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.
In 2013, Celgene (NASDAQ: CELG) won FDA approval for paclitaxel (Abraxane), a drug that it acquired through its 2010 buyout of Abraxis Bioscience. Paclitaxel is an injectable chemotherapy drug that the FDA approved for use alongside gemcitabine, the standard of care. Last year, Cambridge, MA-based Merrimack Pharmaceuticals received FDA approval for its pancreatic cancer drug, an injectable nanotherapy. This irinotecan liposome injection (Onivyde) is derived from the old chemotherapy drug irinotecan. Merrimack developed this compound to target tumors more specifically, and for a longer time, than conventional chemotherapies.
But several pancreatic cancer drug efforts have fizzled. In May, Berkeley, CA-based Aduro Biotech failed in clinical trials with a drug that combined two immunotherapies. OncoMed Pharmaceuticals, a drug developer based in Redwood City, CA, has three compounds in clinical trials for different cancers, including pancreatic cancer. One of them, tarextumab, stumbled at the beginning of the year when an interim look at a mid-stage trial studying the compound in pancreatic cancer found “low probability” that it would extend the life of patients. Two other OncoMed compounds being studied in pancreatic cancer are still in the early stages of clinical development.
Apexian’s drug could offer some advantages compared to other pancreatic cancer treatments, Carchedi says. Unlike many cancer drugs that are injectable, APX3330 is a pill. The Apexian drug is also selective; it only targets APE1/Ref-1, a protein that Carchedi says is not needed by healthy cells. He points to Eisai’s 10 clinical trials testing 422 patients, which showed that the compound was safe and produced no side effects. While that sounds promising, Apexian still needs to demonstrate that safety in cancer patients. The FDA has given the green light for Apexian to proceed with a Phase 1 clinical trial in pancreatic cancer expected to enroll between 20 and 40 patients.
Carchedi is now charged with raising money and laying the groundwork for pharma partnerships. He came to Apexian in October from Cornerstone Pharmaceuticals, a Cranbury, NJ-based company he led as CEO for two years. His cancer drug experience also includes posts at Mallinckrodt Pharmaceuticals, as well as Johnson & Johnson (NYSE: JNJ), where he was the global marketing leader for that company’s oncology division. At Eli Lilly, Carchedi was director of the oncology product group.
Apexian aims to raise $10 million from outside investors to support its clinical research. Since inception, ApeX Therapeutics had raised more than $3.5 million from investors, according to securities filings. Angel investors and IU’s Innovate Indiana Fund supported the company early on before it secured venture capital investment from BioCrossroads and Pearl Street Venture Funds, both based in Indianapolis. While Apexian pursues additional investors in the near term, Carchedi says the company will eventually seek out larger pharmas as partners. Apexian’s drug might work best alongside other cancer treatments, such as immunotherapies. Partnerships could offer a way to test such combinations, he explains.
Though pancreatic cancer is Apexian’s first target, Carchedi says the company’s lead compound could have broader applications. In animal studies, APX3330 stopped cancer growth in 13 cancers including breast, prostate, renal, head and neck, and colorectal cancers—all cancers dependent on the APE1/Ref-1 protein, Carchedi says. Apexian also has two additional compounds in its drug pipeline. But first, the company needs to prove that its approach to its targeted protein pathway works. Carchedi expects Apexian will begin enrolling patients in the pancreatic cancer clinical trial early next year.
Image of pancreatic cancer cells courtesy of the National Cancer Institute.