Scientist Stories: Julie Gerberding, Pandemic Preparedness

Okay, I know people are still coming in, but I think we'll get started since I know we're a few minutes late. Hello, and thank you to everyone around the world for joining us for this week's lab meeting. My name is Kristin Aboud. I am the science editor at the Human Vaccines Project, and I will be your moderator today. After a downward trend, deaths due to COVID-19 are once again on the rise globally. The World Health Organization reported last week that deaths due to the disease are climbing in Europe and Southeast Asia while declining in parts of Africa, the Middle East, and some parts of Asia. The countries reporting the highest number of deaths per capita in recent weeks are in Eastern Europe and the Caribbean, where far less than half of the population has been vaccinated. Equitable access to vaccines continues to be a critical issue. According to Our World in Data, less than 1% of COVID-19 vaccine doses have been administered in low-income countries. At the opening of the G20 summit, world leaders called for increasing supply of COVID-19 vaccines in poor countries, calling the gap in access morally unacceptable. On a positive note, US pharmaceutical company Merck announced last week that they have entered a voluntary licensing agreement with the UN-backed Medicines Patent Pool to facilitate affordable global access to the company's antiviral pill that has been shown to cut hospitalizations and deaths from COVID-19 by half. This agreement will allow companies around the world to manufacture the pill following regulatory approvals and make it available in low and middle income countries. The drug, if authorized, would be the first oral COVID-19 therapeutic. It was invented at Emory University and developed by Ridgeback Biotherapeutics and Merck. It is currently awaiting emergency use authorization by the US FDA. And I'm sure we'll hear a bit more about this from our speaker today. Before we begin today's presentation, I just want to note, we ask that you not reproduce or disseminate any of the information presented. This session will be recorded and made available on our website and our social media channels for for you to review. With that, I am very happy to introduce Dr. Julie Gerberding, Executive Vice President and Chief Patient Officer at Merck and Company. Dr. Gerberding joined Merck in 2010 as President of Vaccines. In that role, she was instrumental in increasing global access to the company's vaccines. She then oversaw the communications and global public policy functions. In her current position, Dr. Gerberding is responsible for patient engagement and corporate social responsibility. Prior to joining Merck, Dr. Gerberding was director of the US Centers for Disease Control and Prevention, where she led the agency through the SARS outbreak and more than 40 other emergency responses to public health crises. She currently serves on the boards of the Cerner Corporation and MSD. Welcome, Hilleman Laboratories, a nonprofit that develops new technologies for developing countries. She also co-chairs the Center for Strategic and International Studies Commission on Strengthening America's Health Security. Please send me your questions for Dr. Gerberding using the Q&A function in Zoom rather than the chat. I will ask our speaker a broad selection of your questions after the presentation, and we'll have plenty of time for discussion. With that, it is my pleasure to now introduce Dr. Julie Gerberding.

Thank you, Kristen, and thank you so much for your investment in this conversation, but also I thank the organization for bringing these conversations forward. Timing is perfect. I'm going to talk a little bit today about the broad outlook on the pandemic, but I will start just by framing how I see it because obviously it's not over yet, and I think we have gone gone through a series of kind of stages of response that are worth recapturing. The metaphor I use for, for the SARS-CoV-2 pandemic is really a marathon. At the very beginning, we were way behind the virus. It got out in front of us before we even knew we were running a race. And unfortunately, it globalized under our noses without our really recognizing the asymptomatic transmission potential that this particular coronavirus had. But fortunately, we were able to initially begin to catch up with the virus by implementing our non-pharmaceutical interventions. For a while, we could flatten the curve, slow down transmission. In some regions of the world, even really contain and curtail the ongoing spread. That was an optimistic, we're catching up phase of the pandemic. But unfortunately, we saw two things. First of all, it was very difficult to sustain those non-pharmacologic interventions, particularly in more libertarian societies. But second, the variants began to emerge, and we saw Alpha, Beta, Gamma, Delta, and particularly Delta really take off. And of the juxtaposition of some relaxation in the NPIs and then a virus that was particularly suited for rapid and silent transmission. So that put us behind again in the race, and now we are beginning to benefit from the availability of vaccines somewhat selectively because certainly we have a long way to go before we have achieved global access. But slowly but surely we're developing pockets of populations who are relatively resistant to the severe complications of infection. But as we're learning in all too many regions of the world, that protection is not absolute. And the breakthroughs with Delta virus, even among fully vaccinated immunologically, immunologically protected people is still a major factor in propagating the transmission on an ongoing basis. I was really discouraged this morning to read about the situation in Colorado in the United States where the hospital systems in the state have now decided that it will be okay and permitted for hospitals to turn away patients because the surge of the number of COVID cases is weakening their overall ability to provide essential services and the virus Even though the population of Colorado is ostensibly 80% vaccinated, we're still seeing this incredible surge competency. We're coming in, in many societies, to the holiday season with several important holidays that bring people together. I was in the airport this weekend, and I can certainly see from a US perspective there is plenty of travel going on, and not everyone is uniformly following the requirements for masking, et cetera. So I think We cannot lull ourselves into the false sense of security that we're, that we're winning this race right now. This is neck and neck, and we have a long way to go before we get to any kind of a finish line. So I don't mean to sound pessimistic, but I think that's all the more reason why we should be talking about what tools are missing, what tools do we need to improve, what products must we continue to innovate and invest in. But second, how can we improve the efficiency, the affordability, and the availability of those countermeasures and other tools so that we hopefully can have a broader protection network around the world? And then three, what kind of partnerships are going to be necessary to achieve this in the timeframe necessary to begin to attenuate the tremendous mortality that we're experiencing on a global basis? 5 million deaths is really an incomprehensible fatality presentation in the 2 years that we've been in this. And as I said, we're not over yet. And probably we're undercounting because many parts of the world have ongoing transmission and no means of diagnosis or really conducting the kind of surveillance that would improve the reliability of those numbers. So let's talk a little bit about products. I think the great news in all of this is that science really is on our side. What we've seen in the last 2 years is breathtaking. I would not have predicted in January of 2020 that we would be having the benefit of the incredible vaccines, immunologic and antiviral tools that are now increasingly coming out of clinical trials and entering the authorized phase and hopefully the approved phase in the not distant future. So, you know, these products, I have to emphasize to people who are less familiar with the process, are not products that suddenly were inspired and popped into being in January of 2020. These are countermeasures that are building on the science that's been going on over a long arc of time, both the scientific capabilities in kind of a generic sense, but also the specific coronavirus work that was sort of catalyzed in 2003 with the first SARS outbreak and then emphasized with MERS as we began to see how that coronavirus was propagating and the incredible force of mortality with, with the MERS virus. And then the recognition with SARS-CoV-2 just kind of building on a broadening of our understanding of coronavirus biology but also the necessary components of an effective coronavirus immunology. So one piece of the product development really is the understanding of the virus. And of course, we still have a long way to go with that as well. But the second piece of that is just kind of our overall vaccinology know-how, our antiviral know-how, the kinds of things that have broadened our overall armamentarium of tools And then the mechanisms that were in place to try to foster that kind of development, so-called just-in-case development of countermeasures. In the US, of course, we've had BARDA. More recently, globally, CEPI, just kind of coincidentally launched in the aftermath of the Ebola outbreaks in West Africa and the DRC, but clearly an idea that presaged the incredible challenge that we're facing right now with the pandemic. And in a sense, unfortunately, proof of concept of why this kind of advanced preparation is really increasingly going to make sense. So we've got great science of coronavirus. We've got great broadening scientific tools and platforms for the creation of not just vaccines, but also antivirals and immunologics, and a lot of experience in applying those tools for other public health challenges. But obviously, we also needed a lot of other things that we've kind of been rapidly pulling together in the context of the pandemic. One of those really is the capacity to do effective clinical trials over broad geographic areas in unprecedented period of time. So one of the major categories of new innovations in this, in this pandemic really been the innovations around planning for clinical trials. I give a lot of credit to ACTIV at the NIH, NIH Foundation that really pulled together the consortium of so many public and private partnerships— point I'll come back to later— to really try to develop harmonized protocols, agree upon approaches and endpoints, and then working with the regulatory construct to develop some framework for regulatory harmonization. For me personally, one of the big milestones in that process was May of 2020 when the FDA came out with its guidance on what would be necessary to approve or authorize a pandemic vaccine, because that created some certainty around what was needed from a regulatory perspective, but also what wasn't needed, and allowed the people who were involved in vaccine development to really focus their energies in the shortest path to finding a safe and effective vaccine as quickly as possible. That kind of harmonization is hopefully something that we can build on going forward, because if we can accelerate the development of pandemic countermeasures, why not be able to apply some of those same approaches to the acceleration of other essential medicines that are missing, not just in the developed countries, but around the world. So I think that kind of product development innovation is something we need to spend more time focusing on and really master those lessons so that we can take the best of what we've learned and pull it forward. Of course, the downside of the accelerated product development has been mistrust. People who are used to being told that it takes years to develop a vaccine or antiviral are suddenly finding them happening very fast. And folks who aren't informed about the fact that this is building on science that's accumulated over a number of years, are suspicious that safety shortcuts were taken. So I think it's also an important lesson that the industry players in this space signed a pledge last year that basically said we will not take safety shortcuts as we prosecute our antiviral portfolios. There are many things we can do in parallel to accelerate the process of clinical development, but acquiring the appropriate level of safety data is not one of them. And I think you've seen that when the early vaccine trials came forward, there was the robust safety data set. And in fact, in the pediatric trials, the FDA specifically asked the mRNA vaccine process to extend the timeline to make sure that they built out the appropriate safety profile. And the safety doesn't end with authorization. Obviously, we continue to monitor and will continue to monitor the safety of all of these countermeasures as we go forward in time. So when you step back and say science is on our side, clearly we have an agile biopharmaceutical biotechnology industry, and I should include in this that the diagnostic industry and some of the other sectors that have been extremely important and contributory in this effort. But we have players who are agile enough to accelerate and innovate on the fly and take risks. We have governments that are willing to support and help de-risk that effort. So we've got a lot of the important pieces in really creating countermeasures now. But we're going to need to sustain that investment because in some ways we are sort of at the 1.0 level of our countermeasure development and If the past predicts the future, I imagine that we will need to have improvements in some of these countermeasures, and we will need to continue to invest and de-risk and work on global distribution, affordability, and hopefully durability of the relevance of these products. The two major product worries in that space are, of course, the durability of protection with vaccines, in part because we know that the virus is continuing to vary. And while so far Delta is not overcoming vaccine protection entirely, it certainly can break through. But we've got a lot of places in the world that have no protection, have very rapid ongoing virus transmission. And so there are plenty of new chances for variants to emerge, and we might not be so lucky with the next variant. But I also think just generally speaking, we are seeing the waning of immunity over time, at least the biologically measurable markers of immunity in the bloodstream in terms of antibody titers. So we need to be thinking about how do we sustain that level of protection until we either don't need it or we have moved into the very endemic phase of the coronavirus. That becomes less problematic. So durability of protection is a major challenge to the ongoing countermeasure portfolio. I think the other potential issue in the future is resistance. Certainly we've seen with every other RNA, single-stranded RNA virus that we've dealt with, that there is a worry about drug resistance. We've seen this with influenza, hepatitis C, HIV. So we're going to have to be on the watch for that with, with this coronavirus as well. This is a big virus. It has some apparatus that reduces tendency for evolution compared to the little single-stranded RNA viruses. But as the variants have taught us, we are certainly not in a position to believe that this virus is not capable of developing opportunities for drug resistance or immunologic resistance going forward. So We just are, you know, on the ball watching what's going on, but we have to be prepared for successive iterations of the inventions that we have created so far and continue to sustain the investment as well as the mindset that globalization and availability are going to continue to march hand in hand with the scientific evolutions that we are taking a lot of pride in. Think about 830 innovative products were in clinical development for the coronavirus pandemic by the end of 2020. Now, obviously, most of these don't make it or are never going to get out of clinical trials, but on a global basis, that's an astonishing demonstration of what science can do for society. And now we have to be able to harness that so that the totality of society is included in that effort. And that brings me a little bit to the discussion of platforms. So I said products, platforms, and partnerships. Let's talk a little bit about platforms. We're all conversant in the mRNA platform and the advantages that that has created in the context of this pandemic, but we need to be thinking about other platforms. And one of the areas that I think people have less insight into really relates to the platform opportunities in manufacturing, not just the mRNA as a platform for vaccinology, but the innovations that allow, for example, continuous manufacturing, where instead of making a vaccine in step 1 and then measuring it and assaying it and then moving on to the next step of the vaccine manufacturing process, checking that out, going through a lot of measurements and technical operations and then moving to the next phase. Each phase has downtime. Each phase takes time. Each phase reduces the amount of effective time that that equipment is being utilized for vaccine manufacture. So if you can think about a more continuous process where you start and the process continues uninterrupted from beginning to end, but periodically sampling and analysis of what's going on in the vaccine incubator is undertaken so that you have an accelerated production time, but you also can expand the volume and the yield from that production by having real-time monitoring and not finding out, you know, days later that, oh gee, you missed the boat here, you needed to let this one run a little bit longer, etc. So there are incredibly exciting changes afoot in the way we approach the manufacturing of large molecules. And I think the FDA has a working group on this, but the interest in the continuous manufacturing has certainly been heightened by the understanding of what a difference that would make in our ability to scale the manufacturing of some of these countermeasures. And as we're thinking about locating manufacturing capacities in new areas of the world that lack some of the experience and technical competencies probably need to be thinking about how do we set up this kind of a system so that the processes are more automated, there's less opportunity for human error or downtime, and that really hopefully can create the most modern approach to vaccine development, for example, or immunologic development that we can conceive of at this point in time. And ultimately, in the long play, really change how we approach the global scale necessary to create these and future countermeasures. So I think that platform concept really needs to get broadened out to not just think, how do we solve the specific problem of coronavirus, but more broadly, how do we think about a world where at any moment we could need to scale countermeasures to meet the needs of a global population very quickly? And I say that again, not to sound like I'm pessimistic or gloom and doom, But there is nothing in the world today that suggests to me that we won't be seeing new viruses emerge with pandemic potential, whether they are spillovers from the animal kingdom or accidents or intentional releases. We live in a world where everything is conspiring to make this kind of event happen more often and potentially be as severe, if not even more severe than the one we are experiencing. My worst nightmare is the coronavirus spillover that has a fatality rate that looks more like MERS than SARS. And that is not a wild imagination. So I do think we have every reason to take this investment in platform development and think about it with the same sense of urgency and commitment that we've thought about the urgency and commitment to specific countermeasures that we're working on right now. So that kind of leads me then to the concept of partnerships. Private-public partnerships has kind of become a buzzword. We use it all the time. We have lots of panels on private-public partnerships and lessons learned and so forth. But I think we're really dealing here almost with a Mandelbrot scale where we've got kind of a fractal presentation of private-public partnerships at the most local level expanding out into private-public partnerships at a global macro level. And every iteration of that expansion is relevant to what we need to accomplish. So let me maybe start with the local level, because we don't always think about the importance of these kinds of partnerships at the frontline of the pandemic. But we know in communities, I mentioned the situation in the United States, Colorado earlier in this conversation, conversation at the community level. No one can manage this pandemic. We need the local government, of course, to have the leadership and provide the public health guidance, et cetera, make decisions about allocation of scarce resources. But we need the private sector. We need the private sector as it participates in the healthcare system. We need the private sector, for example, employers who set guidelines and expectations for their own employees, who serve as trusted reservoirs of communication amidst all of the other mistrusted sources of information that people are receiving. We have an incredible need for the private sector, not just the people who make countermeasures, but the people who are trusted at the community level, influence vast numbers of employees, community leaders, etc. Those kinds of public-private partnerships at the community level are really the backbone of what is successful about this pandemic. But it's not something that's really seen the light of day and that's something that a lot of people are really focusing on. Where is that working well? Where isn't it? What can we do to help improve that local community effort? When I was at CDC and we were planning for an influenza pandemic, Secretary Mike Levitt understood the importance of these partnerships at the local level to the extent that he actually took his senior team, leader of the CDC, NIH, along with cabinet secretarial level experts from the Agriculture Department, Education Department, the Housing Department, et cetera. And we went to basically every state in the country and met with the governors and many of the cabinet leaders that were kind of the parallel to the federal cabinet people who were involved, and then cascaded that into the community where we did tabletop exercises that included the faith-based organizations, the leaders of the universities and colleges and community colleges, the health system, of course, the public health system, education system, transportation, banking, and had these people come together and sit around tables and practice what they would need to know, believe, and do if an influenza pandemic came to their community. And I think that effort was abandoned as our attention turned to other threats and issues that we as a country face. But nevertheless, that experience of recognizing that the frontline is a public-private partnership, and we need to respect it in that manner. But let me blow up the scale then to the global private-public partnership scale and think about the new mechanisms that have been created to help with the pandemic. I champion CEPI. I was lucky enough to participate in the formative board of CEPI when it was first evolving post the Ebola tragedy in Western Africa. So I kind of had a fly-on-the-wall experience of seeing how the thinking progressed and have nothing but extraordinary respect for Dr. Richard Hackett and the team of people at CEPI It's heartening to see CEPI be taken to the next level because it is a private-public partnership. It is governments, but it's also the private sector and the industry players, but also the nonprofits and civil society really coming together and saying, we need a broad portfolio of just-in-case countermeasures that are developed to the point that they can be rapidly deployed in the event of an emergency. And that is, you know, really an important pillar of our protection. And it's not the only one. Certainly the effort that the WHO has made with GAVI and CEPI to extend that into the vaccine allocation efforts, the clinical trial efforts, and the broader availability of countermeasures surveillance and guidance is just taking that to the next, to the next level through the COVAX mechanism. But we also now have engaged the G20, obviously the G7, but the G20 and their commitments. And I think the next layer of this that I believe was sort of peeking around the corner at the most recent climate change conversations at the G20 is that these these really challenging problems in the world are connected. That climate change is a major force of emergence and spillover of infectious diseases. That it is not just a unidirectional phenomenon. Animals are at risk in the same way that humans are at risk. Our food supply is at risk. This is a very complex ecosystem challenge we're facing here. And it is going to take private-public partnerships to be able to sit down and really mutually understand what needs to be done in that space as well. So in kind of a whirlwind way, I've tried to talk about products as, you know, the thing we're all focused on right now because we want to believe that that will be the solution to what we're trying to solve for today. But I've brought platforms into it because I think we have to lean into the future and begin with scale in sight as we plan for pandemic preparedness. And that will take a variety of platforms, clinical development platforms, surveillance platforms, product development platforms, and ultimately distribution and uptake platforms. And we are a long way from succeeding in any of those dimensions. And then finally, the only way to pull all this together, de-risk it, incentivize it, pay for it, and do a much better job assuring the equity of it is to work collaboratively in new alliances and partnerships that really bring the wise crowd together. And hopefully the wise crowd will learn to cooperate much better than we demonstrated in some of our past approaches to these challenges, to really concentrate on doing what we need to do, not just to save lives in the pandemic, but to save our planet. So I'll stop there and maybe we can move to some questions, Kristin.

Yeah, that would be wonderful. Thank you so much, Dr. Gerberding, for all of that information. And it's a lot to think about. And so I would like to maybe just ask, because you of course talked about how CEPI came, the formation of CEPI came in response to the Ebola outbreak. And I'm wondering from Merck's perspective, specifically working to develop the Ebola vaccine as a public-private partnership, what were some of the lessons that came out of that experience experience for Merck about what would be a better partnership or a more effective partnership going forward?

Yeah, thank you for that, because I think the Ebola vaccine development process really is an exemplar of a series of complex private-public partnerships. And let's just start with the government, because it was really the public health and the Department of Defense in Canada that first started the work on what became Erbivo, Merck's licensed Ebola vaccine. And that, that work led to a partnership with the US Department of Defense. And then ultimately that work didn't go any further, but a small biotech company in Iowa took on the challenge of developing a commercially viable vaccine and made significant progress so that when the tragedy of the outbreak began to unfold in West Africa, the recognition of how many doses would be necessary and how fast the actual clinical assessment of that potential vaccine would need to be scaled is just something that many smaller biotech companies struggle with. So it made sense that Merck, with our broader reach and our ability to capitalize and our vast experience in clinical trials, that we could step in and help coordinate that. But a private company can't do that alone. We have needs for the vaccine in 3 and possibly additionally additional countries in West Africa. We had governments of those countries and the health system in those countries who needed to be part of the planning and participation in the design of the trials. And then we had other federal agencies, particularly the NIH and the CDC in this country, but many other public health entities. And then Medicines Sans Frontiers, if it weren't for their leadership on the ground and their know-how and their ability to generate trust and sustain that trust in almost impossible circumstances, and on and on and on. So I think the various stages of the development of ERBIVO really demonstrated the relevance of harmonizing these partnerships. You know, in a sense, it's like saying, well, plan horizontally across all the different stakeholders that have something to contribute some wisdom to contribute to the strategy or the design. But at the end of the day, you also have to be able to execute vertically. And, you know, to plan that in an emergency in areas of the world that had no experience with complex clinical trials or, you know, placebo control or any of these jargon ideas that we who are accustomed to clinical trials take for granted was really a heroic undertaking. Behind the scenes, however, there is some additional layers of the cooperation that most people haven't seen. I'll just give you a couple anecdotes. Before vaccines could be used in the clinical trials, the phase 3 studies in West Africa needed to have safety data. And those safety data were developed with collaborators, for example, in Europe, in Germany, in Switzerland, et cetera, et cetera. And moving an unapproved product such as a candidate vaccine from one country to another and the diagnostic tools and reagents necessary to do the testing of what you're finding, these all require things like import permits and all kinds of regulatory bureaucracy that normally take forever to solve for. So the partnerships that came together to work all that out in an expeditious manner, just like that's a whole book by itself. And some of the And those changes really, I think, have helped with what we're trying to do now as the countermeasures for the SARS pandemic have been prosecuted. The other piece, of course, is the supply chain. And the wonderful stories, particularly involving the DRC and moving a product requiring cold chain from the United States to the Democratic Republic of the Congo is another long series of private-public partnerships that really represent the best of humans and their organizations and something that, again, many lessons learned that have paid off as we've approached the movement of vaccines and products, for example, for the coronavirus. So it takes a village. In other words, it takes a series of private-public partnerships. Right.

Well, I mean, just hearing you talk about that, the complexity, you know, you just say public-private partnerships and it sounds so simple, but the complexity in all the different partnerships that really need to come together to make this happen. And of course, you have all the different organizations. You have BARDA, you have CEPI, you have, you know, in this case with COVID you had Operation Warp Speed. So the coordination of all of that, I'm imagining, also has to be quite challenging. And so I'm wondering, just in terms of partnerships, how much of that can you put in place in advance without knowing what the product will require and where it's going exactly and all of that?

Yeah, I think one of the things that frustrates me the most about our overall preparedness planning is that we haven't been able to land on kind of the generic structure that we will reliably move to. So every time there's a new I'll just use the United States as an example. Every time we have a new crisis like this, we solve for the leadership in a different way. This time we had Warp Speed. We've had czars in the White House. We've hired ambassadors to lead the effort. We keep coming up with a series of solutions that are not sustainable when one administration changes to another. So we do need to decide what kind of governance within a country and then what kind of governance you know, on a more global basis is going to make sense to give us the most robust reproducible strategy, because that strategy and that connectivity needs to be exercised. Right. And as you point out, it's really difficult to invent this wheel every time you need it, because people change and, you know, our complacency sets in, so we forget what we've learned. So I think that's one really important thing is to create a structural solution We need a financial solution that sustains the investment to be able to support a consecutively improving process of global health security. But we also then really need to be thinking about how do we build, I guess, the culture of protection. We tend to still, even today, 2 years into this, that we've seen the devastating economic consequences geopolitical disruption this has created, we still mainly think of it as a health problem. And so we invest in it sort of with the scale that we use for other public health problems, which is woefully inadequate almost everywhere. We really need to change the culture of this to resemble something that is more like national security, because in a sense, biosecurity is national security. And we need to make investments that we hope and pray we never use, but they're there if we need them.

Yeah, absolutely. So we have a question on the development of platforms. The private sector has a greater incentive to focus on targeted products rather than broad platforms. So the question is, what is the appetite now or the model for industry to develop products in the absence of a specific target?

You know, I might disagree a little bit with that premise because, you know, I'm kind of molded in the influenza model, which obviously has some limitations to the current situation. But, you know, when we were planning for influenza, we had in our minds this dual-purpose concept because we knew the systems and the tools and the approaches that we were using to plan an exercise for an influenza pandemic would serve us well for ordinary public health public health challenges as well. And I think industry has a little bit of the same mindset. If you have an mRNA platform, and all you have to do is look at Moderna to understand this, um, you have value in the product that you're creating, but you also have an imagination and you can see how that platform can be repurposed for other things that may not have to do with pandemics, but cancer or other infectious disease problems. So I think modernizing and creating a more efficient, scalable platform that has a lower cost of goods and a more reliable production cycle, and basically an innovation that creates efficiencies as well as effectiveness. That's something we all are aiming for across the board. So it's relatively product agnostic, and I think that's why I put so much emphasis on on the potential value of investing in platforms.

Right, right, absolutely. So we have a question on whether you think we will actually need new COVID-19 vaccines or whether we should just invest in improving or altering our existing and expanding production of the, of the currently licensed vaccines. And how do you foresee the licensure of new vaccines in this sort of complex environment where we have licensed products that are so effective?

You know, it's too soon to say what is going to happen because, you know, as I said earlier, there's one issue, just durability of protection from an immunologic standpoint as it wanes over time. And we don't know whether or not some of the viral-based vaccines will have an advantage in terms of more sustained durability versus the mRNA vaccines or not. So that's That jury's still out. But then on the other hand, we have the virus and it's changing. And everything we can see right now tells us that we continue to have good cross-protection for the variants that we are aware of, but that doesn't mean that will stay the same. And so where we are today, it makes sense to utilize the vaccines that we have to the best of our ability to achieve full coverage and full immunization. Immunization, and that is variable depending on what specific subgroup you're talking about and what specific vaccine. But we also need to be fully prepared for the fact that if a variant emerges where there is truly a reduction in immunologic coverage, then we'll have to change the backbone of the vaccine. And, you know, if we're preparing for a more endemic solution, or we are getting our heads around the fact that coronaviruses are going to be an ongoing threat wherever they're spilling over from. You know, we have to be thinking about bivalent vaccines that have more than one component of the coronavirus in them or have more than one coronavirus in them. You know, we have to be thinking about how do we create maybe something that operates more like influenza vaccine where where each year what's in the vaccine is chosen based on what we can reliably predict or reasonably predict about the most likely challenge in a given community or given region of the world. So too soon to really predict that, but we need to be prepared for the fact that, as I said, we're sort of at the 1.0 level here, and there will be a 2.0 chapter, I'm sure, if not a 3.0 or a 4.0.

Right. So we have another question with regard to COVID vaccines. If you could speak to the manufacturing challenges globally and how that should be managed for the different platforms, whether it be RNA or adenovirus-based vaccines, and what, what do you think the solutions are for the sort of global manufacturing shortage?

Yeah, you know, at the moment, at least with the 1.0 generation of vaccines, we actually have a plan to provide the number of doses of vaccine that we need. So I might start at the other end of this, which is what is the point of having a lot of vaccine if it's mal-distributed or it is not used? And that uptake, the last inch, so to speak, is equal if not more important than the absolute number of doses that we can create in a period of time X. So I— everybody has been focused on the number of doses as if that was the solution to the problem, and if only we could make more doses in more places that we would have a better outcome. But I don't think it's that simple. The other thing to say is, and I have learned this the hard way during my my tenure as the president of Merck Vaccines, vaccine manufacturing of any sort is not for the faint-hearted. You have to make a product that does not start sterile and ends up sterile, reliably consistent, safe enough in many cases for use in tiny little babies. And there is zero tolerance for any variability in the safety profile or the efficacy profile, but particularly the safety profile of the product. It's a really hard situation. When I started in Merck Vaccines, half of our vaccines were not in the market because we had one challenge or another in the manufacturing space. So there's magic thinking that, oh, now we have mRNA vaccines, those are easy, everybody can learn how to do this. That is not true. This is extremely challenging and it requires a whole cadre of technical training and development which is not to say it can't be done. It just means that we need to expand the effort and build the broader knowledge systems, the training, the experiential learning, et cetera. And it's kind of hard to do that right now because all hands are on deck just trying to make the vaccines that we're coming out with at the moment. When Merck said, well, we will try to help J&J make its vaccine, and many other companies have done the same thing to take our know-how and our surge capacity and apply it to this problem, even though it's not a profit driver by any stretch of the imagination. In fact, it has opportunity costs because it slows down some of the other vaccines that we are working on. But it's an effort to really acknowledge that it's not just vaccines that are a scarce resource. Vaccine technical competency and capability is a globally very scarce resource. And I think that's part of our future planning is how do we build that capacity? And it's awfully hard to do it on the fly in the middle of an emergency.

Yeah, I'm sure that's right. Can you talk about the role that Merck's antiviral, COVID antiviral might play in low and middle income countries, particularly where vaccine rollout has lagged behind?

Yes, thank you. And I can now confidently say that the molnupiravir antiviral was authorized in the UK by the MRHA this morning. So we are now able to talk about, you know, it as an authorized product in at least one region of the world. You know, it's not a magic bullet, of course, but to have an oral medicine that's pretty easy to manufacture at a cost of goods that will be affordable, especially as volumes increase, that is hopefully useful in keeping people out of the hospital. And that's what our Phase 3 data indicate, that there's significant reduction in hospitalization and death from treatment at the onset of symptoms. I mean, this is so important, and it's especially important in places that don't have vaccines or where the distribution system and the medical infrastructure just isn't able to reach people or there isn't good hospital care for people. So we're hoping that it will be helpful in developed countries, but we're especially hopeful that it will offer something that fills the gap in the developing world. And that's really why, long before we had even a glimmer of information from phase 3 that would suggest that it will be valuable, we gave voluntary licenses to several generic manufacturers in India who supply 100 or so of the lowest resource countries. But then with the transfer up to the Medicines Patent Pool, that expands the ability of generic manufacturers in other countries to be able to utilize the patent to make additional doses available wherever they are in the world. So hopefully that will be a contribution to reducing the morbidity and mortality from the infection Of course, we have ongoing studies to see whether or not it would also have a post-exposure prophylactic effect. I suppose someday possibly even a pre-exposure prophylactic effect, although those studies are not in progress. So, um, it's a, it's an oral medicine right now, sort of a capsule. Um, and it's several capsules a day. So, you know, we'd like to formulate it so it's a little bit easier for people to take. And we We know that it's only right now a 5-day course for treatment. That seems like it's a pretty tolerable duration of treatment. But, you know, if we can find formulations that offer pharmacologic advantages to reduce that or change the dosing requirements, et cetera, there will be hopefully improvements going forward. But boy, it's something. And I really hope that people will be able to benefit from it.

Yeah, that's very exciting. So we have a question for you about what sort of changes at the state, local level in terms of partnerships that you think should be implemented immediately.

Yeah, so, you know, this has been a really tough time because I have enormous appreciation and respect for our public health system at the local and state, territorial level. And I know many of the people who are on those front lines. I am horrified by the threats that they have received for some of the guidance and recommendations. I am very sad by the number of resignations and the diminution of the leadership of our public health system under the stress and strain of this pandemic. And it truly breaks my heart to see that catastrophe unfolding. So in many communities, the system is, it's not just healthcare workers at the bedside of intensive care units who are exhausted. Our entire public health workforce has been running a marathon at sprint speed and they are worn out. They are treated badly. They are underpaid. They are under-resourced. And it really has revealed another underbelly of our public health system. And I don't think that's unique to the United States. I think that is the situation in many countries around the world. So another opportunity to take a cold hard look at the reality that we're operating under. Having said that, I do really believe that there's been amazing ingenuity. When you think about how many millions of doses of vaccine have been successfully delivered in most countries, the public health leadership and the local jurisdictions have really created that agility and those opportunities. I went to a community immunization clinic here in Pennsylvania, and I was just blown away by how efficient it was and how safe I felt being there and how confident that I was really getting the best possible care under the most trying circumstances. But it was a public-private partnership. Health department, but the local pharmacies participated and several other people chimed in as well. So, you know, it's happening and it's just a tribute to the agility and resilience of a lot of very clever, creative, and I would say very tired people.

Right, very tired, I'm sure. Well, thank you so much, Dr. Gerberding, for taking the time today to talk to us about these really important issues and for answering the questions from our audience. We really appreciate your time.

Thank you, and I just want to say stay safe. It's not over yet.

It isn't over.

That's absolutely right.

I'd also like to thank all the attendees for participating in today's webinar and for submitting such great questions for our speaker. We're always fortunate to have such an engaged audience for our lab meetings. And with that, I invite you to join us 2 weeks from today on November 18th Our speaker that day will be Dr. James Crowe, Director of the Vanderbilt Vaccine Center. His presentation will be on monoclonal antibodies for infectious diseases come of age: prophylaxis for COVID-19 and beyond. And if you're interested in more research on COVID-19, please do sign up for the HVP COVID Report, a biweekly newsletter that provides insights from experts around the globe and highlights highlights the latest scientific articles and data. And finally, please visit our website and follow us on LinkedIn, where we will upload a recording of today's webinar. And with that, I'll say thank you again for participating today. Thank you, Dr. Gerding. Stay safe, everyone, and we hope that you'll join us again on the next Global COVID Lab meeting. Thank you so much.