This is a single-center, 2-part (Part A and Part B) study in healthy participants. Part A (Dose Finding) is an open-label, SAD study to identify the dose for Part B. Part B (TQT Study) is a randomized, double-blind (with respect to aficamten and matching placebo), positive- and placebo-controlled, single-dose, 3-way crossover study to evaluate the effect of aficamten administration on QT/QTc interval.

Inclusion Criteria:

• Healthy, adult, male or female, 18-45 years of age, inclusive, at the screening visit.

• Continuous non-smoker who has not used nicotine- and tobacco -containing products for at least 3 months prior to the first dosing based on participant self- reporting.

• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 at the screening visit.

• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the PI or designee, including the following:

  • Supine blood pressure is ≥ 90/40 mmHg and ≤ 140/90 mmHg at the screening visit.
  • Oxygen saturation (SpO2) is ≥ 95% at the screening visit.
  • Liver function tests (e.g., bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]) considered not clinically significant in the opinion of the PI or designee at the screening visit.
  • Estimated creatinine clearance ≥ 90 mL/min at the screening visit.

• No clinically significant history and presence of ECG findings as judged by the PI or designee at the screening visit and first check-in, including each of the following:

  • HR between 50 bpm and 100 bpm, inclusive.
  • QTcF interval is ≤450 msec (males) and ≤460 msec (females).
  • QRS ≤110 msec; if >110 msec, result will be confirmed by a manual over read.
  • PR ≤220 msec.

• LVEF ≥65% at the screening visit.

Exclusion Criteria:

• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.