Cytokinetics (CYTK) Status Update summary

Key data presentations and clinical findings

• Six presentations and four simultaneous publications at ESC 2024 reinforced aficamten's safety and efficacy, with new analyses supporting its potential as a disease-modifying therapy for obstructive HCM.

• SEQUOIA-HCM CMR substudy showed significant improvements in LV mass index and cardiac remodeling, suggesting structural heart changes and disease modification.

• Echocardiographic and patient-reported outcomes demonstrated improved ventricular structure, function, exercise capacity, symptoms, and biomarkers, with about one-third of patients experiencing major symptom relief.

• Integrated safety analysis across multiple trials showed low rates of LVEF reduction, no heart failure events, and similar rates of atrial fibrillation and syncope compared to placebo.

• FOREST-HCM data indicated many patients could withdraw from standard therapies and maintain efficacy and safety on aficamten monotherapy.

Safety and long-term use of aficamten

• Integrated safety analysis across three clinical trials (206 patient-years, 283 patients) showed aficamten was well-tolerated, with adverse events similar to placebo and no dose interruptions or discontinuations due to decreased LVEF.

• Incidents of LVEF <50% occurred in 3.9% of aficamten-treated patients, none associated with clinical heart failure, and all managed by dose down-titration.

• Low incidence of new onset atrial fibrillation, myocardial infarction, and similar syncope rates compared to placebo reinforce aficamten's safety profile.

Withdrawal of standard of care (SoC) medications

• In the FOREST-HCM study, 47% of patients attempted SoC withdrawal; 92% succeeded, with 64% discontinuing at least one SoC medication and 71% achieving monotherapy with aficamten.

• No significant differences in efficacy or safety were observed post-SoC withdrawal, with similar rates of adverse events and cardiac function measures between groups.

• Data suggest aficamten may be effective and well-tolerated as monotherapy in obstructive HCM.