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Protagonist Criss-Crosses Pacific, in Search of New Peptide Drugs

Xconomy San Francisco — 

If your definition of hard work depends on getting to the office at 7 am every day, then Dinesh Patel might sound pretty lazy. He doesn’t usually pull out of his driveway for work until 9 am.

He has a business reason for starting late, and it has little to do with beating traffic (although that’s a nice bonus). The reason is that his company, Menlo Park, CA-based Protagonist Therapeutics, has half of its scientific team located 17 hours ahead in Brisbane, Australia. And if you want people in different countries and time zones to work on the same page, it helps to get them on a daily work rhythm that’s at least somewhat similar.

“When it’s 3 pm in California, it’s 8 am the next day in Australia, so we have a lot of good time working together from 3 pm to 7 pm our time,” Patel says. “It’s challenging, but once you master the distance, there are advantages.” (One advantage is getting work done around the clock. The downside? Occasional after-dinner business calls.)

Protagonist, founded in 2007 by researcher Mark Smythe in Brisbane, has found a way to make progress in this unusual structure for a biotech startup. The company has raised about $9 million from a set of investors in Australia (Starfish Ventures, QBF, and IMB) as well as a name more familiar in the states, Lilly Ventures. The investment, and a couple of drug discovery partnerships with Cambridge, MA-based Ironwood Pharmaceuticals (NASDAQ: IRWD) and Copenhagen, Denmark-based Zealand Pharma, has come together around Protagonist’s idea for making new peptide drugs. These drugs are being designed so that they can be given as oral pills, or to hit molecular targets that were very tough to bind with, or might only have been reachable in the past with injectable protein drugs.

Dinesh Patel, CEO of Protagonist Therapeutics

It’s a complex drug discovery challenge. But if Protagonist can keep its small team of 22 people working on it seamlessly in two countries, it could end up with a big payoff. The ultimate prize would be oral pills against autoimmune disorders that affect millions of people.

“We want to make oral peptide drugs. It feels good to say that, but it’s a challenging task. We believe we are ready,” Patel says.

Patel has a long history of biotech entrepreneurship, as a co-founder of Vicuron Pharmaceuticals and Miikana Therapeutics, companies that ended up being acquired by Pfizer for $1.9 billion, and by Entremed for $39 million, respectively. Based on his experience in managing partnerships with drug companies, researchers, and contract research firms around the world, Patel says he developed a personal bias toward companies that have global footprints. So when he was approached about becoming Protagonist’s CEO late in 2008, his first reaction to the Aussie connection wasn’t “Geez, I’ll have to spend a lot of time on planes.”

“Most people shy away from these kind of arrangements, for me it was an added attraction,” Patel says. “It’s a personal bias, but I think there’s much to be gained from different cultures and different setups. Most find it challenging with the time zones and travel. For me, it’s fun going to Brisbane.”

Traveling to Brisbane might sound pretty good to an American tourist, but of course it takes real commitment to make a startup prosper when it has small teams so far apart. So Patel has made sure to keep the Aussie and American teams integrated on a daily basis. “I don’t want us to do ‘A’ in one place and ‘B’ in another. On purpose I’m doing cross pollination. It really encourages scientists to work together,” Patel says.

Protagonist’s teams are working together on “disulfide rich peptides” which can be engineered to have convenient drug properties, either as oral pills, or infrequent injections patients can give themselves under the skin. Most companies tend to focus on either small molecule drugs made through chemical synthesis, or genetically engineered “large molecule” proteins, while shying away from peptides that could be classified as “mid-sized.” That’s because chemists haven’t traditionally been able to make peptides into convenient oral pills (like small molecules), and it has been tough to keep them stable in the bloodstream for long periods commonly seen with larger protein drugs. But the idea of making peptides that combine the best of both small and large molecules has been pursued by a number of startups for some time—Cambridge, MA-based Aileron Therapeutics is one member of the class—and Ironwood and Zealand have both had success overcoming some challenges with peptides.

Protagonist has sought to bring together a computational program to design the peptide molecules, coax them into millions of different shapes and sizes in phage libraries, and then use medicinal chemistry techniques to tweak molecules to get the ideal drug properties.

The company isn’t saying much about the specifics of what it is working on, but Patel gave some sense of its direction when we spoke a couple weeks ago at the Biotechnology Industry Organization conference in Boston. Ironwood, for example, has its orally-available peptide drug, linaclotide, that aims at a molecular target for irritable bowel syndrome called GC-C. But irritable bowel syndrome, and other diseases of the gut, are usually the result of many different kinds of proteins being out of whack, in need of inhibition or stimulation. Various inflammatory protein molecules called cytokines—IL-6, IL-23, and tumor necrosis factor—are three particularly good targets, Patel says. “We envision huge applications,” for autoimmune diseases, Patel says.

Protagonist’s partnerships, so far, are pretty traditional discovery deals in which it does some of the early-stage R&D, and then hands over molecules for its partner to take further in development. Essentially, he wants his small team to do a few things, and do them well, rather than get overextended. And the deals are structured so that Protagonist has the freedom to develop some of its own drugs, meaning the employees get the potential upside of working for a biotech startup. Now that’s an idea the Australian and American teams can surely agree on, over a pint in Australia or Silicon Valley.