Although precision medicine is—or should be—applicable to many diseases, mutation-specific treatments are most commonly thought of in the context of cancer. Magdalene Cook, M.D., CEO of Renovacor, thinks the approach should catch on in heart disease as well—and with $11 million in new financing in hand, she’s leading the charge with a gene therapy for a rare, potentially fatal heart disease.
“I think cardiovascular disease is at the point where oncology was 10 or 15 years ago, when we used to treat all lung cancers as lung cancer. We’ve since learned that we can look for specific genetic mutations and develop targeted therapies addressing those mutations of a specific cancer,” Cook told FierceBiotech. “We can detect causative genetic mutations for certain subpopulations and develop precision medicines to address those, as opposed to treating all cardiovascular disease with more of a broad brush.”
The Philadelphia-based biotech is taking aim at dilated cardiomyopathy (DCM), a condition in which the heart’s left ventricle becomes enlarged, reducing its ability to pump blood. This condition appears in many patients with heart disease stemming from narrowed coronary arteries. But a subset of DCM patients—about 35,000 in the U.S., by Renovacor’s count—develop it because of a mutation in the BAG3 gene.
Renovacor picked up $11 million in series A financing from Novartis’ venture arm, Broadview Ventures, BioAdvance, New Leaf Venture Partners and Innogest Capital to push forward a gene therapy that could ward off disease progression in this group of patients, sparing them from drastic measures such as a heart transplant.
“The BAG3 gene affects the contractility of the heart,” Cook told FierceBiotech. “This reduces the amount of blood that can be pumped with each contraction. When that occurs, some blood is left in the heart and that is what causes the dilation, the heart blowing up like a balloon.”
The gene also plays a role in the remodeling of the heart muscle, which refers to changes to the heart’s shape, structure and function. Remodeling can be a good thing, such as in the case of the heart muscle adapting to physical exercise. But it’s bad news for DCM patients.
“[The BAG3 gene] is also involved in the remodeling of the heart, so in apoptosis and autophagy—the functions of cell death and the clearance of cell debris—in heart failure patients,” Cook said. This remodeling leads to scarring of the heart tissue, which reduces its ability to pump, she said.
A 129-patient study published last year found that BAG3-related DCM happens earlier than DCM caused by coronary artery disease. The study also found that men with BAG3-related disease had a “high risk of progression to endstage heart failure and a worse prognosis.” The findings appear in the Journal of the American College of Cardiology.
All DCM patients get the same care whether they have a BAG3 mutation or not. This includes lifestyle changes as well as drugs to lower blood pressure, slow the heart rate and remove excess fluid from the body. Patients who worsen may eventually need a heart transplant or a medical device to help their heart work.
Based on the research of Temple University’s Arthur Feldman, Ph.D., Renovacor’s treatment replaces a missing BAG3 gene to potentially halt DCM progression in its tracks. Eventually, it could even become a preventive treatment in patients who test positive for a BAG3 mutation, stopping the disease before it even starts.
The study found 80% of patients with BAG3 mutations had DCM, “so the potential for preventative treatment is there with that high of a level of penetrance,” Cook said. But that would be very far off.
For now, Renovacor is using its $11 million haul to move its gene therapy toward the clinic, starting with toxicology and biodistribution studies in large animals and then filing an IND application. It will also have to set up a manufacturing operation ahead of phase 1 trials.