Hartford Business Journal

www.HartfordBusiness.com September 5, 2016 • Hartford Business Journal 21 'American Dream' pursuit brings Liang to UConn, Cornovus By John Stearns jstearns@HartfordBusiness.com C onnecticut Innovations is investing more than $1 million in Cornovus Pharmaceuticals, not just because of its promising heart medication, but also because of the doctor behind it. That person is Dr. Bruce Liang, a clini- cal cardiologist and researcher at UConn Health since 2002 and dean of the UConn School of Medicine since 2015. When Connecticut Innovations (CI), the state's quasi-public venture arm, first met with Liang a few years ago to weigh an ini- tial $150,000 investment, the agency had the standard questions about the science and the business, "but you don't really leave questioning Bruce," said Dan Wagner, CI's managing director-investments. "That was always the thing. … We believed that it was worth a shot, an investment." When Cornovus hired longtime pharma- ceutical executive Glenn Mattes as CEO last December to guide the company's business as a com- plement to Liang's science, the pic- ture was complete. " O b v i o u s l y, all these deals are risky in capi- tal, but we really do try to invest in people," Wagner said. "When they found Glenn, that combination kind of tips it over, you have two good folks … they're going to give it their all, and they're easy to work with — that's really it." Liang feels good about Cornovus' chances given early results from animal testing of its molecule to help people with advanced heart failure. Those results helped the company land about $3.5 mil- lion in investor money to fund additional preclinical testing over the next 18 months to apply for investigational new drug (IND) status from the U.S. Food and Drug Administration, a prerequisite to human testing. Getting the money is a victory in itself, as many therapeutic concepts never get that far, Liang said. Going from early academic invention to IND is so risky it's called the Valley of Death of therapeutic discovery, he said. "It's like walking through the Valley of Death because most of us won't make it," he said, acknowledging being in the valley now. But he's optimistic about Cornovus' chances, as its technology has shown enough innovation and prom- ise to get funding on its way toward a hoped-for IND. Liang, 60, joined UConn as chief of the Division of Cardiology and as the Ray Neag distinguished professor of cardio- vascular biology and medicine. He gained administrative experience heading the cardiology group and was appointed inter- im dean of the medical school in 2011 and 2015, before landing the job permanently. He's also been director of the nationally recognized Pat and Jim Calhoun Center for Cardiology since 2003. Seeing patients as a clinical cardiologist, he gained insights on a condition that rep- resented an unmet medical need: helping patients with advanced heart failure who, for various reasons, don't qualify for a heart transplant or ventricular assist device. He wanted to help such patients avoid further decline in heart function. Working with Kenneth Jacobson, a chemist at the National Institutes of Health, the two collaborated on developing a mol- ecule they say fills that unmet need. Liang became interested in cardiology at Harvard Medical School. He thought he wanted to be an endocrinologist because he was curious how things worked, desiring to do endocrinologic science and be a clinician. But in med school, he was exposed to more research in cardiology and did a rotation in it. He discovered the quick gratification, compared to other specialties, from help- ing heart patients by opening blocked arteries and watching patients walk out the door in a couple days or shocking hearts back into rhythm in 30 seconds. He was fascinated by the ability to do research and help patients, a joy he con- tinues today. He does his Cornovus work on the side, separate from his day job as dean, as he pursues a scientific therapy to help people with heart failure. 'American Dream' Liang came to the U.S. in 1972 from Tai- wan with his parents when he was 15. His mother, an accountant, and father, a mer- chant marine and later a sea captain, moved to be nearer to other family members who had previously moved to the U.S., but "more importantly, they wanted to give me and my brother and sister a better educational opportunity, or life opportunity, as immi- grants, the American Dream," Liang said. They initially settled in New York City before moving more upstate, where Liang finished high school before going to Har- vard for his bachelor's degree and medical degree, which he earned in 1982. He did his residency at the University of Penn- sylvania, then returned to Harvard for fel- lowship training in cardiology at Brigham and Women's Hospital, a major teaching affiliate of Harvard Medical School. He then returned to Penn as a med-school faculty member to teach cardiovascular medicine and practice clinical cardiology before joining UConn 14 years ago. CI's Wagner said Liang has the ability to interact well with people and clearly explain Cornovus' science. Mattes, the Cornovus CEO, called Liang extremely bright and hard working, holding a formidable job at UConn and collaborating with Mattes on Cornovus after hours or on weekends. "He's very committed to seeing this through to success," Mattes said. Liang also has an attribute important to Mattes. "One thing … I look for in these folks that are more in the academic or clinical side is, 'Do they respect and appreciate people of other industry skills?' " Mattes said. "And that was clear that he respected the experience that I have. He's willing to listen and partner with me." n that category number around 6 million in the U.S. and 5 million to 6 million in Europe, "so then you're talking about 12 million patients at any given time could be benefiting from a medication like this." It's possible that such a medication, initially envisioned to be infused via a catheter in a vein or through something akin to an insulin pump, could replace the need for a ventric- ular-assist device, he said, expanding the patient universe even more. Those devices cost about $110,000, require mainte- nance, and can carry the risk of infection and clots, he said. Key advantages So what are the risks or challenges that could confront Cornovus? There's always the possibility another new treatment could arise, but Liang isn't aware of anything similar with the kind of properties Cornovus' medication has. Key to its medica- tion is that it doesn't lower blood pres- sure in sick dogs that already have low blood pressure because of their heart failure, he said. That's an impor- tant feature since further lowering of blood pressure can be deadly. "So that's a big advantage because that means if it's true in humans with end-stage heart failure, you could go ahead and give it without worrying about dropping their blood pressure, which is a big no-no because they could die from low blood pressure," he said. "To our knowledge, there's not another drug out there in develop- ment that has this unique property." That's a feature attractive to investors, which included Connecticut Innovations ($1 million) and longtime UConn supporter Ray Neag ($2.5 million). Neag, a UConn alum after whom the Neag School of Education and The Carole and Ray Neag Comprehensive Cancer Center at UConn Health are named, was one of four founding members of Arrow Interna- tional Inc., a Reading, Pa. manufacturer of cardiac and critical-care products. Cornovus also is receiving help from NIH through its SMARTT program, Sci- ence Moving towArds Research Translation and Therapy. SMARTT provides regulatory support, manufacturing and pharmacology/toxicol- ogy services to speed translation of research from the lab to submission of an IND applica- tion with the FDA, according to NIH's web- site. SMARTT gives Cornovus additional support to do some of the studies needed for making the compound in large scale under good manufacturing guidelines so that it can be put in patients. CEO with chops Dan Wagner, managing director-invest- ments at CI and its point person with Corno- vus, said the quasi-public venture firm invested $150,000 in the company four or five years ago to help get it off the ground, before its latest $1 million commitment. CI's investment is based on more than the drug potential, but also the Cornovus team, Wagner said. The hiring of CEO Glenn Mattes in December was important because he has the connec- tions to execute Cornovus' business plan, Wagner said. Mattes has more than 30 years of experience in the p h a r m a c e u t i c a l industry in execu- tive roles, including with Rhône-Poulenc Rorer (the phar- maceutical opera- tions of which are now part of Sanofi); Centocor Biotech; Ortho-McNeil, John- son & Johnson's largest operating company; and CEO at Arno Therapeutics. For the last five or six years, he's worked with smaller companies like Cornovus that are in the preclinical stages or with companies in early clinical development and has advised large private equity firms on healthcare acquisitions. Mattes said he looks for companies that are founded by a quality person like Liang, with a strong medical school or academic relation- ship, "somebody who's got a great reputation in their specialty field and where they're working on a unique therapeu- tic product for unmet medical needs," he said. "So the biggest attraction, quite frankly, to Cornovus was Bruce, given his background, and also the product I think has an awful lot of promise," Mattes said. "Of course, there's still a long way to go." But Mattes likes the company's chances of getting funding for clinical trials. The idea is to hire staff locally as the company ramps up, said Mattes, who lives outside Philadelphia and will have an office locally as well. He spends about half his time now working for Cornovus, which is expected to increase. Cornovus is seeking office space in UConn's Technology Incu- bation Program, or TIP, at 400 Farmington Ave., Farmington. UConn saw promise in Cornovus early on, investing in its patent portfolio and supporting Liang's endeavors with the company, said Rita Zangari, director of innovation programs and external rela- tions in the Office of the Vice President for Research at UConn. Wagner said the chemistry is licensed from NIH, where Jacobson is, and use of it in cardio therapy is licensed from UConn, with the two pieces together in-licensed to Corno- vus. Wagner noted that CI is trying to support UConn and UConn technologies. Yale University has a history of taking technologies and making them companies and getting them out the door, he said. "UConn continues to build that and I think [Cornovus] is one of the better things that have come out of UConn in my time here," Wagner said. "This could be a big-market drug." n Dan Wagner, managing director-investments, Connecticut Innovations Glenn Mattes, CEO, Cornovus Pharmaceuticals Inc. Dr. Bruce Liang, dean, UConn School of Medicine ▶ ▶ Liang formed Cornovus Pharmaceuticals Inc. in 2011 to pursue a treatment for what he says is an unmet need for … heart-failure patients because there's no medication for them. The name represents "cor," for heart, and "novus," meaning new.

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