Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Technical Presentation (August 2025)
18 slides from Cytokinetics's technical presentation, Aug 30, 2025
Slide 1: Aficamten vs Metoprolol as Monotherapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy
Aficamten vs Metoprolol as Monotherapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy Pablo Garcia-Pavia1,2, Martin S. Maron, Ahmad Masri, Bela Merkely, Michael E. Nassif, Maria Luisa Peña-Peña, Roberto Barriales-Villa, Ozlem Bilen, Melissa Burroughs, Brian Claggett, Juan Pablo Costabel, Ed
Slide 2: Disclosures
Disclosures • Pablo Garcia-Pavia reports speaker fees from Bristol Meyers Squibb, and consulting fees from Alexion, Biomarin, Bristol Meyers Squibb, Cytokinetics, Edgewise Therapeutics, Lexeo Therapeutics, and Rocket Pharmaceuticals.
Slide 3: Background
Background • Obstructive HCM (oHCM) is characterized by a hypercontractile left ventricle, hypertrophy, and left ventricular outflow tract (LVOT) obstruction, resulting in limiting symptoms and reduced exercise capacity.1 • Aficamten is an investigational, next-in-class cardiac myosin inhibitor that
Slide 4: Beta-blockers have been first-line treatment for symptomatic oHCM for nearly 60 years
Beta-blockers have been the first-line treatment for symptomatic oHCM for nearly 60 years despite limited evidence 1968 2023 ESC Guidelines2 Chronic Beta Adrenergic Receptor Blockade in the Treatment of Idiopathic Hypertrophic Subaortic Stenosis1 Recommendation Classa Levelb By Lawrence S. Cohen and
Slide 5: MAPLE-HCM: Objectives and Endpoints
MAPLE-HCM: Objectives and Endpoints • Evaluate the safety and efficacy of aficamten monotherapy compared with metoprolol monotherapy in patients with symptomatic oHCM. • Primary Endpoint: – Exercise capacity (pVO2) • Secondary Endpoints: – Symptoms (NYHA Functional Class and KCCQ-CSS) – Valsalva LVO
Slide 6: 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 +
Slide 7: Results: Baseline characteristics
Results: Baseline characteristics Patients had milder oHCM disease phenotype by design than was previously studied in SEQUOIA-HCM Characteristic Aficamten (n=88) Metoprolol (n=87) Characteristic Aficamten (n=88) Metoprolol (n=87) Age, y 58.9 ±13 56.5 ±13 KCCQ-CSS 65.5 ±17 66.0 ±16 Female sex 36 (40.
Slide 8: Results: Doses achieved
Results: Doses achieved • The majority of patients were exposed to the highest doses: – Metoprolol: 62% received 150 or 200 mg – Aficamten: 76% received 15 or 20 mg Did not tolerate 1 Metoprolol dose Aficamten dose 0 mg 0 mg 10 5 • At Week 24: 50 mg 12 5 mg 31 15 34 100 mg 10 mg – 10 patients did no
Slide 9: Results: Primary endpoint – change in pVO2
Results: Primary endpoint – change in pVO2 Mean Change from Baseline to Week 24 22 Mean (95% CI) pVO2 (mL/kg/min) 21 LSM difference (SE) 20 vs metoprolol 19 2.3 (0.39) mL/kg/min 18 P<0.0001 17 BL 24 Week Aficamten Metoprolol Δ, change; BL, baseline; LSM, least squares mean; pVO2, peak oxygen uptake;
Slide 10: Results: Pre-specified subgroups show no heterogeneity in pVO2
Results: Pre-specified subgroups show no heterogeneity in pVO2 Aficamten Metoprolol LSM Difference no. of patients (95% CI) in pVO2 Overall 88 87 2.3 (1.52, 3.07) Gender Male 52 50 2.18 (1.2, 3.16) Female 36 37 2.16 (0.99, 3.33) Age Group < 65 Years 50 61 2.29 (1.31, 3.26) ≥ 65 Years 38 26 2.43 (1.0
Slide 11: Results: Overview of all secondary endpoints
Results: Overview of all secondary endpoints Secondary Endpoints Proportion of patients with ≥1 class improvement in NYHA 1 functional class from baseline to Week 24 P<0.001 2 Change in KCCQ-CSS from baseline to Week 24 P<0.002 3 Change in NT-proBNP from baseline to Week 24 P<0.0001 4 Change in post
Slide 12: Secondary endpoints: Functional class and symptoms
Secondary endpoints: Functional class and symptoms NYHA Functional Class By Week Change From Baseline in KCCQ-CSS Washout Aficamten Metoprolol 25 Aficamten Metoprolol Washout Washout 100 20 Least Squares Mean (95% CI) Patients in each NYHA class, % 80 15 Change in Score 60 10 5 40 0 20 LSM Diff at W
Slide 13: Secondary endpoints: Change in LVOT obstruction at Week 24
Secondary endpoints: Change in LVOT obstruction at Week 24 Resting LVOT gradient Valsalva LVOT gradient Washout Washout 60 Aficamten Metoprolol 100 Aficamten Metoprolol LVOT Gradient (mmHg) Mean (95% CI) Valsalva LVOT Gradient (mmHg) Mean (95% CI) Resting 75 40 30 50 20 25 LSM Diff at Week 24 = ‒30
Slide 14: Secondary endpoints: Change in NT-proBNP and LAVI at Week 24
Secondary endpoints: Change in NT-proBNP and LAVI at Week 24 NT-proBNP Left Atrial Volume Index Washout Aficamten Metoprolol Aficamten Metoprolol 750 50 45 Geometric Mean (95%) NT-proBNP (pg/mL) 500 LAVI (mL/m2) Mean (95%) 40 35 250 30 125 LSM Diff at Week 24 = ‒7.0 mL/m2 P<0.0001 81% reduction at W
Slide 15: Safety
Safety Aficamten (n=88) Metoprolol (n=87) Patients with any SAE 7 (8.0) 6 (6.9) Patients with any AE that led to early treatment withdrawal of aficamten or metoprolola 1 (1.1) 3 (3.4) Patients with AE that led to temporary interruption of aficamten or metoprolol 1 (1.1) 1 (1.1) Patients with dose re
Slide 16: Conclusions
Conclusions • In patients with symptomatic oHCM, 24 weeks of treatment with aficamten monotherapy was superior to metoprolol monotherapy, with statistically significant and clinically meaningful improvements in: – Primary endpoint of exercise capacity (measured by pVO2). – Secondary endpoints of sym
Slide 17: 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
Slide 18: ESC Congress 2025 Madrid / NEJM publication
ESC Congress World Congress 2025 Madrid of Cardiology Th NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy P. Garcia-Pavia,"? M.S. Maron,? A. Masri,“ B. Merkely,> M.E. Nassif,°7 MLL. Pefia-Pefia,® R. Barriales-Villa,? O.