Christopher Reinhard will tell you there is nothing unusual about the 20-plus years he’s spent getting an experimental heart therapy to late-stage clinical trials.
“Very rarely will you get a short story on development of a drug,” said Reinhard (above), who is a principal investor and the CEO of San Diego-based Angionetics. Two decades “is about what you would expect” for a new drug-making method, Reinhard said.
That may be true, but it doesn’t begin to convey the tortuous path that Reinhard has followed to get Angionetics where it is today. The biotech is starting a phase 3 trial in the next few months that seeks to enroll some 320 patients with myocardial ischemia—when clogged coronary arteries reduce the flow of oxygen-rich blood to the heart.
To treat the disease, Angionetics isn’t testing some new type of cholesterol-lowering drug, or a stent to help open clogged arteries.
Rather, it’s attempting a risky and less-proven method—gene therapy, in which new genetic instructions are transported into the body to help produce a specific protein. Gene therapies have been in development for decades, but are only now starting to come of age thanks to a variety of technological advances. Two therapies are approved in Europe, from UniQure (NASDAQ: QURE) and GlaxoSmithKline, both for ultra rare immune and metabolic diseases. Spark Therapeutics (NASDAQ: ONCE) this year is expected to file the first ever U.S. approval application for a gene therapy, a treatment for a form of childhood blindness.
Angionetics’ gene therapy, Ad5FGF-4 (Generx), is intended to stimulate the growth of new blood vessels in the heart. A catheter inserted through the groin delivers the genes—carried within modified viruses—into heart cells, where they are supposed to produce a protein, fibroblast growth factor-4, that helps grow new blood vessels.
The hope is to ease chest pain and relieve the effects of clogged coronary arteries by stimulating the growth of new blood vessels in areas in the heart where there is insufficient blood flow. “We’re just taking the heart and trying to enhance its ability to grow more blood vessels,” Reinhard said.
While gene therapies are more advanced than ever, and several experimental treatments aimed at heart disease and heart failure are being tested, none have yet succeeded. A heart failure gene therapy from San Diego’s Celladon, for instance, failed in 2015.
Still, the potential prize is substantial. Of the estimated 16.5 million Americans with coronary heart disease, Angionetics’ Reinhard said about half experience heart-related chest pain.
The current standard of care offers two principal methods of treatment. The first course of therapy is usually to prescribe drugs like nitrates that temporarily dilates blood vessels to ease chest pain (angina) or the long-term use of beta blockers, calcium channel blockers, or metabolic modulators that reduce the heart’s demand for oxygen. In cases where this approach, known as “medical therapy,” is no longer appropriate, the next step would be to consider an interventional procedure intended to increase the supply of oxygen-rich blood to the heart by inserting a coronary stent or by coronary bypass surgery.
Angionetics aims to establish its gene therapy as an option for patients who no longer respond to drugs and who are not good candidates for bypass surgery or stents, Reinhard said. He estimates that as many as 1 million Americans might fit this description. “Our view is that inside this population, there is room for another alternative, and that is what we call ‘medical revascularization,’” he says.
One of the biggest questions that has dogged Ad5FGF-4 development in recent years is why, in previous studies, some patients have responded to the treatment and others haven’t.
“What we learned was that cell transfection [i.e. getting new genes into heart cells], appears to be enhanced by patients with higher levels of ischemia” Reinhard said. The company believes that means people with a higher degree of ischemia would tend to have a better response to Ad5FGF-4. So Angionetics intends to be highly selective about the patients to be enrolled in its upcoming “Affirm” trial, which is set to take place at dozens of medical centers around the country, Reinhard said.
With the company on the cusp of its pivotal moment of truth, Reinhard also reflected on the twists and turns that Angionetics has taken since 1995 to get to this point.
For Reinhard, the saga began in 1996 when he joined the San Diego startup Collateral Therapeutics to advance research findings from UC San Diego on coronary heart disease. After forming a strategic partnership with Schering AG, Collateral went public in 1999, and advanced its technology to mid-stage trials. In 2002, Schering acquired Collateral Therapeutics for $160 million. A few years later, Schering ended its cardiovascular R&D activities, throwing the Collateral team into limbo.
“Schering ran into trouble, and got acquired by Bayer,” Reinhard recalled. Around 2005, “Bayer made a strategic decision to abandon gene therapy.”
San Diego’s Cardium Therapeutics acquired Collateral’s technology, and continued work on various aspects of the technology. In 2014, under a deal with China’s Shanxi Taxus Pharmaceuticals , Cardium became Taxus Cardium Pharmaceuticals.
A year later, Angionetics was established as a subsidiary of Taxus Cardium to advance work on Ad5FGF-4, and sold a 15 percent stake to China’s Huapont Life Sciences for $3 million. Eventually, Taxus Cardium plans to fully spin out Angionetics.
Reinhard told me he’s now approaching the culmination of what has been a two-decade odyssey.
“Usually in biotech you only get one chance at Yankees Stadium,” he said. “You get to go to the plate, and take your swings, and if you strike out, that’s it. You don’t get another chance.