Friday, September 9, 2016

Making bread safe for celiacs

By Alix Stuart, Boston Globe Correspondent
March 11, 2013
(Reprinted without permission)

When Leslie Williams, a former pharmaceutical executive, agreed to meet a visiting professor from Australia in Boston for a lecture, she thought it would be a routine lunch in her role as a business mentor.  But the meeting, three years ago at the Boston Cambridge Marriott, turned into an intense five-hour discussion as Dr. Robert Anderson explained how his research into celiac disease promised to render the destructive disorder obsolete.

An autoimmune disease triggered by gluten proteins in wheat, barley, and rye, celiac disease affects­ some 3 million Americans. Untreated, it can destroy digestive tract tissue and can lead to anemia, osteoporosis, infertility, neurological dysfunction, or even cancer.

Currently, the only solution is to avoid gluten altogether. That means not eating standard versions of bread, pasta, and pizza, or anything else that contains even traces of wheat, including soy sauce and some candy, such as Twizzlers.  Dr. Robert Anderson’s research is zeroing in on a potential vaccine against celiac disease.

But as Anderson explained that afternoon to Williams, his research was zeroing in on a vaccine to cure celiac disease.  
The science “struck me as quite special and possibly­ game-changing,” Williams recalled.

She agreed to work with Anderson, and in short order Williams lined up seed capital from an angel investor and then went to Australia to unravel legal­ agreements around Anderson’s research and his company. Within the year, ImmusanT was formed, with Williams as chief executive and Anderson­ as chief scientific officer. By its first ­anniversary, the firm had $20 million in venture funding.

ImmusanT is headquartered in the biotech boomtown of Kendall Square in Cambridge and is conducting clinical trials for its vaccine, NexVax2, under “fast-track” designation from the Food and Drug Administration for diseases for which no comparable therapies exist.

“If it works, you’ll see the entire paradigm of treatment for celiac changed,” said Sundar Kodiyalam, managing director for the venture investor Vatera Healthcare and an ImmusanT board member. His firm was so enamored of the science that it invested before the company had persuasive clinical data.

Beyond ImmusanT, Boston has become a locus for research into celiac disease. Massachusetts General Hospital scored a coup when it recently convinced a leading researcher, Dr. Alessio Fasano, to head its new celiac treatment and research center. “Our mission is to make life normal for people with celiac disease,” Fasano said at a ceremony marking the opening of the Mass. General center in February.

With similar research units at Beth Israel Deaconess Medical Center and Children’s Hospital Boston, the city now has “a critical mass of expertise” in celiac disease, said Dr. Ronald Kleinman, physician in chief of Mass. General’s pediatric unit.

“I’m not sure that I see miracles happening” with the research underway now, said Lee Graham, chairwoman of Healthy Villi, a 900-member support group for celiac sufferers in New England. “But the gathering that’s happening in Boston is terrific, and tremendously encouraging to us.”  Formerly at the University of Maryland, Fasano in 2003 published a landmark analysis in which he determined that celiac disease affects many more people than previously thought: about 1 out of 100 people. Up to that point, the scientific wisdom was that celiac was relatively rare, and that a gluten-free diet worked as a sufficient “cure.”


But Fasano and others have since shown that some patients who avoid gluten continue to suffer gastric distress, leading to the conclusion that diet alone is not enough.  Not surprisingly, with the market for gluten-free foods at $4.2 billion, ImmunsanT has some company in the race for a solution.   One rival is Alba Therapeutics, a Maryland company that Fasano helped start in 2005. (He is no longer involved in the company, though he owns some stock.) The other is Alvine Pharmaceuticals, of San Carlos, Calif., spawned from research at Stanford University.

Both companies are working on pill-based therapies to counteract the unintentional consumption of small amounts of gluten; complements to the gluten-free diet rather than replacements. And both are preparing for Phase 2b clinical trials to determine if their medicines work, and at what doses.  Alba’s compound targets zonulin, a protein that is believed to contribute to “leaks” in the gut that allow gluten to infiltrate the digestive system. Cephalon Inc., now owned by Teva Pharmaceuticals, has a $7 million option to buy Alba if its drug proves effective.

Alvine’s therapy involves an enzyme that decomposes gluten into harmless particles before it reaches the gut. Patients in its most recent trials who consumed gluten for six weeks while taking the Alvine compound showed little or no damage to their intestines, with some even showing improved conditions.  
ImmusanT’s drug is at a much earlier stage of development. At the time he lunched with Williams, Anderson was a professor at the Walter and Eliza Hall Institute in Melbourne, Australia. He had a start-up, Nexpep Pty Ltd., and was in need of funding to continue developing a celiac vaccine.

Anderson said he was struck by how many patients struggled with a gluten-free diet, which can be less healthy than typical diets.   “Having a treatment that would allow full recovery and return to normal diet would be life-changing for patients, and may motivate more patients to be checked for celiac disease,” he said.

Williams, meanwhile, had worked at Merck, GlaxoSmithKline, and other drug makers and was chief executive of Ventaira Pharmaceuticals when it was sold to Battelle in 2007.

In his research, Anderson had latched on to a key catalyst: the three gluten peptides that are believed to be at root of the reaction patients suffer from gluten. NexVax2 essentially tries to reeducate the immune system to tolerate those peptides. Initial study results indicate that ImmunsanT has identified the correct peptides, and that Nexvax2 is safe to take — two important steps.

Still, there are many questions. For one thing, ImmunsanT’s early volunteers maintained gluten-free diets during the study, so its not clear how well the vaccine works in the presence of gluten. And it will work only for an as-yet undefined subset of celiac sufferers.  Even so, Fasano, who has no connection to the company, calls the concept behind the ImmunsanT’s vaccine “the holy grail” that would allow patients to eat regular bread, pasta, and other gluten-rich foods.


Though ImmusanT and the other firms are small, Williams and others in the field said the pharmaceutical industry has a keen interest in their research.   Moreover, because celiac disease is currently the most well understood autoimmune disorder, many scientists believe the research could serve as a springboard to drugs for larger markets.  “It’s not just about curing celiac,” Fasano said. “It’s about treating MS and diabetes, and all these other autoimmune conditions, and that is where industry really takes an interest.”


Carolanne Le Blanc

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