October 9, 2023 — Rejuvenate Bio announced new preclinical efficacy data for RJB-0402, a gene therapy targeting key disease-mediating pathways. RJB-0402 demonstrated efficacy in a mouse model of arrhythmogenic cardiomyopathy (ACM), an inherited disease caused by mutations in one of several genes encoding desmosomal proteins. A single dose of RJB-0402 was able to significantly improve cardiac function, preserve cardiac structure, and dramatically reduce premature ventricular contractions (PVCs) to normal levels.
RJB-0402 was superior to gene replacement regarding its ability to normalize arrhythmias and demonstrated comparable effect on preservation of cardiac structure and function in this mouse model of ACM, which recapitulates human disease by disrupting the structure of the cardiac desmosome. Desmosomal proteins are essential for maintaining the integrity of cardiac muscle and individual muscle cells. Desmosomal protein mutations can disrupt the normal function of the heart and may result in life threatening heart rhythms and other cardiac issues, such as ACM, a rare and severe genetic heart condition that can be debilitating and life threatening.
The current standard of care for patients with ACM consists of medications targeting arrhythmia management and heart failure, implantable cardioverter defibrillators (ICDs), and cardiac catheter ablations, none of which are curative. Even with optimal treatment, life-threatening arrhythmias and disease progression still occur, and can lead to heart failure. There are no disease-modifying treatments for ACM, other than cardiac transplant for late-stage disease. ACM therefore presents a profound unmet medical need for patients with the disease.
“RJB-0402 shows exciting potential to be a significant breakthrough for patients suffering from this severe, life-limiting disease, who have an urgent need for better treatment options. If this approach proves effective to treat ACM, it would have a dramatic impact on the profound burden this disease has on patients and their families,” said Hugh Calkins, MD, Professor of Cardiology and Director of the Johns Hopkins Arrhythmia Service and the ARVD/C Program.
“What makes RJB-0402 especially promising is its superior performance in the ACM nonclinical model, outperforming gene replacement therapies in reducing PVCs. Since RJB-0402 is not a mutation-specific gene therapy, this suggests that it has the potential to address all causes of ACM including those without known mutations, estimated to be 130,000 individuals, rather than being limited to a specific genetic subgroup, like gene replacement therapies,” said Daniel Oliver, CEO & Co-Founder, Rejuvenate Bio.
“ARVC is a progressive genetic disorder that can affect multiple generations of family members. One of the first symptoms of ARVC can be sudden cardiac arrest, which can lead to sudden death. Therapies that are agnostic of the individual’s specific mutation are a vital avenue of investigation and we are thrilled to learn of Rejuvenate Bio’s continued progress in this area. This research gives much-needed hope to all families affected by ARVC,” said Alice Lara, President of the Sudden Arrhythmia Death Syndromes (SADS) Foundation.
RJB-0402 is a liver-targeting adeno-associated virus vector-based gene therapy that drives over expression of FGF21. Since the doses required to overexpress FGF21 in the liver are meaningfully lower than those required for traditional AAV gene replacement therapies, this approach may have a beneficial effect on the safety profile of the investigational product and could also dramatically reduce manufacturing costs. The initial clinical study for RJB-0402 will focus on patients with Desmoplakin-related arrhythmogenic cardiomyopathy (DSP ACM) at high risk of life-threatening ventricular arrhythmias and sudden cardiac death.
“We see great promise for this therapy to treat this severe, life-threatening disease and improve the quality of life for patients with DSP ACM and look forward to engaging with the FDA in the near future to align on the requirements to initiate an IND,” said Deborah Ascheim, MD, Chief Medical Officer, Rejuvenate Bio.
For more information: www.rejuvenatebio.com