Slide 1: Long-Term Functional Improvement With Zeleciment Basivarsen in the Phase 1/2 ACHIEVE Trial
Long-Term Functional Improvement With Zeleciment Basivarsen • Long-Term Functional in the Improvement With Phase Zeleciment1/2 ACHIEVE Basivarsen Trial1/2 in the Phase ACHIEVE Trial • Karlien Karlien Mul, Mul, MD, MD, PhD PhD , Guillaume 1, Guillaume 1 Bassez Bassez2, Jordi , Jordi Diaz-Manera Diaz-
Slide 2: Disclosures
Disclosures Disclosure • Dr. Mul has served as a paid consultant for Dyne Therapeutics, Avidity Biosciences, and Sarepta Therapeutics. She received research funding from Vertex Pharmaceuticals and PepGen Inc. • Zeleciment basivarsen (z-basivarsen, also known as DYNE-101) is investigational or otherw
Slide 3: Z-Basivarsen Addresses the Central Pathobiology of DM1 to Enable Broad Functional Improvement
Z-Basivarsen Addresses the Central Pathobiology of DM1 to Enable Broad Functional Improvement1 Robust and Early DMPK degradation in MBNL release and Functional outcomes widespread clinical the nucleus splicing correction delivery effect CUG expansion MBNL trapped: Splicing defect Muscle Strength: Fa
Slide 4: ACHIEVE Multiple Ascending Dose Study
ACHIEVE Multiple Ascending Dose Study Population 6-Month Placebo-Controlled Period (MAD Cohorts) Transition to 6.8 mg/kg1 • Ages 18–49 years 6.8 mg/kg N=8 (3:1) Q8W, Placebo Primary endpoints Open-label 5.4 mg/kg extension (OLE) • Safety and tolerability N=8 (3:1) Q8W, Placebo 3.4 mg/kg Additional e
Slide 5: ACHIEVE MAD Study: Efficacy Analysis of Pooled Dose Group
ACHIEVE MAD Study: Efficacy Analysis of Pooled Dose Group • Previous long-term analysis included N=6 assigned to 6.8 mg/kg (registrational dose) at baseline1 • To determine if similar trends hold in a larger sample, we analyzed 12mo efficacy of a pooled dose group (N = 26) • The pooled dose group in
Slide 6: Z-Basivarsen ACHIEVE MAD Clinical Update
Z-Basivarsen ACHIEVE MAD Clinical Update Safety Data from ACHIEVE MAD as of April 20, 2026 Data from 6.8 mg/kg cohort and analysis of Pooled Dose Group: • vHOT Efficacy • Clinical outcome measures of muscle strength and function • Patient-reported outcomes Divergence From Analysis of ACHIEVE versus
Slide 7: ACHIEVE MAD Baseline Characteristics
ACHIEVE MAD Baseline Characteristics Placebo 6.8 mg/kg Q8W Pooled dose group Mean (SD) (N=14) (N=6) (N=26) Age (years) 32.6 (9.6) 37.2 (9.7) 35.6 (8.0) BMI (kg/m2) 24.4 (4.7) 23.4 (5.6) 22.7 (3.9) CASI-22 0.68 (0.20) 0.74 (0.25) 0.73 (0.19) CTG repeats 597 (246) 542 (191) 527 (243) vHOT (middle fing
Slide 8: Favorable Safety Profile With No Serious Related TEAEs
Favorable Safety Profile With No Serious Related TEAEs1 Summary of treatment-emergent adverse events (TEAEs)1 Most TEAEs were mild or moderate in intensity1 o 10 serious TEAEs unrelated to study drug Participants with ≥1 TEAE, n (%) Atrioventricular block first degree (1)3 Pneumonia (2 events in
Slide 9: Pooled Efficacy Data Continue to Support vHOT as an Early Indicator of Functional Improvement
Pooled Efficacy Data Continue to Support vHOT as an Early Indicator of Functional Improvement vHOT Middle Finger: Mean Change From Baseline (SEM) Pooled Dose Group Pooled Dose Group QMT Total 4.8 (%p) -2.0 2 Change From Baseline (Mean ± SEM) -10 -5 0 5 10 1 +0.4 sec. 4.8 +5% Δ from BL Hand Grip -2.5
Slide 10: Improvement in Strength Is Sustained at 12 Months, as Measured by QMT
Improvement in Strength Is Sustained at 12 Months, as Measured by QMT (%p) Quantitative Muscle Testing (QMT) Total Score Pooled Dose Group (N=26) 6.8 mg/kg Cohort Change From Baseline (Mean ± SEM) Change From Baseline (Mean ± SEM) 15 15 Improvement +10.3 10 10 +20.1% Δ from BL QMT Total (%p) QMT Tot
Slide 11: Improvement in Motor Function Is Sustained at 12 Months, as Measured by 5xSTS
Improvement in Motor Function Is Sustained at 12 Months, as Measured by 5xSTS Timed Function Test 5 Times Sit to Stand Pooled Dose Group (N=26) 6.8 mg/kg Cohort 2 2 Change From Baseline (Mean ± SEM) Change From Baseline (Mean ± SEM) Improvement 1 1 +0.48 +5.2% Δ from BL 5×STS (sec) 5×STS (sec) 0 0 -
Slide 12: Improvement in Patient-Reported Disease Burden Is Sustained at 12 Months, as Measured by MDHI
Improvement in Patient-Reported Disease Burden Is Sustained at 12 Months, as Measured by MDHI Total Score Myotonic Dystrophy Health Index (MDHI) Total Score Pooled Dose Group (N=26) 6.8 mg/kg Cohort Change From Baseline (Mean ± SEM) Change From Baseline (Mean ± SEM) 5 5 Improvement +1.9 +10.0% Δ fro
Slide 13: END-DM1 Assesses Natural DM1 Progression
END-DM11 Assesses Natural DM1 Progression END-DM1 is an ongoing, international, prospective DM1 natural history study designed to expand understanding of DM1 disease progression and to establish biomarkers and endpoints appropriate for interventional studies1,2 Propensity-Matched Baseline Characteri
Slide 14: ACHIEVE Pooled Dose Group Improves From Baseline and Diverges From Natural History
ACHIEVE Pooled Dose Group Improves From Baseline and Diverges From Natural History in Strength and Ambulation 1 Year Mean Change from Baseline (SEM) 4.8 %p QMT Total ACHIEVE Pooled High ACHIEVE DoseDose (N=25) (%p) END-DM1 END-DM1Matched (N=41) -4 -2 0 2 4 6 8 4.3 %p Hand Grip ACHIEVE Pooled High AC
Slide 15: Improvement in MDHI in ACHIEVE Exceeded MCID
Improvement in MDHI in ACHIEVE Pooled Dose Group Exceeded MCID MDHI Total Score Year 1 CNS-Related MDHI Subscales Pooled Dose Group (N=25) vs END-DM1 (N=410) Change From Baseline, Mean (SEM) 6 Fatigue 4 4 2 0 -2 -4 -6 -8 -10 -12 2 -25.2% -1.7% Sleep MDHI Total Score Δ from BL Δ from BL Improvement 0
Slide 16: Summary: Z-Basivarsen ACHIEVE MAD Clinical Update
Summary: Z-Basivarsen ACHIEVE MAD Clinical Update Safety Safety findings through April 20, 2026, remain favorable • 6.8 mg/kg cohort demonstrated durable functional improvement in myotonia, motor function, and strength1 • Data continues to support vHOT as an early indicator of functional improvement
Slide 17: Acknowledgments
Acknowledgments • ACHIEVE participants, families, investigators, and site staff • Myotonic Dystrophy Clinical Research Network (DMCRN) and END-DM1 participants, families, and research personnel • Members of the DM1 community who have provided feedback, insights, and questions To view the presentatio