Cytokinetics, Incorporated · NASDAQ:CYTK

Cytokinetics — Technical Presentation (August 2026)

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

  1. Slide 1: Aficamten vs Metoprolol Monotherapy in Obstructive HCM According to Pretrial Treatment in MAPLE-HCM

    Aficamten vs Metoprolol Monotherapy in Obstructive Hypertrophic Cardiomyopathy According to Pretrial Treatment in MAPLE-HCM Fernando Dominguez1,2,3, Pablo Garcia-Pavia3,4, on behalf of the MAPLE-HCM investigators 1Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, Majadahonda, Spain; 2CI

  2. Slide 2: Disclosures

    Disclosures • Fernando Dominguez reports speaker fees from Alnylam, Amicus, Bayer, BMS, Cytokinetics, Pfizer, Sanofi, and Takeda and consulting fees from Affinia Therapeutics, Alnylam, Bayer, BMS, Chiesi, Cytokinetics, Lexeo, Pfizer, and Takeda.

  3. Slide 3: Background & Aims

    Background & Aims • MAPLE-HCM1 demonstrated that aficamten monotherapy was superior to metoprolol monotherapy in patients with symptomatic oHCM. Further, metoprolol failed to demonstrate any improvement in LVOT gradient • Prior analyses of metoprolol dosing in MAPLE-HCM demonstrated that metoprolol

  4. Slide 4: MAPLE-HCM: Study Design

    MAPLE-HCM: Study Design Patients had: Metoprolol + placebo for aficamten Randomization 1:1 Adults with: • LVOT gradient ≥30 mm Hg at (n=87) End of Study rest AND/OR ≥50 mm Hg with • Recently diagnosed or Valsalva treatment-naïve oHCM • NYHA class II‒III or • LVEF ≥60% • Chronic oHCM on SOC Aficamten

  5. Slide 5: Methods

    Methods Participants randomized to aficamten (5–20 mg daily) or metoprolol (50–200 mg daily) for 24 weeks were grouped according to their pretrial medical therapy: Any SOC therapy for at least 12 months BB at time of screening? prior to screening? Group 1 Group 2 Group 3 BB no BB yes SOC no N=52 N=1

  6. Slide 6: Methods

    Methods Efficacy endpoints examined according to pretrial medical therapy: • Primary endpoint: – Exercise capacity (change in pVO2 from baseline to Week 24) • Key secondary endpoints: − Symptoms: KCCQ-CSS, NYHA functional class − Hemodynamics: Valsalva LVOT gradient − Biomarkers: NT-proBNP KCCQ-CSS,

  7. Slide 7: Results: Baseline Characteristics

    Results: Baseline Characteristics BB no BB yes SOC no N=52 N=123 N=22 Age, y 55.7 ± 14.3 58.6 ± 12.7 55.0 ± 12.5 Female 17 (32.7) 56 (45.5) 7 (31.8) HCM-causing gene variant 9 (17.3) 19 (15.4) 3 (13.6) Family history of HCM 11 (21.2) 23 (18.7) 4 (18.2) Time since diagnosis, y 4.3 ± 4.1 5.8 ± 6.9 3.2

  8. Slide 8: Results: pVO2 Change From Baseline to Week 24

    Results: pVO2 Change From Baseline to Week 24 Treatment with aficamten improved pVO2 compared with metoprolol, regardless of participants’ pretrial medical therapy. BB no BB yes SOC no 2 Mean change in pVO2 (mL/kg/min) Mean change in pVO2 (mL/kg/min) 2 Mean change in pVO2 (mL/kg/min) 3 1 2 1 LSM dif

  9. Slide 9: Results: Symptoms – KCCQ-CSS and NYHA Class

    Results: Symptoms – KCCQ-CSS and NYHA Class KCCQ-CSS and improvement of ≥1 NYHA functional class favored aficamten regardless of pretrial treatment. Change in KCCQ-CSS at Week 24 Difference N Aficamtena N Metoprolola (95% CI) P BB no 24 15.1 27 8.4 7.6 (-0.3 to 15.6) 0.06 BB yes 63 16.0 59 8.9 6.5 (

  10. Slide 10: Results: Valsalva LVOT-G

    Results: Valsalva LVOT-G BB no BB yes SOC no Washout Washout Washout 100 Metoprolol n=26 100 Metoprolol n=59 100 Metoprolol n=12 Valsalva LVOT-G (mm Hg) Valsalva LVOT-G (mm Hg) Valsalva LVOT-G (mm Hg) 75 75 75 50 50 50 25 25 25 Aficamten n=23 Aficamten n=60 0 Aficamten n=8 0 0 0 2 4 6 8 12 16 20 24 28

  11. Slide 11: Results: NT-proBNP

    Results: NT-proBNP BB no BB yes SOC no Washout Washout Washout Metoprolol n=27 Metoprolol n=59 Metoprolol n=13 750 750 750 Geometric mean NT-pro BNP Geometric mean NT-proBNP Geometric mean NT-proBNP 500 500 500 (pg/mL) (pg/mL) (pg/mL) 250 250 250 125 125 125 Aficamten n=24 Aficamten n=63 Aficamten n=9

  12. Slide 12: Safety

    Safety Aficamten Metoprolol BB no, n (%) n=24 n=28 Any SAE 2 (8.3) 3 (10.7) Any TEAE 16 (66.7) 22 (78.6) Any AE leading to early treatment withdrawal (including death) 0 2 (7.1) Any AE leading to treatment interruption 0 0 LVEF <50% 0 0 BB yes, n (%) n=64 n=59 Any SAE 5 (7.8) 3 (5.1) Any TEAE 49 (76

  13. Slide 13: Conclusions

    Conclusions • The results of this MAPLE-HCM substudy support the primary study results regardless of pretrial treatment status: BB use at screening and prior SOC status • These findings suggest that there is no confounding by selective enrollment of BB-resistant patients • Aficamten can be considere

  14. Slide 14: Acknowledgements

    Acknowledgements The MAPLE-HCM trial is funded by Cytokinetics, Incorporated. We thank the following individuals for their contributions to this clinical trial: • Participants and their families. • Investigators and study-site staff. • Co-authors: Fernando Dominguez, MD, PhD; Roberto Barriales-Villa

  15. Slide 15: Simultaneously Published in JACC: Heart Failure

    Simultaneously Published in JACC: Heart Failure

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