Many in Georgia’s life sciences community are familiar with the remarkable work done by the Drug Innovation Ventures at Emory’s (DRIVE) work in infectious diseases, particularly influenza, HBV, HCV and alphaviruses.
How is DRIVE putting its drug development expertise in infectious diseases such as SARS and MERS coronaviruses to bear on the global community’s attempts to contain and treat the latest coronavirus dubbed COVID-19/SARS CoV-2? On behalf of Georgia Bio, Write2Market’s Paul Snyder recently spoke with DRIVE COO and Chief Intellectual Property Officer David Perryman and Program Manager – Antiviral Nucleotides Gregory Bluemling to learn more.
How closely is COVID-19 related to SARS?
Gregory – “The International Committee on Taxonomy of Viruses recent report stated COVID-19 is caused by the same species of coronavirus as SARS, but a new strain. The most striking difference in the new strain is its ability to infect people even when the infected person is asymptomatic. One of our ribonucleoside drugs, EIDD-2801, showed promise in SARS, MERS, bat coronaviruses, and other human coronaviruses. ”
How closely is your work on COVID-19 related to DRIVE’s success in HIV treatments?
Gregory – “Viral infections classify by genetic makeup. SARS, MERS, influenza and COVID-19 are all RNA based viruses. HIV is a retrovirus that copies its RNA genome into DNA for insertion into host cell DNA. But all viruses must replicate their genetic material through the use of a polymerase enzyme. The same principles apply to interrupting replication for RNA and DNA viruses, but the drug molecules that disrupt replication are structurally different.”
David – “The core work and success George Painter, Dennis Liotta and Emory had with HIV drugs led to the formation of DRIVE and our focus on nucleoside analogs, the same general type of drug as their earlier HIV successes. In the business world, it was to maximize the chance of success by focusing on something you are or can be among the best in the world. Our small molecule antiviral, EIDD-2801, is a nucleoside analog that has shown activity and efficacy against many viruses, all RNA-based. Our compounds are intended to be effective against a broad spectrum of RNA viruses which are most typical viruses in epidemics and pandemics, one of those, importantly today, being the new coronavirus.”
Gregory – “RNA viruses cause epidemic disease and are responsible for 80% of the viral disease burden worldwide. They are the major contributor to the pool of emerging and reemerging infectious diseases. Therefore our concentration is aimed at viruses that have RNA as their genetic material.”
How do you approach new viruses and emergent situations?
David – “As a core business and scientific strategy, we initially look for broad spectrum compounds. If a compound shows an initial ‘hit’ against a known, RNA-based, virus, we work with government collaborators and labs to test it against the new viruses and other potential viral threats as well. If it shows activity, if we show that it works across multiple viruses, the question becomes how do we get it safely and efficiently to patients? That’s when our work with government funders, regulators, testing partners, research universities and manufacturers begins. This advanced development stage to achieve a de-risked higher impact inflection point is where our model is very different than a typical research University.”
How close is EIDD-2801 to being administered to patients with COVID-19?
David – “It has not yet been tested in humans. But our conversations with government authorities who have been reaching out to us have been productive. We anticipate guidance from the FDA in early March about a hoped for approval pathway for patient testing. It could then move very fast due to the new coronavirus outbreak or follow a more traditional deliberate path. Typically there are four phases of human trials in the FDA approval pathway, from safety to various levels of efficacy and further safety to approval. Is EIDD-2801 more toxic in humans than in animals? Those questions have yet to be determined. We know from our extensive testing to date that there is a window where EIDD-2801 looks efficacious within a safe dose range in animals, that needs to be shown in humans.
“One important advantage EIDD-2801 has over another compound being tested in China for coronavirus in the same class is that EIDD-2801 could be taken in a pill form, not requiring an IV infusion in a hospital setting to treat the coronavirus. This distinction could be critical as a pill, once approved, could be quickly and broadly disseminated in a pandemic. Another advantage of our compound is that it also has activity and has been extensively tested in animals against influenza, so it potentially could be used across multiple pandemic viruses. The data on EIDD-2801 was published in Science Translational Medicine and public comment around the publication and its unique ability to cause catastrophic lethal mutations in the influenza virus led to it being on the front page of Reddit. I like to say, the antiviral became viral.”
Note: A significant portion of DRIVE’s funding comes from milestone driven government contracts with critically important entities like the Defense Threat Reduction Agency (DTRA) and the National Institute of Allergy and Infectious Diseases (NIAID) for the proactive development of new drugs for biodefense and emerging infectious diseases. Through these entities, we tap translational funding, an area not typically tapped by research universities.
What is happening to put more drugs “on the shelf” or “antigens in the freezer” in a proactive battle against the next “surprise” new virus?
David – “That’s the type of work we do every day. We are focused on what the world’s needs, regardless of commercial potential, compared to big pharma, which is mostly focused on profits. We are filling a need that capitalism unfortunately does a poor job of addressing, but is critical for world health. Thus, we are also laser focused on the development of antiviral therapies that the government wants and the world needs, and in some cases are commercially valuable. In this respect, we are targeting a pull market that we know will pay a fair price for our drugs if we are successful. This is distinct from a typical research University where new scientific discoveries typically ‘bubble up’ from basic research and then the process begins to try to find a buyer/partner.
“Our work strives to put drugs on the shelf to cover a broad spectrum of viral threats. There are many families of RNA viruses, existing and potential, against which our potential coronavirus compound, EIDD-2801 is not effective. We have identified a follow on compound that has some overlap in the type of viruses it blocks but also has some unique activity against a broader set of viruses. The new compound has the potential to fill some gaps adding up to ‘blanket’ coverage against RNA-based viruses. These compounds, if approved as drugs, could proactively sit on the shelf anticipating the next pandemic.”
How has Georgia’s life sciences industry been coalescing around the response to COVID-19?
David – “There is great synergy in our ecosystem with GaBio at the hub. Everyone wants to build together and pitch in, which incrementally gives everyone a better opportunity to make a difference. How our potential coronavirus treatment, EIDD-2801, came to be is a great example of this collaborative ecosystem in Georgia and the Southeast. Our initial funding came from Emory University and Dennis Liotta (a pioneer in HIV antivirals). He and Emory’s general counsel Steve Sencer formulated the strategy from the Emory side and they took money from past successes in HIV drugs to double down on DRIVE to try to develop novel treatments for pandemic viruses, biodefense and other diseases.
“This led to the successful recruitment of DRIVE’s CEO, George Painter, a world renowned antiviral drug development expert and serial successful entrepreneur from North Carolina. George thankfully also brought his wife Wendy Painter, an MD and successful Chief Medical Officer with a focus on antiviral drugs into the community, a much needed skill set. After EIDD-2801 was discovered, GRA provided early synergistic funding. DRIVE in turn collaborates on some nasty viruses with the CDC, viruses you can’t test outside of high containment. We also collaborate with Georgia State and other regional university partners like Vanderbilt and UNC (Mark Dennison at Vandy and Ralph Baric at UNC are world experts on coronavirus and our collaborators on testing of our compound). DRIVE works with Emory’s OTT and local patent and corporate attorneys to license compounds and set the strategy for success. And, of course, Hartsfield Jackson International Airport makes it all easier to reach. Through this community, we have an exciting potential treatment for coronavirus when it is needed most.
“Together, we are making great strides to try to provide nearly immediate treatments when new viruses ‘pop out.’ In addition, although they take time to prove efficacy in a new outbreak, vaccines for viruses are critical and provide a powerful one-two punch with antiviral drugs to try to help keep the global human population safe. That is where Georgia-based companies like Geovax come into the picture to provide vaccines to hopefully go along with our antivirals.”
This news indicates we may well need it. Its long-term commercial viability remains in question, which underscores the importance of DRIVE’s work.
For a more detailed look into the labs where scientists are working to fight the latest outbreak, we recommend reading this piece from the Washington Post that includes insights from DRIVE CEO George Painter III.
For the most up-to-date information on the Coronavirus Disease 2019 (COVID-19) visit: https://www.cdc.gov/coronavirus/2019-ncov/index.html