BioWorld Today Contributing Writer , by Catherine Schaffer
A lot of companies start with an idea, and build a business around it. Jupiter, Fla.-based GLG Pharma LLC started with a business, in search of an idea.
Its management team, having more than 100 years of combined experience in drug development, and with an aggregate of 15 drugs on the market, knew that in order to be successful in the crowded field of cancer therapeutics, they had to pick a winner. Their search led them to STAT3 (signal transducer and actibators of transcription 3) technology from the Moffitt Cancer Center and Research Institute in Tampa, Fla.
"We looked around the world for technologies in cancer. We were lucky enough to find the best technologies right in Tampa," GLG CEO Hector Gomez told BioWorld Today.
Gomez and founding partners Michael Lovell and Richard Gabriel were not the only people interested in the STAT3 technology. They had big pharma competition. However, a commitment to keep the company in Florida won them a license to the products, which they signed in September 2010.
GLG Pharma is now leveraging the experience of its founders, together with the latest in computational biology to get its STAT3 inhibitor compounds into the clinic at a time when early stage venture funding is difficult to find.
STAT3 proteins are thought to be involved in signaling pathways for cellular growth and division, movement and apoptosis. Normal cells switch STAT3 on and off by phosphorylating it in response to external stimuli.
"It appears location is extremely important," said Gomez, explaining that the STAT3 inhibitors affect signaling pathways at the end. "More than 10 signaling pathways are important in cancer. These compounds are very specific, and only affect cancer cells. They don't touch normal cells:'
In addition to cancer, STAT3 also may be involved in psoriasis, Crohn's disease, inflammatory bowel disease and others. Moffitt researchers found that cancer cells have persistently high levels of activated STAT3 (p-STAT3), which suggested the protein may contribute to the out-of-control growth of cancer cells.
GLG Pharma's pipeline products attack STAT3 in a number of different ways.
GLG-101 inhibits STAT3 phosphorylation. GLG-202 and GLG-302 inhibit dimerization of p-STAT3. GLG-401 inhibits binding of p-STAT3 dimers to DNA.
GLG has good preclinical and toxicology data on its compounds, and expects to advance a lead compound into the clinic this summer.
"We plan to do clinical trials in the modern way. We have to be a little more scientific and more rationaL ... In the past, it was completely trial and error," Gomez noted.
Any clinical candidate will include a targeted therapy strategy. "These compounds will only be effective in patients with activated STAT3," he explained. Because the clinical trial design will include a requirement for patients with activated STAT3, GLG is developing a companion diagnostic.
The other way that the clinical trial experience will be modernized is the incorporation of computational biology.
"We are planning all of our experiments first in silico. ...Once we initiate clinical trials, we will write better clinical protocols," Gomez said.
He also pointed out that typically it takes a good six months to write up the results of a Phase I trial. GLG contended it can streamline that process by starting out with more efficient protocols.
In addition to unspecified start-up funds, GLG Pharma has been funded by a number of grants. Most recently, in November, the company received a cash grant of $733,438 from the U.S. government's Qualifying Therapeutic Discovery Project.
Other groups looking at STAT3 inhibitors include academic and biotech researchers in Japan. Otsuka Pharmaceutical Development Co. Ltd., ofTokyo, has a STAT3 inhibitor in a Phase I study sponsored by the M.D. Anderson Cancer Center, of Houston. That open-label, dose-escalation, nonrandomized study will assess the pharmacokinetics, dose-limiting toxicity and maximum-tolerated dose of compound OPB·31121 in people with advanced solid tumors.
Another group of Japanese researchers published preclinical results for a STAT3 inhibitor, WP1066, in the May 2010 issue of The British Journal of Cancer.