Anthony H. Cincotta, a neuroendocrinologist, is founder, president and chief science officer of VeroScience LLC, a privately-held company in Tiverton. VeroScience has developed the only circadian-based neuroendocrine therapy for Type 2 diabetes, Cycloset, an oral medication taken in the morning.
Cincotta earned his undergraduate degree in biochemistry and molecular biology from the University of California, Santa Barbara and his master’s degree and doctorate in physiology from Louisiana State University. After joining the faculty at Harvard Medical School and Massachusetts General Hospital, Cincotta founded and directed two biotech companies – one of which was VeroScience. He talked recently with Providence Business News about prescription-only Cycloset, which was approved for use in the United States by the U.S. Food & Drug Administration in 2009, and Cycloset’s beneficial effects on glucose control in individuals with Type 2 diabetes.
PBN: Tell us about VeroScience, its focus, revenue stream and key staff.
CINCOTTA: VeroScience is a biotechnology company focused on the development of therapies and products to improve human health. Since 2011, it has been helping diabetic patients, with its Type 2 diabetes drug, Cycloset, whose revenues fund VeroScience’s research and development activities.
By investigating and mimicking nature’s means of regulating biochemical physiology for survival of vertebrates in the wild, VeroScience develops treatment strategies, not products per se, aimed at redirecting pathological biochemistry back toward its “normal” physiological organization. VeroScience has pioneered the Circadian Neuroendocrine Resetting Therapy platform technology, which looks at the natural therapeutic benefits of properly adjusting disrupted biological clock activities in the brain that control normal health, including metabolism.
CNRT studies and identifies integrated circadian neural activities within specific sites of the central nervous system that regulate physiological activities such as immunity, growth, reproduction, behavior, metabolism and cardiovascular and renal physiology. We know that environmental or genetic disruptions to these circadian neuroendocrine regulatory systems may have major adverse consequences for an individual’s biological integrity and health. As such, resetting these aberrant circadian neurophysiological regulatory systems back toward their normal temporal organization may lead to improving the biological disorders presented by such circadian disruption.
Cycloset was developed, formulated and administered based on research of circadian neuroendocrine systems, which began some 50 years ago.
In addition to me, VeroScience employs seven scientists with doctoral degrees, one physician, one clinical-studies project manager and three laboratory technicians; in addition, we work with a host of consultants in the fields of business, law, research and development and the biomedical/pharmaceutical industry.
PBN: Describe Cycloset’s efficacy as a drug for those with Type 2 diabetes.
CINCOTTA: For more than 50 years, researchers have been examining how the body’s biological clock in the brain influences metabolism. Cycloset represents a new therapeutic approach in the management of Type 2 diabetes, based upon those decades of study highlighting the important role the body’s biological clock system plays in regulating metabolism.
It is the first drug for patients with diabetes that targets the body's brain dopamine activity, a chemical messenger between neurons, or nerve cells, within the nervous system. Unlike other diabetes drugs, Cycloset works to correct aberrations in the body’s natural circadian rhythm that facilitate diabetes and, thereby, improves glycemic control via the neuroendocrine system.
Clinical studies have demonstrated the drug’s efficacy in improving glycemic control in Type 2 diabetes subjects when Cycloset is used as the sole therapy or taken with one or two other oral diabetes medications. Cycloset has been shown to improve insulin sensitivity and reduces post-meal glucose levels without raising the plasma insulin level. In a large double-blind placebo-controlled study of Cycloset’s impact on cardiovascular disease outcomes, Cycloset therapy demonstrated a 42 percent improvement over the placebo in preventing myocardial infarction, stroke, hospitalization for congestive heart failure, unstable angina and revascularization surgery.
An oral medication, Cycloset is approved as a monotherapy or add-on therapy with other anti-diabetes agents to treat hyperglycemia in patients with Type 2 diabetes. We are constantly publishing new study results with the therapy for individuals with Type 2 diabetes who take diabetes medication.
PBN: Explain the company’s recently published clinical research about Cycloset. What implications does that research have on individuals with Type 2 diabetes?
CINCOTTA: In the past several years, VeroScience has published in scientific journals and/or presented at scientific meetings on many basic and clinical science studies demonstrating the impact of CNRT in regulating metabolism and of Cycloset in managing abnormalities in blood glucose levels in a wide variety of Type 2 diabetes subjects.
At the 2016 American Diabetes Association conference in New Orleans, VeroScience presented six papers that reinforce how the therapy improves glycemic control in individuals with Type 2 diabetes and reduces risk factors for cardiovascular disease. Five of these papers, presented by VeroScience’s researchers, provide insights into Cycloset’s sympatholytic, insulin-sensitizing effects for Type 2 diabetic patients. Dr. Bindu Chamarthi, of Brigham and Women’s Hospital in Boston, presented research that highlights Cycloset’s ability to reduce elevated resting heart rate (a risk factor for cardiovascular disease) and dysglycemia, or blood-glucose-level abnormalities, in patients with Type 2 diabetes.
PBN: What is the domestic market for Type 2 diabetes medications and how much of that market share has Cycloset captured? What growth do you anticipate in the next several years?
CINCOTTA: Currently, approximately 30 million Americans have Type 2 diabetes and, unfortunately, that number is growing. Cycloset has been available by prescription in the domestic market since about 2011.
Even more worrisome than the number of patients with diabetes in the United States are the numbers of individuals who can be classified as pre-diabetic, which includes an additional 86 million Americans, according to the American Diabetes Association. For these patients, prevention and proper management of this condition is absolutely key to prevent the progression to Type 2 diabetes.
Importantly, the Western diet, high in saturated fat that is well known to predispose to insulin resistance and glucose intolerance (pre-diabetes) in humans across the globe, decreases the daily peak dopamine signaling to the brain’s biological clock and increasing the likelihood of insulin resistance. The high glucose levels associated with Type 2 diabetes can be lessened by taking a dopamine agonist – Cycloset – at the appropriate time of day, in the morning, within two hours of waking.
PBN: Describe VeroScience’s relationship with S2 Therapeutics. What entity has the exclusive worldwide licensing rights to manufacture and distribute Cycloset?
CINCOTTA: S2 Therapeutics is a partner of VeroScience and assisted with a portion of the final financing of the development program needed to attain FDA approval of Cycloset. VeroScience and S2 Therapeutics jointly licensed the manufacturing and marketing rights for Cycloset to Salix.