David Hangauer, associate professor of chemistry at UB and senior vice president of Kinex Pharmaceuticals, developed a new anti-cancer drug after 15 years of research at UB, which has recently begun its first phase of human testing.
According to Hangauer, the new drug called KX2-391 was created to inhibit a certain kinase called SRC ("sark"), which is a type of enzyme that allows for the survival of cancer cells. By being able to inhibit this particular enzyme, they will be able to attack the cancer cells without damaging surrounding cells, which is a common side effect in many currently available cancer treatments.
"Our drug binds where the protein or peptide substrate binds, and this is a unique binding cavity, so it allows us to have our drugs be far more selective than (other drugs)," he said. "You have over 500 different kinases in the body, and you only want to inhibit one or a few; if you bind where ATP binds, since it binds to all the kinases, there's a good chance you're going to inhibit more than one kinase."
Being able to inhibit only the SRC kinase prevents toxicity and other side effects that are caused by drugs that inhibit more than one kinase at a time, Hangauer said.
According to Hangauer, this drug has shown promising results for all types of cancer in all previous testing.
"As far as we know, it's effective against every type of cancer; it includes solid tumors as well as liquid tumors," he said.
KX2-391 also proved to have a wider therapeutic window, meaning the difference between the levels of the drug needed to work against the cancer and the levels that produce toxicity will be very great, Hangauer explained.
According to Hangauer, phase one of human testing began this past Monday at Roswell Park in downtown Buffalo and MD Anderson Cancer Center in Houston, Texas.
"(During) phase one, we want to discover the maximum tolerated dose. We want to determine what dose shows good responses in the biomarkers and how different those two doses are," he said.
Phase one involves testing to see how long the drug lasts in the body, how high of a dose is acceptable before you reach toxicity levels and whether the drug is doing what it is intended to do, Hangauer said.
According to Hangauer, patients will take a single dose of the drug for a week; a week later, they take the drug twice a day for 21 days and then have a seven-day washout. Following that, they take the drug for another 21 days and then have another seven-day washout for as long as they continue to show positive results.
If the drug succeeds, as they are expecting it will, they will continue on to phase two and phase three of testing, Hangauer said.
"Phase two is when you try the drug in a bigger number of cancer patients and certain specific cancers and you know approximately what dose to use," he said. "Phase three is a further expansion of the trial, usually a comparison to other drugs, and finally it would go to market after that."
Hangauer noted that if KX2-391 proves to be successful after phase one, Kinex Pharmaceuticals will most likely arrange a deal with a large pharmaceutical company.
"It costs a lot of money to do phase two and phase three trials and market the drug," said Hangauer. "It goes beyond what a small company can do by themselves, so you have to partner with a big company in order to bring a drug like this to the market and have it distributed worldwide."
Before human testing could occur, KX2-391 went through various tests and precautionary measures.
"The FDA requires that you do animal toxicity studies before you can dose a human, so toxicity studies have been done in rats and dogs before it went into humans, and you need that to determine what dose you're allowed to start in a human with," Hangauer said.
According to Hangauer, a project like this is just what the Western New York economy needs.
"This is what the residents of Western New York, the taxpayers of Western New York, the legislature, the governor and everybody has been hoping for," he said. "Technology developed at UB is spinning out to a new startup company in the biotech industry, which can lead to local jobs that are good paying jobs and to help revive the Western New York economy."
According to Hangauer, KX2-391 is the first drug to ever be discovered and developed in Buffalo.
Photo: Courtesy of Laron Fomby
