Cocrystal, Led by Icos Vets and Stanford Nobelist, Hunts for Next Big Thing for Hepatitis C

One of the older tricks in biotech is to sign up a Nobel Laureate as a scientific advisor, and hope some of his or her credibility impresses investors. Never mind if the renowned scientist only shows up for a company meeting a couple times a year. But Gary Wilcox, the CEO of Cocrystal Discovery, didn’t duck when I asked him how much time Stanford University’s Roger Kornberg actually spends on advising the startup.

“He’s involved every day,” Wilcox says. “Roger e-mailed me just 15 minutes ago. He’s incredibly excited.”

Cocrystal has kept a low profile since it was founded three years ago, but this startup with labs in Bothell, WA, and Mountain View, CA, struck an interesting deal last week. Cocrystal said it had formed a collaboration with Israel-based Teva Pharmaceutical, the giant generic drugmaker, in which Teva is investing $7.5 million upfront to gain development access to a hepatitis C compound in early development, among other assets. Cocrystal has now raised a little more than $18 million from Teva, government grants, and a founding equity round led by The Frost Group, the investment vehicle of billionaire Philip Frost.

Cocrystal was started in 2008 by a couple of veterans of Bothell, WA-based Icos, as well as Kornberg, who won the Nobel Prize in 2006 for his work in describing how DNA gets copied into RNA. The big idea at the startup is to use new X-ray crystallography technology to get vivid pictures of replication enzymes within viruses that are critical to making the viruses dangerous. The crystallography techniques provide images with resolution down to the level of individual atoms, and enable Cocrystal to account for how atoms move in real-time, as opposed to taking a more simplistic snapshot image, Wilcox says. Once scientists have that deeper understanding of every nook and cranny in the target, and its range of motion, Cocrystal uses proprietary software to select the ideal small-molecule candidates to bind with the target, Wilcox says.

This approach has enabled a small company like Cocrystal, with about 20 employees split between its Bothell and Mountain View labs, to avoid the massive small molecule screening campaigns that Big Pharma companies have been finding notoriously costly. It’s too early for Cocrystal to get cocky since it is still probably a couple years away from its first clinical trial, but it has been enough to keep Kornberg interested, and for Cocrystal to set up a lab not far from his office at Stanford.

“We have a really good molecule in preclinical development,” Wilcox says. “But probably what’s equally important is we have a giant step forward with our general approach. We have a way of doing things different and better.”

Kornberg himself offered a pretty straight-laced reply when I asked for his comment, but he made plain he’s interested in the broad potential of the Cocrystal platform: “Our technology offers a systematic approach to the development of exceptionally effective drugs against any targets for which crystal structures may be obtained,” he wrote in an  e-mail.

Getting teams in two different cities working together can be a challenge, especially when people are so absorbed in a demanding and collaborative task like leading-edge drug discovery. Wilcox says the Seattle and San Francisco teams use Skype video calls quite a bit to keep people on the same page. One advantage of being in two places, Wilcox says, is that the company can recruit a team of top people that it would never be able to attract in just one location.

It’s still too early to say how Cocrystal’s drugs might be applied in the medical world. But like many other scientists and executives, Wilcox says hepatitis C is going down the road of cocktail antiviral therapy, much like HIV. Vertex Pharmaceuticals and Merck have made headlines this year with new protease inhibitors that have greatly boosted the cure rate for hepatitis C therapy, although scientists now want to combine those drugs with other antivirals that can help stop resistance, and eliminate other co-medications that cause side effects.

Cocrystal in particular is focused on a polymerase inhibitor, and a helicase inhibitor which could be part of a cocktail regimen. Princeton, NJ-based Pharmasset (NASDAQ: VRUS) is one of the most visible contenders in the polymerase inhibitor field.

Cocrystal has paid close attention to what the competitors are up to, Wilcox says. While others might make it to the market first, that may not be a bad thing, he says. Sometimes drugs that are second or third to market have the advantage of looking at the structures of the lead compound, and working around some of the undesirable properties, or side effects, produced by the lead drug. That was what Icos did in the late ’90s when Pfizer introduced sildenafil (Viagra) for erectile dysfunction, and Icos followed with a longer-lasting version called tadalafil (Cialis).

Both drugs are billion-dollar sellers today, even though Viagra hit the market five years earlier. Wilcox says he can imagine history repeating itself, as Cocrystal looks at the existing drugs in the works for hepatitis C and tries to one-up them.

“Competition makes you better,” Wilcox says. “Whenever you compete, you rise to levels of competence you might not otherwise reach.”

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