This original article was published on October 2nd, 2018 in ConvergenceRI.

PROVIDENCE, RI – The U.S. Food and Drug Administration announced on Tuesday, Oct. 2, that the federal agency has awarded EpiVax and CUBRC a $1 million contract over two years to establish best practices and procedures to evaluate generic peptide drugs for immunogenic potential and related impurities.

“EpiVax has worked hard to be at the forefront of immunogenicity assessment using our proprietary immuno-informatics tools,” said Dr. Annie De Groot, the CEO and CSO at EpiVax, a Providence-based firm that recently celebrated its 20th birthday at its new headquarters in Olneyville.

“These tools make it possible to perform risk assessments accurately and expeditiously. We look forward to working with FDA scientists to set new standards for immunogenicity risk assessment for generic peptide drug products.”

CUBRC, headquartered in Buffalo, N.Y., will leverage its technical expertise in biomedical research to work in collaboration with EpiVax to execute the research effort, explained Katie Edwards, Ph.D., who is CUBRC’s prime technical program lead.

“CUBRC plans to leverage its ongoing partnership with EpiVax to provide systems integration and program management expertise to advance EpiVax’s highly specialized immuno-informatic tools to help the FDA with the evaluation of new generic peptide drugs,” Edwards said.

The contract comes at a time when the market for new peptide therapeutics is rapidly expanding, with some 80 drugs in the next few years expected to come off patent. In turn, companies looking to manufacture generic versions will need to submit applications to the FDA.

The global peptide therapeutics market is expected to reach $48 billion by 2025, according to a 2017 report by Grand View Research.

[The FDA grant announcement comes one day after the 2018 Nobel Prize in physiology/medicine was awarded to James P. Allison of the U.S. and Tasuku Honjo of Japan for their work unleashing the body’s immune system to attack cancer, a breakthrough that has led to an entirely new class of drugs, according to a story in The New York Times.]

[On Wednesday and Thursday, Oct. 3 and 4, EpiVax will be in Silver Spring, Md., attending the “Predictive Immunogenicity for Better Clinical Outcomes” workshop sponsored by the FDA, where the firm will be presenting its latest work in protein therapeutics and T cell epitopes.]

The context for the FDA contract
ConvergenceRI asked a series of questions to the principals working on the FDA contract at EpiVax and at CUBRC, in order to get a better understanding of the context and importance of the new two-year, $1 million award.

The answers were provided by Dr. Annie De Groot, the CEO/CSO of EpiVax; Brian Roberts, Protein Therapeutics Manager at EpiVax, and Katie Edwards, Ph.D., who is CUBRC’s prime technical program lead.

ConvergenceRI: How does this new FDA contract validate the strategy of EpiVax to develop its proprietary immuno-informatics technology and maintain ownership?
The FDA contract solidifies ongoing collaboration between the FDA and EpiVax. FDA’s focus, where drugs and biologics are concerned, is safety. Unwanted immune responses can cause significant side effects.

Take, for example, the story of erythropoietin, a human protein that is given to patients who have anemia, to induce new red blood cell expansion. A new formulation of “Epo” developed in the early 2000’s caused patients to have an immune response to their natural Epo and to become blood transfusion dependent because they were unable to make new red blood cells.

EpiVax tools were able to predict this risk signal even prior to the event [but our warning was not heeded], and because of that validation [and many other examples where our predictions were validated], EpiVax has become a leader in the field of “immunogenicity risk assessment” for biologic drugs.

Over the years, EpiVax and FDA scientists have explored [in official and unofficial collaborations] the nature of immunogenicity, and its polar opposite, tolerance. The new contract “formalizes” FDA’s interest in using our state-of-the art in silico tools. We anticipate that EpiVax tools will be put to very good use by the FDA to assess generic peptide drug risk, and to set new standards for Accelerated New Drug Approvals in the Generic Peptide field.

ConvergenceRI: How does this FDA contract position EpiVax for future growth, pushing beyond the boundaries of the firm’s initial efforts to develop safer, more effective vaccine targets?
Up until now, EpiVax scientists have focused their efforts on assessing the immunogenicity risk of larger molecules such as biologic drugs [monoclonal antibodies, blood factors like Factor VIII], and enzyme replacement therapy [such as GAA for Pompe disease].

The FDA’s Office for Generic Drugs came to visit more than a year ago, because they believed that our tools would be helpful for peptides. Peptide drugs are small, usually between 10 and 100 amino acids in length. All of the tools that we have developed will be very useful to check these drugs and their impurities [truncated or altered peptides that may be present in the drug due to problems encountered in synthesis] and the potential for immunogenicity.

ConvergenceRI: What is the market/demand for assessing generic peptides and related impurities for immunogenic potential, related to the fact that some 80 drugs will be coming off patent and those companies looking to make generics will need to submit applications to the FDA?
There is a huge demand. There are literally hundreds and hundreds of companies making generic peptides all over the world. Each large country has their own manufacturer.

Some examples of drugs that are made by these manufacturers include insulin, used for the treatment of diabetes, and glucagon, calcitonin, and corticotrophin [also known as ACTH], all of which are drugs that can be made synthetically.

You are right, there are more than 80 such drugs that are going to be coming off patent in the next few years. We are very excited about expanding our offerings and adding new team members so as to be able to respond to the demand that our Peptide Abbreviated New Drug Application [PANDA] program and collaboration with the FDA will generate.

ConvergenceRI: How does the development of the EpiVax’s proprietary In Silico Immunogenicity Screening Toolkit, or ISPRI, with its high throughput screening of partial and complete sequences for protein therapeutic candidates, fit into the equation?
 ISPRI is designed for proteins and peptides. So we’re all set – no updates are needed, the ISPRI toolkit is exactly what is needed for evaluating Generic Peptide drugs and their impurities.

We are looking forward to developing the “what if machine” [WhIM] which will help us anticipate how impurities in generic peptide drugs could add to their immunogenicity.

We can do an initial “what if” in silico, which can inform further evaluation, in vitro.

ConvergenceRI: How will the new FDA contract interact with EpiVax’s Protein Therapeutics group and its PANDA [Peptide Abbreviated New Drug Application] program?
The Protein Therapeutics group is charged with in-house development of de-immunized biologics and providing commercial services for evaluating the immunogenicity of biologics developed by drug manufacturers.

The FDA contract fits within the scope of the group’s mission and we [Protein Therapeutics] will be leading the program at EpiVax, in active collaboration with CUBRC.

In fact, we have actually been performing PANDAs for clients for a couple of years now.

Early this year, we were made aware that the FDA had put out a broad agency announcement [BAA] calling for improved scientific approaches to evaluate generic drugs, one method of interest to them being computational approaches.

Over the 20 years that EpiVax has been in business, we have been an industry leader in in silico immunogenicity prediction and in vitro validation, and we believe that the application of our tools to generic peptide drugs is a natural fit.

ConvergenceRI: How does this new contract fit into the work of what EpiVax is calling its “What If” machine, to predict the effects that common impurities, such as truncations, deletions and duplications have on immunogenicity?
The idea for the “What If” machine [WhIM] is that many generic peptide drug impurities can be anticipated – for example, when synthesizing a peptide, sometimes instead of adding one amino acid at the end of the amino acid chain, two of the same amino acids are added, due to synthesis errors.

Since we can anticipate these impurities, we can write a program that takes all of the possible, or probable, impurities that could occur into account. WhIM will be a valuable addition to our tools because it will allow us to look at the sequence of a peptide drug and predict, ahead of any peptide synthesis, and anticipate whether common manufacturing related impurities will affect the immunogenicity of the generic drug.

Since some impurities have the potential to drive immune responses, we can then help our clients develop methods to avoid or reduce the likelihood of these impurities being generated and contaminating the target drug during synthesis, we can save manufacturers significant time and money during the early stages of generic peptide drug development.

ConvergenceRI: How important is the collaborative nature of the work with CUBRC?
 Very important. CUBRC has extensive experience and expertise working as a federal contractor. In addition, they provide an excellent project management service, which will ensure that deliverables will be delivered on time and within budgetary constraints.

ConvergenceRI: What are the potential applications of the new CUBRC partnership with EpiVax to develop an immunogenicity risk assessment tool for national security concerns?
 FDA plays a significant role in the nation’s counterterrorism capability. FDA fulfills this responsibility by ensuring the security of the food supply and by fostering development of medical products to respond to deliberate and naturally emerging public health threats.

The health of the U.S. population is dependent on new medical countermeasures, and more affordable, generic drugs that are approved via the FDA. While there are no [or few] peptide drugs currently approved for emerging threats, there are many nontraditional therapeutic products [including peptides and biologic drugs] currently in development.

The EpiVax tools that are being further refined during this program will allow for a more streamlined approach to immunogenicity assessment in silico that could change the paradigm for approval of peptide drugs going forward.

ConvergenceRI: What is the value of the learning continuum involved in this work?
 Given these EpiVax-developed in silico tools are constantly evolving, a major advantage of this approach is that the outputs of the tools and in vitro validation from this program will inform the in silico algorithms and further refine this novel approach.