FRANCIS COLLINS: Thank you for joining us today. I'm Francis Collins, the NIH director. And it's a real pleasure to launch this important listening session on the proposed Advanced Research Projects Agency for Health-- or ARPA-H as we will call it for the rest of this 75 minute session. As you probably know, we're working closely with White House science advisor, Eric Lander, and his staff at the Office of Science and Technology Policy-- that's OSTP-- on this bold proposal of the Biden administration. We're grateful for your interest and for taking time to attend the session. ARPA-H is a high priority for President Biden and his administration, and is designed to catalyze ambitious ideas and approaches that will shape the future of health and medicine for all Americans. As designed, ARPA-H will follow a model built upon the DARPA experience focused on high risk and high reward programs led by visionary program managers recruiting research contributors who might otherwise never apply to NIH for support, and driven by explicit milestones. Today, NIH and OSTP want to hear from you, our stakeholders. This is, I believe, the eighth of 10 stakeholder outreach sessions that we have been holding. And each of them has had a theme. Today, the theme is about allergy, infectious disease, and global health. To set the stage we're going to be hearing from NIH and OSTP leaders. Then, I will hear from select speakers representing advocacy for research in the areas that we're focused on this time. And then after they have each spoken for 4 minutes each, we'll have a live Q&A session. And that will be an opportunity to encourage you to submit your questions during this event. The way to submit your questions will be to use the Q&A box. The chat box is not being utilized for this purpose because it is not visible to all of the speakers. But please consider, if you have issues you want to raise, use the Q&A box. And you don't have to wait until all the presentations have happened to begin to put questions in there. I want to emphasize from the beginning that, while we are excited about ARPA-H at NIH, we are also very excited about NIH traditional ways of supporting research. And this is intended to be an additional opportunity to promote acceleration of projects that currently is more difficult for us to support. But we want to continue to see the remarkably successful track record, built over the 27 institutes and centers over many decades, to continue. So this should not be seen in any way as subtracting from that. Now, I'd like to hand it over to Dr. Tara Schwetz, who is the assistant director for biomedical science initiatives at OSTP, who's been a major architect of our plans thus far. So, Dr. Schwetz, please take the floor. TARA SCHWETZ: Great. Thank you, Dr. Collins. And thank you to everyone who has joined this listening session here today. We very much appreciate you being here and really look forward to a thoughtful and lively discussion on ARPA-H. And I'm excited to share a bit of information about the importance of ARPA-H and how it will aim to be transformative for a variety of diseases and conditions and societal challenges related to health. So, as I'm sure you all know, we have an incredible biomedical ecosystem here in the US, much of which is bolstered by the important fundamental research supported by NIH. And this is work that is often leveraged by the vibrant biopharmaceutical industry to create products for patients in a multitude of disease areas. And NIH continues to be a keystone in this US biomedical enterprise. The work it supports has made incredible progress in uncovering the underlying mechanisms of health and disease. But our system has some gaps and blind spots. And we all know of ideas that fall into the gap between what can be and what is advanced through traditional public support mechanisms and industry. And these ideas have the potential to bring disruptive innovation to health and health care. And that's exactly the gap that ARPA-H will fill. Well, it's not the model that should be used for everything, it will provide us with a new lens for thinking about exciting biomedical science and how to improve human health. So if we imagine, just for a minute, if we could program mRNA to pre-vaccinate us against the top 50 mutations that cause cancer, giving your body the ability to target and eliminate those cells before they can ever even create a tumor. Or what if we had the ability to quickly deploy any vaccine through an easy to apply, self-administered skin patch to allow for rapid massive vaccination campaigns? Think about how that would have changed COVID. And what if we could develop drugs that have very precise molecular ZIP codes that would allow for unprecedented targeting, even across the blood brain barrier, to specific cells in your body? You could get therapeutics with dramatic accuracy, and without any side effects, potentially-- or, at least, very minimal side effects. And these are just a couple of examples, of course, of the types of capabilities and platforms that ARPA-H could develop. And I'm sure you all have ideas as well. And we'd like to hear those. And they're likely ones that are much more exciting and ambitious than even those that I just mentioned. And so, advancing these ideas is going to require a novel approach to supporting biomedical research. And this has been applied to other areas of R&D. Think about DARPA, ARPA-E, I-ARPA, and others. And our goal here is to create a distinct and bold entity where ARPA-H leadership will have the autonomy, independence, resources, to tackle some of the biggest challenges facing human health. Though it's not applicable for all research questions, we do know this model works. And we think it's about time we deployed it to lay the groundwork for disruptive innovation and health. So with that, I will thank you and turn it back to Dr. Collins. FRANCIS COLLINS: Thanks very much, Dr. Schwetz. And yes, we do know this model works from my experience, now having been in NIH director for almost 12 years. Certainly, the last year and a half with COVID was a great example of how we-- because of the great pressure of making progress rapidly against the pandemic-- put together programs that moved in a very rapid fashion, very much along the lines of the way that DARPA would approach an issue, almost like we became venture capitalists. But it had to be done in a one-off fashion. And it was focused solely on COVID-19. And we believe that same kind of approach could be applicable across the board-- everything from molecular questions to societal questions. And that's why we're excited about ARPA-H and how this could bring that new capability to NIH for those special circumstances where it would be a good fit. So I'd now like to introduce the next two speakers from NIH. I will ask each of them to speak for three minutes. And then I will ask the first one to hand it off to the second one. The first speaker is Dr. Hugh Auchincloss, who is the deputy director of the National Institute of Allergy and Infectious Diseases. The second speaker will be Dr. Roger Glass, the director of the Fogarty International Center our focus on global health research at NIH. So, Hugh, can I turn it over to you, please? HUGH AUCHINCLOSS: Thanks very much for that, Dr. Collins. First of all, I need to apologize to our guests, because it should be Dr. Anthony Fauci, the director of the institute, speaking to you today. But as has happened regularly during the past year and a half, he's off working with the Biden administration on the COVID response. And so, you get his deputy instead. We've been very excited to think about ARPA-H at NIAID. Indeed, as Dr. Collins suggested, we feel like we've been living ARPA-H over the past year and a half. Dr. Collins was directly responsible for spearheading the public-private partnerships that, first of all, delivered three effective vaccines to EUA status in record time, but also joint efforts to come up with diagnostics to deal with MIS-C and to understand PASC, or long COVID. We've been very proud of these joint bold efforts to approach the COVID problem. But people have begun to be thinking, how can we do it even better next time? And if you go to the op-ed page of The Washington Post today and see Eric Lander's piece, you'll see that he's suggesting, next time, we should have vaccines within 100 days, and we should be able to vaccinate the entire world in 200 days. So there are bold challenges ahead. I don't think it's just about vaccines. I think one of the surprises to me in the pandemic response was what a small role monoclonal antibodies played in our armamentarium. We didn't get them produced fast enough, or combinations fast enough. And, mostly, we didn't figure out a way to get them into people's arms fast enough, or early enough in the course of the disease to really make a difference. We've got to be able to do better. We're also interested in trying to develop really good therapeutics. We've developed a program that will try and mimic the success of the HIV therapeutic program from the 20th century. But today, we're in the 21st century, and there should be new tools that we can bring to bear, such as artificial intelligence, which can tell us what a protein structure will look like when we have the genetic sequence. Maybe we can work backwards to create designer drugs. And finally, let me just say that we don't think of this strictly in terms of the pandemic response. ARPA-H could be terribly important in addressing huge problems-- such as antimicrobial resistance, food and drug allergies-- so it's really going to be a lot of fun over the next couple of years to see how creatively we can use the ARPA-H resources to address these really challenging problems. So thank you very much for your time. And let me now turn you over to Dr. Roger Glass, the director of the Fogarty International Center. ROGER GLASS: Thank you very much, Hugh. And let me share my gratefulness for the opportunity to speak with you. We at Fogarty see great potential for global collaboration in the ARPA-H space to address health challenges in the US and around the world. Dr. Auchincloss has already highlighted the value of global health studies in infectious diseases and accelerating advances. I want to focus on the NCDs and issues with innovation in the equitable delivery of care. We never know where the best ideas will come from. Global collaboration gives us access to diverse investigators with remarkable insights and expertise beyond our borders, broadening the scope and accelerating the pace of discoveries envisioned by ARPA-H. Great innovation is already taking place globally with frugal and novel technology such as mobile phone based applications in devices and populations that have leapfrogged traditional approaches. The use of drones to deliver blood and drugs to remote communities in Rwanda and Ghana, the reduction in the number of doses of HPV vaccines required to prevent cervical cancer, are a few of the innovations from accelerated global health research that have advanced medical practice worldwide. So casting a global net for progress could bring great rewards. A global dashboard can link researchers to diverse populations with unique environmental exposures, diets, toxins, pollution, unusual cultural practices, and the impact of climate change. Each presents an opportunity for ARPA-H to consider assessment of health exposures, impacts from wearable devices of exposures, point of care diagnostics, satellite imaging, and other big data to predict and prevent disease spreads. This could be accelerated by ARPA-H. And the genetic lens brings diverse populations into focus who have rare diseases or unusual presentations of common diseases. Studies of Alzheimer's disease in Colombia and Huntington's [INAUDIBLE] in Venezuela are clear examples that have advanced our knowledge. So ARPA-H could work to develop low-cost genomic chips to expand newborn screening, or cancer screening, or genomic profiling and more, benefiting from international studies. Equity is a foundational principle of Fogarty programs and would be the basis of international collaborations in ARPA-H. We'd expect bidirectional sharing of expertise, innovations, and benefits, as we already experience in NIH's existing global research enterprises. So in a globalized ARPA-H, we would envision Fogarty partnering with other NIH institutes and centers in bringing to the table our global network of researchers, our expertise in establishing highly productive and sustainable partnerships, and our track record of strengthening health research capacity of individuals and institutions while building leaders in health research around the world. So you can see I'm very excited about the opportunities for ARPA-H to enhance its impact by embracing a global perspective. Thank you. FRANCIS COLLINS: Thanks very much, Hugh and Roger, for giving us your perspective from leadership of NIH. We're now going to hear from six stakeholders, who are also in the general space of global health research, allergy infectious disease research, to give us their views. The way this is going to work, each of them have been given 4 minutes to reflect on the topic at hand. A bell will ring when there's 30 seconds left, just to be a signature here that we are trying to maintain a tight schedule so that we'll have plenty of time for the Q&A. I see there are 136 people now listening to this presentation. Again, to remind those who are listening who want to pose questions, we're going to use the Q&A function in the Zoom call. I can see, already, three people have put in questions. That's a great start. Once we get through the very interesting presentations from the stakeholders, we'll open it up to that. And Dr. Schwetz and I will seek to see if we can moderate the Q&A. And we might draw Dr. Auchincloss and Dr. Glass into that if it feels like that would be a good way to address some of those questions. So that's where we're going. With that, then, let me invite the first stakeholder. And I'm not going to give long, involved introductions, though all of these people deserve them. Just for time, I will simply state name and current professional role. So this is Dr. William Repicci, who is president and CEO of the Lymphatic Education and Research Network, whose last name I hope I have not butchered too badly. Please proceed. WILLIAM REPICCI: No, that was just fine. And thank you so much, first of all, for your tireless efforts as this pandemic rages across the globe. On behalf of LERN and myself, thank you for this honor of presenting the case today on behalf of the hundreds of millions of people living with lymphatic diseases worldwide. I also send best wishes to you from LERN spokesperson and actress, Kathy Bates, who fondly recalled our talks with you and Dr. Fauci at the Research America awards dinner the year she was honored. And the event also provided us the opportunity to bring our case directly to President Biden, who keynoted at that event. I thought, initially, I would begin my remarks today by making the case for why the time has come for significant investment in lymphatic research. I plan to describe the physical suffering of those with progressive, debilitating, deforming, and incurable diseases like lymphedema and lipedema; the hopelessness, psychosocial trauma, and the incredible medical costs and loss of [AUDIO OUT] I thought to tell you about the robust community of hundreds of lymphatic researchers prepared to give us tomorrow's breakthroughs, and to bring to you the lament of the medical community that feels their hands are tied in treating lymphatic diseases without research providing them treatments to offer patients. However, looking at the esteemed group here today, it occurs to me that you are already prepared to make bold moves. And as such, I simply offer myself as a partner in this quest. I recall my first lymphatic research conference a decade ago. There was this palpable excitement among researchers who saw themselves as explorers who had landed on a previously undiscovered island full of riches. Here was a system playing a significant role in a continuum of diseases such as cancer metastasis, diabetes, heart disease, rheumatoid arthritis, obesity, AIDS, and a host of immunological diseases, with Alzheimer's disease and multiple sclerosis now added to that list. And then there were the estimated 10 million Americans in 250 million worldwide living with lymphedema. Regardless of whether the onset of lymphedema was due to cancer, physical trauma, genetic or hereditary factors, or lymphatic filariasis, the treatments were the same-- compression therapies and therapeutic massage. There is still not a single drug on the market to treat lymphedema, nor is there a major pharma company preparing to do so, as they look to NIH for the necessary path breaking fundamental research. There are now surgeries such as lymph node transfer, LVA, debulking-- however, these insurers call cosmetic and deny coverage due to the lack of research proving their efficacy. Now, surgeons believe that they can prevent lymphedema by offering these surgeries prophylactically. But we also need to know the genetic profile, and the link of lymphedema to the genetic profile, as we approach this. With NIH's new 5 year strategic plan focus on enhancing women's health, you will not find a disease more aligned with your goals than lymphedema and lipedema, the majority of which are women. Dr. Fauci recounted to me how NIH's investment of $3 billion a year helped make AIDS a treatable disease in 2015. And a formal meeting with staffers at NIH's lymphatic symposium determined that a minimum of $75 million a year in lymphatic research funding was needed to truly begin advancing the field. Currently, we estimate that NIH has allocated approximately $5 million a year in lymphedema research grants, and investing a total of approximately $25 million for all lymphatic disease research. I dream of a Manhattan Project-like effort to find new treatments and cures for lymphatic diseases. I grow hopeful envisioning NIH creating a national lymphatic commission. I ask that you consider establishing a lymphatic center focused on the broad continuum of lymphatic research across all NIH institutes. I ask that NIH then consider funding that center with $100 million annually for grant awards, with up to $50 million of this dedicated to finding a cure for lymphedema. Dr. Collins, we look to you to catapult lymphatic research into the 21st century. Thank you again for this opportunity. FRANCIS COLLINS: Thank you very much. Again, I hope stakeholders particularly refer to ARPA-H, which is our topic today, as the kind of a mechanism that, perhaps, can provide opportunities that we previously have not had. So appreciate where you're coming from. And, again, for the Q&A folks, I see we're starting to see questions. Again, if you have ideas about specific ways that ARPA-H can make things possible that have not previously been so, we're going to be very interested in those. Let's now go to Dr. Bruce Roberts, who is chief research, science, and innovation officer for the Food Allergy Research & Education. Dr. Roberts? BRUCE ROBERTS: Thank you, Dr. Collins. Thank you for the opportunity to speak today on behalf of the food allergy community. My name is Bruce Roberts, and I am research strategy and innovation officer at FARE-- Food Allergy Research & Education, the world's leading non-governmental organization engaged in food allergy advocacy and the largest private funder of food allergy research. We agree the United States stands at a moment of unprecedented scientific promise and applaud the creation of ARPA-H as a vehicle to tackle this challenge. What more can we do collectively to accelerate the pace of breakthroughs and transform medicine and health? First and foremost, FARE would encourage the list of diseases for which ARPA-H would develop breakthroughs, to include food allergy. Given the growing nature of this disease, which affects some 32 million Americans of all ages. It's not just children. Our community of parents, caregivers, households affected by food allergies and food intolerances totals 85 million. ARPA-H can play a major role in promoting awareness of food allergy disease burden and identify research gaps such as adult onset food allergy and support innovative research in the field of new drug discovery and novel therapies. Second, we concur with Dr. Collins and colleagues in their recent science commentary. Quote, "Bold ideas involve creating platforms, capabilities, and resources that may be applicable across multiple diseases," end quote. FARE firmly believes that innovative approaches are critically needed and encourage the agency to include food allergies as a priority given there's only one approved agent at this point in time, and it's peanut specific. It doesn't benefit individuals who have other food allergies. And it is currently limited to just children and teenagers. Their innovative approaches should extend to regulatory approval processes for new therapies and diagnostics. The food allergy drug pipeline is diverse and includes novel agents such as food derived proteins, probiotics, immune modifying antibodies, vaccines that can basically modify an immune response would represent new classes of agents and call for new ways of devising clinical development. Furthermore, innovative approaches are required to build upon the successful treatment of a single food allergy and extrapolate to multiple food allergies. We would like to see ARPA-H activities focused on moving faster to market solutions that could lead to better solutions for communities, but at the same time maintain the integrity of evidence based science and safety based reviews. Thirdly, there's a genuine opportunity to prevent the development of food allergies, and thereby reduce the burden of disease. The pioneering LEAP study, published in 2017, demonstrated early dietary introduction of food allergens during infancy can prevent the development of food allergies-- in this case, peanut allergy. These findings form the basis for NIAID's addendum guidelines for the prevention of peanut allergy in the United States and are embodied in federal nutrition policy in the 2020-2025 Dietary Guidelines for Americans for the majority of food allergies. Our recommendations are critically important to meeting the needs of the food allergy community as this acceleration of collaboration to achieve innovation with research outcomes. FARE hopes that ARPA-H will be successful in meeting contemporary needs for nimble research and collaboration, as well as streamlining regulatory pathways to approval. On behalf of FARE and our food allergy community, we thank you for the opportunity to provide input at this NIH-OSTP listening session. Thank you. FRANCIS COLLINS: Thanks very much, Dr. Roberts. Next, we're going to hear from Dr. Stephen Morrison, who is senior vice president and director of Global Health Policy for the Center for Strategic and International Studies. Dr. Morrison. STEPHEN MORRISON: Good morning. And thank you, Dr. Collins and Dr. Schwetz, for the opportunity to speak here this morning. It's an honor. And congratulations in advancing ARPA towards becoming a reality. It's a bold, timely, exciting innovation with great promise. It's also such a pleasure to be among so many friends and so many experts, whom I've admired over the years. I have four points. I'm a political scientist. I'd like to start with some political and operational advice to those of you setting this operation up. Back in 1993, '94, I had a role in conceptualizing and standing up a similar sort of operation at USAID, the Office of Transition Initiatives, which was charged with creating fast, nimble, bold, new initiative to operate in conflicted settings outside the normal procedures and culture of the institution. I also have observed closely over the years other related organizations-- DARPA, PEPFAR, the State Department's Bureau of Conflict and Stabilization Operations. A few big lessons when you look at these institutions. There's a few big lessons about how to stand them up and guarantee their success. First of all, creating a culture of risk-taking and nimble action and boldness is a three to five-year project at minimum. Protecting and nurturing that new culture is a very major challenge. Expect resistance and open and passive hostility from within the establishment, who will be threatened by this initiative and attempt to capture it. Expect comments over the years that will stretch forward and surprise you, when people continue to come to you and say, "I still don't understand what they do and why we need them." Pick a leader who is nontraditional with considerable gravitas. That person should have a deep understanding of the bureaucracy, be highly skilled at using significant funding strategically to build new partnerships. She or he has to be able to sell the concepts aggressively and widely, manage media and expectations, and build bipartisan support in Congress. She or he has to cultivate a ring of dedicated champions and truly consequential partners. Anticipate and plan accordingly for the possibility that, in 2022, Republicans return to power in the House of Representatives and, two years later, may control the White House. Transfer of power could be highly disruptive if you don't plan accordingly. Who is going to protect the leader of ARPA-H? Who's going to do the block and tackling? Who's going to ensure that this leader has sufficient space to move? Before even starting, you need clear answers to these questions. The answers lie within NIH leadership, within the White House, and within Congress. At the outset, do not insist on overbuilding and defining things too precisely. Focus on getting things going. Focus on getting a few strategic initiatives going rapidly. There will be pressure for quick results. Figure out what those may be, because your game is going to fundamentally be a long term game, where quick results may not come, but the pressures will be there. Last on the operational side, stay on campus. Be different. Remind people constantly that you're different. But stay there and remain connected. I don't think separation-- physically or geographically-- makes any sense on a political and operational basis. Second point, ARPA-H should build into its equity goals ensuring there's a pathway for all products to reach low and middle income countries. These products need to be scalable, have safety and efficacy affordability, and ease of access. Creating R&D scientific capacity, the next generation of investigators, and strengthening field trial networks' laboratories should be a conspicuous priority. We cannot afford to repeat the catastrophe unfolding today surrounding access by low and middle income countries to COVID-19 vaccines. We need an antidote to the resentment, anger, and damage to the reputation credibility of the United States and other western powers in this period. We need an answer to the rising fear in low and middle income countries that their gains in HIV, TB, malaria, and elsewhere are going to get washed out in the midst of this raging pandemic. My institution, CSIS, can play an important role in convening experts at the nexus of foreign policy and science public health. We're well positioned to raise awareness within diplomatic and national security circles of the importance of innovation and international collaborations in the proposed ARPA-H. Make use of us. We're ready and willing, as are my peer institutions. Thank you so much, and back to you, Doctor Collins, FRANCIS COLLINS: Thanks very much for those thoughtful and very appropriate comments about what we are going to be facing here in terms of putting in place an organization that has a different culture than what people are used to. Those resonate with Dr. Schwetz and me-- believe me, because we have been worrying a lot about how to pull this off in a fashion where the initial enthusiasm doesn't give way to carping and complaints about why do we still need this. So, thanks. That was really helpful. I was taking careful notes. Next, we're going to hear from Dr. Judy Wasserheit, who is founding board chair and research committee co-chair of the Consortium of Universities for Global Health-- CUGH. Dr. Wasserheit. JUDY WASSERHEIT: Good morning, Dr. Collins. On behalf of the Consortium of Universities for Global Health, and an organization of over 170 academic institutions around the world addressing global health challenges, thank you for this opportunity to comment. In our community, there is tremendous enthusiasm and excitement about the creation of an agency focusing on accelerating breakthrough technologies specifically for health, leveraging the best aspects of the DARPA-H model, including explicitly seeking transformational advances and embedding these efforts in a robust innovation ecosystem that includes academic, as well as corporate and governmental, partners. This vision is inspiring. And the opportunity supercharges the imagination, I'd like to highlight four points to consider as you translate this vision into reality. First, as has been thrown into relief by the COVID pandemic, health, like security, must be tackled globally. ARPA-H must prioritize and invest in development of breakthrough technologies for use in low and middle income countries-- LMICs. As Steve just emphasized, as well as for our tertiary care facilities and sophisticated labs here in the US, there must be a clear and explicit mandate for projects to address health needs in LMICs with substantial budget allocations. This is essential in order to end pandemic disease as we know it and transform emerging diseases with pandemic potential into rapidly contained outbreaks with limited morbidity and mortality, which should clearly be one of the initial priorities for this new agency. It will simultaneously address health needs for other diseases such as Alzheimer's, diabetes, and cancer in our own marginalized communities here in the US. And both ethically and to advance our diplomatic and economic development goals, it's the right thing to do. Second, in setting priorities, ARPA-H will be likely to have the greatest impact by matrixing consideration of the most pressing, complex global health challenges such as pandemic disease, antimicrobial resistance, climate change impacts on health, malnutrition-- both under- and overnutrition-- and diseases of aging, with the most promising scientific and research opportunities across an extremely broad range of disciplines and systems-- not only in more traditional areas like biomedical sciences, bioengineering, modeling, and network analysis, but also in other fields, such as information and communication technology, agriculture, and environmental and climate sciences. Third, there are multiple challenges along the R&D path of every major innovation. And the more transformative the innovation, usually, the greater the challenges. But consistently, some of the most profound challenges are in implementation and scale-up to achieve population impact. We've got to develop program and policy platforms in parallel with the innovative technology platforms and other research advances. And we've got to build robust implementation science capacity if we really want to achieve transformational changes. This also means that the perspectives and priorities of nations and communities that will use the innovations must be engaged early and consistently in development and conduct of the research. We need to build receptor sites for research innovations at policy program and lay public levels. Finally, universities have critical roles to play as partners in this enterprise. The faculty bring tremendous expertise in the design, conduct, and analysis of research. They have robust relationships and experience working with colleagues in LMICs, both on the ground and at the policy development levels in ministries of health. And they are profoundly committed to expanding existing global health research, capacity, and developing the next generation of global health researchers. In addition to providing research grant opportunities for university-based investigators, ARPA-H could leverage the strengths of universities and build strong partnerships by establishing a fellowship program analogous to the National Defense Science and Engineering Graduate Fellowship Program, which was started by DARPA. But make that program open to applicants from LMICs as well as US citizens, and also by offering sabbatical opportunities to junior faculty. Congratulations on this landmark initiative. And thank you again for the opportunity to comment. FRANCIS COLLINS: Thanks very much, Dr. Wasserheit, for those thoughtful comments. By the way, those who are listening-- the 130 or so of you-- if you have things that you would like ARPA-H planners to know about that don't fit conveniently in the Q&A format that we're going to come to, there is also a comment box that we're maintaining, which people will be looking at. It's just arpahcomments-- that's all one word, no spaces, no period-- @nih.gov. So arpahcomments@nih.gov. Next, we're going to hear from Jamie Bay Nishi, who is director of the Global Health Technologies Coalition. Please proceed. JAMIE BAY NISHI: Great. Thank you, Dr. Collins. Thanks, everyone. I serve as the director of the Global Health Technologies Coalition. It's a group of nearly 40 nonprofit organizations, academic institutions and aligned businesses advancing policies to accelerate the creation of new drugs, vaccines, and diagnostics, and other tools for poverty-related and neglected diseases, or PRNDs. So I'm just going to say PRNDs a few times during this next four minutes. Thank you for the opportunity to share our perspective on the proposed ARPA-H at NIH. Dr. Collins, you touched on this at the beginning of the meeting. But I wanted to say up-front that, if ARPA-H is created, support for this agency must be additive and not detract funding or technical expertise from any of NIH's existing institutes, or other US agencies, advancing late stage R&D. If the goal for ARPA-H is to produce transformative innovation where there otherwise would be none, we believe that few areas offer as much potential for R&D impact as poverty-related and neglected diseases. This includes HIV/AIDS, tuberculosis, malaria, neglected tropical diseases, and antimicrobial resistance. PRNDs have been an area of historic underinvestment relative to the burden that these diseases produce. The private sector has historically been hesitant to invest in research in PRNDs because, as diseases often associated with poverty, they offer limited potential for profit. In 2016, the global private pharmaceutical sector spent approximately $159.9 billion on R&D for health overall, but only $511 million, less than 1/3 of 1%-- less than 1/3 of 1%-- on R&D for neglected diseases. ARPA-H is a significant opportunity to balance this global inequity and bring innovation to a place of historic market failure. NIH and other US agencies have made laudable scientific progress against many PRNDs over the years. But many high impact innovation gaps remain. For example, neglected tropical diseases affects nearly 1 billion people globally. But we lack the tools to accurately track the prevalence of many of those diseases. A platform diagnostic for these diseases is one potential ARPA-H project that, if successful, could have immense global benefit. Another gap is the need for a highly effective malaria vaccine. Some experts believe that mRNA technology could be used to produce an effective vaccine against this enduring parasite, which is still responsible for hundreds of thousands of deaths annually. If the goal of ARPA-H age is to foster transformative breakthroughs, then we should remember that investments in infectious disease research pay dividends across the health R&D landscape. Investments in HIV/AIDS research led to the immunological breakthroughs critical to understanding the pathogenesis of COVID-19. Research on malaria has produced anti-malarial drugs that are being evaluated as promising anticancer treatments. And the BCG tuberculosis vaccine is now being evaluated for its potential therapeutic and protective effects against type 1 diabetes, Alzheimer's, and other diseases. So if ARPA-H is realized, GHTC supports an agency framework that closely monitors that of DARPA-- has the flexibility. This should include policies that would give ARPA-H program managers maximum flexibility in how they distribute funding, enabling them to place high risk, high reward bets with strategic partners. I won't go into that further, because I think Steve covered it well in his remarks. Furthermore, any work on PRNDs-- ARPA-H program managers should be encouraged to work with global partners and end-user communities, policies that would both strengthen global research capacity and benefit the final design of products. We understand that launching ARPA-H will require a thoughtful balance among competing disease priorities dependent on public health need, scientific neglect, and breakthrough potential. We believe that a focus on PRNDs is a high impact opportunity for ARPA-H to benefit the health of our most vulnerable. We stand ready to work with you to further the ARPA-H proposal and are grateful for the opportunity to provide input today. Thank you, Dr. Collins. FRANCIS COLLINS: Thanks very much-- very helpful comments. I'm learning a lot this morning from all of you. Our final stakeholder presentation is from Suraj Madoori, who is the US and Global Health Policy Director of the Treatment Action Group and also Research Working Group of the Federal AIDS Policy Partnership. Please proceed. SURAJ MADOORI: Thank you, Dr. Collins and NIH leadership, for this opportunity to speak today. I'm glad I'm going after Stephen and Jamie, because they relayed a lot of points that I was going to raise in my remarks. So, as you know, my name is Suraj Madoori. I'm with Treatment Action Group, and I'm representing 60 organizations of the Federal AIDS Policy Partnership's Research Work Group, which I co-chair with Kevin Fisher at AVAC. First, we thank the NIH leadership foremost for the incredible work in the current pandemic to save lives and moving us in a direction of a hopeful end. We applaud the NIH and the administration for its vocal pursuit of ARPA-H, an agency that could catalyze biomedical research on the heels of unprecedented success in the rapid deployment and development of COVID-19 vaccines. Today, I will seek to reflect the guidance and priorities for ARPA-H from the HIV community, which has a long and deep history of engagement with our government's publicly funded research institutions. First, we implore NIH leadership and the administration to include HIV and comorbidities such as tuberculosis, STIs, and viral hepatitis as priorities in a portfolio ARPA-H. These infectious diseases take millions of lives every year and require an accelerated research agenda to end these epidemics, particularly amongst communities of color and marginalized populations. The HIV research sector can be a partner to ARPA-H's portfolio that can be leveraged to advance more rapid breakthroughs. The history of HIV research at NIH has shown that health interventions need to incorporate a community perspective and patient-centered design to be acceptable and, therefore, ultimately effective. One area in which the DARPA model could learn from HIV research is how to integrate community and informed community input. Community input into trial protocols, trial enrollment strategies, and even scientific priorities at the NIAID Clinical Trials Network, has been translated into research successes, both in the HIV arena as well as other diseases. As public health professionals and researchers, you understand that crosscutting nature of health outcomes and research investments. In health research, there's a tendency to work in silos instead of fostering a collaborative environment that can leverage the expertise and knowledge across multiple internal and external partners. Collaboration with unique partners will address systemic gaps that exist in discovery development and delivery continuum. Here, again, HIV research, with its decades of coordination and collaboration across institutes, provides an important precedent and example for ARPA-H. The FAPP Research Working Group strongly supports efforts to address structural racism across NIH and increase the leadership of early stage investigators from disproportionately-impacted communities by leveraging existing partnerships and fostering new collaborations. ARPA-H provides an opportunity to design funding programs to increase the recruitment and funding for BIPOC and Latinx researchers. This will bring unique perspectives to research questions and strategies concerning access delivery and effectiveness of care in BIPOC and Latinx communities. It is also very important for ARPA-H research portfolio to reflect diversity and prioritize the engagement of populations into research that affect morbidity and mortality in their communities. ARPA-H must also consider strategies that address commercialization, implementation, and affordability and accessibility of publicly funded research. For example, ARPA-H should require full disclosure of the cost of product development and raw materials within agreements made between the US government and industry. ARPA-H should also carefully consider industry incentives, which have historically resulted in access restriction to patients that most need promising new therapies. Greater transparency is needed on the part of the government and the industry to foster community trust. As Stephen has said in his comments, we've seen this really with the rollout of the COVID-19 vaccine, particularly around low income, middle income countries. So we really feel that ARPA-H is positioned to address some of these issues around downstream access. Finally, NIH institute incentives also must include at the center of any plan's community. This includes centering community and development, implementation, and dissemination of new technologies. Without the live experience and expertise of those with research subject matter experience and the community who are the ultimate consumers, research and development, as well as the final use of new interventions, will be unsuccessful. We have seen that the result of the failure to engage communities most hit hard by the COVID-19 epidemic has resulted in vaccine hesitancy. So we strongly encourage ARPA-H to lead with a robust structure for community engagement throughout its portfolio and strongly urge ARPA-H also include infectious diseases as a core part of its portfolio. Thank you for the opportunity to speak today. Back to you, Dr. Collins. FRANCIS COLLINS: Well, thanks very much. So we've had six terrific stakeholder presentations. And we are now ready to move into the Q&A section of our session. And we've got about 25 minutes or so for that. And Dr. Schwetz and I will attempt to see what we can do to moderate the Q&A, starting with the questions that have come in from the chat. Let me just say, I think that a number of them are really trying to understand how it is that projects get selected for ARPA-H. Because there's a lot of ideas here that you all have put forward-- and reminds me to tell you that, of course, you are one of 10 sessions we are holding. And every one of them has had some really interesting suggestions about how we might mount various projects that would fit into ARPA-H. But they would need to fit. So part of the question, I guess, is exactly what is the nature of a perfect ARPA-H program? Well, it would need to be something that basically can't be currently done within the existing public and private sector research support system. So you're looking for projects which really need this kind of scaling that would be use-driven that are aiming for outcome that is going to change the practice and have a major impact on biomedical research. And they would need, of course, oftentimes to involve partnerships that maybe don't naturally just come together by somebody submitting a grant to NIH. I thought I'd read you-- because we are paying some attention to the way in which DARPA has identified the right criteria for a successful project-- something called the Heilmeir Catechism. So, what's that about? Well, George Heilmeier was DARPA director back in the 1970s. And he crafted this very simple set of questions to help agency officials think through and evaluate proposed research programs-- about whether they were a good fit or not. These are very simple, but they're worth thinking about in terms of how we will, with ARPA-H-- which is very much trying to adopt that same DARPA attitude-- apply this to health. So here are the questions. First, what are you trying to do? Articulate your objectives using absolutely no jargon. OK. Second, how is it done today, and what are the limits of current practice? Third, what is new in your approach, and why do you think it will be successful? Next, who cares? If you are successful, what difference will it make? Next, what are the risks? After that, next, how much will it cost? And then, next, how long will it take? And finally, this is an important part of an ARPA-H project, what are the midterm and final exams to check for success? These projects are going to have to have explicit metrics that you can assess early on whether the progress is actually happening. Because you expect ARPA-H to have a fairly high failure rate. Otherwise, we're not taking enough risks. But you don't want failures to be discovered five years later. You want failures to happen early, if they are going to happen. And hence, you have to have those metrics and then really hold the projects accountable. So this is rather different than many academic projects, where you give a five-year grant and you hope for the best. And admittedly, that has worked great for an awful lot of what NIH is supporting in biomedical research. But ARPA-H projects are going to be different. They're going to have those kinds of very explicit milestones. Otherwise, they're probably not a very good fit. So, as we're talking about this, please keep that in mind. Let me ask Dr. Schwetz, because there's a question here, also, about how the program managers, and maybe the director, will be recruited in order to try to achieve that kind of bold mindset. I think Dr. Morrison was certainly telling us how critical the culture was. So, Tara, how are we going to, with the personnel that are going to be critical here, try to achieve that? TARA SCHWETZ: Sure. So for the program managers in particular, we're really thinking about recruiting folks that are outside-of-the-box thinkers-- people who may even have some level of frustration with the current state and have an idea of an innovative solution and approach to tackling that challenge. And they're going to be folks who have a range of experience-- so those from industry, academia, nonprofits, elsewhere-- and hired for the ideas that they can bring to the organization in addition to any experience and expertise that they have. And these are going to be shorter term positions-- so somewhere in the neighborhood of three to five-year appointments. It also helps to promote that sense of urgency that has been mentioned throughout this listening session. The folks that I talk to at DARPA often will say, the expiration date on your badge-- you see it every single day, and you get reminded of the sort of ticking clock that you have in order to accomplish all of the amazing things that you want to get done. And it really does foster the sense of urgency that we have, in some ways, been living with the COVID-19 pandemic. And we're talking about expanding that beyond that one area. So that's for the program managers. And I think, in some ways, we want a similar type of person who can lead the organization. This first director will really set the stage and the tone for the culture going forward. And we want to bring on someone who, in addition to being a technical expert, is a really adept leader and an ambassador for the organization, and can really help empower their program managers and other staff to embrace the mission of ARPA-H and all the tenets that we have outlined previously. FRANCIS COLLINS: Tara, maybe you could say another word about the various inputs that you anticipate will be available for ideas about ARPA-H projects. Obviously, a big one is these program managers. They generally will arrive already with an area of specific interests. And they'll want to do their own bit of surveying that part of the landscape and then pitching programs to the ARPA-H director-- maybe according to the Heilmeier rules to see if they fit. But we don't want to limit ideas just to that set. How are they going to be sent forward from other perspectives? TARA SCHWETZ: One thing to note as part of that process-- the program managers will bring ideas with them. And the pitch will likely be part of an interview process. But these have to be really well formed ideas. And as a program is being developed, a lot of feedback has to be gathered from stakeholders in a variety of different sectors. They have to be able to answer all those Heilmeier questions-- and many others, I'm sure, they'll get peppered with. And part of that is really doing a sort of landscape analysis and market research and getting feedback more broadly. And whether that is through-- and I think it's going to be a combination of these things, a combination of direct communication with experts-- through just one-on-one, or small group meetings, whether that's through workshops, RFIs, or other mechanisms. I think one important point, too, to mention is that in developing these programs, I think that the input that will be gathered will be not just broadbased, general input, but really tailored to each individual program. And that external feedback will, in some sense, be more frontloaded, maybe, even than what we're typically used to doing at NIH. So, there'll be multiple pathways for engaging the stakeholder community. FRANCIS COLLINS: Another thing we ought to be clear about, just because this is a very different way of funding research, is how the review of project proposals will happen. This is not your typical study section, second level of a council, year long process. We anticipate projects. Once they're pitched forward, if they're going to be considered, you want them started within about three months. So, Tara, how's the review process, other than the director saying yes or no? Is there other inputs here to decide whether something gets a green light? TARA SCHWETZ: Yes. The process for reviewing the applications that come in will likely-- we're still working through all the details of everything, of course, so the caveats are there. But it will likely mimic that of this sort of ARPA model, wherein people will submit a concept and get a fairly quick yes or no, interested or not interested, in exploring this idea further. And then they will be invited to send full applications in. And those applications will be reviewed internally by a group of federal experts with diverse expertise in the area of interest. And so this will be a rigorous review process. It will just be a different process than, I think, the typical two-stage peer review system. And those applications or proposals that are reviewed, they're going to be reviewed slightly differently. And there's a high likelihood that we will not be doing the standard ranking and priority score that is done at NIH. And I'll tell you, for an example, the DARPA model. They don't even give any kind of score. It's a yes or a no. If it's suitable for funding and it matches the criteria outlined in the request, or it's not. And then, the program manager reviews all the applications and pulls together a portfolio of a few programs that are complementary, that take different approaches to achieving the goal, and pulls together this diverse portfolio. So you could imagine something similar for ARPA-H. FRANCIS COLLINS: Yeah. And one of the things we can do with ARPA-H, which is difficult in our current circumstances, to actually reach out to partners who would never write an NIH grant because they're not familiar with that-- and many of those might be small businesses-- but who have a particular technology that is going to make something work, and figure out how to bring them alongside as a collaborator so that you can build the appropriate network of expertise for a project that might otherwise be hard to do. Well, I'm sorry. I'm taking a lot of the time of Q&A by giving you additional background. But it does reflect some of the questions that people are asking. So we're now going to the Q&A. And we'll probably jump around a little bit. The first question, though, very much is being reflected by several people, probably because this is the stakeholder outreach where we're talking about global health research. Will ARPA-H fund research teams that include foreign participants, particularly in support of global health needs for infectious disease, or will awards be restricted the US team? Well, I would say we would be crazy to restrict this just to domestic research efforts. The world doesn't work that way, whether we're talking about infectious disease, or climate change, or whatever. And NIH, as the largest supporter of global health research in the world, would like to continue that with the ARPA-H effort. The programs, of course have to fit the model. But I will be personally quite disappointed if some of what ARPA-H- invests in does not include global health research. I hope I'm not going too far there, Tara, in terms of what you think the rest of the administration would support. But this is our view of what our opportunity, and our responsibility, is. TARA SCHWETZ: In the COVID pandemic, we have seen-- and it has emphasized-- the fact that diseases and pathogens don't know boundaries. And we need to be thoughtful in how we're going to address them. And then, of course, ideas come from all different sources. And we want to make sure that we are capturing the best ideas possible to solve the challenges that we're trying to tackle with ARPA-H. FRANCIS COLLINS: Yeah. There's a question, Hugh Auchincloss, about how this ARPA-H effort might fit together with what's being talked about in terms of prototype vaccines against 20 families of viruses. I don't know if the IT people can actually get Dr. Auchincloss on the screen. Yes, there you are. What do you see as the relationship between ARPA-H and other things that are being talked about for a pandemic preparedness-- recognizing that these are two different planes we're trying to build at the same time? HUGH AUCHINCLOSS: Well, exactly. Dr. Collins. You probably know more about it than I do. We are looking for funds for the pandemic preparedness prototype vaccine program from other sources. But I do think that, in some sense, it's sort of an ARPA-H-like activity. I just don't know that the funds will actually come from that particular source. Let me just make the comment that the prototype vaccine approach, which is to figure out how to make a good vaccine for a member of a viral family, was the approach that actually turned out to have been used for COVID. The vaccine that was developed was really developed before the pandemic by Barney Graham and his colleagues defining two specific mutations-- the S2P mutations that stabilize the COVID spike protein for MERS-- turns out to be exactly the right way to stabilize the SARS-CoV-2 molecule. And for that reason, it was four days from the time we got the pandemic virus sequence to the time that manufacture of the vaccine began. It's really a fine example of what we're trying to do for these other viral families. FRANCIS COLLINS: Thanks, for pointing that out. And, again, Hugh suggests that I know more about how we're going to fit pandemic preparedness in ARPA-H together than he does. But none of us are really quite clear about that. We are trying to build these programs at the same time. That op-ed you saw today in The Washington Post from Eric Lander, which was just referred to, was about pandemic preparedness. And Lander is also, with me, one of the major proponents of how we're going to build ARPA-H. But we've got to figure out exactly how those things fit. At the moment, they are both more hypothetical than actually possessed of real dollars. So it's probably good not to be too explicit until we know they're real. But there are great potential there for synergy. A number of the questions in the Q&A are about specific applications from groups that have a particular passion about areas of research. And we heard that from the stakeholders as well, whether it was about lymphatic diseases, or whether it was about HIV. Let's be sure that, as we contemplate uses of this, we don't forget that these are critical needs. I guess I would just say-- whether you're asking about herpes simplex virus, or tick-borne diseases, or sepsis-- these are all highly appropriate areas to consider. But you'd have to figure out how to frame that in the kind of a project that fits the ARPA-H model and it is not currently possible to pursue with more traditional public and private sector initiatives. So that's going to be the challenge, I think, to all of our stakeholders-- and all of us involved in ARPA-H-- is to say, what is a program that's ARPA-H-able and isn't otherwise going to get done, and where ARPA-H, if invested in this, could accelerate progress in a use-driven way? That's one of our key words here-- use-driven-- not curiosity-driven, but use-driven way to, perhaps, make things happen twice as quickly as they would otherwise, with the willingness to take on high risk, and expect, again, that many of these projects are not going to succeed, but also associated with the willingness to define explicit milestones and be willing to pull the plug if those milestones are not met, which is different than a lot of academic research. So I hope you really get the flavor of how this is really different. Earl Freeman is asking, is ARPA-H the health care version of DARPA? Yeah, it kind of is. And that was sort of what we were trying to achieve. Now, obviously, DARPA does have some biotech innovations. Actually, DARPA was involved a bit in the mRNA vaccine efforts a few years ago. So I don't mean to say that DARPA hasn't already been in this space. But DARPA remember, has a single customer, which is the Department of Defense, whereas ARPA-H is going to have customers, essentially, of everybody who's hoping for health advances to happen. But we are trying very much both to learn from the lessons that DARPA has put forward of things that work, but also things that didn't work so we don't have to stumble over things where we already have evidence of what's going to be successful. Scott Kilroy is asking, are novel prevention devices a category being considered for funding with ARPA-H? I think that's a great question. We are the National Institutes of Health. But some people think of us, really, as the national institutes of disease, because it seems like most of our research investments are focused on people who are already sick. And I think we'd all agree it would be better not to get sick. So I would say, enthusiastically, yes. The range of what ARPA-H might want to support would vigorously include prevention-- and, maybe, particularly if it plays out in a fashion that touches on health disparities. We haven't said much-- and I'm going to ask Tara to say a little bit more in a second-- about how critical it is that ARPA-H and everything it does has the notion of health equity really baked into the whole plan. That is such a critical issue for us at NIH. And it needs to be thought about-- not as an afterthought, but right from the beginning, in how this program is formed. And, certainly, prevention strategies-- if they're going to be successfully investigated-- need to particularly be done in a fashion that recognizes that health equities do not necessarily fit with our current circumstance and need to be addressed. Tara, do you want to say anything more about the equity issues? TARA SCHWETZ: Yeah. That's such a critical component of ARPA-H, and something that has been highlighted over the last year and a half-- some of the distinct disparities that exist in the current system. And equity considerations are really going to be woven throughout all of the decisions within ARPA-H. So whether that is referring to hiring staff and program managers who are going to be developing programs all the way through the actual programs themselves, these are going to be elements that will be considered in the design of programs. And each of the programs, I think, will want to consider equity in a meaningful way. And we can imagine, too, that there will be some specific programs that target challenges in this space directly, not just have it be a component of everything that we do. And I think it will be key, too, to have a designated senior leader within the ARPA leadership team that is responsible for ensuring that these issues are considered as part of ARPA-H's work. FRANCIS COLLINS: Totally agree. This has got to be integrated in everything we do. A couple other questions-- we've got about another five minutes-- question about how we balance the investment in critical, urgent responses like pandemics versus long term investment in complex diseases and complex opportunities. That'll be sort of a daily challenge for the director, obviously. Urgency does tend to require response, and pandemics being the most dramatic example of that, but not the only one. So, as in everything, that's going to have to fold in somehow in this matrixing of what the opportunities are. But a lot of what ARPA-H is going to work on will not be in that urgent category of a recent pandemic, but will be more across the long sweep of health and illness and what could be done in that space that hasn't currently happened. And some of those, by the way, will not be specific disease approaches. Maybe we've overemphasized the idea that every program is going to be built on a disease application. Some of the most exciting applications are going to be platforms where ARPA-H could develop-- as, I think, Tara mentioned as an example-- something that allows you to ZIP code a gene or a drug to the tissue in the body, or even the cell in the body, where it needs to go, without landing in other places. Imagine if you had that platform what you could do with it. That kind of thing will be also very appealing as ARPA-H projects. Other things that we might try to touch on-- coming back, because we did have this question about, is global health research on the table? And I answered, enthusiastically, yes. And then an anonymous attendee is saying, OK, but how about led by research institutions and allowing middle income countries, as opposed to having them as subcontractors, with the actual driving of the research coming from outside? This is an area of personal passion. I think we have to get away from the colonial model of how global health research is done. And I think we've successfully seen how to do that. Look at programs like H3Africa, for instance. I would personally very much want to see ARPA-H push that envelope. There's a great deal of talent and capability outside of the most highly developed countries. And we should be absolutely empowering that capability to go forward. Maybe Roger Glass, if you're still on-- I know you're in Berlin or somewhere like that-- if you want to say a word about how important that has been for us is to empower those institutions in low and middle income countries. ROGER GLASS: I think we've seen great creativity when we've done that. And I'm also involved with the MEPI program, the Afrihealth. Those leaders have taken on their own organization, the first organization across Africa, to deal with the medical schools, nursing schools, interprofessional educations-- they really rose to the challenge and did things which we never would have anticipated. So it's been exciting to see them take charge. And especially with COVID, where we have less access through travel, they've really picked up the leads and have shown their capability in spades. They're just absolutely terrific partners. I think that's the move we're trying to make with this decolonization or democratization of what we're doing. Thanks, Francis. FRANCIS COLLINS: Thanks, Roger. Well, we've reached time. And I know everybody's awfully busy. And so I think we will draw this to a close. But I want to thank all of you again-- the stakeholder presenters, the Institute representatives, Tara Schwetz, and all of you who have been listening in-- about 135 at one point-- for your input perspectives, both today and what you can send us afterwards. This is just one way to engage with us. I gave you the email address previously. I'll give it again-- arpahcomments@nih.gov is a comment box that remains open for stakeholder input-- arpahcomments@nih.gov. We're looking closely at the ideas that come in through there. And we're continuing to hold listening sessions over the next week or two. Those are all publicly broadcast. And you can find information about those, if you want to participate in others, on the NIH web page. So, thank you, everybody. We really look forward to seeing what can be done with this exciting new opportunity to catalyze progress in biomedical research in new and bold ways. And we are going to do that successfully if we all do it together. Thanks for your time. Thanks for your input. Have a wonderful day, everybody. We are adjourned.