Our Clinical Program: AFTX-201

AFTX-201 is an investigational gene therapy being evaluated for the treatment of BAG3-associated dilated cardiomyopathy (DCM) in the UPBEAT© clinical trial in the U.S.

BAG3-associated dilated cardiomyopathy (DCM)

BAG3 DCM is a devastating monogenic heart disease affecting more than 70,000 people in the Canada, U.S., Europe, and U.K. regions. The BAG3 gene, or Bcl2-associated athanogene 3, encodes for a protein that is critical to the normal structure and function of muscle cells, particularly those in the heart. People affected by BAG3 DCM have a defect in the BAG3 gene resulting in an insufficient amount of functioning BAG3 protein thereby causing heart failure that typically begins in young adulthood and progresses rapidly. Whereas there are treatments for general heart failure, these do not address the underlying genetic cause of BAG3 DCM and unfortunately, almost 25% of patients require a heart transplant.

AFTX-201, an investigational gene therapy for BAG3-associated dilated cardiomyopathy

Using our engineered heart capsid, ATC-187, we’ve rationally designed an investigational gene therapy, AFTX-201, for BAG3-associated dilated cardiomyopathy (BAG3 DCM). AFTX-201 is intended to target the tissues most affected by the disease, allowing a dose that is 5-10 times lower than that required by conventional capsids such as AAV9 or AAVrh74 and potentially improving safety and effectiveness.

Affinia designed AFTX-201 to address the underlying root cause of the disease by delivering a full-length, fully human functional copy of the BAG3 gene to the cells that need it most, heart cells. AFTX-201 is meant to be administered as a ‘one-and-done’ therapy, via a simple IV infusion. In a genetic mouse model of BAG3 DCM, which mirrors the human disease, AFTX-201 resulted in the desired increase in BAG3 protein level in the heart, improvement in structural abnormalities of the heart, and complete restoration of cardiac function eight weeks after a one-time IV dose. In contrast, the same gene construct delivered using a conventional capsid did not show adequate improvement in cardiac function in the same genetic mouse model. The dose we studied is much lower than what is currently being tested in other gene therapy clinical trials for cardiac diseases. We’re excited to evaluate this product candidate in the UPBEAT© clinical trial in order to provide hope and potentially transformative benefit to people affected by BAG3 DCM.

We’ve presented our findings at multiple scientific conferences. To see this breakthrough science, please click here.

The UPBEAT© clinical trial

The UPBEAT© trial is a clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of AFTX-201 in adults with genetically confirmed BAG3-associated dilated cardiomyopathy. The trial is planned to be conducted at multiple sites currently in the U.S. It is a single-arm open-label study, meaning all participants receive AFTX-201, the investigational gene therapy. The AFTX-201 dose given is one that has been deemed to be safe and efficacious based on preclinical studies. AFTX-201 is administered via a single IV infusion and participants are followed periodically at outpatient settings (not in a hospital) for a year after the dose is administered to obtain key safety and efficacy measurements. There are a number of steps that have been taken to ensure the safety of participants as well as the potential for clinical benefit, including careful selection of the dose, close laboratory and other follow ups, and oversight by an independent safety committee of world-renowned experts. Interested participants are encouraged to reach out via clinicaltrials@affiniatx.com. We’ve presented our findings at multiple scientific conferences. To see this breakthrough science, please click here.

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