A small, clinical-stage biotech is taking on one of medicine’s most difficult challenges: bringing the promise of gene therapy to millions of patients suffering from cardiovascular disease.
The gene therapy realm has often been associated with rare, inherited diseases, where a single mutation holds the key to a patient’s well-being. Cardiovascular conditions, on the other hand, are far from rare and stem from a number of genetic and environmental factors.
Medera, led by CEO and co-founder Ronald Li, recently completed enrollment for a phase 1/2a trial of its gene therapy SRD-002 for heart failure during a time when questions of safety and efficacy put the genetic approach in a difficult position. Lasting success at a scale this large is unprecedented.
Cardiovascular disease is the leading cause of death in the U.S., according to a report published last week by the American Heart Association. And heart failure alone comprises more than 64 million global cases, Li said, calling the condition “a point of no return” that can be slowed but not stopped by the currently available medications.
“We have put a lot of effort over the past 30 years into understanding the underlying mechanism of heart failure and other forms of cardiomyopathy,” Li said. “We happen to have identified a target that is the master switch, not just one particular mutation, and that should allow us to address a huge patient population for the two forms of heart failure.”
Launched 10 years ago by Li and fellow co-founder and chief medical officer Dr. Roger Hajjar, Medera has its roots in the academic hallways of biomedical engineering and cardiology at Johns Hopkins University and Harvard University.
Now, it’s looking to generate the clinical data that will put gene therapy on the map for cardiovascular patients.
Shoulders of giants
Like many biopharma leaders, Li doesn’t stand alone. The work from Li and the Medera team expands upon technological leaps that came before.
“We’ve learned so much over the years and decades, and we see ourselves as the third generation of cardiac gene therapy,” Li said, pointing to several drugmakers that helped drive the effort forward.
The first generation began at the turn of the millennium with the biotech Celladon, where Hajjar also served as a co-founder. Celladon not only developed the first cardiac gene therapy, Mydicar, but was one of the first dedicated gene therapy companies in the industry. But Celladon ran into trouble after a failed phase 2 trial, and the company has since shuttered.
Around the time Celladon was losing ground, UniQure made strides with a second generation of heart failure gene therapies. The company signed a licensing agreement with pharma giant Bristol Myers Squibb to potentially succeed where Celladon had stumbled. But after seven years, BMS terminated the collaboration in 2022.
Now, fellow cardiovascular gene therapy developer and Bayer subsidiary AskBio is also chasing a similar goal. AskBio has embarked on a phase 2 trial of its candidate for congestive heart failure, and Li said the two biotechs have learned a lot from one another.
The time could now be right from a technological and regulatory perspective to bring effective therapies through the developmental gantlet, learning from the failures of the past and leveraging new norms in genetic medicine.
“Back then, they were shooting in the dark,” Li said. “They didn’t know the right dosages, and the FDA capped the amount of virus they could inject into patients, 100- to 250-fold lower than companies are routinely using these days.”
Currently, Medera is developing two gene therapies for heart failure: SRD-001 for reduced ejection fraction and SRD-002 for preserved ejection fraction. The company is exploring preclinical programs in pulmonary and vascular conditions, as well.
The master switch
Rather than targeting a specific gene, Medera’s candidates target a calcium-handling pathway that regulates cardiovascular function. This “master switch” underlies all forms of cardiomyopathy, Li said, giving way to wide-ranging effects if targeted by a gene therapy.
That gives Medera a massive potential patient population, but among the high-profile safety issues surrounding gene therapy, scrutiny is bound to follow.
“Gene therapy companies are forced to think about safety more so than before with a lot of people questioning the commercial viability,” Li said. “So we have to think about the practical aspects of organ-specific delivery and manufacturing methods that will get gene therapy to work.”
Medera’s preclinical work makes use of testing technology from its subsidiary Novoheart — a jar-sized disease modeling platform. From a safety perspective, Medera can use the mini-heart to screen for toxicity as well as early signs of efficacy, Li said.
Taking a broader disease approach to gene therapy could have wide implications for future versions of genetic medicine. And Medera is pushing for gene therapies that offer practical solutions to bigger problems.
“Gene therapy is a high-profile field with a lot of scrutiny, but that is also a positive sign because it tells us the field is maturing,” Li said. “Now we have to think about the practical aspects of how we get this done.”
