PROVIDENCE – Getting into the clinic has always been a bit of a stumbling block for EpiVax, a creative vaccine design firm headquartered in the former Jewelry District, with its pioneering immuno-informatic tools.

Now, EpiVax is on the cusp of getting one of its designed vaccines into the clinic – an optimized, H7N9 flu vaccine, working in partnership with Protein Sciences Corporation, a Meridian, Conn.-based firm.

EpiVax has been involved in analysis of the H7N9 flu since its widespread outbreak in China in 2013, labeling it as a “stealth” virus, because it contained far fewer epitopes than other flu strains, making the traditional flu vaccine far less effective.

In response, EpiVax was then able to use its immuno-informatics tools to design a “fix” for the vaccine to make it more effective.

In turn, Protein Sciences has developed an FDA-approved influenza vaccine manufacturing process, using the company’s proprietary protein expression technology that can produce high quality recombinant proteins quickly, reliably and at a low cost.

Its current flu vaccine product, known as Flublok, does not use the influenza virus or chicken eggs in its manufacturing process. It has been approved for use by adults 18 years or older.

Protein Sciences’ vaccine manufacturing process has the advantage of a faster startup in the event of a pandemic, because it is not dependent on an egg supply or limited by the selection of vaccine viruses that are adapted for growth in eggs.

If all goes well, EpiVax’s new optimized H7N9 vaccine will be brought to the clinic and go into production later this year through a partnership with Protein Sciences, funded through a contract with the Biomedical Advanced Research and Development Authority, or BARDA, Dr. Annie De Groot, the CEO at EpiVax, told ConvergenceRI in an in-depth interview last week, talking about the firm’s future growth.

“We’re getting all of the pieces together,” De Groot said, saying she hoped to have good news later this summer.

It will depend on whether BARDA will fund the production of the protein needed for the vaccine manufacturing at Protein Sciences. “We have a recipe for it; we know exactly what we have to produce, but someone has to pay for it be produced,” De Groot said.

Protein Sciences’s Flublok, one of the first recombinant flu vaccines, had been produced under a BARDA contract, De Groot explained. ‘It’s a very effective vaccine; it’s been all the way to the clinic, it’s safe, it’s non-toxic.”

To move ahead with EpiVax optimized flu vaccine for H7N9, she continued, “It’s just a matter of getting the funding to do this.”

If you’re thinking of stockpiling the vaccine, which would you, as a taxpayer, rather have, De Groot asked. “A fairly effective vaccine, or a much more effective vaccine, in case there’s an H7N9 outbreak?”

Proof of principle
What’s so exciting about the pending H7N9 project, De Groot continued, is that it would be a clinical proof of concept for a vaccine that EpiVax designed, where the vaccine was improved by inserting epitopes, or, in the case of the H7N9 vaccine, deleting a regulatory piece, a tregitope, to make a better vaccine.

“Regulatory T cell epitopes are particularly prevalent in the pathogens that have adopted to the human immune system,” De Groot said, explaining that they turn off the human immune response. 

They have been found in the HIV vaccine, which has been trialed in Thailand, and they’re present in the malaria vaccine that has been trialed in Malawi in Africa.

For De Groot and her team at EpiVax, the potential is there to develop a whole new product line of biobetter vaccines, using the firm’s proprietary immuno-informatic toolkit.

“Let’s take these vaccines that have already been in the clinic and been show to be somewhat efficacious but also safe,” she said. “And, if we can tweak them, change the amino acids very slightly, and then get them back into the clinic without extensive studies, which don’t necessarily have to be repeated if you know what you’re doing and why you’re doing it, that’s an exciting concept that we’d like to see if we can get moving forward.”

Better cancer vaccines
When EpiVax attended Bio International in Philadelphia this month, the largest biotech business event in the world, as well as when it attended the Biotech Showcase, [a conference for independent or privately held companies held earlier this year in San Francisco in conjunction to J.P. Morgan’s Healthcare Conference], many of the meetings were with companies and entrepreneurs focused on the cancer vaccine sector.

“When we were at the Biotech Showcase, we had 40 meetings over three days, and about half of those meetings were about vaccine design,” De Groot said. “Why is that? Because there is traction in the cancer vaccine sector.”

The cancer vaccine folks have been the first to understand how important EpiVax’s type of vaccine design is, De Groot continued. “They have moved forward with epitope-based vaccines. They understand that you have to combine checkpoint inhibitors, which are these new molecules [emerging] through biologics development, and epitope-based vaccines, to make a difference in cancer patients’ lives,” she said.

One of the most exciting meetings, De Groot said, was with a company from Europe that was using fast sequencing of cancer tumors from individual patients, with the goal to make personalized cancer vaccines.

“I think that’s the most exciting potential use of our technology,” De Groot said. “We’ve thought about it for years. We want to make personalized vaccines; we talked about doing this for infectious diseases. But I think the first way we’ll get into the clinic with this type of [treatment] will be with personalized cancer vaccines.”

EpiVax is now moving ahead with plans to actualize this dream; it is preparing a memorandum of understanding with this European company to form a strategic partnership, which may be announced sometime later this year.

Rhode Island as a creative biotech hub
When talking about EpiVax and its relationship to Rhode Island, De Groot begins with the fact that Rhode Island is the “creative capital.”

“There are a lot of designers here,” she said. “We are very well known for creative design. One thing that’s never recognized is that we are actually a vaccine design shop. That’s what we do.”

De Groot continued: “We have unique tools, we have a creative vision, and we’re a design shop; that’s where we bring our expertise to the table.”

Other companies may be more expert in pancreatic or lymphatic cancers, she explained. “We need to partner with these folks, not only to identify the correct antigens, or targets that we should be focusing on, so we can design the vaccine using those antigens.”

De Groot believes that there should be greater recognition of the biotech industry in Rhode Island. “There should be a better understanding that the kinds of jobs being created are really high-value jobs; we’re not talking hot dog vendors, we’re not talking popcorn vendors and beer vendors,” she said. “We talking about high-paying jobs, and a whole range of mid-sector jobs that [provide support work] for those high-paying jobs.”

The potential, she continued, “for the biotech sector to really boost the economy of Rhode Island is huge. There are companies that have some really exciting developments; look at EpiVax, look at Nabsys. What I think is lacking is the connection with the legislature.”

There are some groups that are gaining some traction, De Groot continued, citing R.I. BioScience Leaders and its success in getting some new shared funding mechanisms in place for SBIR award winners.

“But it would be really great for the legislators to come down from the hill, and maybe go on a tour of companies, and come meet the people,” she said. “To be honest, I think that they may be a little afraid.”

[ConvergenceRI held up a bottle of water with the EpiVax logo and its slogan, “Science without Fear,” and De Groot laughed, saying: “Yes, science without fear.”]

“The concept would be to take the fear out of science, to let the legislators meet the people who are doing this really cool science in Rhode Island, so that there could be a relationship, a rapport and [better] understanding,” she said.

De Groot also stressed the need to support and invest in workforce development programs, such as the one at the University of Rhode Island, as well as to support funding for workforce training for existing employees in new skills.

Getting bio-betters to market
In response to a question about how to mitigate the increasingly high cost of new biologics and new cancer drugs, De Groot offered up a potential solution.

“I think in order to change the market, what we really need to be able to do is to take scientific approaches to improving drugs and not require that they go through extensive clinical trials,” she said.

There’s a whole movement happening around how to make drugs better, De Groot continued. “Take a drug like Humira that costs $10,000 a year. It has significant side effects, but those side effects can be removed by re-engineering the drug, making minor amino acid changes to its sequence,” she said. “We know how to do that, for example.”

De Groot posed the questions: Would the re-designed drug require a full-blown series of preclinical safety and toxicity trials? Or should FDA be able to change its approval procedures, ones that don’t cut back on safety, but at the same time, doesn’t require these extensive and very expensive studies, before you can get a bio-better to market?

“We already do it for flu vaccines, when you think about it,” she said. “We have flu vaccines that are produced in eggs. Every year we slot in a new gene, from the current strain of the circulating seasonal flu, and slot it into the virus to produce the flu vaccine.”

De Groot continued: “We should be able to do similar things for drugs. We’re really talking about minor changes, not even a whole gene, less than a gene, pinpoint changes to the gene, a few amino acid changes. Why shouldn’t we be able to throw products right into the market the way we do the seasonal flu vaccine?”