Improving Health From Within

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BY AMBER LEPAGE-MONETTE

In 1928, Alexander Fleming made a discovery that was nothing short of revolutionary. Noticing that bacteria could not grow in the presence of the Penicillim mould, Fleming went on to create the world’s first antibiotic, penicillin, turning everyday infections from fatal diagnoses into minor inconveniences. But overuse of antibiotics has brought us to the stage where humans could soon be as vulnerable to bacterial infection as those who lived before Fleming’s time. What was once one of the greatest medical breakthroughs, could soon become useless.

In light of what Robert Hancock, PhD points out, that no new major class of antibiotics has been introduced since the late 1960s and that several large pharmaceutical companies have pulled out of the ‘antibiotics game’ in recent years, an alternative needs to be found. And that is exactly what Hancock and fellow University of British Columbia (UBC) researcher Brett Finlay, PhD are setting out to do.

Bringing it all Together

Working on different, yet complementary areas of research relating to bacterial infection, Finlay and Hancock have combined their efforts to focus on fighting infections at the source, by strengthening the innate immune system. The result would be a more effective immune system capable of handling larger numbers of bacteria, paving the way for a time when there could be no need for antibiotics and no risk of antibiotic resistance. This is the technology behind Inimex Pharmaceuticals Inc. (Vancouver, BC), founded by these two accomplished microbiologists.

Finlay, who obtained his PhD in biochemistry from the University of Alberta and completed a post-doctoral fellowship at Stanford University (Stanford, CA), was awarded the 1998 E.W.R Steacie Prize for scientists under 40 who have made significant contributions to research, established the Canadian Coalition for Safe Food and Water and has developed an E. coli cattle vaccine designed to prevent livestock from shedding the bacterium.

Hancock, who obtained both his undergraduate degree and PhD from the University of Adelaide in Australia, and completed his post-doctoral work at the University of Tübingen in Germany, was a founding scientific director of the Canadian Bacterial Diseases Network, is an officer of the Order of Canada and has developed variants of cationic peptides, described by Hancock as “nature’s antibiotics,” to fight bacterial infection.

The two brought their work together and started Inimex in 2001, thanks to their graduate students collaborating on microarrays.

“Bob’s and my research are sort of parallel, very complementary. I work on the diseases, he works on how to kill the organism causing the diseases,” Finlay explains. “And then when these two students started in, it was kind of like the lights going on.”

Microarrays perform fast and accurate analyses of gene expression, and for Inimex, allow better analysis of the innate immune response. Before microarrays, Finlay explains, researchers had to look at one or two genes in isolation. With microarrays, they are able to take a comprehensive look at the whole immune response.

“Once we know that response, we can then use Bob’s compounds to then try and tweak that response to enhance the ones we want to activate, but not activate others to then make that much better anti-infective,” he says.

The innate immune system is found in all organisms, from humans to flies, and acts as a first line of defence, keeping our daily exposure to over 100,000 organisms from developing into serious bacterial infections. Studying human cell responses to cationic peptides, Finlay and Hancock have been able to upgrade the innate immune response while actually suppressing the harmful inflammation response that often occurs when using other molecules to boost immunity — a response that can lead to sepsis.

“The usual way of turning up the innate immune system has potential to cause harm,” Hancock explains. “Think about it as a sort of tactical nuclear strike concept, where you might destroy the enemy, but you also destroy some of the surrounding territory at the same time.”

Finding Alternatives

Development of new antibiotics could be one answer to the problem, but it inevitably places us in a similar situation of antibiotic resistance. One of the most positive aspects of Inimex’s technology is that it addresses this issue.

“To my mind, this is the first one (antibiotic alternative) that has come through that offers some of the advantages of antibiotics, can actually work together with antibiotics and, because it is not an antibiotic — because it is not acting directly on the bacteria but rather it’s acting to boost the host — you’re not going to see antibiotic resistance,” Hancock says.

Upon realizing its potential and that they were going to be able to fill such a need, Finlay and Hancock had no hesitations about whether or not to commercialize their technology.

“If you’re generally aware that commercialization is an option…that it is compatible with your research career and you see a phenomenal opportunity, what else could you do?” Hancock says.

Though they describe Inimex’s development as an inevitable step in their research, it was the first company either had ever started from scratch. Not that they are new to the business world; Finlay was heavily involved in the design and development of his E. coli 0157 cattle vaccine, marketed through Bioniche Life Sciences Inc. (Belleville, ON), and Hancock’s work on cationic peptides was commercialized through Micrologix

Biotech Inc. (Vancouver, BC).

Because of the complementary nature of their work, their pairing to have started a company seems natural. But it’s their personalities and friendship that make this partnership seem made in heaven.

“I think I would have been reluctant to do it just by myself,” Hancock says. “Having Brett there was really a huge bonus for me.”

Finlay couldn’t agree more. “I always thought I wouldn’t actually start a company. But having Bob, who is quite happy doing lots of this other stuff and letting me play with the science, I think it was the perfect combination,” he says.

When Finlay speaks of the “other stuff,” he is referring to the hands-on roles both had in the early days of Inimex. Hancock served as CEO and president, and Finlay served as vice-president of Research.

Currently, Hancock is a member of the Board of Directors, Finlay is still vice-president of Research, and both are members of the Scientific/Medical Advisory Board and Research Management Committee.

Hancock has recently taken on a new role as co-director of a project titled Functional Pathogenomics of Mucosal Immunity (FPMI), an alliance between Inimex, Genome Prairie (Calgary, AB) and Pyxis Genomics Canada Inc. (Saskatoon, SK), which provides the companies with $27 million to research how bacteria infect humans and animals. Pyxis brings to the table its animal models that are so well developed, Finlay explains, they are actually real animal infections. The project combines Inimex’s technologies with Pyxis’s models, allowing the scientists to pursue further levels of research.

The funding also frees them from what Hancock says was one of the primary concerns they had with starting a company: the issue of gaining financing while maintaining scientific autonomy.

“Once you start getting money from outside investors there’s a pressure to start producing a product, and that’s a reasonable pressure,” Hancock says. “But in the process of fulfilling your duties to start to move products into clinical trials, often you don’t have the time and space to be able to do the basic science that’s really required. FPMI is providing the really hard science underpinnings for Inimex.”

With the opportunity the money has afforded for work on its potential lead compounds IMX735 and IMX775, Inimex hopes to be in clinical trials within the next two to three years.

“That’s an incredibly, incredibly aggressive platform for a company,” Hancock says. “But we feel that we have the basic information that gives us a good possibility of achieving our aggressive platform.”

Money is, however, the name of the game, and both realize that companies are about making money. What is important, Hancock says, is to realize that making good science and making money don’t have to be conflicting goals.

“They (the scientists) have to concentrate on building the science foundation of their company and they should recognize that that’s not necessarily going to be compatible with the business that every single company has to be involved in, which is making money,” Hancock says. “I think the scientist’s job really is to ensure that the quality of the science within a company is impeccable and provides the foundation for making money.”

Dual Roles

Not that being a scientist and being an entrepreneur aren’t compatible either. Both Finlay and Hancock feel that these roles are, in many ways, intrinsically combined.

“If you’re a good scientist you’re an entrepreneur,” Hancock says. “Because basically, entrepreneurs take risks and good scientists take risks too.”

Finlay agrees. “I think as a scientist you have to be an entrepreneur even within science. You are always out selling yourself and showing the stuff you’re doing is good…They kind of go hand in hand, ” he says.

Switching between science and business roles seems to be something neither has a problem doing, and that may have something to do with where they work. With its highly developed University-Industry Liaison Office, created in 1984, UBC supports a great number of its scientists who decide to commercialize their technologies. As Finlay and Hancock describe it, UBC was an integral part of Inimex’s development, and the support of the university was invaluable in the formation of the company. For both scientists, it seems, their continuing roles at UBC and becoming entrepreneurs are also roles that are highly intertwined.

“A professor does many things at the university, and this is one of them, as well as running the lab and doing your teaching,” Finlay says. “So I think it’s just sort of part of the bigger package…It’s sort of this mentality at UBC that this (commercializing) is part of your job.”

It is because of this support — helping Inimex through the licensing process and helping define what is reasonable practice and what is conflict of interest — that UBC was one of Inimex’s first investors. “We decided basically right up front that we were going to give a chunk of Inimex to UBC,” Hancock explains. “We believe this is reasonable recognition of the fact that, number one, we’re part of the UBC community and we wish to remain part of the UBC community. But also, the amount that UBC has done for us as scientists interested in the commercialization process.”

To hear them describe it, starting a company is not only the natural progression in a scientist’s career, but also immense fun. And in the end, that is the advice they would give others going through the process.

“Only do it if you think you’re going to enjoy it,” Hancock says. “Money’s the worst reason of all to do this. Do it because you feel you’ll make a difference, do it because you’ll enjoy it, do it because it’s exciting for you.”