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Life Sciences Roundup

Parasitic worms could help fight Crohn’s disease

Xconomy.Com / July 25, 2011

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It’s not often a biotech company asks permission to run human tests of a remedy derived from parasitic worms. But the Food and Drug Administration will probably be entertaining just such a request when Coronado Biosciences Inc. files an Investigational New Drug application for CNDO-201, a brew that contains 2,500 eggs from a parasite found in pigs.

The company, which is moving from New York to Boston in August, plans to test the therapy in patients suffering from Crohn’s disease, an autoimmune condition that strikes the intestinal tract.

Coronado, around since 2006, recently came out of stealth mode in a rather dramatic fashion. On July 6, it revealed it had raised $25.8 million in a funding round led by National Securities Corp., following a $21.6 million private round in November.

Last week, Coronado filed a Form 10 with the SEC to become a public reporting company, the first step in the process of entering the public markets.

That will make financing Coronado easier, says chief executive Bobby Sandage. “We don’t intend to partner our products, so we will need to raise more money,’’ he says.

The decision not to seek Big Pharma partners may seem bold; many cash-strapped biotechs need all the help they can get. But Sandage and his team of seven are confident their two experimental treatments, CNDO-201 and an anti-cancer molecule called CNDO-109, are so promising they can afford to handle the research themselves, and hold onto all the profits.

While the two drugs may seem quite different, they’re similar in that they take an immunotherapeutic approach to combating disease. By harnessing NK cells, CNDO-109 follows a well-known technique for fighting cancer. But drugs generally used to activate NK cells are toxic. So Coronado is developing a way to remove NK cells from family members of acute myeloid leukemia (AML) patients, activate the cells in a test tube, and infuse them back into the patient.

In a trial with seven patients at University College London Business, which developed the molecule, remission times were lengthened and patients suffered few side effects, Sandage says. Coronado plans to file an IND early next year to study the drug in AML. The treatment has also shown early promise in breast, ovarian, and prostate cancer, as well as in multiple myeloma, he says.

The parasite treatment, CNDO-201, offers a different approach to modulating the immune system. The treatment was inspired by the “hygiene hypothesis’’ - an observation by some academics that the incidence of autoimmune diseases has increased along with the cleanliness of society because lack of exposure to parasites may predispose humans to inflammatory diseases. Parasites similar to the pig worm Coronado is studying actually regulate cell mechanisms that prevent excessive T-cell activation - a major cause of autoimmune disorders.

The idea is to give patients eggs from the pig parasite every two weeks or so. “Because humans aren’t the right host, the worms can’t colonize,’’ Sandage explains. “The eggs stay there a couple of weeks and then dissolve.’’

But with regular dosing, the eggs seem to spark a positive immune response: In small trials in inflammatory bowel disease, upward of 70 percent of patients achieved total remissions. If the FDA accepts Coronado’s IND, the company will start a trial in Crohn’s early next year, Sandage says.

Sandage says moving to Boston is a matter of logistics. Coronado’s chairman, Glenn Cooper, is based in Boston, as is scientific cofounder Joel Weinstock, who did the original work on CNDO-201 and is now chief of gastroenterology/hepatology at Tufts Medical Center.

Arlene Weintraub

The pharmaceutical business tends to split into two camps: Molecules ought to be small, or they ought to be large. But some interesting work is happening in the middle, where Cambridge-based Ensemble Therapeutics Corp. has been toiling since 2004 - carving out a niche based on work in David Liu’s lab at Harvard University - to synthesize mid-size molecules known as macrocycles.

The idea is to combine the best of both worlds with small and large molecules. The mid-size drugs are supposed to have a big advantage of traditional small-molecule drugs - their ability to be made into pills - along with the precision targeting capability of large-molecule biotech drugs, like antibodies or other engineered proteins.

Ideally, the mid-size candidates should hit biological targets inside cells that bulkier protein drugs can’t reach.

There have been plenty of skeptics. Macrocycles are complex molecules found in nature. Scientists know they can be made into pharmaceuticals, including antibiotics like erythromycin, but no one has developed a fast, cheap, industrialized way to synthesize new macrocycle drugs. Only in the last year, Ensemble chief executive Mike Taylor says, has the company hit its groove, developing a method that had created a vast library of about 3 million new macrocycles (soon to be an estimated 4.2 million) with potential to run through screening campaigns against some of biology’s hard-to-reach targets.

Ensemble’s molecules are still in their infancy and need to run the usual gauntlet of tests in animals before the company thinks about advancing them into clinical trials. But Ensemble has gotten much positive feedback from its partners, Pfizer and Bristol-Myers Squibb, and is in position to add a third or maybe a fourth partner, Taylor says.

Ensemble has been granted key patents on its technology, putting the company, with just over 30 employees, in a position to do what Big Pharma companies do - run industrialized campaigns to see if certain new drugs can hit a target and elicit the desired biological activity.

“We’ve become very productive; we can screen millions of macrocycles against dozens of targets in a short period of time. It’s extremely efficient and fast,’’ Taylor says.

Taylor has a PhD in medicinal chemistry and was a senior vice president of R&D at Pfizer Inc. He has been joined in this effort by Nick Terrett, Ensemble’s chief scientist, another Pfizer veteran and co-inventor of the erectile dysfunction drug Viagra.

They know that Big Pharma companies have huge libraries of small-molecule compounds. For Ensemble to have something new and valuable, it has to bring new molecular structures to the table with the ability to hit new targets. And it needs to be done cheaply, because R&D costs have been rising.

“Big pharma had so many compounds in its collections, it was getting too expensive to screen,’’ Terrett says.

Taylor adds it could sometimes cost $4 million to screen an entire library of small molecules against a biological target before starting the long and expensive work of animal and human testing.

Ensemble is still playing a lot of its cards quite close to the vest. Taylor did not name the targets, and the company has not published any description of what it has done with macrocycles, but plans to do so, Taylor says.

Luke Timmerman

Inotek Pharmaceuticals Corp., of Lexington, has bumped its latest financing up to $23.6 million, with nearly $10 million in new funding, according to an SEC filing. The drug developer raised $14.3 million last summer from investors such as Devon Park Bioventures, Care Capital, Rho Ventures, MedImmune Ventures, and Bio*One Capital.

This report was compiled by the editors of Xconomy, a news website focused on the business of technology and innovation. For more New England coverage, visit www.Xconomy.com/boston.