There are lots of little biotech companies with dreams of beating the big boys, and one of those classic storylines is playing out in South San Francisco at CytomX Therapeutics.
CytomX has fixed its attention on making an engineered antibody drug (which it calls a Probody) that is more precisely targeted to cancer cells, and packs more wallop, than Eli Lilly’s cetuximab (Erbitux) and Amgen’s panitumumab (Vectibix). This program is still in early development, with a goal of filing regulatory paperwork for clinical trials by the end of 2013, but CytomX has hit enough of its technical milestones to start talking publicly about this bold new initiative, says CEO Sean McCarthy.
The biomarker on cancer cells that the Lilly and Amgen drugs are designed to hit—the epidermal growth factor receptor (EGFR)—is “one of the most clinically and commercially validated targets out there in oncology,” says McCarthy. Lilly’s Erbitux was first approved by the FDA in February 2004 for patients with colorectal cancer, and was later cleared for cancer of the head and neck. Along with Amgen’s rival product, these two drugs collectively generate almost $2 billion a year in worldwide sales. But they have their limits, as the EGFR target is found on skin and gut cells, which means many patients who get these drugs suffer from moderate to severe rashes, and severe gastrointestinal effects like nausea. And while the side effects are unavoidable, scientists have learned that the drugs don’t work for about 40 percent of patients who have mutant forms of a gene called KRAS.
CytomX, founded in 2008 with technology from UC Santa Barbara, is wagering that its technology will make it possible to make a drug that only hits the EGF receptors found on tumors, and that such a drug can be combined with a toxin to get it extra tumor-killing punch. Third Rock Ventures and Roche Ventures bet $30 million back in September 2010 that CytomX could turn this concept into a reality. If CytomX is ultimately proven correct, it could crack open a much bigger market for EGFR inhibitors, by getting rid of the nasty rashes, and offering a new treatment for the 40 percent of KRAS mutant patients who don’t benefit from today’s drugs.
Quite a lot happened behind the scenes at CytomX in 2011, McCarthy said during a meeting at the JP Morgan Healthcare Conference back in January. For starters, he was promoted from chief business officer to the CEO job in September, after Nancy Stagliano left for iPierian. While the leadership changed, the company made progress on its operations and technical goals, McCarthy says. The company added a lot of capabilities during the year, growing from eight to about 20 employees, and settling in to a new 13,000 square foot facility in South San Francisco. They worked on the company’s basic concept, which is to combine a peptide with the antibody, so that the drug only gets activated in the presence of certain enzymes (proteases) in diseased cells. This way, the antibody will remain inactive while it circulates in the bloodstream, and then get activated when it comes into contact with these disease-related proteases.
CytomX’s big technical step in 2011 was when it found what McCarthy calls a “relevant animal model” to test its concept. The company showed it was able to inject one of its “Probody” drug candidates into rodents that had EGFR-overexpressing cancer that mimics what is seen in humans, both in the tumor, and the surrounding microenvironment, McCarthy says. CytomX scientists saw that their drug was able to hit the
