Cytokinetics, Incorporated · NASDAQ:CYTK

Cytokinetics — Technical Presentation (November 2025)

13 slides from Cytokinetics's technical presentation, November 2025

  1. Slide 1: The Effect of Aficamten vs Metoprolol on Cardiac Biomarkers in Obstructive HCM

    THE EFFECT OF AFICAMTEN VS METOPROLOL ON CARDIAC BIOMARKERS IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY A secondary analysis from MAPLE-HCM Neal K Lakdawala, MD1; Pablo Garcia-Pavia, MD, PhD; Martin S. Maron, MD; Ahmad Masri, MD; Bela Merkely, MD; Michael E. Nassif, MD; Maria Luisa Peña-Peña, MD; Rob

  2. Slide 2: Financial Disclosures

    FINANCIAL DISCLOSURES Neal Lakdawala, MD • Research grants: Pfizer and BMS, O’Hare and Steggall Family Foundations • Consulting: Cytokinetics, Tenaya, Alexion, BMS, Bayer, Gemma, Kardigan, Akros, Bridge Bio, Lexeo and Nuevocor • Trial leadership: Kardigan, Cytokinetics, Neuvocore • Clinical Events C

  3. Slide 3: MAPLE-HCM: Aficamten vs Metoprolol in Symptomatic Obstructive HCM

    MAPLE-HCM: AFICAMTEN VS METOPROLOL IN SYMPTOMATIC OBSTRUCTIVE HCM LSM difference (SE) vs metoprolol • Beta-blockers have been guideline-directed 2.3 (0.39) mL/kg/min P<0.0001 first-line therapy for patients with oHCM 22 despite limited evidence. • MAPLE-HCM (aficamten vs metoprolol monotherapy) Mean

  4. Slide 4: MAPLE-HCM: Study Design

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

  5. Slide 5: MAPLE-HCM: Key Baseline Characteristics by Quartiles of NT-proBNP

    MAPLE-HCM: KEY BASELINE CHARACTERISTICS By Quartiles of NT-proBNP n (%) or mean ± SD or median NT-proBNP Q1 NT-proBNP Q2 NT-proBNP Q3 NT-proBNP Q4 [IQR] [51, 198] [200, 468] [471, 968] [980, 4659] n=44 n=44 n=44 n=43 P Value Randomized to aficamten, n (%) 20 (45.5) 21 (47.7) 23 (52.3) 24 (55.8) 0.30

  6. Slide 6: MAPLE-HCM: Key Baseline Characteristics by Quartiles of hs-cTnI

    MAPLE-HCM: KEY BASELINE CHARACTERISTICS By Quartiles of hs-cTnI n (%) or mean ± SD or hs-cTnI Q1 hs-cTnI Q2 hs-cTnI Q3 hs-cTnI Q4 median [IQR] [2.3, 7.2] [7.3, 12.8] [12.9, 28.6] [29.9, 663] n=45 n=43 n=44 n=43 P Value Randomized to aficamten, n (%) 21 (46.7) 20 (46.5) 22 (50.0) 25 (58.1) 0.27 Age,

  7. Slide 7: Results: Relative Changes from Baseline in NT-proBNP by Treatment Group

    RESULTS: RELATIVE CHANGES FROM BASELINE IN THE CONCENTRATION OF NT-proBNP BY TREATMENT GROUP +42% +60% from baseline +40% (p<0.001) +20% NT-proBNP concentration Return to baseline 0% after washout –20% -81% –40% Max reduction treatment effect -73% >50% reduction: evident at 8 W (p<0.001) from baseli

  8. Slide 8: Results: Relative Changes from Baseline in hs-cTnI by Treatment Group

    RESULTS: RELATIVE CHANGES FROM BASELINE IN THE CONCENTRATION OF hs-cTnI BY TREATMENT GROUP +30% -17% +20% Max reduction from baseline +10% evident at 8 W (p<0.001) Return to baseline after hs-cTnl concentration 0% washout –10% -43% –20% -28% from baseline –30% treatment effect (p<0.001) (p=0.001) –4

  9. Slide 9: Results: Changes in Efficacy Metrics Stratified by Quartiles of NT-proBNP Change

    RESULTS: CHANGES IN EFFICACY METRICS STRATIFIED BY QUARTILES OF NT-proBNP CHANGE AT 24 WEEKS Change in Change in Change in Change in NT-proBNP Q1 NT-proBNP Q2 NT-proBNP Q3 NT-proBNP Q4 P Value n=44 n=43 n=43 n=43 NT-proBNP ratio 0.13 0.46 1.07 2.32 NT-proBNP, baseline (pg/mL) 784 [470, 1292] 304 [16

  10. Slide 10: Results: Change in NT-proBNP or hs-cTnI vs Changes in Peak VO2

    RESULTS: CHANGE FROM BASELINE IN NT-proBNP or hs-cTnI VS CHANGES IN PEAK VO2 FROM BASELINE +15 P<0.001 P=NS +10 +15 pVO2 change from pVO2 change from +10 +5 baseline (%) baseline (%) +5 0 0 –5 –5 –10 –10 –15 –15 Quartile 1 Quartile 2 Quartile 3 Quartile 4 Quartile 1 Quartile 2 Quartile 3 Quartile 4

  11. Slide 11: Conclusions

    CONCLUSIONS • As monotherapy for oHCM, aficamten led to statistically significant reductions in NT-proBNP and hs-cTnI compared with metoprolol monotherapy. • Reductions in NT-proBNP and hs-cTnI were associated with clinically meaningful improvements in efficacy markers. • These results provide mecha

  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: Thank You

    THANK YOU 333 Scientific ‘=? Sessions #AHA25

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