Cytokinetics, Incorporated · NASDAQ:CYTK

Cytokinetics — Technical Presentation (August 2026)

20 slides from Cytokinetics's technical presentation, Aug 29, 2026

  1. Slide 1: Effect of Aficamten on Cardiac Structure and Function in Symptomatic nHCM

    Effect of Aficamten on Cardiac Structure and Function in Patients with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy Results from the ACACIA-HCM Trial Sheila M. Hegde1,2, Xiaowen Wang2, Scott D. Solomon2, on behalf of the ACACIA-HCM Investigators Co-authors: Ankit Bhatia, Maria Luisa Peña P

  2. Slide 2: Background (I)

    Background (I) • Limited proven therapies are available for patients with symptomatic nonobstructive HCM (nHCM) • Symptom burden in nHCM has been attributed to diastolic dysfunction, impaired myocardial energetics, microvascular ischemia, and myocardial fibrosis • Aficamten, a next-in-class cardiac

  3. Slide 3: Background (II)

    Background (II) • In the phase 3, randomized, placebo-controlled ACACIA-HCM trial, aficamten also significantly improved both symptoms and exercise capacity in patients with symptomatic nHCM.1 • This pre-specified exploratory analysis evaluated the effect of aficamten on cardiac structure and functi

  4. Slide 4: Methods: Study Design

    Methods: Study Design Patients with Aficamten (5 – 20 mg) Randomization 1:1 symptomatic HCM: n = 258 • Dose range: 5 to 20 mg. Screening N = 517 • NYHA FC II‒III • Titration by LVEF through Week 6. EOS • KCCQ-CSS ≤85 • LVEF ≥60% Placebo • NT-proBNP ≥300 pg/mL n = 259 • Prespecified Exploratory Analy

  5. Slide 5: Methods: Study Design

    Methods: Study Design Patients with Aficamten (5 – 20 mg) Randomization 1:1 symptomatic HCM: n = 258 • Dose range: 5 to 20 mg. Screening N = 517 • NYHA FC II‒III • Titration by LVEF through Week 6. EOS • KCCQ-CSS ≤85 • LVEF ≥60% Placebo • NT-proBNP ≥300 pg/mL n = 259 • Prespecified Exploratory Analy

  6. Slide 6: Baseline Characteristics

    Results: Baseline Characteristics Characteristic Aficamten (n=258) Placebo (n=259) Age, years 56 ±16 55 ±16 • Mean Age: 55 ± 16 years Female sex 140 (54) 137 (53) • Female Sex: 54% Race White 200 (78) 188 (73) • Race: 75% White, 13% Asian Asian 30 (12) 39 (15) Black 17 (7) 16 (6) Other 28 (11) 32 (1

  7. Slide 7: Baseline Echo Characteristics

    Results: Baseline Echo Characteristics Aficamten Placebo Characteristic (n=258) (n=259) • Normal LV systolic function. LV Structure and Function 68 ± 4 68 ± 3 LVEF, % 68 ± 4 68 ± 3 • Mean max wall thickness: 2.3 ± 0.5 cm. Maximal wall thickness, cm 2.2 ± 0.5 2.3 ± 0.6 LV end-diastolic volume index,

  8. Slide 8: Left Atrial Volume Index

    Results: Left Atrial Volume Index Change in Left Atrial Volume Index over Time Trend towards improvement in LAVI with longer aficamten treatment Stabilization of LAVI with aficamten Baseline Values: W36 EoT Analysis excludes those Treatment Effect Treatment Effect Aficamten: 38.1 ± 15.1 −1.3 mL/m2 −

  9. Slide 9: Diastolic Function During Titration

    Results: Diastolic Function During Titration Change in Peak E Velocity Change in Septal e′ Velocity Change in Septal E/e′ over Time over Time over Time Incremental changes in diastolic function observed with dose titration of aficamten Week 8 Aficamten dose: 0 mg, 5 (2%); 5 mg, 14 (6%); 10 mg, 17 (7

  10. Slide 10: Diastolic Function

    Results: Diastolic Function Change in Peak E Velocity over Time Baseline Values: Aficamten: 74.5 ± 24.5 W36 EoT Placebo: 70.3 ± 23.7 Treatment Effect Treatment Effect 5.1 cm/s (2.2, 8.0) 2.9 cm/s (0.2, 5.5) P=0.001 P=0.034 Treatment effect assessed by linear regression adjusted for baseline values,

  11. Slide 11: Diastolic Function

    Results: Diastolic Function Change in Peak E Velocity over Time Change in Septal e′ Velocity over Time Change in Septal E/e′ over Time Baseline Values: Baseline Values: Baseline Values: Aficamten: 74.5 ± 24.5 W36 EoT Aficamten: 5.1 ± 1.7 W36 EoT Aficamten: 15.9 ± 7.4 W36 EoT Placebo: 70.3 ± 23.7 Tre

  12. Slide 12: Prevalence of Abnormal Diastolic Function Measures

    Results: Prevalence of Abnormal Diastolic Function Measures 2025 ASE Guidelines Normal Abnormal Placebo Aficamten abnormal ranges1 Baseline 26% 74% 26% 74% Septal e′ • Septal e′ ≤ 6 cm/s Week 36 25% 75% 39% 61% • Lateral e′ ≤ 7 cm/s Normal Abnormal Normal Abnormal • Septal E/e′ ≥ 15 • Lateral E/e′ ≥

  13. Slide 13: Prevalence of Abnormal Diastolic Function Measures

    Results: Prevalence of Abnormal Diastolic Function Measures 2025 ASE Guidelines Normal Abnormal Placebo Aficamten abnormal ranges1 Baseline 26% 74% 26% 74% Septal e′ • Septal e′ ≤ 6 cm/s Week 36 25% 75% 39% 61% • Lateral e′ ≤ 7 cm/s Normal Abnormal Normal Abnormal • Septal E/e′ ≥ 15 • Lateral E/e′ ≥

  14. Slide 14: LV Systolic Function and LV Wall Thickness

    Results: LV Systolic Function and LV Wall Thickness Change in Left Ventricular Ejection Fraction over Time Change in Maximum Wall Thickness over Time Baseline Values: W36 EoT Baseline Values: W36 EoT Aficamten: 68 ± 4 Treatment Effect Treatment Effect Aficamten: 2.2 ± 0.5 Treatment Effect Treatment

  15. Slide 15: LV Volumes

    Results: LV Volumes Change in Left Ventricular End-Diastolic Volume Index Change in Left Ventricular End-Systolic Volume Index Baseline Values: W36 EoT Baseline Values: W36 EoT Aficamten: 35.4 ± 7.2 Treatment Effect Treatment Effect Aficamten: 11.4 ± 3.2 Treatment Effect Treatment Effect Placebo: 34

  16. Slide 16: RV Size and Function

    Results: RV Size and Function • Modest changes seen in RV structure and function with aficamten: RV Structure RV Function RV Hemodynamics − Increase in RV volumes. RVEDA RV FAC Peak TR Velocity − Decline in TAPSE. 1.0 mL/m2 (0.5, 1.5) −0.5% (−1.6, 0.6) -10.4 cm/s (-19.9, -1.0) − Decline in RV s′ vel

  17. Slide 17: Relationship Between Change in Outcomes and Echocardiographic Measures

    Relationship Between Change in Outcomes and Change in Echocardiographic Measures in Aficamten-Treated Patients pVO2 KCCQ-CSS NT-proBNP (per 1-unit increase) (per 5-unit increase) (per 50% reduction) Septal e′ Septal E/e′ Septal e′ Septal E/e′ 0.08 cm/s (0.01, 0.14) −0.22 (−0.42, −0.03) 0.35 cm/s (0.

  18. Slide 18: Aficamten in Symptomatic nHCM

    Aficamten in Symptomatic nHCM • Aficamten demonstrated significant improvement in LV Diastolic Function measures of cardiac structure and function at 36 weeks or E wave with longer treatment. Septal e’ − Improvement in measures of diastolic function. RV Hemodynamics Lateral e’ Peak TR Velocity Septa

  19. Slide 19: Acknowledgments

    Acknowledgments The ACACIA-HCM trial is funded by Cytokinetics, Incorporated. We thank the following individuals and groups for their contributions to this clinical trial: • Participants and their families. • Investigators and study site staff. • Brigham and Women’s Hospital Cardiovascular Imaging C

  20. Slide 20: Effect of Aficamten on Cardiac Structure and Function (Authors)

    Effect of Aficamten on Cardiac Structure and Function in Patients with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy Sheila M. Hegde, MD, MPH; Xiaowen Wang, MD, MPH; Ankit Bhatia, MD; Maria Luisa Peña Peña, MD; Mark V. Sherrid, MD; Estevao Lanna Figueiredo, MD, MSc; Michael Arad, MD, MSc; R

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