PROVIDENCE – At age 15, EpiVax is one of the more “mature” biotechnology companies residing in what’s now known as the Knowledge District.

The firm’s first digs were in a nearby building that’s now a tattoo studio. The space EpiVax currently occupies on Clifford Street adjacent to Chestnut Street was once the home to a bindery company and a company that made slide shows for corporate customers – in the era before digital cameras and PowerPoint.

In the future, EpiVax founder and CEO Dr. Anne S. De Groot is excited about the possibility to move her lab to a prospectively designed space within the redesigned Dynamo House building. “We would like to have a planned, designed space that would be cutting-edge to do this work,” she said.

Since its first days as a startup in 1998, EpiVax has been at the forefront of scientific advances, a thought leader in immunology and bioinformatics.

“When we first spun out of Brown, our concept was to create an HIV vaccine,” she told ConvergenceRI in a recent interview. The Slater Fund provided the founding seed money, followed by a SBIR award. “We’re still wedded to that concept; we still plan on making an HIV vaccine,” De Groot said. “We still think that an epitope-based HIV vaccine will work.

The funding stream, she continued, is currently devoted to other ways of doing the vaccine. “Everyone is chasing the wild antibody while we’ve remained focused on T cells. We’re going to continue to push that work forward, with or without NIH funding. That’s the foundation of the company.”

Following Sept. 11, 2001, EpiVax branched out, following the funding stream, moving from solving global health problems to focusing on bio-defense, or as De Groot put it, “How we can keep the bad people from killing us with biologic agents.”

The rationale was that by advancing bio-defense vaccines, EpiVax could gain knowledge it needed to help move epitope-based vaccines into the clinic.

“We’ve developed this incredible expertise on figuring out what T cell response is, and what triggers T cell response, using computational tools. That’s been our sweet spot for 15 years,” she said.

Today, Epivax’s work is focused on two sides of the same scientific issue – working to drive immune response on the vaccine side, and then, how to shut down that immune response on the biologics side – a yin yang balance of two portfolios of knowledge.

Immunogenicity and personalized medicine
If you were to do a Google trends on immunogenicity, De Groot continued, as she did recently, the topic takes off in 2004.

What happened, she said, is that it became clear that there was a problem, related to some work that Genentech was doing: they developed a product that induced platelets, to be used for people with platelet deficiencies, with the idea that the company could harvest and sell the platelets.

When the new product was given to normal human controls in trials, the response was unexpected, according to De Groot. “It caused an immune response, and they lost every single platelet in their body,” she said. The researchers, she continued, “They were like, ‘What happened?’ This is a human protein. It shouldn’t drive any immune response in the normal person.’”

That was the launch point of immunogenicity with biologics, enabling scientists to identify through genetic sequencing and determine what’s driving the immune response, setting the state for the development of personalized vaccines.

Today, EpiVax is working on two immunogenicity efforts with large market potential. One is trying to decipher why someone else's HIV vaccine trial failed; when people were immunized, they became more susceptible to HIV after they got the vaccine. “We’re trying to help them understand what happened,” she said.

A second will look at a malaria vaccine that proved to be around 30 percent effective in a particular area of West Africa. “We’re going to be looking at who got the vaccines, what the genetic make-up of that population was, and what the circulating strain of malaria was, so that we can predict who the vaccine worked for based upon their genetic make-up,” De Groot said. “The work is the basis for personalized medicine, for personal vaccines.”

De Groot cited what she called a perfect example of how the process could help improve the efficiency of drugs and lower their development costs. A company developed a drug to treat people with lupus, a peptide, with low side effects. But it was only effective for about 30 percent of the population, and it’s not on the market because it failed after a big, expensive clinical trial and more than 30 years of research,” according to De Groot.

“We could have predicted that,” De Groot said. “In fact, we wrote [the company] saying this is why your drug failed because the patients who are going to respond to it have this particular HLA [human leukocyte antigen]. If they have it, they will respond. That’s the key.”

Bringing Tregitope technology to the clinic
A new division was recently formed at EpiVax, focused on bringing its propriety Tregitope technology to the clinic, according to De Groot.

“We decided to do this because we had a greater than 35 percent increase in gross profit this year, and we have the internal funding to move the product forward,” De Groot said.

Tregitopes were discovered by De Groot and Bill Martin at EpiVax; the original discovery was published in the journal Blood in 2008.

By selectively activating regulatory T cells, Tregitopes can dampen unwanted immune responses. The application of Tregitopes is being developed as a platform technology by EpiVax. Preliminary studies carried out by EpiVax and collaborators indicate that Tregitopes may be useful for inducing tolerance to transplants, protein drugs, and blood replacement therapies and also in the treatment of allergies.

“We are committed to bringing this important, paradigm-shifting technology to the clinic and willing to commit our own resources to make that happen,” De Groot told ConvergenceRI. “We now have three divisions: Vaccines, Tregitope, and Protein Therapeutics.”

De Groot said that EpiVax’s innovative approach is finally getting traction – in part because her generation of immunologists are now coming of age.

“We’re finally getting into positions where we are making decisions; before we were just making recommendations,” she said.

Her generation is now in charge, the decision-makers. If you’re a young scientist, she continued, “as I was at Brown, you’re the person suggesting things, not making decisions.”

Now, her colleagues who are at the companies and the academic research centers are now coming into positions where they can actually drive the research focus. “They get it; it’s a generational thing.”