Poxel SA announced that preclinical data for PXL065 in hypertrophic cardiomyopathy (HCM) has been accepted for presentation at the 2025 European Society of Cardiology Congress, scheduled for September 1st in Madrid, Spain. The deuterium-stabilized R-enantiomer of pioglitazone demonstrated significant therapeutic benefits in preventing pathological myocardial remodeling in an established mouse model of the genetic cardiac disorder.
Promising Preclinical Results Target Unmet Medical Need
The study revealed that PXL065 successfully prevented hypertrophy and fibrosis in the heart, key pathological features of HCM that contribute to disease progression and complications. Prof. Dr. Cordula Wolf, Director of the Center for Rare Congenital Heart Diseases at the TUM University Hospital German Heart Center, emphasized the clinical significance of these findings.
"The compelling results obtained in this study illustrate the potential of PXL065 in HCM, the most common genetic cardiac disorder," Wolf stated. "Current treatments have important limitations in efficacy, safety, or patient applicability. There is a clear unmet need for safe and effective disease-modifying therapies."
Dual Mechanism of Action Addresses Disease Pathophysiology
PXL065's therapeutic potential stems from its dual mechanism of action, targeting both mitochondrial pyruvate carrier (MPC) inhibition and Acyl CoA Synthetase 4 (ACSL4) inhibition. This approach directly addresses the underlying metabolic dysfunction characteristic of HCM, including oxidative stress, inflammation, and fibrosis that result from mutations in sarcomere protein genes.
The preclinical study was conducted through a collaboration between Poxel and the TUM University Hospital German Heart Center, with funding from the German Center for Cardiovascular Research (DZHK). The research built upon Poxel's existing patent portfolio for PXL065 and Prof. Wolf's previous work on disease mechanisms and therapeutic applications of thiazolidinediones (TZDs) in HCM.
Significant Disease Burden Drives Development Priority
HCM represents a substantial clinical challenge, with an estimated prevalence of 0.2% or approximately 1 in 500 adults, and an incidence rate of 5 per 100,000 person-years. The genetic disorder is characterized by myocardial hypertrophy, cardiac fibrosis, ventricular dysfunction, arrhythmias, and an increased risk of sudden cardiac death, making effective treatment options critically important for patient outcomes.
Thomas Kuhn, CEO of Poxel, highlighted the significance of presenting at one of the world's leading cardiovascular medicine forums. "We are pleased to have the data with PXL065 in HCM be presented at one of the world's leading forums for cardiovascular science and medicine, which underscores both the quality and relevance of these findings," Kuhn said. "We look forward to further supporting PXL065 development for the treatment of HCM based on these promising results."
Expanding Pipeline Beyond MASH Applications
The HCM data represents an expansion of PXL065's therapeutic potential beyond its primary indication in metabolic dysfunction-associated steatohepatitis (MASH), where the compound met its primary endpoint in the Phase 2 DESTINY-1 trial. This diversification demonstrates the broad applicability of PXL065's mechanism of action across multiple disease areas characterized by metabolic dysfunction.
Poxel's broader pipeline includes PXL770, a first-in-class direct AMPK activator being developed for adrenoleukodystrophy and autosomal dominant polycystic kidney disease, and TWYMEEG (Imeglimin), which is already marketed in Japan for type 2 diabetes through a partnership with Sumitomo Pharma.
