Cytokinetics, Incorporated · NASDAQ:CYTK

Cytokinetics — Technical Presentation (November 2025)

14 slides from Cytokinetics's technical presentation, November 2025

  1. Slide 1: Effects of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive HCM

    EFFECTS OF AFICAMTEN VS METOPROLOL ON PATIENT-REPORTED HEALTH STATUS IN OBSTRUCTIVE HCM Michael E. Nassif1, MD; Pablo Garcia-Pavia, MD, PhD; Ahmad Masri, MD, Bela Merkely, MD; Maria Luisa Peña-Peña, MD; Roberto Barriales-Villa, MD, PhD; Ozlem Bilen, MD; Melissa Burroughs, MD, Brian L. Claggett, PhD,

  2. Slide 2: Disclosures

    DISCLOSURES Dr. Michael E. Nassif, MD • Institutional research and grant support from Bristol Meyers Squibb and Cytokinetics. 2

  3. Slide 3: Background

    BACKGROUND • Beta-blockers have been guideline-directed Primary Endpoint – ∆ pVO2 first-line therapy for patients with oHCM 22 Mean (95% CI) pVO2 (mL/kg/min) despite limited evidence. 21 LSM Change (SE) from Baseline to Week 24 • MAPLE-HCM (aficamten vs metoprolol monotherapy) demonstrated the super

  4. Slide 4: Objective

    OBJECTIVE • This pre-specified substudy compares the impact of aficamten or metoprolol monotherapy on patient-reported health status as measured by KCCQ and SAQ. KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire; SAQ, Seattle Angina Questionnaire. 4

  5. Slide 5: Methods

    METHODS 175 patients with oHCM in Individual participant experiences on MAPLE-HCM aficamten vs metoprolol were described by ​KCCQ-CSS ≤ 90 comparing overall change and categories of within-participant change: 88 patients randomized 87 patients randomized to aficamtena to metoprololb monotherapy mono

  6. Slide 6: Statistically Significant Benefits for Aficamten vs Metoprolol Across All KCCQ Domains

    RESULTS: STATISTICALLY SIGNIFICANT BENEFITS FOR AFICAMTEN VS METOPROLOL WERE OBSERVED ACROSS ALL KCCQ DOMAINS Dmean score baseline to W24 Aficamten * * 8.3 * 7.3 * Metoprolol 20 * 6.9 7.8 (2.2, 12.4) 9.3 (2.5, 14.1) (2.6, 11.2) (3.3, 12.3) (3.8, 14.9) * 6.4 (2.0, 10.9) Adjusted between-group 10 diff

  7. Slide 7: SAQ-SS Improvement in Aficamten vs Metoprolol Primarily Driven by SAQ-PLS

    RESULTS: SAQ-SS IMPROVEMENT IN AFICAMTEN VS METOPROLOL WAS PRIMARILY DRIVEN BY STATISTICALLY SIGNIFICANT IMPROVEMENT IN SAQ-PLS Dmean score baseline to W24 * Aficamten 10.1 20 (3.9, 6.2) Metoprolol 4.6 3.1 (-4.0, 10.3) (-0.3, 9.5) 1.0 (-2.9, 4.8) Adjusted between-group 10 difference (95% CI). * P<0.

  8. Slide 8: Improvements in KCCQ-OSS and SAQ-SS Were Rapid and Sustained

    RESULTS: IMPROVEMENTS IN (A) KCCQ-OSS AND (B) SAQ-SS WITH AFICAMTEN VS METOPROLOL WERE RAPID AND SUSTAINED A. Aficamten Metoprolol B. Aficamten Metoprolol KCCQ-OSS change from BL, 20 20 SAQ-SS change from BL mean (95% CI) 15 15 mean (95% CI) 10 10 5 5 0 0 0 2 4 6 8 12 16 20 24 0 4 8 12 16 20 24 Week W

  9. Slide 9: Very Large Improvements in KCCQ-OSS More Frequent With Aficamten

    RESULTS: VERY LARGE IMPROVEMENTS IN KCCQ-OSS WERE REPORTED MORE FREQUENTLY IN AFICAMTEN PATIENTS; WHILE LARGE WORSENING WAS REPORTED MORE FREQUENTLY BY METOPROLOL PATIENTS 38.6% vs. 18.4% Aficamten Metoprolol 80 Very Large Improvement NNT 5 Change in KCCQ-OSS from BL 40 60 Proportion of participants

  10. Slide 10: Very Large Improvements in SAQ-SS More Frequent With Aficamten

    RESULTS: VERY LARGE IMPROVEMENTS IN SAQ-SS WERE REPORTED MORE FREQUENTLY IN AFICAMTEN PATIENTS AND LARGE WORSENING WAS REPORTED MORE FREQUENTLY BY METOPROLOL PATIENTS 80 36.8% vs 24% Aficamten Metoprolol Very Large Improvement Aficamten Metoprolol NNT 8 60 Change in SAQ-SS from BL 40 Proportion of par

  11. Slide 11: Conclusions

    CONCLUSIONS KCCQ-CSS • In this first head-to-head trial 15.8 vs 8.7 20.0 comparing CMI and beta-blocker 15.0 monotherapy, 24 weeks of 10.0 treatment with aficamten provided greater symptomatic and functional 5.0 improvement than metoprolol for SAQ-SS 0.0 KCCQ-OSS 13.9 vs 8.4 16.6 vs 8.9 patients wit

  12. Slide 12: Acknowledgments

    ACKNOWLEDGMENTS The MAPLE-HCM trial is funded by Cytokinetics, Incorporated. Steering Committee Members: Pablo Garcia-Pavia (Co-PI), Michael Fifer (Co-PI), Edileide Correra de Barros, Ozlem Bilen, Melissa Burroughs, Juan Pablo Costabel, Anne Dybro, Perry Elliott, Neal Lakdawala, Amy Mann, Ajith Nair

  13. Slide 13: Simultaneously published in JACC

    Simultaneously published in JACC 13

  14. Slide 14: Thank You

    THANK YOU 23 Scientific ‘=? Sessions #AHA25

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