Cytokinetics, Incorporated · NASDAQ:CYTK
Cytokinetics — Technical Presentation (August 2026)
23 slides from Cytokinetics's technical presentation, August 2026
Slide 1: Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy
Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy Primary Results of the ACACIA-HCM Trial Ahmad Masri, MD, MS1, Caroline J. Coats, MD, PhD, Martin S. Maron, MD, Carolyn Y. Ho, MD; on behalf of the ACACIA-HCM investigators 1Oregon Health & Science University, Portland, Oregon, USA
Slide 2: Disclosures
Disclosures • Ahmad Masri has received research grants from Attralus, Cytokinetics and Janssen, and consulting fees from Cytokinetics, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, Intellia, Bayer, Imbria, Braveheart, AstraZe
Slide 3: Background
Background • Nonobstructive hypertrophic cardiomyopathy Small vessel disease, (nHCM) is a common heart disease associated with Small LV cavity myocardial bridging significant disease burden and no effective therapies.1 • Patients with nHCM experience debilitating symptoms with exertion that limit th
Slide 4: Methods: Study Design
Methods: Study Design Randomization 1:1 Patients with symptomatic nHCM: • NYHA FC II‒III Aficamten (5–20 mg) Screening • KCCQ-CSS ≤85 n=258 N = 517 EOS • LVEF ≥60% • NT-proBNP ≥300 pg/mL Placebo • Resting LVOT gradient < 30 mmHg n=259 • Peak Valsalva LVOT gradient <50 mmHg Part 1a Part 2b EOT/ EOSd
Slide 5: Methods: Endpoints
Methods: Endpoints • Dual Primary Endpoints – Change from baseline to Week 36 in KCCQ-CSS. Graphical multiplicity testing with – Change from baseline to Week 36 in pVO2 on CPET. equal alpha-split (0.025) for each • Secondary Efficacy Endpoints (hierarchical) – Changes from baseline to Week 36 in: ▪
Slide 6: Results: Baseline Characteristics
Results: Baseline Characteristics Aficamten Placebo Aficamten Placebo Characteristic Characteristic (n=258) (n=259) (n=258) (n=259) Age, y 55.7 ± 16.2 54.5 ± 16.0 Implantable cardioverter-defibrillator 107 (41.5) 105 (40.5) Female sex 140 (54.3) 137 (52.9) KCCQ-CSS 66.3 ± 16.2 65.0 ± 15.4 Race or et
Slide 7: KCCQ-CSS Dual Primary Endpoint at Week 36
Results: KCCQ-CSS (Dual Primary Endpoint at Week 36) 18 Titration LSM Difference at Week 36: Washout 3.0 (P=0.021) 16 LSM Change in KCCQ-CSS 14 12 10 Δ 3.1 8 6 4 2 Aficamten Placebo 0 0 2 4 6 8 12 24 36 48 60 72 EOT EOS No. of Patients Weeks since randomization Aficamten 258 258 257 253 250 252 242
Slide 8: KCCQ-CSS Dual Primary Endpoint Over Time
Results: KCCQ-CSS (Dual Primary Endpoint at Week 36) At all other time points beyond week 12 KCCQ-CSS change was 4.8 to 7.0; all P≤0.005 18 Titration Washout 16 LSM Change in KCCQ-CSS 14 12 Δ 5.1 Δ 5.0 Δ 7.0 Δ 5.6 10 Δ 4.8 8 6 Δ 0.5 4 2 Aficamten Placebo 0 0 2 4 6 8 12 24 36 48 60 72 EOT EOS No. of
Slide 9: Change in pVO2 (Dual Primary Endpoint at Week 36)
Results: Change in pVO2 (Dual Primary Endpoint at Week 36) Placebo 1.0 Aficamten LSM Change in pVO2 (mL/kg/min) 0.5 LSM Difference: 0.67 mL/kg/min P=0.003 0.0 −0.03 mL/kg/min 0.64 mL/kg/min −0.5 (95% CI, −0.35 to 0.28) (95% CI, 0.32 to 0.95) Placebo Aficamten No. of Patients 240 233 LSM, least squar
Slide 10: Consistent Results for Both Endpoints Across Prespecified Subgroups
Consistent Results for Both Endpoints Across Prespecified Subgroups Subgroup Aficamten Placebo KCCQ-CSS Estimate pVO2 Estimate Subgroup Aficamten Placebo KCCQ-CSS Estimate pVO2 Estimate no. of patients (95% CI) (95% CI) no. of patients (95% CI) (95% CI) Overall 258 259 3.0 (0.5, 5.5) 0.7 (0.2, 1.1)
Slide 11: Improvement in ≥1 NYHA Functional Class
Results: Improvement in ≥1 NYHA Functional Class 100 Week 36 Aficamten Common Rate Difference: Placebo 14.1 (P<0.001) 60 58 26 101 (54%) (53%) 50 111 108 (48%) (45%) (44%) 96 42 Patients (%) 40 82 (38%) (37%) (33%) 70 72 13 68 (31%) 65 62 (29%) (29%) 30 53 (27%) 55 (26%) (25%) (21%) 44 48 (22%) (19%
Slide 12: Improvement in Comprehensive Exercise Performance
Results: Improvement in Comprehensive Exercise Performance CPET Z-Score Peak Oxygen Uptake (pVO2) Ventilatory Efficiency (VE/VCO2) Placebo Placebo LSM Change from Baseline to Aficamten Aficamten LSM Change from Baseline to 1.0 1.0 Week 36 in VE/VCO2 Week 36 in pVO2 (mL/kg/min) 0.5 LSM Difference: 0.
Slide 13: NT-proBNP Concentration Over Time
Results: NT-proBNP Concentration Over Time Geometric Mean NT-proBNP (pg/mL) Titration Washout 1000 750 Week 36 Geometric LSM Ratio 0.43 (P<0.001) 500 250 0 Aficamten Placebo 0 24 6 8 12 24 36 48 60 72 EOT EOS No. of Patients Weeks since randomization Aficamten 258 257 256248 249 251 241 239 205 107
Slide 14: LAVI and Time to First Cardiovascular Event
Results: LAVI and Time to First Cardiovascular Event Change from BL at Week 36 in LAVI Time to First Composite Cardiovascular Eventa 70 50 HR (95% CI): 1.132 (0.62–2.07) LSM ∆ = −1.3; P=0.058 P value: 0.678 40 60 ∆ from BL = 1.1 Cumulative incidence (%) LAVI (mL/m2), Mean ± SD ∆ from BL = −0.2 30 50
Slide 15: Safety Outcomes: LVEF
Results: Safety Outcomes • Aficamten was generally well-tolerated without 100 Titration Aficamten Washout new safety signals 90 Placebo • Aficamten was titrated to maximum Left Ventricular Ejection Fraction (%) 80 tolerated doses as guided by LVEF 70 • 80.7% of patients were on 15-20 mg by the 60 end
Slide 16: Results: Safety Outcomes
Results: Safety Outcomes Aficamten Placebo Event, n (%) (n=258) (n=259) Any AE 207 (80.2) 217 (84.1) All heart failure events Any nonfatal AE that led to treatment discontinuation 18 (7.0) 5 (1.9) in aficamten treated patients occurred during Any nonfatal AE that led to early study discontinuation 9
Slide 17: Global Efficacy of Aficamten in Nonobstructive Hypertrophic Cardiomyopathy
Global Efficacy of Aficamten in Nonobstructive Hypertrophic Cardiomyopathy A Pre-specified Analysis Ahmad Masri, MD, MS1, on behalf of Martin S. Maron, MD2 and the ACACIA-HCM Investigators 1Oregon Health & Science University, Portland, Oregon, USA 2Lahey Hospital and Medical Center, Burlington, Mass
Slide 18: Methods
METHODS ACACIA-HCM Phase 3 Trial to Evaluate Efficacy and Safety of Aficamten Patient Global Impression of Change (PGI-C) in nHCM 259 Patients 258 Patients Please choose the response below that Randomized to Randomized to best describes the overall change in your Placebo Aficamten symptoms and overa
Slide 19: Effect of Aficamten vs Placebo on Clinical Efficacy Outcomes
Results: Effect of Aficamten vs Placebo on Clinical Efficacy Outcomes Risk Difference NNT (95% CI) 95% CI ≥1 improvement in NYHA class and/or +18.3% 5.5 reported improvement in PGI-C (+10%, +26.5%) pVO2 increase ≥0.5 mL/kg/min +7.1% 14.0 (–1.3%, +15.6%) NT-proBNP ≥50% reduction +58.7% 1.7 (+52.2%, +
Slide 20: Global Efficacy across Five Domains
Global Efficacy across Five Domains at Week 36 50 Clinical response (≥3 outcomes) Placebo Aficamten Aficamten: 136 (53%) Placebo: 36 (13%), P<0.001 40 Patients with nHCM (%) 30 20 10 0 0 1 2 3 4 5 Number of clinical efficacy outcomes achieved nHCM, nonobstructive hypertrophic cardiomyopathy.
Slide 21: Conclusions
Conclusions • Aficamten improved exercise capacity, patient-reported health status, and symptoms, as compared with placebo in patients with symptomatic nHCM. • Over 36 weeks of treatment, aficamten yielded statistically significant improvements in efficacy as compared with placebo: – Dual primary en
Slide 22: Simultaneous Publications in New England Journal of Medicine and in Circulation
Simultaneous Publications in New England Journal of Medicine and in Circulation
Slide 23: Acknowledgements
Acknowledgements The ACACIA-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. • Data Monitoring Committee members. • Steering Committee members