For People with BAG3 DCM: The UPBEAT trial

Affinia Therapeutics is a biotechnology company developing rationally designed gene therapies with the aim of improving safety and providing meaningful benefit to patients. The company does this by developing proprietary technologies in gene therapy with the potential to change patients' lives. The Affinia team is a passionate group of experienced life science leaders who collectively have successfully led more than 50 investigational new drugs into clinical trials and secured regulatory approvals for treatments in more than 20 diseases, including ZOLGENSMA® (onasemnogene abeparvovec-xioi), a transformative gene therapy for a fatal disease called spinal muscular atrophy which affects children. Affinia is currently focused on developing AFTX-201 for BAG3 DCM.

A clinical trial is a research study to evaluate an investigational medicine in people living with a particular disease or condition. The study is overseen by principal investigators, who are physician experts specializing in the treatment of that disease and experienced in conducting clinical trials. The clinical trial outlines eligibility criteria for participants, the doses to be tested, and how study participants will be followed over time. The design of the clinical trial aims to increase the chance of seeing a treatment benefit and manage the risk of side effects occurring.

Gene therapies have been studied for decades. They are medicines that modify or replace the function of defective genes in the body. Genes are the building blocks of nature that provide instructions to cells to produce proteins. Proteins are essential for cell and body functions.

The BAG3 gene, for example, provides instructions to muscle cells such as those in the heart to produce BAG3 protein. The BAG3 protein plays an important role in maintaining healthy proteins in the cell, especially under conditions of stress such as muscle contractions. In BAG3 DCM, the BAG3 gene is defective and muscle cells do not produce enough BAG3 protein, compromising the ability of the heart cells to contract. The affected person cannot exert normal activity. Gene therapy for BAG3 DCM has the potential to address the underlying root cause of this genetic disease.

AFTX-201 is an investigational gene therapy being developed by Affinia for people living with BAG3 DCM. AFTX-201 provides a functioning BAG3 gene so the heart cells produce enough BAG3 protein. In animal studies, AFTX-201 showed increased BAG3 production in heart cells, normalization of the heart function, and reversal of the structural defects of the heart. AFTX-201 is being evaluated in the UPBEAT clinical trial; it has not yet received marketing approval by the U.S. Food and Drug Administration or any other regulatory agency.

AFTX-201 is given as a one-time infusion into a vein. There is no repeat infusion. AFTX-201 is currently only available via the UPBEAT clinical trial to eligible participants.

The UPBEAT clinical trial (NCT07426419) is a study to evaluate the safety and efficacy of AFTX-201 in adults diagnosed with BAG3 DCM who are 18 to 55 years of age and have some difficulty performing normal physical activities. Study participants are not required to have an implantable cardioverter defibrillator (ICD).

In the UPBEAT clinical trial, all participants receive a one-time IV infusion of AFTX-201 at a dose that has been considered safe and efficacious based on preclinical studies. Patients are evaluated for benefit to AFTX-201 treatment and for any side effects. The evaluations are done a few times in the one year after the infusion typically on an outpatient basis (meaning not in the hospital). The visits are more frequent in the first week after the AFTX-201 dose is administered and much less in the last nine months of the clinical trial.

The UPBEAT clinical trial is designed with input from patients, physician experts for BAG3 DCM, and regulators, and informed by the preclinical studies completed in animals. An independent safety committee of experts in BAG3 DCM and gene therapy has been set up to prioritize the safety of trial participants. The UPBEAT clinical trial is available at a number of institutions across the U.S. and Canada. The names of trial sites are updated on a rolling basis at clinicaltrials.gov (Intervention/Treatment: AFTX-201) and via the company, Affinia (clinicaltrials@affiniatx.com).

Patients will not have to pay to take part in the UPBEAT clinical trial and treatment is provided at no cost. However, you or your health insurance company will be responsible for costs related to your current medications.

Accommodations will be made and costs reimbursed for travel and stay for interested participants and their immediate family members if they do not live near these institutions, including those outside the U.S.

Gene therapies have three components: a capsid (a delivery tool that serves as an envelope to carry the normally functioning gene to the right tissue to correct the genetic disease), a transgene (a functioning gene that performs the biological activities that are defective in the disease), and a promoter (a control element that "instructs" the transgene where to produce the protein).

In addition to AFTX-201, there are currently two other investigational gene therapies for BAG3 DCM being evaluated in clinical trials. These gene therapies differ principally in the capsid (the delivery tool or envelope) that is used: AFTX-201 uses ATC-187, Affinia's engineered capsid designed to reach heart cells, at a 5-10-fold lower dose. The other investigational gene therapies use conventional capsids called AAV9 and AAVrh74. Affinia has conducted head-to-head studies in animals showing its ATC-187 capsid is more effective and safe than AAV9 or AAVrh74.

Participants in the trial may help advance science by addressing the underlying root cause of BAG3 DCM. This study will also help researchers learn more about AFTX-201. The hope is to improve the lives of people living with BAG3 DCM in the future.

Potential risks include side effects from the investigational medicine, from other drugs the investigational medicine is used with, or from procedures that may be done in the trial. These risks are outlined in a form called the informed consent, which is provided to eligible participants by the principal investigator (the physician offering the trial) when the patient is considering enrolling in the trial.

Participation in a clinical trial is a very personal decision, taking into account risks, benefits, and individual circumstances and should be done in close partnership with the medical team at the clinical trial site.

Anyone interested in the UPBEAT clinical trial is encouraged to reach out to Affinia via clinicaltrials@affiniatx.com or to a participating trial site. UPBEAT clinical trial sites can be found at clinicaltrials.gov (Intervention/Treatment: AFTX-201).