Deal Flow

Immuno informatics tools developed by EpiVax come of age

Focused on doing “great science,” the pioneering Rhode Island biotech firm is experiencing a significant growth spurt, with plans to launch a spinoff, EpiVax Oncology, in the coming months

Photo by Richard Asinof

Dr. Annie De Groot, CEO and chief science officer at EpiVax, talked about her plans to launch a new subsidiary, EpiVax Oncology.

By Richard Asinof
Posted 1/2/17
EpiVax plans to launch a new spinoff, EpiVax Oncology, to develop a platform for cancer vaccine development that utilizes many of the immuno-informatic tools that the Rhode Island firm has developed, seeking to raise $2 million in a seed round.
When will the value of “doing great science” be recognized as a key component in growing companies within the Rhode Island innovation ecosystem? How will the community of engaged patients change the way that cancer treatments are being developed, changing the equation away from one-size-fits-all drug development to a more personalized approach? Why is there such a preponderance of glioblastoma in Rhode Island? What are the opportunities to develop checkpoint inhibitors for breast cancer here in Rhode Island?
In many ways, the success of EpiVax has followed a non-traditional path in the world of successful companies. The firm chose to remain privately held, rather than seeking out venture capital to fund its expansion of its immuno-informatic technologies and tools. The firm also chose to invest in “doing great science” here in Rhode Island as it expanded its networks in Europe and Japan. In addition, the firm was willing to work collaboratively in sharing its analysis of the stealth qualities of the H7N9 flu.
Rather than following a traditional road in its entrepreneurial pursuit, EpiVax has chosen a different path toward success, and that seems to have made all the difference.

PROVIDENCE – What a difference the last year has made for EpiVax CEO Dr. Annie De Groot and her team: the company grew its business by 30 percent and its team by 20 percent in 2016.

And, there is more projected growth on the horizon for one of the original pioneering biotech firms in Rhode Island.

EpiVax, in partnership with CUBRC, a Buffalo, N.Y., firm, and scientists at the University of Florida, was recently award a four-year, $1.87 million grant from the Defense Threat Reduction Agency within the U.S. Department of Defense.

The work is focused on developing an effective vaccine for Burkholderia pseudomallei, a bacterial infection, by understanding how the bacterium evades the human immune system, using EpiVax’s first-in-class immuno-informatics tools to speed the pace of vaccine development.

In addition, the privately held company is planning to launch a new spin-off, a subsidiary called EpiVax Oncology, seeking to raise $2 million in initial seed money from venture capital and angel investment to get the company up and running.

EpiVax Oncology will offer an efficient, secured and innovative approach to identify high-quality, patient-specific data related to each patient’s genetic background and cancer.

One of the first potential research projects is a collaborative effort, working with Sadhak Sengupta at Brown University, to develop a potential vaccine for glioblastoma, a form of deadly brain cancer that is highly prevalent in Rhode Island’s population.

As De Groot explained it to ConvergenceRI, Sengupta would provide EpiVax with the genetic sequences of the glioblastoma tumors in a mouse model and, in turn, EpiVax would design a personalized cancer vaccine for the tumors in the mouse model, and then test it.

“It will actually be a great proof of concept,” De Groot said. “We’re actually going to look at two vaccine platforms that we’d like to license as part of the new company.”

EpiVax has applied for an Innovation Voucher from CommerceRI to support the pilot research project. “If we were to get that Innovation Voucher, it would definitely assist us with the development of a new company, hiring new people and creating new jobs. We are excited about the Governor’s efforts to fund these small pilot projects that would actually generate the preliminary data that would be required for federal funds to come into [Rhode Island]. That’s huge.”

The new subsidiary will seek to address problems in the further development of anti-cancer therapies: the onset of self-immune disorders by such therapies, known as checkpoint inhibitors, because they target regulatory T-cells and can leave the body’s critical organs defenseless. It will also seek, using the platform of EpiVax’s immuno-informatic tools, to identify specific tumor mutations, to then be able to target the mutations that are distinct to the cancer.

De Groot believes that EpiVax and its development of its immuno-informatic tools have reached a tipping point.

“We do feel that way, where finally, we have reached our tipping point, where people understand the importance of this approach to developing vaccines and drugs, and that computer programs can assist with the selection of the best candidates,” De Groot said.

She continued: “When you want to invest your drug and vaccine development funds wisely, you definitely want to have immuno-informatics involved. So, that’s the tipping point; that has happened, we’re here.”

What excites De Groot most about her work is the potential for applying this technology for making vaccines for individual people.

“If I achieve anything in my life, it will be to make a personalized vaccine. That is the dream of any immuno-informatic vaccine developer – to make personalized vaccines, whether it’s for cancer or for another target. I think that’s what really going to be exciting, in the next few years, seeing that dream come to fruition, because I’m confident that it will happen.

Here is the ConvergenceRI interview with Dr. Annie De Groot, the CEO and chief science officer at EpiVax, talking with her at her office in the heart of the former Jewelry District, offering an insightful, in-depth look at how immuno-informatic tools are reshaping drug and vaccine development.

ConvergenceRI: EpiVax keeps evolving, keeps changing and keeps growing. Can you talk about what is driving the 20 percent growth in staff and the 30 percent growth in business? That’s remarkable.
DE GROOT:
We are responding to demand. It’s about the increase in the request for services.

The way many people access our services is through the Internet. They find out about us because they are searching for solutions: what do I do about my protein that’s immunogenic? Or, I’m worried that it might be immunogenic? And they find us.

We have a contact form on our webpage, and we’ve been just getting tons of contacts. That started a year and a half ago.

When A.J. Vincelli was here, she and Steven Vessella [who works in Business Development] put together a way to be responsive to those requests.

We have also added staff. We added a European representative a year ago, and we also added a new Japanese representative.

The new European representative is Oréda Boussadia, she’s a real go-getter, with a great network.

Our Japanese colleague is Dr. Takuya Tsunoda. He is the former CEO of a cancer vaccine company.

We’ve also expanded the business development team, and, as a result, the business has significantly grown.

In terms of sales, I would consider us to be at least on a par with our other competitors. We do that without expensive advertising; we do it simply by doing great science.

The word about the great science gets out there. Our customers are happy, our clients are happy, and we have turned that into a successful program that basically allows biologic developers to screen drugs [more effectively so] they can get to the clinic.

People have turned the corner on immuno-informatics in the biologics field; they really understand the importance of pre-screening and the validity of immuno-informatics tools

The combination of the great science that is being done by the team – and the reputation for the work that we do here, our presence in the scientific world, and our accessibility on the Internet has made a huge difference. That’s kind of the reason for the growth.

Since we’re privately held, what do you do with all that growth? You have to hire people to help you do the work.

We’ve increased the team from – I think we were about 20 – to 24. We plan to add about two to three more people this year, so we will really be growing a third by June,

We add people very carefully. We add people who are compatible, and who bring a diverse set of skills.

Right now, we’re looking for a scientific director who would direct the protein therapeutics program, a Ph.D.-level researcher with some clinical experience.

We are also hiring in the division of business development. We just added Katie Porter from Amgen, she’s fabulous. Steven Vessella, he’s also fabulous, we stole him from Apple.

We are also looking hire one more person, to work in the lab. So all three new hires will be at the top level, at the business level. And we plan to add an immuno-informatics person, probably in February.

ConvergenceRI: Last year, at this time, you were about to head out to JP Morgan in San Francisco and the parallel Biotech Showcase to talk about your partnership with Aceno Biotherapeutics, focused on creating bio-superiors. How did that contribute to EpiVax’s growth spurt?
DE GROOT:
What happened is that people started writing us. One client, he wanted to know about his wife’s cancer mutation sequence. He had already had it analyzed by someone else in Europe, and he wanted us to verify the results.

This really started happening the fall, [perhaps] as a result of a couple of publications about the importance of the tumor mutational burden.

It turns out that all these new drugs that have been developed, that are really making a difference in cancer, are really only effective if patients have a lot of mutations in their tumors.

They discovered, perhaps not surprisingly, that the key targets for tumor immune response [using] checkpoint inhibitor therapy were all these mutations.

It was not the immune response directed at the cell, which is what the tumor is, but the mutations to the cell, which is what the tumor mutations are.

That was really important in terms of discovery. Checkpoint inhibitors made it possible to understand that, and computers make it possible to discover that from the genome sequence of the tumor.

ConvergenceRI: What do you expect to find at the Biotech Showcase and J.P. Morgan this year?
DE GROOT:
We have decided to spin out a company, and right now it is called EpiVax Oncology, a fully owned subsidiary of EpiVax, but venture backed. We will basically take venture funding to [support] the new company, but only as a subsidiary, to fund an end-to-end cancer vaccine solution.

Meaning, you give us your patient’s mutated sequences, and we deliver a vaccine at the end of the process. We can do that at the end of a couple months, at the very longest, and hopefully within four to six weeks at the shortest.

It builds upon our FastVax program, which was developed for our biodefense work. We’re now working with DTRA; we’ve also been working on Q fever now for almost a year and a half with a group at Massachusetts General Hospital and a group in Holland.

ConvergenceRI: Have you secured any investments for EpiVax Oncology yet?
DE GROOT:
We’ve started putting together a pitch doc and a business plan. The company will be privately held; we are looking to get seed money. So we are looking for angel or even venture investment for that initial round.

We need to raise about $2 million to stand up the company, in order to hire the CEO, develop licenses in the vaccine delivery platform, to enable us to offer a proof of concept with that platform in an animal model.

So that’s about $2 million in the first year, and by 2018, we’d be looking to a Series A [round of investment].

We actually identified a CEO candidate, and he’s been meeting with us since October. Gad Berdugo is a seasoned biotech executive, who brings more than 25 years of operational, business and corporate development, strategy and financial experience, mainly gained at Abbott, Baxter, Lazard and several emerging biotech companies.

ConvergenceRI: On one hand, you’re growing the firm through direct contact with patients, by word of mouth through the Internet. At the same time, you are expanding potential platform with a new subsidiary. How does that all fit together?
DE GROOT:
The immuno-informatics piece that’s really growing our business is the biologics, the immunogenicity screening platform that’s been in existence now for 15 years.

We’re really turning the corner on that and it’s becoming a stable business. The cancer vaccine program has really been an offshoot, because the same immuno-informatic tools can be applied to cancer.

And, we are experts in the identification of Class II epitopes, which is relevant to biologics, but it is really relevant to cancer.

We also developed the Janus Matrix tool in 2013, which you’ve written about. That tool is turning out to be extremely important in the identification of key epitopes in cancer mutanomes.

So, all the tools that we developed before are now being applied to the cancer vaccine platform. That makes it possible to say: here’s a set of tools for biologics, here’s a set of tools for vaccines, and here’s a set of tools that are for personalized vaccine development.

And that’s what’s going into the EpiVax Oncology business [platform].

ConvergenceRI: The new company coincides with the launch of the federal “cancer moonshot.” How does that play with the work you plan to undertake at EpiVax? It seems that you have discovered a way to become directly involved with patients, to tap into an engaged community with patients.
DE GROOT:
I think what we can do is to provide information to patients; patients are now getting more involved in understanding what their options are.

If you look at any of these cancer moon shot companies that are involved in that program, on their websites, they always have a patient page.

That’s because patients are now looking to these companies to understand what their options are.

Those options include finding if your tumor has a specific target for checkpoint inhibitors. That’s one thing that people can do. The other thing that patients can do is to find out if their tumor has a [specific mutational] burden.

Those two pieces are critically important for checkpoint inhibitor therapy.

If you have a lot mutational background, that’s probably where you need help with vaccines, by driving and focusing the inhibitors on mutations that do exist.

Right now, there is sort of a two-path approach to cancer. One is, if you have the ideal scenario, you can go with checkpoint inhibitors. If it’s somewhat less than ideal, you may want to try the vaccine route. And, the vaccine route is looking to be much more effective.

ConvergenceRI: As I hear what you’re saying, rather than developing a one-size-fits-all approach, the future work is about designing personalized therapies around an individual. Is that correct?
DE GROOT:
Our work is definitely about personalized therapies. That’s really exciting, because it means that people can’t do one-size-fits-all.

I think that’s where [the work on cancer is going], and it’s leading the way on the rest of the therapies that we are going to be developing.

Imagine the day when we actually design vaccines against infectious diseases that are based upon your genetic background? Wouldn’t that be great?

One reason that is exciting is because of the side effects of checkpoint inhibitors, [where] we start getting auto-immune diseases, which is what happens when checkpoint inhibitors are given as a systemic therapy.

Basically, you get a drug that keeps your natural immune system off-switch from functioning. That’s great to treat your tumor, because the tumor has activated the off-switch, and that off-switch needs to be released by the checkpoint inhibitors so you can generate an immune response to the tumor.

However, everywhere else in your body, where the drug also goes, all of the cells that normally would not react to your self tissue are now reacting, so the side effects that are now being reported in the New England Journal of Medicine include things like inflammatory bowel disease as well as cases of encephalitis, an auto-immune disease of the brain, and myocarditis, an auto-immune disease of the heart tissue.

ConvergenceRI: All of which seem to be inflammation related.
DE GROOT:
Yes, because what is happening is that the tumor shuts down inflammation, and you take checkpoint inhibitors to allow for the inflammation to occur. But then inflammation happens everywhere else in your body as well.

And that’s the double-edge sword that I was talking about in my recent blog post. You have this great immune response against the tumor, but you also unleash auto-immune disease elsewhere in your body.

ConvergenceRI: When you try to explain al this, does it seem like you’re getting into the weeds? Is it difficult for the patient to understand all this?
DE GROOT:
The patients are experiencing it; they’re experiencing all this. They are also choosing the risk, because they know how the drugs work.

That’s the exciting thing. We’re seeing success, not necessarily 100 percent, but significant increases of success in this therapy of cancer patients, a 20 to 30 percent increase in the cure rates. Which is significant.

I always say to people who come to me about their cancer: well, there might be some state of the art drugs in terms of chemotherapy. But you really should look to see if anyone has published a study of checkpoint inhibitors [for your cancer], or if there is a clinical study of checkpoint inhibitors for your [kind of] tumor.

The evidence is gathering. They’ve allowed checkpoint inhibitors to be the first line of therapy now for small-cell lung cancer, the FDA approval was really quite rapid.

Instead of toxic chemotherapeutic agents, the first-line therapy is anti-immune modulators. I think that’s the reason why there is so much excitement in the cancer field. There is a complete paradigm shift in the therapies we’re going to be using in the future.

ConvergenceRI: Can you talk about how this can be applied to breast cancer?
DE GROOT:
When we talk about mutations in breast cancer genes, we are talking about modifications of the normal gene that is in the tumor.

The tumor basically has a break that releases mutational mechanisms.

In all the tissues in the tumor, you have normal genes. Some of them are unusual genes, they are fetal genes; they are not very common. But many of them have mutations, and the mutations cause a change in the sequence of the actual gene, even though the protein still seems to function.

It’s not the same as the protein found someplace else in your body, it’s got a mutation in it. That mutation can be seen by the immune system. So that’s the focus of the checkpoint inhibitors. It will turn on a T-cell that will recognize the mutation that has formed. We’re talking about mutations in the sequences.

There’s a glimmer of hope with breast cancer that there is something other than chemotherapeutic agents that poisons you, something that you will generate an immune response.

There are definitely trials for breast cancer tumors with checkpoint inhibitors. There are so many options with breast tumors, I think it is going to be hard to sort through them.

I think where we will see most of the benefits coming from is in tumors where there have not been very good options before, such as non-small cell lung cancer. That was one of the first tumors for which checkpoint inhibitors were approved.

The other cancer that people are testing checkpoint inhibitors on is glioblastoma, another high mortality tumor that has a huge impact in Rhode Island because we happen to have the highest rate of glioblastoma of anywhere in the world.

ConvergenceRI: Why is that?
DE GROOT:
It’s not clear why we should have such a high rate here. Perhaps it’s because of toxic chemicals in our environment.

You should talk with Sadhak Sengupta. He actually moved to Rhode Island to study glioblastoma.

ConvergenceRI: This year, what are your expectations, if any, for the upcoming JP Morgan conference in San Francisco and the Biotech Showcase?
DE GROOT:
We did a launch of our biosimilars concept a year ago, but honestly, it’s not worth it. I learned from that experience.

It wasn’t useful. We paid $2,500 for a 15-minute session to basically speak to a bunch of, might I say, parasites in the economic development sphere. There were lawyers but no investors, by any means. Patent lawyers, people who are mostly interested in profiting from your interest in setting up an endeavor, but they are not interested in investing in it.

So, I felt that it was really a waste of time. We’re not going to do that again.

We will, however, be meeting with investors during the conference. We will also be attending the Biotech Showcase that is part of JP Morgan. And, we’re participating in RESI [the Redefining Early Stage Investments] conference, which is a one-day conference for people who are looking for seed funding.

ConvegenceRI: EpiVax seems to have reached a tipping point. The technological tools you developed are accepted. You have an opportunity in Australia to get a clinical trial up and running. You are launching a new subsidiary…
DE GROOT:
We do feel that way, where finally, we have reached our tipping point. Where people understand the importance of this approach to developing vaccines and drugs. And, that computer programs can assist with the selection of the best candidates.

So, when you want to invest your drug and vaccine development funds wisely, you definitely want to have immuno-informatics involved. That’s the tipping point, it’s happened, we’re here.

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