ChemoCentryx, Pursuing the Dream For Autoimmune Disease, Seeks to Put a Pill in a Bottle

11/4/10Follow @xconomy

One of the big dreams in the pharmaceutical business is to develop a once-daily oral pill that can relieve symptoms of autoimmune diseases. These are the kind of energy-sapping, pain-inflicting, or disfiguring illnesses people get when the body’s immune system goes awry and attacks healthy tissue like it’s a foreign virus.

No one has come close to doing this with a safe and effective pill, but one little-known biotech company plugging away for years in an office park in Mountain View, CA, ChemoCentryx, has recently produced some eye-opening results. If ChemoCentryx can nail its next big trial, it could be a couple years away from delivering a potent new option for patients with Crohn’s disease, an autoimmune disease of the intestines.

“This is the most exciting phase in our development since I started the company 13 years ago,” says ChemoCentryx CEO Tom Schall.

ChemoCentryx has kept a low profile since its founding 1997. The company has scooped up more than $330 million in financing during those years from partnerships, government grants, and venture capitalists and private equity investors. The vision—backed by HBM BioVentures, Alta Partners, OrbiMed Advisors, Jennison Associates, and GlaxoSmithKline among others—is to create small-molecule oral pills that interact with novel protein targets called chemokines and chemokine receptors. By limiting the activity of the chemokine system, the idea is that ChemoCentryx can disrupt a vital process that leads to autoimmunity, without shutting down essential immune defense functions that protect people from infections.

The prize at stake here is among the biggest in the pharmaceutical business. Estimates are that between 14 and 24 million people in the U.S. have autoimmune diseases. Fortunes have been made for Amgen, Johnson & Johnson, and Abbott Laboratories on the back of one-hit wonder drugs for such conditions, including rheumatoid arthritis and psoriasis. Total sales of rheumatoid arthritis drugs alone are estimated to grow from $7 billion in 2007 to $17 billion by 2017, according to Datamonitor. And there are an estimated 80 different autoimmune diseases to tackle, although not all are going to be that lucrative.

Tom Schall

Tom Schall

Plenty of people argued in the late ’90s and early 2000s that the original biotech drugs for autoimmune diseases would flop because patients wouldn’t want to take injectables for a chronic condition. Plenty of companies have tried, unsuccessfully, to create conventional small-molecule drugs that can be made into more convenient oral pills for autoimmunity, figuring that whoever does it, will take over the market.

I’ve covered a few startups in other parts of the country going after such treatments, notably Plymouth, MI-based Lycera and San Diego-based CalciMedica. Both of those companies, however, are at much earlier stages, on the cusp of entering clinical trials.

ChemoCentryx is going about its plan a little differently, essentially to try to carve out a niche as “chemokines-R-us.” Schall, a Stanford-trained cancer biologist with experience at Genentech and Schering-Plough, told me all about this with the kind of enthusiasm I’d expect from a graduate student or postdoc. “I’ve been living and breathing this stuff essentially my entire adult life,” he says.

“This stuff” is the science of chemokines—signaling molecules that control how immune cells move in and out of inflamed tissues—and the receptors on immune system cells that chemokines bind to. The key to ChemoCentryx’s approach, as in many fields of drug development, is to tap deep understanding of these targets in order to craft drugs that act on them specifically, while causing minimal collateral damage in the form of side effects.

Pretty much all of the Big Pharma companies, to varying degrees, have tried or are trying to make drugs like this against chemokine-system targets. Pfizer hasan FDA-approved drug for HIV, called maraviroc (Selzentry), made to hit one of the members of the chemokine receptor family, called CCR5. Others are in development, but no other company, Schall says, has attacked chemokine drug development in such a sweeping way against so many targets, and sustaining effort for such a long time.

“Others have had frustrations, and we think we understand that,” Schall says.

ChemoCentryx’s lead drug, developed in partnership with GlaxoSmithKline, is called Traficet-EN, and is made to hit a chemokine receptor called CCR9. Studies have shown that CCR9 is found mainly on T cells that migrate selectively to the intestines, where they can play a key role in the overactive inflammation found in people with Crohn’s disease and ulcerative colitis. An estimated 1.4 million Americans have Crohn’s or colitis. (Since I’m always looking for that Seattle angle in my hometown, I’ll have you know that Pearl Jam guitarist Mike McCready is a prominent Crohn’s spokesman.)

Schall wasn’t quite ready to talk about his company’s latest clinical results for Crohn’s when I stopped by his office in late September, but ChemoCentryx delivered some really interesting data just a week ago. A study of 436 patients, presented at a medical meeting in Barcelona, showed that half of patients with moderate-to-severe forms of Crohn’s who were randomly assigned to get the ChemoCentryx drug were in clinical remission after 36 weeks, compared with 31 percent on placebo. The company also reported on tests to show that CCR9 is active in both the small and large intestine, to offer more evidence of the underlying biology, which might help explain why patients on the drug appeared to be doing better.

This is still a preliminary finding, of course, meaning it’s not proof, it’s hypothesis-generating.

But the idea is interesting enough that GlaxoSmithKline is pushing ahead with a Phase III clinical trial expected to get underway by the end of this year, Schall says. “They saw the results, they loved the results, and now they are running with it,” he says.

The trial will be a big one, and more than a few other autoimmune disease drugs have failed at that stage. The study will have to enroll a lot of patients to give the FDA a big set of safety data, which the agency typically requires for treatments aimed at highly prevalent diseases, and it will need to follow them for at least a year, which the FDA wants because this is a chronic condition. All in all, the trial will take “a couple years,” to generate the kind of hard proof the FDA wants to see before it will clear a new Crohn’s drug for sale, Schall says.

While this compound could eventually be the first to really validate the ChemoCentryx approach, now is really when Schall sees his company’s story advancing to its next phase. GlaxoSmithKline stands to grab the bulk of the profits from the lead drug, but ChemoCentryx is on track to have seven different drugs in clinical trials from its own internal discovery efforts by the end of this year.

Building up that pipeline, with a team of just 75 employees, is an unusually high rate of R&D productivity. And this being the drug business, all of them could easily fail. But just getting them that far is something.

ChemoCentryx’s strategy over the next five years, Schall says, is to find a way to harness enough cash from that pipeline so it can become a more fully integrated company that discovers, develops, and—the last piece is especially important—sells and markets its own products.

If an IPO window opens up, Schall says he’ll be ready, but he’s not counting on it, and he doesn’t need the money because his company had a cash cushion of more than $100 million at end of the last quarter. Partners are essential if ChemoCentryx is going to market a drug for a common disease like Crohn’s around the world, but that doesn’t mean ChemoCentryx is necessarily destined to end up getting acquired, he says. Of course, that could just be good bargaining position to stake out with Big Pharma companies to coax them to write an even bigger check, but Schall flashes that boyish enthusiasm when he talks about building up his pipeline and someday holding onto 100 percent rights of one of its own drugs in North America.

“Our new five-year working plan is how do we parlay this enormously valuable set of assets, and how do we get to become a ChemoCentryx that makes and sells its own drugs, at least in some parts of the world?” Schall says. “Think North America for a moment. We can make some money from those assets, and use the profits to not only sustain, but expand the enterprise, and pass it on to the next generation. That’s where we’re going.”

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  • LarryW

    While ChemoCentryx maybe have a good drug, it is hardly breaking new ground by developing an oral medication for an auto-immune disease. For example, the FDA just approved Gilenya for multiple sclerosis and there are several other MS drugs in late stage trials.

  • http://www.xconomy.com/author/ltimmerman/ Luke Timmerman

    Larry—it’s true that there’s now an oral drug for MS and that is an autoimmune disease, but there are a lot of other conditions that are ripe for an oral pill, like rheumatoid arthritis, Crohn’s, psoriasis, etc.

  • http://www.northcoastbio.com Johnny T. Stine

    …..and these aren’t just and “drug” it’s the first of many that target the chemokine receptor family that this outfit has been focusing on since it’s inception….

    Tom S. – nice picture! I’ve never seen you without a beard. And I have some great chemokine receptor antagonist antibodies – they just need to be humanized and outlicensed.

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