Poxel Announces Positive Results from a Preclinical Study for PXL065
Poxel Announces Positive Results from a Preclinical Study for PXL065, a Proprietary Deuterium-Stabilized R-Stereoisomer of Pioglitazone, in Hypertrophic Cardiomyopathy
POXEL SA, a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including metabolic dysfunction-associated steatohepatitis (MASH) and rare metabolic disorders, announces the positive top-line results for PXL065 from a preclinical study conducted in a mouse model of hypertrophic cardiomyopathy. PXL065 is a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone (d-R-pioglitazone) which is known to reduce inflammation and fibrosis, improve mitochondrial function, and restore metabolic balance.
Thomas Kuhn, CEO of Poxel, stated: “We are very pleased with these top-line results, which illustrate the potential of PXL065 for treating hypertrophic cardiomyopathy, the most common genetic cardiac disorder. Current therapeutic options for this disease are limited, with either low efficacy, a difficult safety profile or addressing a limited patient population. We look forward to initiating the clinical development of PXL065 in this indication based on these promising results.”
Prof. Dr. Cordula Wolf, Director of the Center for Rare Congenital Heart Diseases at the TUM University Hospital German Heart Center, added: “The findings of the pre-clinical study conducted in collaboration with Poxel represent a major step in the development of a novel therapeutic approach to treat hypertrophic cardiomyopathy, a severe and progressive disease that can lead to life-threatening cardiac events. Results obtained during this preclinical study showed that PXL065 may have the potential to improve the clinical outcomes for patients suffering from this genetic condition by reducing left ventricular hypertrophy, decreasing cardiac fibrosis and improving the underlying pathophysiological mechanisms.”
Hypertrophic Cardiomyopathy (HCM) is a genetic disorder marked by myocardial hypertrophy, cardiac fibrosis, ventricular dysfunction, arrhythmias, and an increased risk of sudden cardiac death. It is caused by mutations in sarcomere protein genes, leading to altered cell metabolism, including oxidative stress and mitochondrial dysfunction. The estimated prevalence of HCM is 0.2%, or 1/500 adults, and its incidence is around 5 per 100,000 person-years.
In connection with the mechanism of action of PXL065 on the inhibition of the mitochondrial pyruvate carrier (MPC) and on the inhibition of Acyl CoA Synthetase 4 (ACSL4) thus acting on oxidative stress, inflammation and fibrosis, PXL065 was tested in an established mouse model of hypertrophic cardiomyopathy. After 10 weeks of treatment, a significant reduction in myocardial hypertrophy associated with a significant reduction in cardiac fibrosis was demonstrated, highlighting the potential of PXL065 in this pathology.
This preclinical study was funded by the German Center for Cardiovascular Research (DZHK) and conducted at the TUM University Hospital German Heart Center by leading HCM expert Prof. Dr. Cordula Wolf. Poxel and the TUM University Hospital German Heart Center collaborated on the pre-clinical study based on Poxel’s existing data and patent portfolio on PXL065 and prior research conducted by Prof. Dr. Cordula Wolf and her group on the disease mechanisms and therapeutic use of TZD’s in HCM. The top-line results available indicate that PXL065 prevents pathological myocardial remodeling in a HCM mouse model, including hypertrophy and cardiac fibrosis.
