Pancreatic cancer’s standard of care includes a drug that does not help most people diagnosed with the disease. Gemcitabine (Gemzar) works in only about 10 percent of patients, says Steve Carchedi, CEO of Apexian Pharmaceuticals.
Carchedi knows about gemcitabine’s limitations because he worked at Eli Lilly (NYSE: LLY) when the FDA approved the Indianapolis-based company’s drug in 1996 to treat pancreatic cancer. Now, after stints at East Coast biotech companies, Carchedi is back in Indiana, minutes from Eli Lilly’s corporate headquarters, and he’s working on a pancreatic cancer therapy yet again.
In recent months, Apexian has assembled a team comprised largely of Eli Lilly veterans, some of whom, like Carchedi, worked on gemcitabine. If Apexian’s cancer research proves successful, Carchedi could find himself bringing another pancreatic cancer drug to market, this one with the potential to supplant the cancer drug he helped commercialize 20 years ago. Apexian is now laying the groundwork to take its compound into clinical trials.
“We like to think we’ve taken it from the research world into the business world in the past year,” Carchedi says.
Apexian traces its origins to Mark Kelley, a professor of biochemistry and molecular biology and currently the chair of pediatric oncology research at Indiana University. Kelley has spent more than 25 years researching protein-protein interaction, the way that proteins work to regulate and manage the various biological processes in a cell.
Some pharma companies have tried to develop drugs that work by affecting protein-protein interaction in disease. Eisai Pharmaceuticals went as far as mid-stage clinical trials with a compound taking this approach in hepatitis C. But the Japanese pharma company shelved that program following the emergence of new hepatitis drugs that cured the disease, such as Gilead Sciences’ (NASDAQ: GILD) sofobuvir (Sovaldi) and the follow-on combination sofobusvir-ledipasvir (Harvoni), Carchedi says.
Though Eisai’s protein-protein interaction work did not lead to commercial success, Kelley saw value in the compound, which targeted the same protein he was studying in cancer, Carchedi says. He licensed the compound and in 2008, formed ApeX Therapeutics, taking the name from the APE1/Ref-1 protein that was the focus of his research. The former Eisai compound became APX3330, ApeX’s lead drug candidate; Kelley became the company’s chief scientific officer in addition to his IU responsibilities.
The Apexian small-molecule drug (the company recently changed its name to Apexian Pharmaceuticals to stand apart from other companies that use “Apex” in their names) works by binding to APE1/Ref-1, a dual protein key in the development and growth in tumors, Carchedi explains. Blocking this protein stops cancer cells from replicating. Apexian made pancreatic cancer its lead target because that cancer is particularly dependent on APE1/Ref-1, he says.
Pancreatic cancer is rare, but it is deadly. Of the estimated 46,000 American diagnosed with the disease in 2014, nearly 40,000 have died, according to the National Cancer Institute. Drug companies have taken different approaches to developing new drugs for the disease.