Avidity Biosciences (RNA) Study Update summary

Regulatory and Program Updates

• The accelerated approval pathway for FSHD is open in the U.S., with written FDA confirmation and CDUX/KHDC1L validated as a surrogate endpoint; FDA and EMA have granted Orphan and Fast Track designations.

• Three successive BLA submissions are planned within a 12-month period starting at the end of 2025, with Delvotax/Del-brax leading.

• The global confirmatory Phase 3 FORWARD trial has been initiated, enrolling about 200 participants in an 18-month, double-blind, placebo-controlled study.

• The 42 biomarker cohort is fully enrolled, with topline data expected in Q2 2026 and a BLA submission in the second half of 2026.

• FDA is aligned with study designs and endpoints for both biomarker and confirmatory studies.

Study Design and Endpoints

• FORTITUDE was a randomized, double-blind, placebo-controlled Phase 1/2 study with dose escalation and biomarker cohorts, focusing on safety, PK, and exploratory efficacy.

• Key clinical endpoints included 10-meter walk run, timed up and go, quantitative myometry, reachable workspace, and patient-reported outcomes.

• The FORWARD Phase 3 trial uses a 2 mg/kg dose every six weeks, with an 18-month placebo-controlled period and open-label extension.

• Quantitative muscle testing is the current primary endpoint, with flexibility to finalize based on ongoing data.

• Both studies include adolescent participants aged 16 and above.

Efficacy and Safety Results

• Delvotax/Del-brax demonstrated consistent improvements in muscle function, mobility, and strength versus placebo at one year, with benefits in 10MWRT, TUG, QMT, and RWS.

• Improvements in functional endpoints exceeded minimal clinically important differences at both tested doses.

• Quality of life and patient-reported outcomes improved, including physical function, fatigue, pain, sleep disturbance, and global impression.

• Safety profile was favorable, with no serious or severe drug-related adverse events, no discontinuations due to adverse events, and most side effects mild or moderate.

• Both 2 mg/kg and 4 mg/kg doses showed similar efficacy, supporting 2 mg/kg for future studies.