Hopkins vaccine initiative. Also joining us is dr. Mike levine. He is at the university of Maryland School of medicine and the founder for the center of Vaccine Development. Dr. Powell off it, the director of the Vaccine Education Center at Childrens Hospital of philadelphia and professor of pediatrics at the university of Pennsylvania School of medicine. And Wilson Rooney the managing director of tr gp investment partners. You can ask our panelist questions using the q a feature and i am excited to get things started. Esther, i will turn it over to you. Thank you so much. Welcome and good afternoon to everyone. We have a terrific panel today. With leading experts to discuss the challenges related to Vaccine Development and the implication of the race to develop a covid19 vaccine or multiple vaccines. As of this morning, there were over 27 million confirmed cases of 2019 and ate her thousand deaths. In the u. S. , we have six point 3 million confirmed cases. 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 covid19 vaccine and the implications for future Vaccine Development. We have a short amount of time and a number of terrific speakers. Get started. Mark, lets begin with you. We have all heard about vaccines under development from pfizer, moderna, all of which are facing phase three Clinical Trials. You have been working to develop a process to fasttrack safe and effective vaccines. Can you fill us in on what that process looks like and where things stand for now . Thank you for bringing this group together. Why research of Americas Mission is important, this is it. It is been impressive to see the amount of progress happening particularly in the area of vaccine. We have been working on this topic for a while. If you go to the website and go or exhilarating therapeutics topics like that, a lot of the information we have 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. The u. S. Backed by government. There are more backed by china and europe and other parts of the world because of the high burden of the pandemic. Not because we are cutting corners. What has changed is moving from a long and linear, uncertain, and questionably funded process with clarity and everything we need to get us to an an effective vaccine. That means clear guidance on what needs to be done from a regulatory standpoint. Agencies came together early on around specific guidance for what was needed for a vaccine. The fda issued detailed guidance. We recommend people who are interested they took a look at it. Some clarity about what is needed to be demonstrated in terms of an substantial size and potential safety. In a bigger population. 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. For the early trials to get started at large scale for pfizer and moderna coming soon astrazeneca has already started to enroll. 30,000 or more enrollees and many of these trials that just started recently are already up to that number. Pfizer is in the second round of vaccination for this two does vaccine that they are developing. The Clinical Trials are happening at an unprecedented pace and 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 going and jointly with many of the manufacturers to build manufacturing capacity here and elsewhere that have tens if not hundreds of millions vaccine promising the will be available by the time the Clinical Trials are completed. There is discussion about whether corners are being cut. From what i am seeing, the answer is no. A very substantial planning process. They got all of these critical steps done at the same time. Looking ahead, there are important decisions coming based upon the evidence being developed and 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 peasant patients clear a safety problem. Isg safety Data Collection going to continue for years as it often does with vaccines to there are any issues. Going to be done has been a subject 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. People should have a clear understanding that the fda and other groups involved have a very transparent process Going Forward. Before the fda approves the vaccine, it may clear it will have an advisory committee. There will be data reported from the companies that they put in their applications. There will be 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. I also emphasized that emergency use for a vaccine would be very different than emergency use for treatment like convalescent plasma. We have seen that used in many other conditions and thousands of patients with serious covid affections, his people who are hospitalized or seriously ill. Because there are many safety concerns, its a different standard than what i have been talking about for vaccines. There are some very important developments over the coming weeks. We will see how fast the trials can go not just in terms of enrolling patients but declining rates of covid in the country. Its a good thing for Public Health, but that means it may take longer for trust to complete. Effectivee just how the vaccines are in terms of reducing the number of covid infections. Boardta safety monitoring will be looking along the way to see when there is a signal that meets the standards. As long as we are following fda standards and clearly defined approach that the fda experts and their biologic center have laid out to get us to this point and help move forward, we do have a very promising outlook for vaccines. We are still weeks to months away from having the definitive evidence. To be sometime before the vaccine gets out to everyone. It may be starting with highrisk or highpriority groups like military personnel and medical responders. 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 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. At topic of the timeline. We have heard 1218 months. We are approaching some part of that and the expectation that we will have some kind of vaccine 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 expect in the beginning or middle of next year and is all of this realistic . Yes im happy to make any prediction you would like as long as you dont hold me to it. 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. Other different kinds of trials, then the definitive phase three trial. Thats the only way you are going to determine efficacy. Now is theppened 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. Andill pay for this massproduce the vaccine. We are willing to throw away doses. Obviously, no company would ever do that. On the one hand, i am not worried about the timelines. We are doing big phase three trials. If we are doing what we say were going to do which is eight 30,000 plus 30,000 vaccine trial. Thats fine. Other thingstwo standing on the way of releasing a vaccine that would be less than safe or effective and that is the data safety monitoring board that charged with overlooking these vaccines. Then if dr. Hahn is true to his oped in he wrote the the journal of the american medical association, he will take the advice of the committee. Its an independent group not associate with the government. I think they will give you their honest opinion. That is all good. Abouts to be concerned that this is not standard procedure. It is likely to go through emergency authorization. The language that surrounds emergency authorization points 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, vaccines are different. They are being given to millions of people who are generally healthy and not likely to die. You certainly want to hold them to a High Standard of safety. I will rate the first two cases that you saw influenced by the to dostration on the fda something that shouldnt have been done. 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 different standard. The pharmaceutical industry got together, Major Players and wrote a letter saying dont worry, they shouldnt have to write that letter. Thats what the fda does. It stands between the american product and the pharmaceutical industry to make sure you get products that are safe. When they write that letter, they said 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. Not just for the november 3 election but that china, russia, the u. K. Will come out with the vaccine before we do. Between the oversight committees and dr. Hahn and his commitment on paper to make sure we hold these to a standard, i feel good. Maybe im a worrier. It does worry me a little bit. I will stop there. Follow up on a couple of points and i will bring others into the conversation, is there a guarantee that we are going to have a covid19 bactine vaccine . Are we guaranteed to have a vaccine that has high efficacy . No. There is no guarantee. Bad coronavirus that is already done things you could never predict. It rages in the summer months. Who would have ever predicted that . And i seen a patient the post infectious phenomenon, no other virus has done what this virus did to this child. Influenza also kills older people but fewer than 10 are those of nursing home. Vasculitis. Not because it reproduces itself in the blood vessels, it appears to be all immunological therefore all organs are at risk. Heart attack, stroke, liver disease, kidney disease. We are meeting that challenge thatvaccine strategies have basically never been used as commercial products in the United States. Is there going to be a learning curve . I cant imagine there wouldnt be. Now,hings we wish we knew the short answer is no, there is no guarantee. Thats what you do the phase three trials. We will come back to the discussion about the level that is needed. I wanted to pick up with the point that is there are a lot of different kinds of technology right now that are and in development that have never gone through to commercialization. What has happened to the past that brought us to this point . Think about that Going Forward . Are we now testing things that you anticipate will have the vaccine for other conditions . Thats great question. As context, let me first state clearly that we look upon vaccines into different baskets. Number one on the vaccines that will be used routinely for ournts, safety is very much area of concern. Vaccinesypical infant are examples. The covid vaccine, the covid19 vaccine is what we would call a Public Health emergency of International Concern vaccine. It is a different ballgame. Its a different handbook that we follow. We have thought about and worried about a pandemic like we are seeing now because once before, a century ago we saw it with an influenza vaccine. We know it can happen. There have been a few signals that stimulated dress rehearsal. 1976 when iback in was a young assistant professor and there was worry about a swine flu pandemic. The modern dress rehearsals 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 all the it became clear consequences and we began to worry more. Out of that epidemic came the for f the coalition this is why it was created. For science to make vaccines to up, we havekly rev seen a number of milestones put to use. Technologies would call them platforms where one can take the , pick thef a virus arias of key interest, or use purified protein or nucleic acid vaccines all become possibilities. Each one of those is a potential shot on goal. There has been a lot of background work on these platforms. Part of what this and other groups have been doing is monitoring looking at what might be the next dangerous organism. 20022004,tbreaks in that was a harbinger of what might happen. The mers virus is a harbinger. He other coronavirus is here comes this beast of a virus beginning in east asia. Very quickly, the sequence of that virus was made public. Very quickly, it 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 vaccine Search Center of nih. Modification so that the prefusion configuration becomes stabilized which erratically enhances the stimulation of neutralizing antibodies. Moment and viral live vectors moment because they are ways to quickly make vaccines. The mrna has theoretical advantage and it has been shown from the sequence to first knock elation in about two months first inoculation in about two months and also the possibility of largescale manufacture. But these are not from the pandemic perspective super perfect vaccines even if they are safe and highly protected. They require two doses. They require a special cold chain. These are not showstoppers. These are solvable, but we are so far along, we are very close potentially to having very good vaccines. At the last point i was make is, this is truly a global problem. We have to have a vaccine not only for u. S. And europe, but we have to have a vaccine for the entire world because as long as there is a reservoir of continuing transmission, the homeland, the u. S. Homeland, the rest of the industrialized countries are at risk. Yes. Jested a nice job laying out the potential for these different technologies, how quickly you can develop the vaccine. Mrna platform as he described. What that means is that we need evidenceprocess for generation and 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. We are looking at enrolling different patients into trials, pregnant women, children for example, the elderly. Highlyow for covid19, impacted populations like minority communities, how important is it that these trials are representative if we can get the answers that we need either for authorization or licensure and we would like to get everyones thoughts on that. Thank you so much. Up a veryu bring important point. All of these considerations are not the same. We should start their and say and sayd start there that pregnant women, children, racial and ethnic minorities, those are not all the same and we should not treat it or lump those together as we think about Clinical Development. I am thinking about this panelist and inking about Lessons Learned for the future about whatcan think we do in this time will inform our future Vaccine Development. When i think of the critical issues, its going to be around inclusion and one of the legacies that this is going to be around inclusion because certainly, this is not a new problem. Problem is speaking particularly about racial and ethnic minorities having a disproportionate of infectious and noninfectious diseases is not a new problem. Lack of inclusion and Clinical Trials is not a new problem. Our focus on this and our efforts to make this right both because we need these data, these are Critical Data for us to think about how we deploy vaccines because we do have a number of vaccines. And iure i am an optimist think we will have vaccines and i think we will have more than one vaccine. How to best use these vaccines. We really need to know how they work in populations and we really need to be able to build trust. As we are doing the trials. Each is abridged to having trust when we deploy vaccines. Theuld say that for all of populations that we consider, we want to think about riskbenefit, different platforms, what we are trying to prevent in terms of vaccination. Are we trying to prevent acute disease . Are we trying to prevent severe disease . Are we trying to prevent transmission which i would remind everyone we are not looking at in any of our u. S. Trials. That is a bit of a jump in our thinking although certainly, we do have many examples of pediatric vaccines for example that have prevented transmission to others. Issues those are all that we will need to thi