Tuesday, October 10, 2023
Rejuvenate Bio announced new preclinical efficacy findings for RJB-0402, a gene therapy aimed at targeting crucial pathways involved in disease progression. In a mouse model simulating arrhythmogenic cardiomyopathy (ACM), an inherited disorder stemming from mutations in genes encoding desmosomal proteins, RJB-0402 exhibited significant effectiveness. The administration of a single dose of RJB-0402 resulted in a notable improvement in cardiac function, the preservation of cardiac structure, and a substantial reduction in premature ventricular contractions (PVCs) to levels within the normal range.
Rejuvenate Bio has recently shared promising data regarding RJB-0402, a gene therapy designed to target essential disease pathways. In a mouse model mimicking arrhythmogenic cardiomyopathy (ACM), a genetic condition caused by mutations in genes responsible for desmosomal proteins, RJB-0402 demonstrated its effectiveness. A single administration of RJB-0402 significantly improved cardiac function, preserved cardiac structure, and reduced premature ventricular contractions (PVCs) to normal levels.
ACM currently lacks a curative treatment, and standard care includes medications for arrhythmia management and heart failure, implantable cardioverter defibrillators (ICDs), and cardiac catheter ablations, none of which offer a cure. Even with these treatments, life-threatening arrhythmias and disease progression can persist, often leading to heart failure. This presents a significant unmet medical need for ACM patients.
RJB-0402 displayed superiority over gene replacement therapies in normalizing arrhythmias and showed comparable effects in preserving cardiac structure and function in the ACM mouse model, which closely mirrors the human disease by disrupting the cardiac desmosome's structure. Desmosomal proteins are critical for maintaining the integrity of cardiac muscle and individual muscle cells. Mutations in these proteins can disrupt normal heart function, leading to life-threatening heart rhythms and conditions like ACM, a rare and severe genetic heart disorder.
Dr. Hugh Calkins, a Professor of Cardiology and Director of the Johns Hopkins Arrhythmia Service and the ARVD/C Program, expressed optimism about RJB-0402's potential to be a groundbreaking treatment for ACM, offering hope to patients and their families. The therapy's superiority in reducing PVCs compared to gene replacement therapies is especially promising. Importantly, RJB-0402 is not mutation-specific, suggesting it could address all causes of ACM, potentially benefiting a broader patient population.
Alice Lara, President of the Sudden Arrhythmia Death Syndromes (SADS) Foundation, highlighted the significance of therapies that are not limited to specific mutations in ACM. ARVC is a genetic disorder that can affect multiple generations of family members and may lead to sudden cardiac arrest and death. Lara welcomed Rejuvenate Bio's progress in this area as a source of hope for all families affected by ARVC.
RJB-0402 is a liver-targeting adeno-associated virus vector-based gene therapy that stimulates the overexpression of FGF21. Its lower dosage requirements compared to traditional AAV gene replacement therapies could enhance its safety profile and reduce manufacturing costs. The initial clinical study for RJB-0402 will focus on patients with Desmoplakin-related arrhythmogenic cardiomyopathy (DSP ACM) who are at high risk of life-threatening ventricular arrhythmias and sudden cardiac death.
Dr. Deborah Ascheim, Chief Medical Officer of Rejuvenate Bio, expressed confidence in the therapy's potential to treat this severe, life-threatening disease and improve the quality of life for DSP ACM patients. The company is looking forward to engaging with the FDA to align on the requirements for initiating an IND (Investigational New Drug) application in the near future.