In 2022, we put out a five-year strategic plan and focus on four goals, preparedness, response, partnerships, and workforce. As part of our preparedness goals, we are interested in developing these host-directed therapeutics. So this is specifically called out in our strategic plan. So the goal is to achieve FDA approval of two threat-agnostic, otherwise known as pathogen-agnostic or insult-agnostic, host-directed therapeutics for severe disease by potentially targeting organ damage. As well as in Objective 1.3, we mentioned the desire to repurpose MCMs against chemical threats and also developing broad-acting threat-agnostic MCMs against families of bacterial and viral pathogens. But the desire to develop host-directed therapeutics is not just in the BARDA strategy. It's also in the larger national biodefense strategy. So these are the three objectives within that plan. And you can see that it's specifically called out that there's a desire to develop pathogen-agnostic therapeutics for the treatment of severe disease. So back to where BARDA typically invests, we typically do advanced development past Phase 1 through licensure, as well as some post-marketing commitments. However, in recent years, we've been involved in some earlier development of partnerships to support companies in early development through CARB-X, our Blue Knight program with J&J, and some opportunities within DRIVE, the division where my office is held. That's the Division of Research, Innovation, and Ventures. But where there's a gap right now, if this is the drug development pipeline, we need to have multiple shots on goal. But there's a gap right now in having these approved products for severe outcomes of infectious disease, so if we think about sepsis and ARDS, for example. Dr. Wu just spoke to some of these perceived challenges, but I'll just go over these again, just because I think it's important to know that we understand some of these challenges and we want to work with our industry partners in addressing some of these, and also mitigate this in our strategy. So there's a lack of precedence for some of these products for pathogen-agnostic indications, especially for infectious disease. There's not always a regulatory framework established. There's this perceived low return on investment, and this is supported by the fact that there has been a low success rate for sepsis and ARDS, and so presumably the cost for development will increase. There's trial complexity because of the heterogeneity and the pathogens involved in disease, and the variation in our individual host response, so that's a lot of complexity and expense to trials and development, and speaks to the need for developing means to subtype or stratify patients, but then that also includes development of a diagnostic. And then there's a lack of understanding of the natural history of disease, and also the temporal effects it has on the patient profile, so when you know when to use a drug for the right patient at the right time, and suggests that maybe we need combination products for the right treatment. But we are working to address this. We're working across government. We have our FEMSI partnership across government and with the FDA. We're working with government on interagency efforts, specifically focused on host-directed therapeutics. Within BARDA, we provide an end-to-end support. We operate like a virtual pharmaceutical company, so we have specific subject matter experts that can be pulled in to support development of the products, including we have a regulatory and quality affairs team that can help each individual partnership. We also, as I mentioned, we do provide funding from early development all the way through product licensure. We have an ability also to engage in venture practices through the 21st Century Cures Act, and we do that through our partnership with GHIC, and we have ability to provide wraparound support through other means, such as through our accelerator network that is broadly dispersed across the country, and our partnership with J-Lab's Blue Knight program. And then we're looking at specific technical approaches to address the challenges that exist with HGTs, such as focusing on repurposing, focusing on more of this precision medicine approach with endotyping and stratification, and then looking to conduct our own platform trials like you just heard from Dr. Wu. So we have a number of programs in BARDA actually focused on funding post-operative therapeutics. I know a bunch of acronyms here, so I'll walk through this with you. So it's the Influenza and Emerging Infectious Disease Division, that's the IEIDD. So that was Dr. Wu's division branch in therapeutics that is interested in this. There's the Chem, Bio, Rad, Nuke division, and the branches of Rad, Nuke Medical Countermeasures and Chemical Medical Countermeasures, as well as the Antivirals, Antitoxins, that's the AVAT. All three of those branches are interested in host-directed therapeutics. And then my office within DRIVE, the launch office, has a specific program called host-directed therapeutics. And all of these branches have focused not just on a threat-specific indication, but also more on what we are calling threat-agnostic or pathogen-agnostic indicationsations that are targeting specific at the cellular level, more at the organ level or the systemic level like ARDS or sepsis. So a little bit about my program. We've been primarily focused more on these threat-agnostic, what we're calling pathogen-agnostic indications to mitigate the severe outcomes of disease. But our more recent interest is in this ability to tailor therapeutic interventions to the patient. So this is what we've been mentioning in terms of identifying and to stratify patients through endotyping. And this could be to identify a disease state of a patient as well as identifying a specific population that would benefit from a given therapeutic. If you have interest in reaching out to the program, you can email me or hosttx.hhs.gov. And these are some other opportunities or mechanisms within BARDA. There may not be active topics right now under all of these solicitations, but I encourage you to check out the websites and continually monitor for opportunities. So the BARDA BAA is our typical solicitation. We do multimillion-dollar awards, typically through advanced development. And all BARDA divisions may have topics open in this solicitation mechanism. Within DRIVE, this is the Division of Research, Innovation, and Ventures where I am housed, we have the EZBAA to support more rapid partnership. Awards thresholds are at $750,000, but there's an opportunity to continue in what we're calling a plus phase that you would be eligible for if you had the initial award with us. And these vary. Again, the topics vary through that solicitation. So check out our website. BARDA Ventures, as I mentioned, this is our ventures partnership where we do take equity investment in our partners. That's through GHIC. You can check out more on our website or email me about that. We have the Accelerator Network and the JLABS Blue Knight Partnership. And then more recently, we just announced our RRPV, which is the Rapid Response Partnership Vehicle, and this should enable easier contracting to respond to emerging threats. You have to join the consortium at rrpv.org in order to learn about those potential topics of funding. So I encourage you to check that out. If you have any questions about this, again, feel free to email me and I can point you in the right direction with points of contact within BARDA or for these solicitations. This is just some information on BARDA, and again, we can be found at medicalcountermeasures.gov. If you'd like to chat with us about your technology or your clinical work, you can register for a TechWatch meeting. You have the opportunity to present to us through that forum. And that is it. So thank you all for your patience. We'll now move to any questions from the audience.

preparedness

therapeutics

partnerships

precision medicine

regulatory support