COLUMBIA – For cancer patients, a loss of weight can be fatal.
Due to shifts in molecules and accelerated metabolisms, cancer patients can suffer from significantly decreased appetites, fatigue and a drastic loss of body mass in muscles, bones and organs.
It’s known as cachexia anorexia syndrome, or cachexia in short. Even patients who take in more calories or receive supplementary nutrition can lose lean body mass.
Cachexia hinders treatment responses and patients’ ability to tolerate treatments. It also can cause the heart, liver, kidneys and other organs to fail. According to the National Institutes of Health, about 20 to 40 percent of cancer patients die from cachexia.
Researchers have long been experimenting with therapeutic approaches to combat cachexia. Thirty years ago, they found a particular class of molecules called melanocortins that control metabolism. But when they began to use it as a potential drug, they kept running into cardiovascular side effects and didn’t understand what caused them, Kenneth Gruber, a cardiovascular specialist, said.
Gruber was the first scientist to solve this problem. In 2009, the idea of setting up a company and developing a drug that could slow down the metabolism without causing cardiovascular problems struck him while he was doing research at the California Polytechnic State University. He founded the company Tensive Controls Inc., but he needed a good home for the start-up.
He found one in Columbia.
The MU incubator
Owned by MU and operated by the Missouri Innovation Center, the MU Life Science Business Incubator at Monsanto Place opened in January 2009.
So far, 22 tenants of the incubator have raised $20 million from federal grants, state programs and private investors, and they have created 50 local jobs, incubator CEO Jake Halliday said.
"We made an active decision as part of our strategy to increase high-quality, high-paying jobs by attracting young companies and creating a high-tech company cluster,” he said.
The biggest selling point for the incubator is its collaboration with MU. There’s an abundance of scientific discoveries, but not all of them grow into commercial products that benefit people — partly because of a lack of necessary help.
“There’s a bottleneck in understanding these inventions, primarily in shaping them to their proper potential market and generating the necessary connections, personnel and exposure to get them off the ground,” Brian Thompson, founder of Elemental Enzymes Inc. said.
A tenant of the incubator since 2011, Thompson's company is developing a new kind of enzyme that is reliable and durable. Its products will find applications in various industries and in pollution treatment.
Existing enzymes are “notoriously unstable,” Thompson said. With the help of the incubator, Elemental Enzymes has been able to move from an idea to a product that will enter the market in 2013.
“The incubator helps critically evaluate scientific ideas and provides a location to further refine these ideas into viable business entities and mature products,” Thompson said.
He said being close to fellow entrepreneurs also helps new businesses avoid the kinds of early pitfalls that doom some companies in their early years.
A relocation for Tensive Controls
Gruber knew access to animal trials would be crucial in his company's quest to develop a drug intended for use with people. So when Wake Forest University took back its promise to let Tensive Controls use its animal facilities, Gruber had to find a new home for his startup.
Thousands of business incubators across the nation are eager to attract new tenants. But when Gruber searched Google for incubators with access to animal trial facilities, there weren’t many. The MU incubator caught his attention because of its access to state-of-the-art animal-trial facilities and the oncology research team at the College of Veterinary Medicine.
MU welcomed the future tenant with a generous offer in addition to the animal facilities. Gruber got a faculty position as an adjunct professor in the Department of Pharmacology and Physiology. He also was offered lab space at the Dalton Cardiovascular Research Center, right across the street from the incubator.
“It’s one-of-a-kind offer," Gruber said. "There’s nothing close to this.”
He immediately seized the opportunity, which he said was “too good to not explore.” Gruber remembers the early afternoon of Labor Day 2010, when he emailed Halliday and received a positive reply within two hours. In January 2011, the company moved to its new home.
Having lab space at the incubator and access to animal-trial facilities could easily save the company hundreds of millions of dollars, Gruber said. The incubator charges him the same amount of money as any faculty member at MU.
“What we get is better facilities than most pharmaceutical companies do and at a much lower cost,” Gruber said.
Carolyn Henry, director of the Scott Endowed Program in Veterinary Oncology, which collaborates with Tensive Controls on its animal trials, said the move indicates a consistent effort to bring researchers of different disciplines together to solve real-world problems.
“It continues to build on our efforts in translational medicine, where we can take an answer to a clinical problem from idea stage, through animal studies, into human clinical trials and eventually to the market – all here on the MU campus,” she said.
Meanwhile, MU could benefit from shared revenue, intellectual property and an enhanced image as a leader in scientific discovery, Henry said. The companies also can provide training for students in biomedical innovation.
Work bears fruit
Tensive Controls conquered the cardiovascular side effects in a little more than two years, which is very fast, Gruber said. Then came the question of how to get the drug to cross various barriers to reach the brain, which controls metabolism. After 1 1/2 years of research, the company improved the drugs so that they could go through the digestive system intact.
The company finally developed two slightly different drugs that could reverse accelerated metabolisms with no cardiovascular side effects.
The two drugs, which Gruber calls “Olympic candidates,” have been undergoing small-animal trials for months, and both are working well.
Tensive Controls isn’t the only one trying to develop drugs that combat cachexia. Three or four drug companies have made attempts to bring similar drugs to the market, but all of them have failed in small-animal trials.
The National Institute of Health gave Tensive Controls a preliminary grant of $200,000, evidence of its confidence in the company. After the two new drugs were developed, the institute awarded it another grant for $2 million. When the final drug candidate is chosen, the company will select a contract manufacturer to produce it in large quantities and use it in large-animal trials.
“Companion animals are the closest we can get to human beings,” Gruber said. “They stay with us, eat what we eat, and the cancers in these animals are quite similar to those in human beings.”
Among all the companies trying to develop similar drugs, Tensive Controls is the first to propose going into companion-animal trials.
“We have faith in our drug," Gruber said, referring to the Scott Endowed Program. "We think we can go into a totally objective study on large animals, conducted by independent clinical trial networks in the vet school.”.
The animals will be recruited from cancerous pets brought to the Veterinary Medicine Teaching Hospital by their owners. The trials have been approved by the National Institutes of Health and the Institutional Animal Care and Use Committee on campus, and they are expected to begin early next year.
Gruber estimated the company won’t get into human clinical trials until 2014. If everything goes well, it would get approval from the Food and Drug Administration for the final drug in 2015 or 2016.
The drug could open a therapeutic window for cancer treatment as patients could tolerate radiation or chemotherapy longer. Gruber said he would be glad to leave a legacy of raising cancer survival rates.
Tensive Controls won’t be the one to produce the final drug, however. If the drug shows great prospect, Tensive Controls would likely be bought by a major pharmaceutical company, marking its graduation from the incubator.
So far, one company, Dietary Innovation LLC, has graduated from the incubator, and its owner, Joe Parcell, decided to keep it in Columbia, Vice President Quinten Messbarger said. Halliday said most companies that graduate from the incubator are likely to stay here, attracting investments from outside and boosting the economy.
Supervising editor is Scott Swafford.