Following the rapid development and commercialisation of Covid-19 vaccines and therapeutics, multiple pharmaceutical companies such as AstraZeneca, Moderna, and Pfizer reported record profits from sales.

Once new Covid-19 strains started emerging, the US Department of Defence (DoD) launched a public-private partnership initiative, Project NextGen, to develop vaccines and therapies for these strains, and to be better prepared for the next outbreak. Project NextGen is led by the US Administration for Strategic Preparedness and Response (ASPER)’s Biomedical Advanced Research and Development Authority (BARDA) and the National Institutes of Health (NIH)’s National Institute of Allergy and Infectious Diseases (NIAID).

In an exclusive interview with Pharmaceutical Technology, Robert Johnson, PhD, director of BARDA’s medical countermeasures programs talks about how an investment into platform technologies helped the agency to rapidly advance measures during the Covid-19 pandemic. He also outlines the future of Project NextGen, funding for other infectious diseases, and diagnostic technologies.

This interview has been edited for length and clarity.

Phalguni Deswal [PD]: There has been a decline in commercial demand for Covid-19 products. Will this impact the funding for Project NextGen going forward?

Robert Johnson [RJ]: Project NextGen was set up with an initial funding of about $5bn that is dedicated to developing Covid-19 products. Although we have allocated a good amount of the $5bn, we still have substantial amounts remaining to go out. There are also multiple funding opportunities available through the DRIVe (Division of Research, Innovation, and Ventures) programme.

With Project NextGen, we have three main lines of effort– vaccines, therapeutics and ‘enablers’.

From the vaccine perspective, NIH is responsible for products in early development while BARDA focuses on the ones in clinical development. We run efficacy trials by comparing them with currently licensed products to see if they might offer broader or better protection that lasts longer relative to the current products.

We are also interested in new technologies that look at alternative routes of delivery—whether oral or mucosal, or through patch technology—as well as technologies that will deliver more antigens. Right now, the licensed vaccines are focused on the Spike protein found on the surface of SARS-CoV-2 viruses. So we’re looking at vectors that could deliver more than just the Spike protein.

For therapeutics, one of the biggest gaps we saw was a lack of options for individuals who don't respond well to current vaccines, such as immunocompromised patients. So that is one of the primary goals for the treatment aspect of the project.

NextGen is also looking at therapeutics that can be used to protect people pre-exposure as a prophylactic. Here the leading candidates are monoclonal antibodies (mAbs), which have some challenges around the virus evolving to develop resistanance. For these, we are looking to target areas of the virus that don't change very rapidly, so the mAbs can work longer even as the virus evolves.

And then finally for the ‘enablers’—these are looking at new technologies. When we think about how we could potentially respond even better and faster for the next outbreak, we have noticed there are a lot of neat technologies that have been developed, but they're not coming into the clinic.  

We're interested in supporting a wide breadth of technologies. For example, we've been looking at alternative ways to express monoclonal antibodies, such as with mRNA. But we are also looking at how to approach vaccine clinical trials a little differently so that the patient population that we enrol represents the population that will eventually be taking those countermeasures.

PD: What are the main focus areas for BARDA, especially in infectious disease space?

RJ: As we cannot guess which infectious pathogen is going to cause the next outbreak, BARDA primarily focuses on having the tools to rapidly develop medical countermeasures against whatever outbreak might come up. We do this in a couple of different ways.

One is by supporting platform technologies, and the second is by supporting threat-agnostic countermeasures. We also support the development of treatments against a syndrome that might be caused by multiple bugs instead of just one, and moving away from the “one bug one drug” type of approach.

Moderna’s mRNA vaccine Spikevax (elasomeran) is a great example of a platform technology. We were working with Moderna for another product, and then the Covid-19 pandemic happened, so we pivoted that mRNA platform to develop a vaccine. We have seen a similar thing with some of the monoclonal antibody technologies. Our new focus is nucleic acid-based technologies, as we think that these could potentially pivot quickly to new threats.

We are also developing the manufacturing capacity and capability, which is a focus area. It doesn't matter if you have a product or a platform if you can't make it.

One of our development foci is novel antibiotics and antifungals that target resistant pathogens. It has been an important part of our investment portfolio to date, and we envision it will continue to be.

While Project NextGen focuses on Covid-19, BARDA has a much broader remit. Its main mission is to maintain and grow the US's capability to respond to public health emergencies and other health security threats. These include chemical, biological, radiological, and nuclear (CBRN threats), as well as influenza, and emerging infectious diseases. We particularly focus on vaccines, therapeutics, and diagnostics, not exclusively, but by far, that's the majority of our work.

PD: Developing diagnostics is one of BARDA’s focus areas. Could you expand on what technologies is BARDA looking at in this space?

RJ: One is artificial intelligence (AI), which is a platform technology, and we expect AI to continue to be important going forward. Another is cartridge technology, which can be adapted to different diseases.

One of the important factors in developing diagnostics is the balance between sensitivity, specificity, and costs. We ideally want new technologies that will allow for a better diagnostic closer to the home. There are different ways for this; whether it's taking the technologies that are less expensive and making them more specific and sensitive, or taking technologies that have high levels of sensitivity and specificity and making them more amenable for in-home use. And so, we're not wedded to any particular approach, but we want to be moving them closer to the home while being as sensitive and accurate as possible.

PD: The chemical, biological, radiological, and nuclear (CRN) threat is a niche area. How does BARDA want to invest in this area?

RJ: One example of that is burn treatments. The reason I like talking about this program is because it shows a couple of different aspects of what we're trying to do. We are trying to build a comprehensive solution for burns, as it is also something that occurs in our standard health daily healthcare system.

We want to develop products that can be used in an event perspective, say a blast, but can also be integrated into the standard health care system to treat burn victims. This makes the product more sustainable, which is one of the challenges in this area as there is not a huge demand for CRN products. Once we develop these products with our partners and take them to licensure, we want to sustain them. And so, integration into the standard public health care system helps us with that model.

BARDA partnerships work beyond funding. We bring technical expertise and an understanding of the regulatory and clinical work. And so, we are looking for a long-term partnership with these developers to take those products to licensure, and then work with them to make sure those products are available.