Cytokinetics, Incorporated · NASDAQ:CYTK

Cytokinetics — Technical Presentation (November 2025)

15 slides from Cytokinetics's technical presentation, November 2025

  1. Slide 1: Clinical Responses to Aficamten vs Metoprolol Monotherapy: MAPLE-HCM Responder Analysis

    CLINICAL RESPONSES TO AFICAMTEN MONOTHERAPY COMPARED WITH METOPROLOL MONOTHERAPY FOR OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY OUTCOMES AND DISEASE BURDEN: MAPLE-HCM RESPONDER ANALYSIS Andrew Wang, MD; Pablo Garcia-Pavia, MD, PhD; Ahmad Masri, MD; Bela Merkely, MD; Michael E. Nassif, MD; Maria Luisa P

  2. Slide 2: Disclosures

    DISCLOSURES Andrew Wang, MD • Research grants: Cytokinetics, Bristol Myers Squibb, Edgewise, Lexicon • Steering committee: Cytokinetics, Bristol Myers Squibb • Speaking fees: Bristol Myers Squibb • Consultant/Advisory board: Cytokinetics, Bristol Myers Squibb 2

  3. Slide 3: Background

    BACKGROUND MAPLE-HCM2 Beta-blockers are a Class 1 Primary Endpoint – Δ pVO2 22 recommendation for first-line treatment Mean (95% CI) pVO2 (mL/kg/min) of symptomatic obstructive HCM, but 21 LSM Change (SE) from Baseline to Week 24 level of evidence is limited to small 20 Aficamten vs. Metoprolol stud

  4. Slide 4: Objectives and Methods

    OBJECTIVES AND METHODS In this pre-specified analysis, we evaluated individual patient 175 patients with oHCM ​LVOT-G ≥30 mmHg at rest and/or responses to aficamten or metoprolol monotherapy across 5 ≥50 mmHg with Valsalva clinically relevant measures of disease burden in oHCM patients: Endpoints Ef

  5. Slide 5: Baseline Characteristics

    BASELINE CHARACTERISTICS Overall Nonresponder Limited Responder Positive Responder Complete Responder n=175 n=22 n=81 n=66 n=6 P Value Randomized to aficamten, n (%) 88 (50.3) 2 (9.1) 17 (21.0) 63 (95.5) 6 (100.0) <0.001 Age, mean ± SD, y 57.7 ± 13.2 55.8 ± 12.3 56.3 ± 14.2 59.8 ± 12.5 61.2 ± 7.8 0.

  6. Slide 6: Results: Clinical Response Measures to Week 24

    RESULTS Clinical Response Measures in Patients with oHCM from Baseline to Week 24 Treatment with Aficamten or Metoprolol Monotherapy Hemodynamic response HF symptoms Biomarker response Patients with complete hemodynamic response, % Patients with ≥50% reduction in NT-proBNP, % 100 100 100 NNT = 2.2 N

  7. Slide 7: Results: Exercise Capacity and Left Atrial Volume Index

    RESULTS Clinical Response Measures in Patients with oHCM from Baseline to Week 24 Treatment with Aficamten or Metoprolol Monotherapy Exercise capacity Left atrial volume index 100 100 Patients with ≥10% reduction in LAVI, % Patients achieving <1 or ≥1 mL/kg/min NNT = 3.5 NNT = 2.1 90 90 80 80 increa

  8. Slide 8: Results: Radar Plot of Multi-Domain Clinical Responses

    RESULTS Radar Plot of Multi-Domain Clinical Responses to Aficamten Monotherapy vs Metoprolol Monotherapy Biomarker reduction (NT-proBNP) 72% vs. 5% 1.0 0.8 0.6 Symptom improvement Cardiac remodeling 0.4 (NYHA and/or KCCQ-CSS) (LAVI reduction) 76% vs. 56% 0.2 61% vs. 13% 0.0 Hemodynamic response Exer

  9. Slide 9: Results: Effect on Clinical Efficacy Outcomes

    RESULTS Effect of Aficamten Monotherapy vs Metoprolol Monotherapy on Clinical Efficacy Outcomes Risk Difference, % NNT (95% CI) (95% CI) Symptom improvement 19.9 (6.3, 33.5) 5.0 (3.0, 15.9) (NYHA and/or KCCQ) Exercise capacity 28.9 (17.1, 40.7) 3.5 (2.5, 5.8) (pVO2) Hemodynamic response 46.2 (33.1,

  10. Slide 10: Results: Frequency of Overall Clinical Efficacy Outcomes

    RESULTS Frequency of Overall Clinical Efficacy Outcomes Achieved at Week 24 by Treatment Arm 50 40 Proportion of patients, % Positive responses 30 in ≥3 outcomes: • Aficamten 78% 20 • Metoprolol 3% 10 0 0 1 2 3 4 5 Number of clinical efficacy outcomes achieved Metoprolol Aficamten 10

  11. Slide 11: Limitations

    LIMITATIONS • The threshold-based analysis may underestimate clinically meaningful improvements in some patients treated with either aficamten or metoprolol. 11

  12. Slide 12: Conclusions

    CONCLUSIONS • In symptomatic oHCM patients, aficamten monotherapy led to superior and broader treatment effects compared with metoprolol monotherapy across several clinically relevant outcome measures of disease burden. • Treatment benefits of aficamten monotherapy were rapid, as the difference in r

  13. Slide 13: Simultaneously published in JACC

    Simultaneously published in JACC 13

  14. Slide 14: 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

  15. Slide 15: Thank You

    THANK YOU #5 Sescions Pets.) #AHA25

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