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'EGF' shows promise to replace livestock antibiotics, help sick children

Years of progress have lead to the toughest challenge – commercialization.

Seeing the potential of EGF to help sick children was "an incredible, emotional experience," says Dr. Andre Buret.

To Dr. Andre Buret the scientist, it's a story of a once-in-a-lifetime breakthrough, rich with professional fulfillment and excitement. To Buret the father and human being, it's a story that depending on the outcome could be heartbreaking.

The journey began 20 years ago when the long-time University of Calgary (U of C) professor and researcher was a graduate student working as part of a U of C team that identified the potential protective and healing abilities of Epidermal Growth Factor (EGF), a natural protein, found in particularly high levels in mother's milk, that increases absorption and other aspects of gut function.

Building on that finding became of the focus of Buret's professional career, with the U of C team making great progress in demonstrating broad potential for EGF to protect against gastrointestinal ailments. Among these, diarrheal disease, which kills five million children under the age of five every year, and Short Bowel Syndrome, another major ailment with no pharmacological treatment.

New hope for infants

The research progress reached a dramatic peak in 2004, when the team led by Dr. Dave Sigalet demonstrated in a special trial with sick children that EGF could be used to help treat Short Bowel Syndrome caused by necrotizing enterocolitis, a devastating and often fatal gastrointestinal disease that mostly affects premature infants.

"It was an incredible, emotional experience," says Buret. "Necrotizing enterocolitis is a disease where the gut or part of it will die off. Surgically you have to cut out a portion of the intestine and rejoin the remnants. In some cases a child can be left with 60 cm of small intestine instead of five metres. In that instance, the prognosis is very bad."

"There is nothing out there to help these children, and on that premise we got special ethical clearance and authorization for a trial to administer EGF to a group of infants suffering from this disease. We demonstrated that EGF can be used to enhance function and length of intestine for these children very quickly. In one case, one child was able to go back to oral intake of solid food instead of being fed intravenously."

Buret and colleagues have established strong prospects for EGF in these and other aspects of gastrointestinal health, both in humans and in animals. In the process, they have garnered more than 30 patents world wide. The findings include great promise to fight against gastrointestinal diseases of calves, adult cattle and other livestock, benefiting producers with healthier, more productive animals.

Critical time

But with the limitations of patent life an increasing concern, the research effort requires a new injection of funding to keep afloat and will soon require backing from a major global player in the pharmaceutical arena, says Buret.

"We're getting to a point now where patents are aging, and you don't want to be in a situation where your patent portfolio is getting overly aged. We're in great shape right now, but time is going by and we need to move now to generate maximum benefit for the user."

For a scientist newly exposed to the business realities of pharmaceutical arena, the challenge ahead is a daunting eye opener.

"You realize there are many things that can make a successful therapy never reach the market," says Buret. "There could be potential cures for cancers that are dying on a shelf somewhere because of the other non-scientific issues."

But despite the tall challenge, Buret and colleagues, with modest yet vital support from Alberta's livestock industry and others, have been determined to fight hard and push forward. Backed by investment from AVAC Ltd, Buret developed a company, AB BioPharma, to help propel the U of C research to a new level and lead the development of products based on EGF.

"Right now with the effort as a whole, we are in an area of our development where we've basically gone through initial proof of concept, in multiple applications, in multiple models, in multiple target species including humans, cattle, pigs and poultry," says Buret.

"We developed a company around that, we've achieved an extensive patent portfolio and we've developed an excellent business plan. What we need to do now are essentially clinical trials, and then bring that progress hopefully to the market with the help of a partner. All of this is directed at getting us in a position to secure major funding."

In the past couple years, AB BioPharma recruited professional management to raise $10 million needed as a first round of funding towards commercialization – an ongoing effort that is making progress. The management team has developed a strong business plan with the goal of having EGF products on the market within four-to-five years.

"Right now, it's all coming down to funding," says Buret. "We've reached the go or no go stage for us, and we're looking for funding very actively."

Funding, partnership needed

The pharmacology sector is a tough area for innovation, he notes. "Particularly in our case, what is needed is technologically not straightforward. It's not as if we have a platform where we make, say, a pill based on dandelion juice that we then sell to help with your toothache. If that was the type of situation we were in, we could do that ourselves – step by step, bit by bit, expand production and then get there . . .ultimately play the game of company development.

"What we're looking at is something that's going to be in the pharmacology sector and potentially in the biotechnology sector. For that we need worldwide marketing systems, which are not feasible from scratch because you're talking about competition with the big pharmaceutical companies. What we ultimately need is to have a partner in one of those companies to bring any product to market."

What gets the attention of the major pharmaceutical companies is a successful, large- scale, independent clinical trial, says Buret. But getting that kind of trial done takes big money.

"On our side, we have completed proof of concept and pilot trials in target species that have all been successful, which is huge – much more than many biotech or pharma technologies are now going forward with. And to have a successful trial in human infants is outstanding."

Human and veterinary products

On the agricultural front, Buret and colleagues have targeted a large scale trial investigating pigs as a model system, as a first priority. "The dairy, beef and poultry industries are also very big priorities. We already have shown that EGF has an effect in each of these areas, but you have to start somewhere and have a strong focus."

As on the human side, the potential for livestock is great. "We believe we could develop products that would allow producers to replace antibiotics in feed. That would be huge, and that's just one example."

Strategizing in both areas is critical, he says. "When you're dealing with a large platform like this, it's absolutely huge. If you do not prioritize, you die. That's why we have established these priorities on the livestock side, and we have done the same in the human sector. It's all part of our business plan. We've strategized not just the importance of a given sector market-wise, but also on the strength of our preliminary results and on the likelihood of success.

"For example, EGF could really help with ulcers, and that's a huge market, but we realize there are already many players in that market so it's not the highest priority for us. On the other hand, Short Bowel Syndrome is a much, much smaller market, but there is nothing out there right now that will help these patients, so we could really do a lot of good and capture a big size of the market in that area."

Hanging in the balance

Timeframes for all priorities will depend on funding, he says. "In the best case scenario, we could move into a clinical trial with short bowel syndrome for humans tomorrow, have results out within three years and have a product on the market within five. On the other hand, the worst case scenario is that AB BioPharma dies and the platform never goes anywhere."

Do or die is not a comforting situation to be in, he acknowledges, but it comes with the territory.

"We are basically looking at any one of the opportunities within that broad scope and hoping to have a bit of luck," he says. "That's just the name of the game."

For children suffering from necrotizing enterocolitis, it's a game with tremendous stakes. "To bring an effective product to the market that would help some of these kids survive, that would really be something special."

Support for the development of this Perspectives on Beef Science article was provided by the Canada Alberta Beef Industry Development Fund (CABIDF). For more information on research supported by CABIDF, visit the CABIDF Web site.

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