delocamten (MYK-224) / BMS - LARVOL DELTA

Copper-Catalyzed C-N Amination for the Synthesis of a Delocamten Intermediate: Mechanistic Insights and Process Development (ACS-Fall 2026) - "Catalyst characterization and mechanistic studies were conducted to elucidate key reaction parameters and guide condition optimization. These insights enabled the establishment of a robust two-step, telescoped process that efficiently delivers the desired aminated product using an ammonia surrogate, with improved reproducibility and operational consistency."

Mitochondrial tRNASer(AGY) 12234A > G Mutation May Contribute to the Clinical Expression of Hypertrophic Cardiomyopathy-Associated tRNAIle 4263A > G Mutation. (PubMed, Hum Mutat) - "Strikingly, the penetrance and expressivity of one pedigree (HCM2) with both m.4263A > G and m.12234A > G mutations are much higher than another pedigree (HCM1) with only m.4263A > G mutation...Furthermore, a marked decrease in mt-RNA transcripts was observed in cells harboring both m.4263A > G and m.12234A > G mutations. Taken together, our study indicated that the m.12234A > G mutation acted in synergy with the m.4263A > G mutation, triggering mitochondrial dysfunctions and contributing to a high penetrance of HCM in a pedigree harboring both mtDNA mutations."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Metabolic Disorders

A Study to Assess the Relative Bioavailability of BMS-986435 and Food Effect on the BMS-986435 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: Bristol-Myers Squibb | N=140 ➔ 240

Enrollment change

AURORA-HFpEF: Study to Evaluate Safety, Tolerability and Drug Levels of BMS-986435/MYK-224 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) (clinicaltrials.gov) - P2 | N=227 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure

AURORA-HFpEF: Study to Evaluate Safety, Tolerability and Drug Levels of BMS-986435/MYK-224 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) (clinicaltrials.gov) - P2 | N=208 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Jul 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

A Study to Assess the Relative Bioavailability of BMS-986435 and Food Effect on the BMS-986435 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Jul 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date

Artificial Intelligence for the Detection of Hypertrophic Cardiomyopathy From Standard Electrocardiogram. (PubMed, JACC Adv) - "The AI ECG algorithm demonstrated highly specific HCM detection confirmed by cMRI and may improve early identification of unrecognized HCM."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

A Study to Assess the Drug Levels and Safety of BMS-986435 in Participants With Normal Hepatic Function and Participants With Different Degrees of Hepatic Impairment (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2026 ➔ Aug 2026 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Enrollment open • Trial completion date • Trial primary completion date • Hepatology

High-Specific-Surface-Area Hollow Carbon Spheres for Efficient Chromium Ion Adsorption in Acidic Wastewater. (PubMed, Nanomaterials (Basel)) - "The results of X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR) reveal that the efficient heavy metal removal performance of HCM2.5 is mainly attributed to its high specific surface area, as well as coordination and redox reactions between oxygen-containing functional groups and heavy metal ions. Furthermore, benefiting from its outstanding specific surface area and well-developed pore structure, a physical-chemical synergistic adsorption mechanism was proposed and systematically elucidated."

Journal

A Study to Assess the Relative Bioavailability of BMS-986435 and Food Effect on the BMS-986435 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Recruiting

Enrollment open

A Study to Assess the Relative Bioavailability of BMS-986435 and Food Effect on the BMS-986435 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Assess the Drug Levels and Safety of BMS-986435 in Participants With Normal Hepatic Function and Participants With Different Degrees of Hepatic Impairment (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial • Hepatology

A Study to Assess the Relative Bioavailability of BMS-986435 and Food Effect on the BMS-986435 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Assess the Relative Bioavailability of BMS-986435 and Food Effect on the BMS-986435 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=140 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

Novel β-MYH7 mutations Causing HCM among Indians (AHA 2025) - "Additionally, several rare compound variations in the β-MYH7 gene were observed in 4 HCM patients, specifically: HCM1, (G354G, M362L & G389K); HCM2, (splice site (SS8) & F244F); HCM3, (E525K & D896N); and HCM4, (A423T, V431M & N602K-fs)... We identified Novel Mutations in the β-MYH7 Gene that lead to HCM among Indians. We provided valuable insights about causative mutations and their impact on the β-MYH7 protein structure, which may facilitate the development of therapeutic strategies for personalised medicine."

Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • MYH7

Cardiac Myosin Inhibitors in the Treatment of Hypertrophic Cardiomyopathy: Clinical Trials and Future Challenges. (PubMed, Biomolecules) - "Keywords included "cardiac myosin inhibitor", mavacamten", "aficamten", "MYK-224", and "hypertrophic cardiomyopathy." Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pediatrics

A Study to Evaluate the Efficacy, Safety, and Tolerability of MYK-224 in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: Bristol-Myers Squibb | Trial completion date: Aug 2026 ➔ Feb 2025 | Active, not recruiting ➔ Terminated; Business objectives have changed

Trial completion date • Trial termination • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

CV029-1018: Study to Assess Relative Bioavailability of BMS-986435 Formulations in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

Trial completion

AURORA-HFpEF: Study to Evaluate Safety, Tolerability and Drug Levels of BMS-986435/MYK-224 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) (clinicaltrials.gov) - P2 | N=198 | Recruiting | Sponsor: Bristol-Myers Squibb | N=48 ➔ 198

Enrollment change • Cardiovascular • Congestive Heart Failure • Heart Failure

Investigation of Flurbiprofen Pharmacokinetics in Rats Following Dermal Administration of Optimized Cyclodextrin-Based Nanogel. (PubMed, Eur J Pharm Sci) - "The optimized nanogel provided prolonged drug permeation and more sustained pharmacokinetic performance compared to FP-HPMC gel."

Journal • PK/PD data • Preclinical

AURORA-HFpEF: Study to Evaluate Safety, Tolerability and Drug Levels of BMS-986435/MYK-224 in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jan 2025 ➔ Jul 2026 | Trial primary completion date: Jan 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

CV029-1018: Study to Assess Relative Bioavailability of BMS-986435 Formulations in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Evaluate the Safety, Tolerability, Drug Levels, and Drug Effects of Single Doses of BMS-986435 (MYK-224) in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

CV029-1018: Study to Assess Relative Bioavailability of BMS-986435 Formulations in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Efficacy, Safety, and Tolerability of MYK-224 in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | N=36 ➔ 18

Enrollment change • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy