NEW YORK – Rick Bright joined the Biomedical Advanced Research and Development Authority in 2010 following a scientific career addressing influenza at the US Centers for Disease Control and Prevention and at PATH, plus a stint in industry at a vaccine development firm.
Now a 12-year-old agency, BARDA was always intended to be nimble and innovative. Lately, however, Bright has been revving it up further, striving to create new funding mechanisms that are even faster and more ingenious — qualities he noted are more typically associated with industry than government.
In the past three years Bright has helped launch two new programs at BARDA: Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X, and the Division of Research, Innovation, and Ventures, also known as DRIVe.
In addition to its focus on promoting development of new vaccines and antibiotics, BARDA is increasingly homing in on diagnostics as the lynchpin of its preparedness approach, Bright said. This includes increased attention to rapid diagnostics, as well as innovative new diagnostic paradigms like home-use testing and wearables.
BARDA makes up a large piece of tens of billions of dollars the US has allocated to bioterror defenses since 9/11. Established in the early 2000's through congressional acts, namely Project BioShield and the Pandemic and All-Hazards Preparedness Act, it is tasked with securing the US from chemical, biological, radiological, and nuclear threats, as well as from pandemic influenza and emerging infectious diseases, and is officially part of the Office of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response.
BARDA's budget for fiscal 2019 – which ends today – was $1.27 billion, with $245 million earmarked for diagnostic tools, vaccines, and immunotherapeutics, international preparedness for pandemic influenza, and emerging infectious diseases, and $510 million for Project BioShield to support late stage development and procurement of medical countermeasures for national security threats. For 2020, the requested BARDA budget is $1.6 billion, including $322 million for advanced research and development, $180 million for CARB-X, $735 million for Project BioShield, and $256 million for pandemic influenza.
Sepsis is a likely sequela of almost every biothreat BARDA is tasked with mitigating and Bright's own experience this year with a bloodstream infection has only strengthened his view that more efficient diagnosis of infection is critical for bioterror defense, as well as for the health of Americans in general.
Bright spoke with GenomeWeb and 360Dx by phone last week. The following is a lightly edited transcript.
What is BARDA, exactly?
Our unique role is to bridge government and private industry. We work in ways that no other group in government does, to partner with companies in the private sector and accelerate the development of medical countermeasures — diagnostics, vaccines, and drugs, primarily — that address many of the big threats that we face. These include antimicrobial resistance, pandemic influenza, anthrax, smallpox; all of the scary things that the department of homeland security says we should be aware of. But also, this includes a lot of the emerging infectious diseases coming out of nature, such as Zika, Ebola, MERS, or the next pandemic influenza outbreak. We have no shortage of threats or targets to keep us busy.
When we were first [set] up by Congress, BARDA focused primarily on medical countermeasures that had already been through levels of validation and evaluation from the National Institutes of Health, or the Department of Defense, or private industry, and had made it past a Phase I clinical trial stage. They were really de-risked in many ways.
What does this support look like, and what is the intended outcome?
We employ subject matter experts from every facet. We have clinicians do clinical trials, manufacturing experts that can build and validate a factory to make drugs, vaccines, and diagnostics, engineers, animal experts for the non-clinical studies, regulatory folks that come from the US Food and Drug Administration – we have all that inside BARDA. That is sort of our secret sauce that we add to these contracts. In addition to money, we put in the technical expertise to work with the companies.
In our first 12 years of being in existence, we've been able to get 49 FDA approvals across these threat areas — we just got our 49th approval on Tuesday for a next-generation smallpox vaccine — that's a pretty good track record.
What is CARB-X and how does it fit in BARDA?
When I look around the world, I see some of the major threats that we face, such as antimicrobial resistance. Three years ago, we realized that BARDA is sitting here in the catch space for advanced development, waiting for stuff to come our way from an earlier pipeline, either from NIH, industry, or the DoD. In the antibiotics arena, we saw there was really nothing coming to us. There is a shortage of new antibiotics, vaccines, and diagnostics to address antimicrobial resistance.
That's why we set up this new entity, called CARB-X. We formed a partnership with Wellcome Trust and committed $250 million, and Wellcome Trust pretty much matched that commitment. The two us formed the world's largest public-private partnership, focused on stimulating that early-stage pipeline to address antimicrobial resistance.
It was the first time that BARDA created an entity that allowed us to reach more upstream and push the pipeline to our advanced research and development programs.
We got a lot of interest from other countries, so soon after we stood that up, the governments of the UK and the German government contributed money into that organization, and now the Bill and Melinda Gates Foundation has also contributed.
Now we have a growing entity, with about 40 different candidates in the CARB-X program. Most of those are next-generation antibiotics. One of the gaps in that area still is diagnostics. We started working in a focused way with the CARB-X program this year pushing diagnostics.
Is there any particular reason why antimicrobial resistance falls into the BARDA portfolio?
We're concerned about some of the biggest biothreats out there, such as anthrax, plague, tularemia ... a number of different bacterial organisms that our homeland security department has said we should be significantly concerned about. We've seen anthrax used as a weapon of terror in 2001. We know that there are synthetic biology ways to modify organisms and create multidrug resistant organisms. So, we are very concerned about the antibiotics we have today and their ability to work on the bacterial threats we face in the light of synthetic biology.
Where does DRIVe fit in?
In 2016, Congress passed the 21st Century Cures Act. ... They said BARDA, specifically, should leverage their credibility and experience to focus more on innovation. Empowered by that, I [formed] a new division last year called the Division of Research, Innovation, and Ventures.
If I look in my stockpile or in my portfolio of drugs and vaccines and new medical countermeasures we've had approved by the FDA, individuals still don't know when to use those, because we don't have diagnostics.
When I look at the field of diagnostics, and I see a lot of the equipment, instrumentation, and methodologies we use today, most of that is sitting in a large clinical laboratory or a public health laboratory.
When I watched the outbreak and emergence of Zika back in 2015 and 2016, I watched women who were potentially exposed experience a lot of anxiety and stress because it was taking [up to] 12 weeks to get a Zika result back from a centralized laboratory. ... It motivated me to look at our programs in diagnostics and change our way of thinking and our strategies. We are moving from developing a lot of big box instruments in centralized laboratories, to starting to push those diagnostics out ... closer to the patient, focusing on point of care, as close as possible to the doctor's office, or to point of need — in an emergency clinic or minute-clinic — and even into the home and onto the body.
Is there a particular focus at DRIVe on wearable technologies?
I started a program in DRIVe called ENACT — an acronym for Early Notification to Act, Control, and Treat. Our entire focus in ENACT is to develop diagnostic tools that would be used in the home or on the body for pre-symptomatic awareness of infection ... to inform a person they've been infected two or three days before they have any symptoms. They can confirm that infection with diagnostics that are point-of-care or point-of-need in a minute clinic or at the doctor's office. And if it is something exotic, they can still be bridged to the big public health infrastructure at the CDC.
This is an entire new ecosystem, built around early notification, utilizing the different layers and tiers of diagnostics in development today.
It's amazing. We've been overwhelmed by applications. Part of it is also because, in DRIVe I've changed the way we do business with industry. They used to have to spend up to $1 million and wait 12 to 16 months to submit a proposal and get an answer from BARDA. With DRIVe ... I want government to move at the pace of innovation, not the pace of government, so I've reduced the application process to a 2,000-word abstract. We can review those quickly, and if we like the idea, we can make an award to that company in less than 30 days.
When you start tapping into that ecosystem of entrepreneurs and innovation, it is really interesting — 58 percent of the applicants we've had in our first year of DRIVe had never had any contact with government [funding] at all. It is a whole new pool of applicants. Thirty-five percent of those applicants are from micro-entities, meaning they have 10 employees or less. That means I am tapping into the entrepreneurs who are working in a lab space, a garage, an incubator, or at one of our accelerators. And 15 percent of those applicants are female- or minority-owned companies.
We've tapped into an entirely new ecosystem. Some of this is earlier-stage development, and that allows us to help shape it and get the right dataset we need for advanced-stage decisions down the road.
Are there any particular projects that are interesting?
In our ENACT program we have seen many exciting, new ways of detecting exposure to a virus or bacteria.
We have companies that have wearable technologies, such as one we've invested in called BioBeat. It is like a smartwatch that is tuned into your biometrics. It will tell you your blood pressure, body temperature, heart rate variability, pulse, oxygen saturation — all of these biometrics that, once it has a baseline on you, we can then look at the fingerprint of the baseline and the fingerprint that changes upon exposure.
We have another technology that attaches to your clothing — to your underwear or something close to you that you're wearing all day — and it is machine washable. It measures a lot of these biometrics. We have a new technology that is a patch that you wear and it samples interstitial fluid, so the fluid right below the surface of your skin. All of the different cytokines, chemokines, enzymes, and different hormones ... in interstitial fluid can change upon infection. We have another technology that samples your sweat. We may not realize it when we sweat, but we're actually sweating out a lot of information about health and exposure to different pathogens.
What we're trying to do in this part of the project at ENACT is look at all the different things that are being measured and correlate them. We have clinical trials going on at five different sites through the influenza season. Students and participants are wearing these different monitors. They might get sick, they might get drunk, they might get infected with influenza, who knows, but we're monitoring all these readouts in a big database. When we find people who are infected with influenza or a bacterial infection, our analysts are looking at all the different patterns and signals, to look for correlations and fingerprints.
We're also, believe it or not, putting technologies into your cell phone. The microphone on your mobile phone can detect breathing patterns, vocal signals, and chemical signals that are in your breath while you're talking on your telephone, that will tell us whether or not you're infected with something. And we are looking at tools like Alexa that are in your home that can monitor your breathing patterns, coughing, or vocal changes, and tell you in a pre-symptomatic way that you've been exposed to something.
We are trying to home in on the right signals, and shape those to a technology that an individual can have on their body or in their home, that says 'Hey, alert! Alert! You've been exposed to influenza. I want you to go to the next step of doing a diagnostic at home or at the pharmacy and getting treatment right now.'
We recently wrote about the home-use diagnostics space, and how getting tests through the FDA clearance process seems to be a bit of a bottleneck. Can BARDA navigate that more effectively than an individual company can?
I have a lot of confidence that the FDA is also focusing on innovation and modernization of tools and technologies. There is a little concern about any type of home diagnosis, but we've gone through this in history with home pregnancy tests ... and HIV tests.
We're investing in two companies right now. One is called Cue, and the other, called Diassess, recently changed their name to Lucira. Both of those are incorporating lateral flow for influenza, but, within their box they can actually incorporate molecular-based technologies as well.
These companies are working closely with the FDA, and I believe the FDA is going to make them validate their test against traditional CLIA-waived influenza diagnostics. With the data I'm seeing from these home tests, and the confidence we have in a number of lab-based molecular biology test for influenza, I believe these home tests will be as accurate as any lab-based molecular diagnostic. They are a little expensive right now, so we'll have to reduce the price of them down to an affordable price to place them in the home. And the companies will also branch out the platform technologies — it might seem like it is a little expensive test for influenza at first, but they may be able to detect flu, bacterial infections, sexually transmitted infections, and other things such as hormonal changes associated with ovulation for family planning, stress enzymes ... or markers associated with heart attacks, like C-reactive protein.
I think we're going to see in the next five to 10 years an entire paradigm shift of having a lot of this diagnostic technology available in the home.
Regarding the venture capital aspect of DRIVe, how will that work, exactly? And have any groups partnered with you yet?
I think ventures is one of the most exciting future initiatives we are building right now in BARDA. The 21st Century Cures Act gave us the authority to [form] a medical countermeasure innovation partnership, or MCIP. In that, they give BARDA the authority to work with a third-party non-profit entity to utilize venture capital practices, to be able to pool our money with private equity dollars to invest in really transformative technologies.
As you can imagine, that is a huge paradigm shift for government. We don't have an example of a venture capital fund in government, for a lot of the right reasons. BARDA has spent two years doing a lot of market research. We've spoken to a lot of venture capital entities, large companies with venture funds, a lot of the non-profit organizations like Gates Foundation, Wellcome Trust, and others who have venture and impact funds. ... Government's not used to talking about money out there in the space, so we have done a lot of market research and we have a lot of ideas.
We put out a request for information last fall to get information from bankers and venture players. We've been following up on that and having interviews with about two dozen or so entities. My goal is to have another solicitation in the near term to test the waters about some of the ideas we've heard and what we envision this venture fund would look like. We've also gone through a lot of legal review internally in government to understand what are the challenges and what are the constraints that ... BARDA would have as a government agency in working in this venture capital world, and how we combine private equity money with our dollars on the same project.
A lot of homework has been done, and I'm pretty confident that we're going to be able to stand up, within the next calendar year, the BARDA-venture fund.
How will this fund be used in a different way?
It will allow us to invest in really early stage, transformative technologies that will improve healthcare.
One of the biggest constraints for wearable technologies is power and battery life, so maybe the venture fund will invest in the next generation of power that would power wearable diagnostics or wearable health technologies, so we don't rely on batteries. Maybe we rely on kinetic power or solar power, but I need to invest in power resources.
One of the other big challenges in diagnostics and wearable technologies is information exchange. They rely on Bluetooth technology today ... which drains a lot of power and is vulnerable to privacy invasion. The BARDA ventures may invest in the next-generation of information transfer. Or, maybe it will be changing the way vaccines are administered completely. Instead of needles and syringes, maybe we move to microneedles and patches that are printed in 3-D printers in your home. Talk about a completely disruptive approach.
Generally speaking, sepsis diagnostics seem to have been a special focus for the different BARDA programs for the past few years — why is that?
There's a graveyard of efforts trying address sepsis. It is probably one of the hardest things anyone has ever tried to do and its not because no one has ever tried to do it.
When I look at all of the threats we face and try to mitigate against in BARDA — be it a bacterial infection, an influenza virus infection, radiation exposure and burns, nuclear exposure, bacterial or viral or nerve agents, or sulfur mustard gas, blistering agents — all of these things can lead to exposure and secondary bacterial infection. All of these things, without the timely and appropriate treatment, lead to sepsis. Sepsis is the underlying threat in every threat that we face at BARDA.
In addition, there are still over 270,000 people who die every single year in the US from sepsis. It costs our country tens of billions of dollars every year in healthcare costs. Trying to address sepsis is something that we do to better protect and recover from any exposure to the threats we face, but at the same time [we are] trying to address the public health threat we face every year.
Sepsis is such a complex illness – how do you try to tackle it effectively?
We started a program that tries to develop tools to first be able to detect the degradation of your health into a "pre-septic" mode.
We also know a lot of people go into the emergency department and they get treated with antibiotics or other things, but the healthcare providers never think sepsis. So, we are developing tools, databases, and ways to put programs in front of your healthcare provider in the emergency department. Once they key in a few of the biomarkers or biometrics that we are showing are associated with sepsis, their instrumentation will flash in front of them, 'Think sepsis! Treat sepsis!'
On the back end, a lot of people spike a fever when they get home from surgery and think, "Oh, I'm just recovering." They don't realize they have a bacterial infection that will lead to sepsis.
We’re building tools and devices that a patient can wear after they leave the hospital, and wear at home, that will monitor some of these biometrics and biomarkers and automatically tell their healthcare provider, 'Hey, this person's just spiked a fever, or these other biomarkers.' The healthcare provider can then reach you and tell you to come back in immediately to get treatment.
We're tapping sepsis from this multipronged, multiphasic approach — early detection and awareness, appropriate diagnostics and treatment, and follow-up care.
I understand that you had a personal experience with a bloodstream infection recently. What happened?
Yes … I had my own run-in with antimicrobial resistance and sepsis, and the lack of a rapid diagnostic.
A year ago, I was gardening, and I had a small nick on the back of my thumb [that got infected]. ... I went to the emergency care on day one, and begged them to take a culture. They finally decided to take a culture, gave me an antibiotic, and sent me home. The next day my thumb was worse, and it was spreading up my arm. I went into the emergency office, they put me on a different antibiotic and sent me home and did not culture.
We have a physician that works here at BARDA, and I said, "Am I supposed to be getting better at this point? I'm on two different antibiotics and its two days out and half my arm is red, my thumb is the size of what it would look like in a baseball mitt." He said, you need to get back to the emergency room immediately.
I went back to the emergency room. Those first two drugs had failed. They put me on three additional antibiotics. We still didn't have a diagnostic [result] that could tell me whether or not I was infected with a bacteria and what drug would work.
They rolled me into the orthopedic ward of a hospital, because [the infection] was in my thumb, so I was on a ward with about 85 elderly people there to get hip and knee replacements. Imagine the impact of a [resistant infection] spreading across the floor of that hospital.
It was five days into the stay at the hospital ... calling the urgent care clinic every single day to try to get the result from the culture they took. They finally got it, after I was on seven different antibiotics and an antifungal. But that emergency care clinic would not tell me my results on the telephone or email that result to me. I begged them, I said, I'm sitting here with three different antibiotics in my veins and an oral antifungal, in the hospital for a week, but we had to find a working fax machine in the hospital … that took two more days.
They found out it was [methicillin-resistant Staphylococcus aureus] ... and they were able to identify the drug I needed to be on. If I had known that, then I could have had the right drug on board in my first visit to the urgent care center, and I would not have had to go through [all I did] … They had already scheduled a surgery to remove my thumb. It was bad.
Has your experience altered your sense of the importance of rapid diagnosis, or informed your interpretation of sepsis-related projects, such as the recently-funded T2 Biosystems technology, for example?
When I talk to T2 [Biosystems] and other companies with new technologies, I beg them to get into this space to help us solve the problem. I met with T2 after I came out of the hospital, and when I've talked to other diagnostic companies, I said, anything you can do to make this better, anything you can do to reduce the time it takes to get a result … T2 told me they could get me that result on the organism and which drug would work in about three to four hours. I said, "We need your technology desperately, now. Push it."
We need all the attention we can get in the area of rapid diagnostics. It is how we are going to address the antimicrobial resistance crisis. It is how we are going to address sepsis. It is how we are going to be able to address all of these [bio]threats. Early detection is going to give us early, appropriate treatment, and nothing is going to save more lives than those rapid diagnostics.