 113 141 169 197 Day 11 Placebo: n=7; WVE-003 30 mg Q8W: n=16 at all time points; * p<0.05, ** p<0.01 M

  12. Slide 12: Slowing of caudate atrophy associated with mHTT lowering, WVE-003 exposure

    Slowing of caudate atrophy associated with mHTT lowering, WVE-003 exposure Normalized caudate volume mHTT lowering associated with slowing caudate atrophy -2 Change from baseline caudate volume Least-squares mean change R: -0.503 Slowing atrophy -3 P<0.05 Slowing atrophy -5.10 -4.68 from baseline -4

  13. Slide 13: Some exploratory clinical measures favored WVE-003, not statistically significant

    Some exploratory clinical measures favored WVE-003, not statistically significant 10.0 TMS 0.5 cUHDRS Improved outcome 7.5 Improved outcome 0.0 5.0 -0.5 Group mean ± SE of change 2.5 -1.0 0.0 -1.5 2 0.4 SDMT TFC 0.2 Improved outcome 1 Improved outcome 0 0 0.2 -1 -0.4 -2 -0.6 -3 Placebo WVE-003 30 mg

  14. Slide 14: Summary of SELECT-HD results

    Summary of SELECT-HD results • 30 mg WVE-003 dosed every 8 weeks was generally safe and well-tolerated - AEs all mild or moderate, no SAEs - Changes in ventricular volume were in line with natural history cohort • mHTT lowering, wtHTT sparing achieved criteria for advancement of WVE-003 - Mean mHTT

  15. Slide 15: Acknowledgements

    Acknowledgements THANK YOU to SELECT-HD participants and their families Clinical Advisory Committee SELECT-HD Investigators • Mayke Oosterloo • Daniel Claassen • Jamie Kulisevsky Bojarski • Tommaso Bovi • Carolyn Orr • Mary Edmondson • Ralf Reilmann • Sylvain Chouinard • Ray Dorsey • Richard Rhys Da

  16. Slide 16: For questions contact

    For questions contact: investorrelations@wavelifesci.com

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