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

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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.

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