嘿嘿视频

From Bench to Bedside: Insect Research Yields Promising New Drug
for Diabetes, Hypertension and Inflammatory Disorders

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Photo: Bruce Hammock, hand on chin, in front of a computer monitor
Entomology professor Bruce Hammock founded a $50 million investment biotechnology company that developed the promising drug.

A new drug developed at the University of California, Davis, to treat diabetes, hypertension and inflammatory diseases has entered Phase IIa of human clinical trials to evaluate its efficacy.

The winding, twisting path that took entomology professor Bruce Hammock from his lab, to collaborative research with other 嘿嘿视频 scientists, to the founding of a $50 million investment biotechnology company, to clinical trials proved as steep as the mountains he loves to climb.

The compound, a soluble epoxide hydrolase enzyme (s-EH) inhibitor called AR9281, is 鈥渁 first-in-class drug, which may treat a suite of major cardiovascular and metabolic diseases,鈥 said Hammock, who with UC Berkeley cell biologist Sarjeet Gill discovered the enzyme in 1969 while researching fundamental insect biology.

鈥淭his is one of the few examples of basic research in an academic laboratory moving through target validation and compound optimization all the way to the clinic,鈥 he said.

Tracing the events that led to the discovery of the enzyme, Hammock recalled doing research at UC Berkeley four decades ago with then-colleague Sarjeet Gill. Gill discovered the enzyme in mammals. Shortly after, Hammock found the novel enzyme in insects.

鈥淏oth of us have been chipping away at this problem ever since,鈥 Hammock said. 鈥淏y 1975 we were convinced that this was a therapeutic target but no one else was. When we finally found potent inhibitors for the enzyme that worked in whole animals, we had a tool to demonstrate that this was a promising therapeutic target.鈥

Hammock was initially interested in regulating the development of insect larvae. With the discovery of the enzyme inhibitor, however, he switched part of his research from 鈥減est control to pain control.鈥

The enzyme is involved in the metabolism of arachidonic acid, a key signaling molecule implicated in diabetes, hypertension (high blood pressure) and inflammatory disorders. 鈥淚t鈥檚 an enzyme in the same arachidonic biochemical pathway where many other common pharmaceuticals such as aspirin, Advil, Aleve, ibuprofen, Motrin and others are active,鈥 he said.

The Phase I trial evaluated the safety, safe dosage range and side effects of the drug candidate. It then entered Phase IIa to test its efficacy.

嘿嘿视频 physicians and scientists praised the new drug as promising.

Nephrologist and cell biologist Robert Weiss of the 嘿嘿视频 Health System said the drug could lead to important health implications for patients with type 2 diabetes, a chronic disease affecting an estimated 23.6 million children and adults in the United States.

Cardiologist and cell biologist Nipavan Chiamvimonvat of the 嘿嘿视频 Health System, a longtime collaborator with Hammock, said many diseases tend to occur together in vascular biology. 鈥淪o, a compound that addresses heart failure, as we have shown, combined with the reduction of blood pressure, inflammation and diabetes is very attractive.鈥

Last year, the researchers showed that the compounds reduced atherosclerosis is obese mice.

The Phase IIa clinical trial is a double-blind, placebo-controlled study. Officials will enroll a total of 150 patients with impaired glucose tolerance, mild obesity and mild to moderate hypertension.

Each patient will receive 28 days of treatment. The AR9281 enzyme inhibitor will be studied for safety, tolerability, reduction of blood pressure and various measures of glucose and lipid metabolism. Results are expected the first quarter of 2010.

At the onset, Hammock faced two major obstacles: financing and moving the drug into clinical trials.

鈥淔inding resources in an academic laboratory to move a first-in-class drug through clinical trials, is difficult,鈥 Hammock said. 鈥淚t costs $700 million to $1.2 billion to get a treatment to the market.鈥

鈥淧ublicly funded research,鈥 the professor said, 鈥渞esults in many new possible pharmaceutical targets that could be exploited by either small molecule drugs or biotechnology. However, society faces a serious problem in that few of these leads are followed and there is a widely held view that universities cannot validate a target, much less optimize a pharmaceutical.鈥

So in 2002, Hammock founded the biotech company Ar锚te Therapeutics Inc. , naming the company with a mountaineering term that means 鈥渟harp, steep ridge.鈥 Specifically, the company is named for the ar锚tes of the Bear Creek Spire of the Sierra Nevada that Hammock, his sons and occasionally other 嘿嘿视频 faculty and students climb.

鈥淚 founded the company because I failed to transfer technology to the public from the University of California by other means in the past,鈥 Hammock said. 鈥淎nd I received nothing more than a passing interest from pharmaceutical companies at that time, but now they are very interested.鈥

In 2003, he and his son, also named Bruce, incorporated the company to move the materials into clinical trials.

鈥淭o get funding we had to make a case for a new drug when current therapy was thought to be adequate,鈥 the professor said. 鈥淭here are few good drugs for end organ failure and vascular inflammation.鈥 Vascular inflammation is involved in diabetes and obesity side effects.

鈥淭he collaborative and interdisciplinary environment at 嘿嘿视频 permitted us, with support from the National Institute of Environmental Health Sciences, to optimize the potency and drug properties of the s-EH inhibitors to the stage where we could present a convincing picture to venture groups of compounds ready to move to the clinic.鈥

In 2005, the company raised more than $51 million in Series A financing led by Frazier Healthcare Ventures, Alta Partners, Three Arch Partners, Burrill & Company and Altitude Life Science Ventures.

Today, the biotech company, based in Hayward, is dedicated to the discovery and development of novel drugs to treat type 2 diabetes, hypertension and inflammatory disorders, Hammock said.

鈥淥ur main goal,鈥 Hammock said, 鈥渨as to set up a system of a science-driven company where we reduce the cost of drug registration by using very good incisive science. We also want to reward and motivate the people who do the work; provide a funding and training environment to help teach students and postgraduates to write proposals; and allow scientists to move between an academic and industrial environment in the early stage to help determine career directions.鈥

Another goal: a low-cost, affordable drug. 鈥淭he sickest people in the world, of course, cannot pay for the drugs they need,鈥 Hammock said. 鈥淭he chemistry developed around the s-EH inhibitors allows us to make powerful but inexpensive drugs that could be produced in developing countries.鈥

Meanwhile, the clinical trials under way represent two firsts, said James Sabry, president and chief executive officer of Ar锚te Therapeutics. 鈥淭his is the first clinical study of a s-EH inhibitor in patients, and the first study designed to establish proof of concept that s-EH inhibition modulates glucose metabolism or blood pressure in patients with impaired glucose tolerance and hypertension."

鈥淭he compound looks quite promising and it鈥檚 an example of how basic work in insect biology led to a $50 million company 鈥 by far the largest Series A financing of an early stage drug in many years 鈥 and a drug in Phase II human clinical trials,鈥 Hammock said. 鈥淭his all shows the value of basic research and what we can do to help humanity.鈥

Hammock, who joined the 嘿嘿视频 Department of Entomology faculty in 1980, holds a joint appointment in cancer research with the 嘿嘿视频 Medical Center and directs the National Institute of Environmental Health Sciences (NIEHS) Superfund Program on the 嘿嘿视频 campus, as well as the National Institutes of Health (NIH) Training Program in Biotechnology, and the NIEHS Combined Analytical Laboratory.

Elected to the prestigious National Academy of Sciences in 1999, he received the 嘿嘿视频 Faculty Research Lecture Award in 2001 and the Distinguishing Teaching Award for Graduate and Professional Teaching in 2008.

About 嘿嘿视频

For 100 years, 嘿嘿视频 has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, 嘿嘿视频 has 31,000 students, an annual research budget that exceeds $500 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges 鈥 Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science 鈥 and advanced degrees from five professional schools: Education, Law, Management, Medicine, and Veterinary Medicine. The 嘿嘿视频 School of Medicine and 嘿嘿视频 Medical Center are located on the Sacramento campus near downtown.

Media Resources

Pat Bailey, Research news (emphasis: agricultural and nutritional sciences, and veterinary medicine), 530-219-9640, pjbailey@ucdavis.edu

Kathy Keatley Garvey, Entomology, 530-754-6894, kegarvey@ucdavis.edu

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