The folks at The Column Group like to back some of the edgiest ideas in biomedicine, and their counterparts at SV Life Sciences tend to avoid some of the risky early steps in cancer drug R&D. So I had to wonder what these two venture firms were thinking earlier this month when they poured $9.2 million in Series A financing into a San Francisco-based startup cancer drug developer called Cyterix Pharmaceuticals.
Cyterix is all about using some nifty chemistry to pursue one of the age-old concepts of cancer drug development—killing tumors while sparing healthy tissue. If this technology is half as good as the founding team says it is, then Cyterix could have a new way to deliver high doses of chemotherapy to tumors without all the nausea, vomiting, nerve damage, hair loss and other side effects that come with the territory in the cancer drug business. And the company shouldn’t have to spend billions of dollars, and a decade of time trying to find that answer.
“I’m very excited about it,” says Lutz Giebel, a managing partner with SV Life Sciences in San Francisco. “The nice thing is you can find out early on whether it works, and how broadly applicable the chemistry is. The clinical risk is greatly reduced.”
Cancer drug development, for those who don’t follow the daily blow-by-blow of the industry, is a very risky proposition. Animal models often don’t help predict what happens in people, so about one out of 10 drugs that enters human testing passes the gauntlet of studies required to become an FDA-approved medicine. Many drugs fail in the final phase of development, as drugs are required to clear higher hurdles, like showing they prolong lives. The industry has grown into an $80 billion a year market, largely on the strength of research that underpins drugs that are better at specifically targeting tumors, compared to old-school chemotherapy that kills all sorts of healthy and diseased cells. But even the successful new drugs usually work for less than half of patients, or they extend survival by only a few extra months, while causing nasty side effects.
Cyterix is looking to come up with more potent targeted compounds, based largely on picking some clever targets, and also through some secret chemistry sauce. The company is developing conventional small-molecule compounds that have the ability to hit certain enzymes known as cytochrome p450s. The compounds can be chemically linked to a potent cell-killing agent (say, a high-dose chemotherapy warhead), which is designed to be selectively sliced off only in the presence of the tumor. This whole package, known as a prodrug, is designed to remain stable in the bloodstream until it encounters the specific p450 enzymes, says CEO Steve Everett.
Some of the early work to flesh out this concept was done at the University of Dundee in Scotland, where Everett headed up a drug discovery research operation before he moved to the Bay Area a year ago to found Cyterix.
Plenty of others have tried to make prodrugs without much success. It took years for scientists to figure out how to really make chemical linkers that remained stable in the blood, and exclusively deposited the toxin in the tumor. But there have been some recent successes with targeted “smart bombs,” that combine antibody drugs with potent toxins—namely a breast cancer drug from Genentech called T-DM1 and another for rare lymphomas from Seattle Genetics called brentuximab vedotin (Adcetris).
What got the investors interested, Everett says, is that Cyterix has
