The CANYON trial demonstrated a 28% average reduction in creatine kinase (CK) levels over months 6 through 12 in sevasemten-treated patients compared to placebo. How significant is this biomarker change in terms of predicting long-term muscle preservation and clinical outcomes in Becker muscular dystrophy?

While the key secondary endpoint showed stabilization of the North Star Ambulatory Assessment (NSAA) scores with a trend toward improvement, it did not reach statistical significance (p=0.16). Can you elaborate on how these trends could still be clinically meaningful for patients with Becker?

The sevasemten group included patients with more advanced disease at baseline compared to placebo. How might this baseline imbalance have influenced the results, and what does it suggest about the therapy’s potential efficacy in early-stage versus advanced Becker patients?

Other functional assessments, such as the 10-meter walk/run, 4-stair climb, and 100-meter timed test, showed trends toward improvement. How should these findings be interpreted, and what additional studies are needed to validate these functional benefits?

The trial reported a 77% reduction in plasma TNNI2 levels in the sevasemten-treated group compared to placebo. What does this significant reduction indicate about the drug's mechanism of action, and how might it guide future biomarker-driven therapeutic strategies?

Sevasemten was well-tolerated with no new safety concerns. How does its safety profile position it as a potential long-term therapy for Becker, and what considerations should be made for its use in combination with other treatments?

With 99% of eligible participants enrolling in the MESA open-label extension trial, what are the key expectations for long-term data from this cohort, and how might it shape the therapeutic landscape for Becker muscular dystrophy?

Edgewise has announced plans to engage with the FDA and EMA regarding marketing authorization filings for sevasemten in Becker. What are the critical factors for securing regulatory approval, and how could this therapy address the current unmet needs in Becker muscular dystrophy?