Cytokinetics (CYTK) Investor update summary

Key clinical trial results

• ACACIA-HCM is the first positive phase III trial in non-obstructive HCM, showing aficamten led to statistically significant and clinically meaningful improvements in exercise capacity, symptom burden, and cardiac biomarkers compared to placebo.

• Dual primary endpoints were met: KCCQ Clinical Summary Score improved by 3 points (P=0.021) and peak VO2 increased by 0.67 ml/kg/min (P=0.003) at week 36.

• Improvements were consistent across all prespecified subgroups and secondary endpoints, including NYHA class, CPET parameters, and NT-proBNP levels, with over 70% of patients achieving clinically meaningful symptom improvement.

• 53% of patients on aficamten showed clinical response in three or more outcome measures versus 13% on placebo.

• Over 80% of trial participants elected to enroll in the long-term extension study, FOREST-HCM.

Safety and tolerability

• Aficamten was generally well-tolerated, though non-fatal adverse events leading to discontinuation and serious adverse events were higher compared to placebo.

• LVEF <50% occurred in 10.5% of aficamten patients versus 0.8% on placebo; most events were manageable and occurred during dose titration.

• Serious heart failure events were more frequent during the titration phase but were manageable and resolved with standard therapy.

• No difference in new onset atrial fibrillation between aficamten and placebo.

• No deaths occurred in the aficamten arm; three deaths were reported in the placebo group.

Clinical and market implications

• Aficamten may become the first therapy to directly address the underlying disease process in non-obstructive HCM, filling a major unmet need.

• The drug's efficacy and safety profile in both obstructive and non-obstructive HCM could simplify treatment decisions and increase adoption.

• Physicians anticipate high patient demand and expect rapid uptake once approved for non-obstructive HCM.

• Positive results in non-obstructive HCM may encourage exploration of aficamten and other cardiac myosin inhibitors in select HFpEF populations.

• Regulatory submission for aficamten in non-obstructive HCM is planned for Q4, with updates on global plans forthcoming.