As of this morning, there were over 27 million confirmed cases covid19, and over 800,000 deaths. Have 6. 3 million confirmed cases and we are approaching 190,000 deaths. We have seen significant economic disruption to businesses and families and normal daytoday activities have been vastly altered. Leading experts have said we need a vaccine to return to normal. Which is why the topic of todays discussion is so critical. We will also discuss the lessons we are learning and developing a learning now in developing a covid19 vaccine, and the implications for future Vaccine Development. We have a short amount of time and a number of really terrific speakers. So why dont we go ahead and get started . Mark, why dont we begin with you. We have all heard about vaccines under development from pfizer, astrazeneca and the university of oxford, all of which are phasing phase three Clinical Trials. You have been working to develop a process to fasttrack safe and effective vaccines. Can you tell us what that process looks like and where things stand for now . Mark thank you. Thanks for bringing together a great group. A very timely topic, and a reminder of why Research Americas mission is important, this is it. It really has been impressive to see the amount of research and Development Progress happening on covid19, particularly in the area of vaccines. We have been working on this topic for a while. If you go to the website and look for accelerating therapeutics or topics like that, a lot of the information that we put together on what has happened this time that is so different because of the very large health and economic consequences of this pandemic. Essentially, we are moving a lot faster, and with multiple vaccines at the same time. There are backed by the u. S. Seven government. More in development in china, europe and other parts of the world because of the high burden of the pandemic. Not because we are necessarily cutting corners. What has changed is moving from a long and linear, uncertain, and questionablyfunded process ,o one that is hyper parallel with clarity and everything we need to get us to a safe and effective vaccine. That includes clear guidance on what needs to be done from a regulatory standpoint. Fda and other regulatory agencies came together early on around specific guidance for vaccine,expected for a free clinical testing getting it into humans. Detailed guidance which i would recommend people , inrested to look at it june, on the develop and process. Some clarity about what is needed to be demonstrated in terms of an impact on reducing the severity of infections, or reducing the number of infections. [inaudible] Clinical Trials of a substantial size and the potential safety effects in a bigger population too. At the same time, the nih and other groups have come together to develop a Clinical Trial network. It is enrolling a large number of people in these trials. So, for the early trials to get started at largescale for moderna, for pfizer coming soon. Astrazeneca has already started to enroll more next month. Expecting 30,000 or more enrollees. Many of these trials that just started recently are already up to that number. Pfizer is already in the second round of vaccination for this twodose vaccine that they are developing. So the Clinical Trials are happening at an unprecedented pace. At the same time, there is a lot of early investment in manufacturing of vaccine at scale before we even know it works. The Government Agency that oversees these countermeasure and Public Health emergency activities is going in jointly with many of the manufacturers to build manufacturing capacity here and elsewhere, to have literally tens if not hundreds of millions of doses promising the vaccine will be available by the time the Clinical Trials are completed. And there has been a lot of discussion recently about cornersthe speed means are being cut. From what i have seen so far, the answer is now. It is really just a very substantial planning process. You have all these critical steps done at the same time. Looking ahead, there are some very important decisions coming based on the evidence that is being developed in the Clinical Trials. The fda has made it clear that a vaccine is not going to be approved, even for emergency use unless there is a clear , clinical signal that meets the standard of effectiveness. Also, no clear data in these tens of thousands of patients who have been tested clear a safety problem. Drug safety Data Collection is asng to continue for years, it often does with vaccines to make sure there are any issues. So, how fast this could be done beenn the subject has the subject of a lot of debate among experts and it seems unlikely we are going to have any of these trials completed to the point where that level of evidence is available before the election. But people should have a clear understanding that the fda and other groups involved in these efforts have a very transparent process Going Forward. So, before the fda approves the vaccine, it has made clear that it will have an Advisory Committee. For the Advisory Committee meeting, there will be data reported from the company that they put in their application there will beuse, a review from the fda staff about what they think of the data, and there will be public discussion about what it all means as a basis for further decision. Let me just emphasize that emergency use for a vaccine would be very different than emergency use for treatment like , say convalescent plasma. Are treatment where we have seen it used in many other conditions, thousands of patients with serious covid infections. It is intended for people who are hospitalized or seriously ill, not for a broad, healthy population. Because there are many safety concerns, it has a different standard than what i have been talking about for vaccines. So, some very important developments over the coming weeks. We will see how fast the trials can actually go in terms of not just enrolling patients but declining rates of covid in the country, it is a good thing for Public Health. But it may take longer for trials to complete. We will see how effective the vaccines really are in reducing the number and severity of covid infections, and the people who are running the trials, their data safety monitoring board will be looking along the way to see when there is a single that that meets theal fda standards. As long as we are following fda standards and a clearlydefined approach that the fda experts and their biologic center has laid out to get us to this point and move forward, we have a very promising outlook for vaccines. That said, i think we are still weeks to months away from having that moredefinitive evidence. It is going to be sometime before the vaccine gets out to everyone. It may be starting with some very highrisk or highpriority groups like military personnel and medical responders. And going out from that, as the evidence accumulates, and we have more supplies of vaccines available. We are at a critical time now but i think were going to be in this phase of uncertainty and continuing to learn for a number of weeks to come. That is a terrific overview. We will pick up on a lot of the things you talked about. Paul, i want to get you into this conversation. The topic of the timeline. Since the early part of the year, we have heard 1218 months. We are approaching some part of that, and this expectation that we will have some kind of vaccine or vaccine candidates available as early as november or december, can you help us understand what this timeline means for Traditional Vaccine Development . What can we expect toward the end of this year and what can we ofect in q1 or the middle next year, and is all of this realistic . Paul yes, i am happy to make any prediction you would like as long as you dont hold me to it. [laughs] mark covered a lot of this. The average length of time that it takes to make a vaccine is 1520 years. You go from preClinical Trials to phase one to phase two phase three. Through small dose trials to larger dose trials, then you get the big definitive phase three trial, the placebocontrolled 30,000person trial which is the only way you will determine efficacy for a large number of people. What has happened now is the government has taken the risk out of the pharmaceutical companies. We have been able to coalesce timelines because the government has said we will take the risk. , we will pay for this and , in some cases, we will massproduce the vaccine. We are willing to throw away doses, if it is shown not to be effective. Obviously, no company would ever do that. That is why it is so much faster. I think on the one hand i am not worried about these coalesced timelines. We are doing big phase three trials. If we are doing what we say were going to do which is eight trial, that is fine. There is also two other thing standing in the way of releasing a vaccine that would less than safe or effective and that is the data safety monitoring board who are charged with overlooking these vaccines as they would any other vaccine. Then, if dr. Hahn is true to his word when he wrote the oped in Washington Post or in the journal of american medical association, he will seek the advice of an Advisory Committee, another group of independent researchers who are not with the government, not associated with the pharmaceutical industry. I think they will give you an honest opinion. None of that worries me. One,ever has to be however, has to be concerned about a few things. This is not standard procedure. It is likely to go through emergency use authorization. Language that surrounds emergency use authorization according to the fda guidelines includes phrases like may be effective. Second thing you worry about if you look at what happened with hydroxychloroquine or convalescent plasma, mark is right, they were given to people who are already sick. Different, they are being given to millions of people who are generally going to be healthy young people who are not likely to die, so you certainly want to hold them to a higher standard of safety. First two that in the cases, you clearly saw influence by the administration on the fda to do something that shouldnt have been done. I think it neither of those should have been approved for use. If people are worried about whether the vaccine is going to be approved for use under a much looser standard. That the pharmaceutical industry got together, Major Players and wrote a letter saying dont worry, these vaccines are going to be held to , they shouldnt have to write the letter. Thats what the fda does. It stands between the American Public and the pharmaceutical industry to make sure that you get a product that is safety. It worries me that they felt the need to do that. What they are doing when they write that letter, they are saying to this country that there is a question about the fdas willingness to stand up to the administration that is going to be under pressure. The pressure is going to come not just from the november 3 election, but the fact that china, russia and the u. K. May well come out with a vaccine before we do. The fdaands, between vaccine Advisory Committee, and dr. Hahn and his commitment on paper to make sure we hold these to a standard, i feel good. But you are a little worried. That is it. Maybe i am a warrio worrier. It does worry me a little bit. I will stop there. Thank you. Just to followup on a couple of points, and i will bring others into the conversation as well, is there a guarantee that we will have a covid19 vaccine, because as many scientists have said, science is hard. You have been involved with science for many decades. Army guaranteed to have a vaccine that is safe and has high efficacy . Paul know, there is no guarantee. This bad coronavirus has already done things you have never predicted. It rages in the summer months. Who would have ever predicted that . The postinfectious phenomenon, i dont know any other virus that has been what this virus does. Influenza also kills older people but fewer than 10 are of those deaths are from nursing homes. Here we had 40 . It causes vasculitis. Not because it reproduces itself in the blood vessels, it appears to be all immunologically stroky disease. That is surprising. We are meeting that challenge with vaccine strategies like , that have basically never been used as commercial products in the United States before. Is there going to be a learning curve . I cannot imagine there would not be. The things we wish we would learn we would know now i guess the short answer is no. That is why you do the phase three trials. We will come back to that discussion about the level of evidence between the emergency use authorization and life insurers. There is a lot of different types of technologies right now that is in development that has never gone all the way through to commercialization. First, what has happened in the past that brought us to this point that we can accelerate the covid19 vaccine with these new technologies and how do you think about that Going Forward . Are we now testing things that you anticipate you will have treasured the vaccine as we go forward . What led us to this point . That is a great question very broad reaching question and very broad reaching. Let me state very clearly that we look upon vaccines in somewhat two different baskets. One are the vaccines that are infants,inely and for safety is very much our area of concern. Our typical infant vaccines are examples. Vaccine, covid19 vaccine is what we call a Public Health emergency of International Concern vaccine. It is a different ballgame. It is a different handbook that we follow. We have thought about and pandemic like a are seeing now because once before, a century ago, we saw it with an influenza vaccine. So we know it can happen. There have been a few signals that stimulated dress rehearsals. 1976 when iback in was a young assistant professor and there was a worry about swine for, a pandemic swine flu, a pandemic. The modern dress rehearsal in my view began seriously with the Ebola Outbreak in west africa, which devastated the health care infrastructure, destroyed the economies and when cases started to appear in europe and north america, it became very clear all the consequences and we began to worry more. 2015 epidemic014, came the birth of the coalition for epidemic preparedness innovation. This is why it was created. For science to make vaccines to quickly grab up, quickly rev up, we have seen a number of milestones put to use. Sequence of ahe ofus, pick out the antigen key interest and use that inuence either expressed sectors or to make purified croteins or to make nuclei acid vaccines all become possibilities. There has been a lot of background work on these platforms. Cepi and other groups have been doing is monitoring and looking at what might be the next dangerous organism. To sars outbreak in 2002 2004, that was a harbinger of what might happen. The mers is a harbinger. Those were beta coronaviruses. Here along comes this beast of a virus beginning in east asia. Very quickly, the sequence of that virus was made public. Very quickly, that was utilized by various vaccine developers. On the way, one of the things that was done was the modification of the sequence so that this is work done at the root the Vaccine Research center of nih. Modification said that the prefusion configuration becomes stabilized, which theoretically enhances the stabilization of the neutralizing antibody. This is mrnas moment. Makeare ways to quickly vaccine. The mrna has the theoretical advantage of going and it has been shown from the sequence to first inoculation in just about two months. Also, the possibility of largescale manufacturing. But, these are not from the , superc perspective perfect vaccines even if they are safe and they are highly protected. They require two doses. They require a special chain. These are not showstoppers. Along. Are so far we are very close potentially to having very good vaccine. Last point i would make is this is truly a global problem. We have to have vaccine not only for u. S. And europe, but we have to have vaccine for the entire world because as long as there is a reservoir of continuing transmission, the homeland, u. S. Homeland, the rest of the industrialized countries are in danger. Ruth, i want to bring you into this as well. Out did a nice job laying the potential for these technologies, how quickly you can develop the vaccine. We have the mrna platform as he described. What that means is we need a robust process for evidence generation. Conducting Clinical Trials in such a way that we can determine which vaccine is the most effective for different populations that may benefit. I know you do a lot of work thinking about these kinds of issues. When we are looking at and rolling different patients into trials, pregnant women, children, the elderly, right now for covid19, this highly impacted patient populations like minority communities. How important is it that these trials are representative if we can get definitive answers we need either for authorization or Life Insurance . I would like to get everybodys thoughts on that. You are on mute before you start to speak. Ruth thanks so much for that reminder. I think you bring up a very important point. I think that all of these considerations are not the same and i think we should start there. And to say that pregnant women, racial and ethnic minorities and of course there are overlaps in those categories, but i do not think it. Hould treat we should lump those together as we think of Clinical Development. In thinking about this panel, i have been thinking about Lessons Learned for the future and how we can think about what we do in this time will inform our future Vaccine Development. What i think is a really critical issue is going to be around inclusion and one of the legacie