Dyne Therapeutics (DYN) Study Update summary

Program and Study Overview

• Dyne presented new data from the ACHIEVE trial for Dyne-101 in DM1 and provided updates on Dyne-251 for DMD amenable to Exon 51 skipping, both leveraging the FORCE platform for targeted delivery to muscle and CNS tissues.

• Both programs are in late-stage development, with registrational expansion cohorts planned or underway and anticipated readouts in 2025 and 2026, supporting potential U.S. Accelerated Approval submissions in 2026.

• Dyne's pipeline includes additional preclinical candidates for FSHD and Pompe disease, all fully owned and supported by a cash position of ~$642M as of 12/31/24, enabling operations into H2 2026.

• The FORCE platform supports expansion into CNS, rare skeletal, cardiac, and metabolic diseases.

Study Design and Objectives

• ACHIEVE is a randomized, placebo-controlled, double-blind Phase 1/2 trial evaluating Dyne-101 in DM1, with a Multiple Ascending Dose (MAD) portion and a planned registrational expansion cohort at 6.8 mg/kg Q8W.

• DELIVER is a Phase 1/2 trial for Dyne-251 in DMD patients amenable to exon 51 skipping, with a registrational expansion cohort at 20 mg/kg Q4W.

• Both studies assess safety, pharmacokinetics, pharmacodynamics, and efficacy, with endpoints including biomarker changes, functional measures, and patient-reported outcomes.

Dyne-101 (DM1) Study Results and Clinical Insights

• The MAD portion of the ACHIEVE trial completed with 56 patients; the optimal dose selected as 6.8 mg/kg for the registrational cohort, which is now enrolling.

• Dyne-101 at 6.8 mg/kg Q8W showed robust DMPK knockdown, splicing correction (CASI >20%), and broad functional improvements at 3 and 6 months, including strength, mobility, and CNS-related endpoints.

• Clinically meaningful improvements were observed in 10-Meter Walk/Run, 5X Sit to Stand, and MDHI, with a 44% improvement in MDHI total score and notable CNS benefits at the registrational dose.

• Safety profile remains favorable, with zero serious related treatment-emergent adverse events, most AEs mild or moderate, and no persistent anemia or thrombocytopenia across ~855 doses and 72 patient-years.