New Analyses Related to Aficamten Expand on its Metabolism Pathways,Treatment Effect Associated with Combination Therapy with Disopyramideand Longer-Term Effect on Cardiac Structure and Function SOUTH SAN FRANCISCO, Calif., March 17, 2025 (GLOBE NEWSWIRE) — Cytokinetics, Incorporated (Nasdaq: CYTK) today announced five presentations related to aficamten, an investigational cardiac myosin inhibitor, and hypertrophic cardiomyopathy (HCM), at the American College of Cardiology (ACC) Annual Scientific Session & Expo taking place from March 29, 2025–March 31, 2025 in Chicago, IL. “We are pleased to be sharing several new analyses relating to aficamten at the upcoming ACC Scientific Session & Expo,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “The presentations describe the drug metabolism of aficamten, the safety of combination therapy with the standard of care medication disopyramide, and the effect of longer-term use of aficamten. Together these analyses add to the strong and growing evidence base supporting the potential for aficamten in patients with obstructive HCM and inform how it may be used in clinical practice.” Evaluation of Cytochrome P450 2C9, 2C19, and 2D6 Inhibition on the Pharmacokinetics of Aficamten in Healthy Participants (1091-139)Poster Presentation, March 29, 2025, 2:00-3:00 PM CT, South Hall. Neha Maharao, Ph.D., Senior Clinical Pharmacologist, Cytokinetics. Data from an open-label, fixed-sequence drug-drug interaction (DDI) study of aficamten in healthy participants will be presented in a poster presentation. A previous study showed that aficamten is metabolized, in part, by the cytochrome P450 (CYP) enzyme 3A41. To further characterize its metabolic pathways, aficamten was evaluated with concomitant administration of three strong inhibitors of one or more of the CYP pathways: fluconazole (inhibitor of 2C9, 2C19, and 3A4), paroxetine (inhibitor of 2D6) and fluoxetine (inhibitor of 2C19 and 2D6). The data show that aficamten was eliminated by multiple CYP pathways, primarily by CYP2C9 (fraction metabolized [fm]=50%), with contributions from CYP3A (fm=26%), CYP2D6 (fm=21%) and CYP2C19 (fm=3%). Safety and Outcomes of Concomitant Aficamten and Disopyramide Use and Withdrawal in Patients with Obstructive Hypertrophic Cardiomyopathy: An Analysis of REDWOOD-HCM Cohort 3, SEQUOIA-HCM, and FOREST-HCM Trials (411-06)Oral Presentation, March 31, 2025, 9:11-9:18 AM CT, S406b. Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University. Data from an analysis of concomitant treatment with aficamten and disopyramide from completed and ongoing clinical trials of aficamten in patients with obstructive HCM will be presented in an oral presentation. The analysis included 50 participants from Cohort 3 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) and FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) who were receiving disopyramide at baseline. Participants were separated into four groups: those on disopyramide who underwent withdrawal of aficamten due to end of treatment in Cohort 3 of REDWOOD-HCM or SEQUOIA-HCM (n=29), patients on disopyramide receiving placebo in SEQUOIA-HCM (n=20), patients on aficamten who underwent disopyramide withdrawal in FOREST-HCM (n=17) and patients on aficamten who maintained treatment with disopyramide in FOREST-HCM (n=27). Combination therapy with aficamten and disopyramide was well-tolerated; the analysis suggests that combination of disopyramide with aficamten did not result in lower left ventricular outflow tract (LVOT) gradients compared to treatment with aficamten alone. The analysis suggests that withdrawal of disopyramide while receiving aficamten did not reduce the efficacy of aficamten and further that withdrawal of aficamten while on disopyramide resulted in the return of LVOT obstruction and symptoms, with an increase in NT-proBNP. There were no safety events reported with either aficamten or disopyramide withdrawal, and no episodes of atrial fibrillation after disopyramide withdrawal were reported. Effect of Aficamten Treatment for Up to 72 Weeks on Cardiac Structure and Function in Patients with Obstructive Hypertrophic Cardiomyopathy: The SEQUOIA-HCM and FOREST-HCM CMR Sub-studies (964-09)Moderated Poster Presentation, March 30, 2025, 12:06-12:13 PM CT, Theater 5. Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University. New data from the cardiac magnetic resonance (CMR) imaging sub-studies of FOREST-HCM and SEQUOIA-HCM will be presented in a moderated poster presentation. At the time of the current analysis, 64 patients had completed a baseline CMR, including 36 patients who had completed a follow-up CMR at 72 weeks, and 28 patients who had completed a follow-up CMR at 48 weeks. Longer-term treatment with aficamten resulted in statistically significant improvements (mean ±SD) in measures of cardiac structure and function including left ventricular mass index (-9.8 g/m2 ±18.1, p