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 the potential to be a platform company that generates multiple product candidates. The investment will go toward validating some new enzyme targets, and plugging in different toxins into the back end of the small molecules. While most clinical trials at the initial stage are about evaluating safety at a variety of doses, Cyterix ought to get a very clear idea early on about its efficacy profile, because if it can really get the drug to accumulate only in tumors, it ought to be able to jack up the dose much higher than most cancer drugs can go today. Many oncologists try to max out the dose of cancer drugs—knowing it’s hard on the patient—because a lot of studies have shown that when patients can tolerate more chemo, they do better.
“We think you can push envelope on dosing,” Everett says.
Investors and researchers have seen this movie before, and like anything, the proof will be in the data. When I asked Everett what he’s afraid of, he said it was the same thing most companies fear—that the drug hits unintended biological targets outside the tumor.
Giebel, of SV Life Sciences, said that’s exactly the risk he sees as Cyterix finishes up its animal tests and gets ready for clinical trials. But what he said he likes is that the technology can be used to soup up existing drugs which are already known to be potent, which reduces the risk of one of those costly late-stage failures.
“What immediately struck me as different here was you can apply this technology to drugs already on the market,” Giebel says. “There could be companies out there with drugs that looked good, but were limited by a maximum tolerated dose, which was not sufficient to get maximum efficacy. But if there’s a way to take a drug and give more of it, and be safe, you can have more efficacy.”
It won’t take a decade of work, and a mountain of cash, to find out in early trials whether Cyterix can jack up the dosing on existing cancer drugs. And while nothing is certain to translate from Phase I to Phase II and Phase III, this is a bet Giebel said he and his partners were willing to make. It’s an unusual gamble for SV, which doesn’t often invest in cancer drug developers because of the risk, he says.
The academic researcher in Everett could go on all afternoon about the chemistry challenges with this platform, but he’s clearly picking up on how to talk the talk with VCs (and journalists). He describes the company in what you’d have to call a simple, straightforward way. “You got to remember it’s about superior efficacy and safety. We’re speaking to both points,” Everett says.