We've pulled together a very impressive assembly of speakers on a on a very important topic here today And we're very grateful to them for joining us Dr. Anthony Fauci Director of the National Institute of Allergy and Infectious Diseases Monsef Slawi from GlaxoSmithKline Chairman of GSK Vaccines Johann van Hoof Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen Research and Development of the Johnson & Johnson Pharmaceutical Companies And Julie Gerberding, president of Merck Vaccines, formerly former director of CDC and Rohit Malpani, director of policy and analysis at the MSF, the medicine solent frontier Access Campaign. So please join me in welcoming all of them For coming here many of them a long distance to be here with us We are at a pivotal moment in the unfolding Ebola crisis as 2004 comes to a conclusion This is a pivotal moment to talk about the efforts that have been underway on an accelerated basis to bring forward the development of Ebola vaccines and therapeutics and to discuss today what lies ahead in 2015 We won't be dealing today too much with diagnostics, and I hope we can come back and revisit that critical issue in the new year In the midst of this urgent fluid and dangerous Ebola emergency Exceptional things have begun to happen at a point early in the fall. I would argue perceptions changed fundamentally and diverse experts Working on Ebola began to argue they began to realize that new technologies Vaccines diagnostics and therapy some of which were in development or had been in development for some time That these would be a strategically essential to bringing about a conclusive Control to arresting the runaway Ebola epidemic That implied that there would have to be An extraordinary effort to undertaken on an expedited basis and that they would be added to the front line of Essential public health interventions We've heard about in which we'll continue to hear about today of efforts to isolate contain Ensure safe burials carry out contact tracing Supply protective equipment introduce effective public communications and engagement of communities to build trust and confidence This triggered in in this fall and accelerated mobilization across many different institutions and a high sense of urgency And that includes the leadership of Liberia Sierra Leone and Guinea leadership scientists ministerial officials community leaders regulatory bodies it included multiple US agencies dedicated to research and development To delivery of programs NIH CDC the Department of Defense USAID regulators at FDA multiple key Industrial players of whom GSK Johnson and Johnson and Merck represented here today Foundations became very important players Bill and Melinda Gates Foundation Paul Allen Mark Zuckerberg Hewlett Foundation International organizations clearly playing a vital role WHO the Gabby Gabby the vaccines alliance Just this past Thursday the board of Gabby committed up to 300 million dollars for purchase of a vaccine once approved by WHO along with 90 million dollars in rollout Support and strengthening of immunization programs the World Bank African Development Bank have joined this effort on the NGO side MSF which has been the standout true heroes of the response over the course of 2014 in the saga not surprisingly have jumped forward to assist with with trials of antivirals Convalescent plasma and we'll hear of possibly of vaccines later in 2015 This mobilization has been remarkable in a in several ways It's an unusual speed and the flexibility and cooperation which we'll hear more about that's been seen across these different institutions There's been there was the I think a pivotal meeting October 23rd hosted by WHO which established a club club of donors Industry revised upwards projected manufacturing capacities a certain pragmatism in debate opening which we'll hear more about About whether it's possible to adhere to classic randomized control trials versus versus less less rigorous but still very important efforts a Lot of demonstrated regulatory flexibility a lot of effort to prepare begin to prepare communities This was driven driven by a number of factors I think the urgency of the threat the high risks of inaction the potential for significant returns that people felt there was a Certain optimism and determination that entered this equation and a commitment to operating good faith for a common cause Also, what was interesting and unusual was the degree to which these these Different institutions began to think in longer term to plan and prepare Beyond the emergency and to think ahead into the even the second generation of technologies and what we're going to be required There obviously was a shared recognition of the security threat the humanitarian imperative and the need for US leadership Both private and public in partnership with other critical institution Money interestingly does not appear to be or it does appear to be less of an obstacle that might otherwise have been the case Or what might have been predicted? That's an unusual and I think very favorable position to be in at this point It doesn't mean that sustainable funding is not still an outstanding question 5.4 billion Emergency funding in the omnibus bill passed by Congress just a short while ago terribly important in bringing forward several hundred million dollars in additional resources in accelerating and Developing and deploying delivering technologies. I've mentioned Gavi the EU the UK and others These developments notwithstanding the flip side is there remain considerable levels levels of uncertainty and obstacles Which we'll talk about here today a first and foremost is the epidemic epidemic itself And the continued uncertainty around its trajectory, but as to pertains as pertains to the new technologies There's a few things that are that are continuing to be at the center of the debate one is around the science and we'll hear more about the efforts to demonstrate safety efficacy dosage to work on thermal stability and Related to that as the ethical challenges in terms of what types of field trials will be possible And and what sort of access will be will be possible in this period There's a lot of this discussion around delivery around manufacturing stockpiles cold chains indemnification There's a lot around coordination. There's so many moving parts that we see here today And the question of how to coordinate those who's going to be at the center of of this effort WHO ostensibly should carry this responsibility and has risen in certain key moments to carry the water But operates with diminished capacities and a damaged reputation. There is a question around how to bring it back Build it back in a more effective way To be relevant and continue to be very relevant thinking ahead strategically. We'll hear more about that today We need to be thinking about a second generation about greater Greater quality in the in the thermal stability and fewer doses and sustained funding in this period so we want to take care today to take stock of what has happened in these last a few very busy months and To look ahead optimistically and very realistically you to what may unfold in 2015 I'm convinced 2015 has considerable promise to be a watershed Not without continued high uncertainty trials and difficult difficulties So we're going to begin with a sequence of opening remarks start starting with dr. Fauci followed by Monsef Slowy of GSK Johan followed by Johan van Hoof From Janssen Johnson and Johnson and Julie Gerberding from Merck and Rohit Malpani and MSF. So please You have their bios. I've introduced them Very briefly. I'm not going to go into great depth Please be patient. We're going to roll through these presentations Then thereafter we'll have about an hour for conversation perhaps more we'll close at five We'll have a conversation among the group and then we'll open to you to hear from you and and please come forward There will be folks with microphones will bundle together three or four comments and Questions at a time and come back to our speakers Please identify yourself and keep your your interventions very succinct So with that I'd like to ask Tony to come forward and roll through his presentation. Thank you so much We get the is it just the next one Next slide slides Steve Okay We sent the slides Tell you what what we've been through over the last few months a bunch of botched slides. I don't mean anything Okay, so Do you at least have them that's what I get for doing the TV Tony we we We received them and loaded them. So there's been some glitch will We'll work that through momentarily if you want to offer some opening. Yeah Well, why don't I just start without them and then we could just to go to show you that I don't really need this So I'm gonna take 10 or 12 minutes and I'm going to outline for you Some of the this just to set the stage first of all the seriousness of this Epidemic this outbreak now as you all know the history of it started with a single case in Guinea Was under the radar screen literally for a few months until March when in earnest the three borders of Sierra Leone Guinea and Liberia Made for what I have spoken about written about as the perfect storm of so many reasons Why in fact We have an explosive Epidemic that is more out of control than anything in the history of this particular Microbe this virus when it was first discovered in 1976 and again people don't maybe not everyone appreciates that since 1976 we've had about 24 outbreaks for a total of about 2400 people infected and 1200 people dead so if you look at the 18,000 infections and eight seven to eight thousand deaths now, which is likely somewhat of a modest undercount this pandemic in this area or epidemic when one thinks of the Africa in general has really been Extraordinary in that it's more than anything that we have seen Combined over that period of time now the efforts that have contained these other outbreaks in the past Have been a variety of things that are essentially Fundamental good infrastructure good response good ability to identify isolate Contact trace and protect health care workers. This was not easy, but it was relatively easy when one thing in terms of the fact that you have very few Situations of traveling back and forth if you look at the original outbreaks that took place in Zaire and in Sudan the kikwik outbreak in the Democratic Republic of the Congo They were all ultimately controlled So now we have something that we are making progress because if one looks at Liberia With the insertion of resources from a variety of governments The United States has been very heavily involved in Liberia the UK In in Sierra Leone, but there have been a variety of agencies involved that have put resources in Things like safe burials, etc. I know there is so I so I just but that didn't happen. Okay Here we go. Okay, so this is where it started. So can I start now Steve? Sure. Thank you Okay, so it started here and then these things happened in May and that's when people were starting to get a little bit concerned in July Things really got bad and then in September and October at least my life changed and turned into an intern in medicine again Which is which translates into getting no sleep When you're involved in a very intense situation Then November and then December and here's what we're seeing actually right now with the Sierra Leone cases essentially overtaking Considerably the cases in Liberia now. I mentioned the public health responses that were actually involved in Keeping these things and the infected countries under control everything really Without looking at things like Ebola specific Therapeutics and certainly not a vaccine education hygienic practices contact tracing safe burials aggressive Supported care. I mentioned the United States getting involved with the construction of Ebola treatment units the Department of Defense Playing a major role when the president called in the Department of Defense and Brought in the ability to do the engineering command and control and the setup of Ebola treatment units became a very very important The CDC did an unprecedented job together with USAID in the number of people that they have now deployed to this area So it's been an extraordinary effort However, we're asking the question now and this is what I want to focus my few minutes on in that will we need Interventions in the form of vaccines and therapeutics for the current outbreak, which is entirely possible Because until you completely snuff out Every case in West Africa as we know about Ebola Until all the embers are out There's always a threat of an outbreak and we've seen that and we know it can happen So that's very important So the two things about vaccine that I want to throw out for discussion is that do we need a vaccine? To put down this epidemic and even if we don't get one in time or we don't prove that it's effective Will we need it and I say yes for the inevitable outbreaks that are occurring now Why am I telling the audience this is because it's going to be very important to know whether the vaccine Works because the thing you don't want to do is to deploy a vaccine that might be harmful Or that you may assume works and then for the next epidemic you have a problem And that's going to be the attention that I hope we get a chance to discuss about the design of a vaccine trial So having said that when one thinks of vaccines that are either Already in well in phase one getting ready to go to phase two three. There were two of them Another booster now with the with the MVA getting involved would make it I would say two and a half or three There's another three that you're going to hear about Not that there any less in quality Because we don't really know about quality until you test but Temporally they have not yet gone into phase one trial and I want people to understand that because I often get asked is this the prioritization of vaccines Yes, and no prioritization and getting it into an advanced trial But not necessarily a predictive value of whether or not it is going to be better Which is why at a meeting we had at the NIH just the other day Monsef himself Are you'd strongly for many candidates to be in play at the same time? So let's focus very briefly on the two that are most advanced Temporally and that is the first what we're calling the NIA ID GSK vaccine Which is a chimp ad no three vector into which was inserted the gene of the glycoprotein? This has gone into phase one trials, but chimpanzee studies have indicated a very favorable protection Using this particular candidate that's good news Also phase one was relatively uneventful. We had individuals 30 20 individuals at the NIH We did it right there at the NIH. It was uneventful. It's been also tested in a monovalent form We did a byvalent in the UK and will be set up to be also tested in Africa In in Mali and other African countries This is the New England Journal of Medicine paper that came out in just literally a couple of weeks ago About the phase one trial and we're now setting up for testing again An advanced trial using this the other candidate is a VSV saying principle the vector is a vesiculosomatitis Virus into which has been inserted the Ebola glycoprotein gene Phase one trials fully enrolled this again in collaboration with the Department of Defense We're doing it at the NIH others are doing it in from the Walter Reed Army Medical Institute By the Department of Defense the United States Army again Now in collaboration also With Merck and you'll be hearing more about that from Julie The new link company is the company that's involved that originated in the public health agency of Canada as they mentioned DoD together with NIAID and the phase one trials are enrolled Merck is involved now You may have heard that the trial was put on hold because of an arthritis people get confused about that There were four individuals that had what was clear inflammation. That doesn't mean it's the end of the vaccine by any means Our througes my alges are very common We saw it in a significant proportion of people when you give a live virus vaccine In fact, you don't even have to give a live virus vaccine and you could see it in the individuals the question is what is that going to mean and That's why you have phase one trials so you can investigate that pretty easily the proposed forward of paths are To and again, this has been in very close collaboration with the Liberian Health officials is the plan of a randomized double-blind placebo-controlled trial in Liberia and a Stepped wedge trial in Sierra Leone with at least two in Liberia the VSV and the chimp ad no and Possibly one or maybe two in Sierra Leone We're working with the CDC now to decide about that the pipeline of therapeutics Again, I want people to really appreciate that none of these have shown to be effective They've been given on compassionate use and we do not know if any of them work Mechanistically you can figure out a way that they may work or not But you're never going to know whether they work and I'm also might make a comment that I think we'll get the chance to discuss the Distribution in a trial in which not everybody gets a particular intervention is Different when you're dealing with a vaccine that you're giving to an absolutely healthy person Compared to a therapeutic when you're giving it to someone who may be drastically ill So when you think about the design of trials, that's the reason why the discussion of that is a bit different Very quickly Z-Map you've heard about it. It's been given to several people on on compassionate use It's an antibody cocktail of three anti-glycoprotein Antibodies that has been shown to protect monkeys small interfering RNA the TKM Ebola There are phase one trials that are ongoing BCX-4430, which is a nucleoside analog which protect monkeys against Ebola also in a phase one trial Brincedophobia, which is a polymerase inhibitor developed for other viruses But shown to have some activity against Ebola and has now been used with Marburg But not yet with Ebola and fathepovir, which is an RNA polymerase inhibitor, which has broad antiviral Usage it protects mice it has not yet gone into a non-human primate the reason I show you this you can argue that these have potential But remember despite the fact that they are either Given in compassionate use and or in a phase one trial Doesn't mean they work and the critical issue is to balance the need for a therapeutic With a desperately ill person and the need to show that it actually works and that you don't hurt them The other is convalescent plasma first trials have been kicked off just a couple of days ago In Guinea and Sierra Leone and Liberia Which is going to be determining whether the antibodies in a person's plasma who has recovered will be protected We have put together with the people in Emery as well as in Nebraska an adaptive trial design to take a look at a couple of these therapeutics With the control on being an enhanced Care in other words intensive intravenous replenishment and fluid and electrolyte balance so it isn't a placebo Because it's different than a situation in which you're giving a vaccine So I'll stop there and hand it over back to Steve. I was in my actually 12 minutes. Thank you. Thank you Thank you very much Tony and sorry for the glitch Monsef floor is yours. Thank you Steve. Thanks for the invitation as you know Just has a long tradition of commitment to global health Whether on the R&D side of things through our 30 years Commitment to a malaria vaccine or now the work on Ebola or on tuberculosis vaccine but also on the supply a manufacturer supply of approved vaccines through our partnership with Gavi and We're very happy to be part of this endeavor to help deal with this this and future Ebola outbreaks and Tony Congratulations to you and to the NIH team for the great and leading job you're doing in actually driving the community to to participate get involved and and help deal with this tragic situation and potentially dramatically impactful not only on on the Western African countries where it's Present but on a worldwide basis But I thought I'll do in the next few minutes is really talk about three things one is Share with you the status of our program to talk about some key enablers that are Have been and are very important in helping us and I think others get incentivized to participate in this effort and three share some learnings and Future-looking ideas on how we can be better prepared in the future to tackling situations like these And then I'll be very happy to of course expand on any one of these dimensions as we get into the Q&A part In terms of the status where we have a first phase one trial as Tony described in partnership with NIH that has been completed and Have the data have been published and I think they are very satisfactory both in the safety But also the kind of immune response induced. We also have three fully enrolled phase one studies Being conducted in the UK in Switzerland and in Mali Data of which including their immune responses would be available the second week of January I say this with precision because our Perspective is that we need to await the integrated analysis of all these trials to help us define what's the best dosage To use in the phase three trials in the field We also are planning to start two large phase two trials in Africa one in adults including almost 3000 subjects and one in children in pediatrics Involving about 800 subjects. They would also start around the middle of January and then to Phase three trials one where we have a commitment with the NIH in Liberia to participate into the trial design that Tony Briefly described and then potentially also participate in the CDC lab trial in Sierra Leone Those are the trials that we have planned We also have a collaboration in discussion with J&J to see how we can not only have a good vaccine That can induce immunity and protect in the short term, but also have a very sustained protection over the long range by providing a booster Vaccine by combining our vaccine with one of the vaccines that J&J is developing So quite a comprehensive effort That should deliver data and information on the effectiveness of this vaccine Before the middle of the year would be my prediction if all goes well and these trials are executed As we hope they will and as we doing the best with the NIH and the CDC to help Set them together now running the trial cannot happen unless you manufacture the vaccine over the past four months we have Dedicated enormous resources from our organization to make sure that we take a bench level type Process to manufacture the vaccine which is where really it was to a level where we can start producing a large amount of the vaccine Our plans are to actually release the first lot for the phase 3 trial Conduct before the end of the year actually our date is December 23rd if all goes well, that's true And then continue to produce Doses of vaccine that are first into the tens of thousands per month And then as of the spring into the hundreds of thousand per month and then as of the phone of 2015 into the million per month to potentially participate into mass vaccination programs if they are deemed to be important some major challenges Face tests and continue to face us in scaling up the production of this vaccine Things like just feeling the vaccine in two vials under several conditions and the conditions required for this vaccine are very challenging to Achieve without derailing the feeling of other life virus viral vaccine That's a very important and established for public health like misers mems repella vaccine or rotavirus vaccine or others also great partnership as You have eluded to with the regulatory agencies to ensure that we have the highest standard of scientific stringency But at the same time the fastest possible track to the release of the vaccine those and making them available for usage so that's on the on the status of the vaccine on the Enablers, I think some very important point first This vaccine would not have been possible for any one of the vaccines that are being developed without Partnership whether it's a partnership with the NIH partnership with Barda We're partnership with the University of Lausanne partnership with the University of Oxford as far as we're concerned partnership with between pharmaceutical companies and I think it's really key as Tony alluded to I was talking at the NIH director meeting last week that the companies here Forget the competitive dimensions and really work together towards achievement of an impact on global health That's one. I think the second thing that's very important is to think forward about access and making these vaccine Deliverable to the populations that need them and very pleased that Gavi bought came to the conclusions that they have To make the funds available for these vaccines to be provided And I think the third dimension has been this critical meeting that took place at WHO Late in October to make sure that all stakeholders around the table come to more or less a common view And it's very difficult to have that many countries come to to a Singular conclusion as well as companies as well as key stakeholders MSF was there J&J was there We were there Merck was there and many many countries and donor countries But I think it was a very important moment to to coalesce our efforts and help us just align them into the Right direction and then the last point around enablers, and it's not an easy and simple one is one around Liability in denification immunity for all the stakeholders involved into this endeavor one of my concerns is that when This vaccine would be introduced whether in clinical trial But even more importantly in a mass vaccination setting in an all in a country where pharmacovigilance Is very limited where under set where many many concomitant diseases exist malaria rotavirus in phyaria tuberculosis you name it a number of parasitic Infections events happen in the population all the time that are unrelated to Ebola They will happen concomitantly with immunization with any vaccine and how are we going to be able to decipher? Which of these events are related to the immunization and which are? The background of events happening in the population is it is a major focus that we need to to have and Could have consequences around my ability claims that we need to Really tackle and we were very very pleased By the US government decision to extend the prep act to the Ebola vaccine I think it's very important to deal with the situation in the US, but it's very important that other countries Where such liability can materialize also take such actions? Finally very briefly on the future perspective This is in the past four or five years the fourth at least major Bio threat, you know the pandemic SARS Antrax Ebola God knows what's going to be next and every time the community is taken by quote-unquote surprise where we have to Really divert our resources that are dedicated Whether to discovering other vaccines or manufacturing existing vaccines or whatever it is that that we're doing to Under emergency situation either manufacture a vaccine that we know how to do or actually accelerate like we're doing here Dramatically the development and supply of a vaccine as we're doing for Ebola We think and we are discussing with various parties that we should have a more proactive approach to this We should set ourselves to to have an organization and infrastructure and an approach that can Pre-prepare technically various technologies for immunization and vaccination to to be highly accelerated for a particular need You know when when when unfortunately the need arise Starting from discovering vaccines against a number of pathogens that are on various existing leads of potential threats To having the facilities to manufacture them because one of the things that we need to be very cautious about It's the opportunity cost that these events represent For the industry and for the community in general when we do them this way were highly inefficient But also we let go of other programs that are also very important for public health And we need to really find a more efficient way So I'd like to conclude just by saying that like in other instances our Companies 100% committed to making this vaccine available To work with all the stakeholders all the companies Our intent here is absolutely not one of return on investment, but one of Assuming our social responsibility Hopefully we will all together be able to tackle this and future outbreaks. Thank you very much Monza But it's more or less. I think you're in the boundaries Okay, I do have presentation. Yes, please Great well first of all, thank you very much I'm really very pleased to be here today to give you an update on the the Janssen Ebola vaccine and before doing that I really would like to echo what monster has really said It's very clear that to this this devastating disease. I really see a lot of sympathy and working together Because all stakeholders and I'm really pleased to see that indeed there are no borders between Companies and we really want to join efforts to make this this fight successful And without all of the stakeholders joining efforts is certainly we will not have been able to be where we are today Now Johnson Johnson as you know with the global health care company and we actually Since there's the start of the crisis back in during summer We realize that as part of our corporate responsibility and in line with the mission of us of our global public health organization We really wanted to leverage all of the capabilities and know how we have internally to fight this disease Today I will focus on vaccine But also we have heavy investments heavy activity ongoing in the area of developing treatment looking at Nucleosides that would be active on the virus and also in terms of diagnostics We know that today and going forward certainly also in the fixie trials It will be very important to have bedside diagnostics that allow you Within minutes to know whether the patient that you're confronted with cares the Ebola virus or not So these are really areas that we are very active Beyond that one. We also are very active You know philanthropic efforts and have the collaborations with several NGOs such as project hope the CDC foundation and partners in health When we look to the Janssen vaccine and actually was already briefly mentioned before We actually have been working on this and thanks to partnership with and sponsorship from NIH where over the years we have been working with several generations of vaccines and We actually just before summer came to a vaccination schedule that was shown to be 100% protective When a highly stringent Virus challenge model was used in non-human primates and what you see here There's actually that there are three vaccination regimens that turned out to be 100% protective One involved Platforms that we have fully in-house which is at no 26 and at no 35 The other one was priming with another 26 or boosting with MVA or vice versa priming the MVA and boosting with at no 26 As you can see in the graphs below all of the animals that are vaccinated with placebo dying within days Why there's full survival of the animals which were vaccinated? In view of the emergency we decided that at moment that we really wanted to accelerate this development Development was initially focused on multi-valent vaccine But we knew very clearly that if we would focus on single-valent vaccine focusing the Ebola strain that we could go faster In addition by ourselves focusing on one of the vaccines and seeking a partner that could produce the other one We also felt that we could shorten the timeline significantly And that's indeed what we have achieved What we actually have is that the vaccination schedule itself composed of two doses There's a prime being given with an additive vector and a boost being given with the Bavarian Nordic MVA The principle is that we are convinced that to have optimal robust protection and durable protection That you really need a combination of the prime dose and a booster dose One of the advantage of the Platforms that we use is that both of these platforms have already been used extensively in the clinic But also in commercial product the Bavarian Nordic MVA is used already in the box virus And they are more than 7,000 subjects vaccinated to date. We have a very satisfying immunogenicity and safety profile and also I don't know vectors have shown to be well tolerated in the different programs We have like HIV tuberculosis and malaria We actually selected those we also selected the dose that the based on our past experience is known to give good Immunogenicity of course, we will have to rate what the immunogenicity is once we conduct the trial with this specific insert One advantage that we see in this is that The work we have invested in these platforms over the past years have helped us to optimize the manufacturing process Just to give you an example at a pilot scale of two times ten liters We have about the yield of at least 150,000 doses that we now have five consecutive ones So we already have substantial amount of vaccine in the freezer that can be released by March of next year Production of MVA is ongoing as we speak in the first results We hear from Denmark is that the yields are in line with expectations Such that we are confident that we will be able to release 500,000 doses by early March of next year An important aspect also is that formulation work has been conducted all these vaccines in the past and that at least is our data for Using this platform, but with other inserts We have seen that the product is thermostable and add in a platform up to two years To two eight degrees for MVA it's up to one year It means that logistically would allow eventually to dispatch the vaccine in a frozen way but locally could be using the Classical distribution channels for the vaccines that already have to be at two to eight degrees This is just a schematic scheme of how it looks The important factor is that it's an heterologous prime boost One of the reasons for that being heterologous is indeed that you avoid immunity against initial vector But certainly there's much more complex immune systems behind this that necessitated bring the benefit of an heterologous prime boost Where we are today is that we actually and coincidence is that our batch releases also December 23rd next week And we are actually in discussions with the centering in Oxford And we really want to have the first patients dose the very early days of January Everything is aligned to make this happen And we will actually accelerate also the readout of this post dose one those data should become available Somewhere by mid-February such that in that time frame we can start thinking around participating to a trial that would allow us to assess the efficacy With regard to production the current Thinking the current plans are to produce at least million doses for next year But recent evaluation and also based on recent yields if need would be we could grow up for next year Up to five million doses and year after at larger scale with be more in the order of magnitude of 15 to 20 million doses And that's actually what I wanted to say again I would like to stress that as most have has indicated we are convinced that We should go beyond the borders of the companies here We really should work together with all stakeholders to be successful in this fight And I also hope that when I see how this partnership with all stakeholders works well now And how it has helped us to compress timelines from years into months. I hope that also this This teaches us a lesson going forward and that we can repeat this in other areas where there's also high unmet need Thank you. Thank you Julie Gerberting president of mark vaccines Julie, thank you, and thank you so much for hosting this and To my co-panelists for their contributions and their partnerships as we try to work through this I thought what I would do is maybe try to put a little more context around some of the things that we're talking about And we open this up for conversation at the end of our discussion One of the things that I reflect on is that this is Predictable surprise You know, this is a zoonotic disease meaning this is a disease that emanated from Contact with probably bats that harbor the virus and that virus spilled over into other Mammalian species sometimes it spills over directly into people, but we've known about this zoonotic Ecosystem for a long time. We didn't know that it had reached the west coast of Africa and quite the way it did But it's there now and there's no reason to believe that we're not going to see this again So we have to be fully prepared for the possibility that even if we're able to quench the particular Outbreak that we're experiencing that this is not the last time we're going to be dealing with Ebola I don't mean to sound like a pessimist, but I think it's very important to have that Longer-term perspective on what lies ahead of us with respect to zoonotic diseases in this one in particular. I Think we also need to really think about The the issue of plausibility From everything you've heard and everything we've seen in the preclinical and the in the early clinical studies that are going on Creating a vaccine for this pathogen is Biologically plausible and that gives me a great deal of optimism that even if the 1.0 vaccines that we're working on today don't prove to be the best vaccine or the ultimate vaccine We need to keep going because it is plausible to develop a safe and effective vaccine that really can prevent infection Either pre or post exposure and that's something that we need to just stay the course tenaciously stick to and solve for it With respect to the vaccine that Merck is partnering with These are early days. This is the VSB virus is a virus that is designed so that there's active cycles of Replication of the vaccine vector when it's in the human host and that has the advantage perhaps of prompting a robust immune system fast You have to watch carefully for side effects of the arthralges that were reported from one study site We're particularly worrisome, but that's why we do clinical studies and phase one and phase two studies So that we are alert to things that could signal reactogenicity or something that would Be a harbinger of a more serious issue down the road I think we also anticipate that The creation of a solution to this is going to have to be pragmatic Lives are at stake today while we're sitting here having this scientific Conversation and we can't move at the pace that we're used to moving at I don't know how to speak for my colleagues and in the other manufacturing pharmaceutical companies, but This is an incredible disruptor of business as usual because we can't we have to be pragmatic We can't take our time. We can't have lots of conference calls and meetings and you know Do all the stakeholder and key opinion leader engagement and on and on and on can't do things in series We have to do them in parallel. So we have to be willing to work faster To move more people mobilize more people To really come to the table inside the company let alone what's going on with the incredible partnerships that we're experiencing outside the company But I can just tell you I think you said it really well about the the disturbance of other Important pharmaceutical work that would otherwise be going on the pull of this vaccine Insights the passion of people certainly in the vaccine business, but across the entire enterprise of Merck We were passionate about this. We know it's the right thing to do We know we have something to contribute. We know we can't do it alone and people are Leaning in to the opportunity to be a part of this process, but at the same time we didn't budget for this We didn't structure our company for this. This just came along as a as a sudden Requirement and we have to step up to the plate and do our share But it comes at an opportunity cost that is something that we feel We have concerns about it doesn't change our commitment But it is something that we have to factor into it and something we need to plan better for going forward into the future This this challenge that we're facing is is also about unprecedented partnerships But I think in this world where we're always talking about public-private partnerships and you know, that's kind of a buzzword There's some very special partnerships that are going on here and one of them is the partnership between people who are Traditionally competitors, but there's a much more robust set of partnerships happening Between people who may share a broad agenda, but who aren't used to working for each other The transnational government partnerships even in the US government government the incredible partnership Barda at the leadership with with the NIH with CDC With with Gavi. I mean how wonderful is it that Gavi has already made a commitment to make sure that this vaccine Will be available to the people who need it most by creating the a macro Investment commitment to bring it forward. I think what the beauty of that to me is the fact that underlying this kind of Glaring public health requirement is the trust that's been developed in the past several years as we've worked together on other problems And so we have developed some understanding of how each other works and some appreciation for who has a stake in what and are Willing to sort of build on that trust and connect these Partnerships even when there's enormous uncertainty about where this is going to land and where we will ultimately end up The last thing I wanted to really talk about was sort of poignancy the The fact is this is about 18,000 people who had Ebola About 35% who are no longer with us, but it's also about you know the whole milieu in which they live and and shared their lives in their families and their memories and their loved ones People who have suffered deeply from this tragic outbreak and the poignancy of being where we are today In the context of a predictable surprise and not being able to do more faster to really contain this this outbreak and Make their lives more secure and reduce the incredible human suffering that surrounds It's not just for the directly affected people but for all the people in the communities who don't have health services and whose lives have been so Disrupted and whose economies have been so disrupted and potentially whose democracies are going to be so disrupted But the other poignancy to me and I because I don't work for the government anymore. I can say this Is It's the poignancy of having been here and done this before We do not have to keep reinventing the wheel. How many SARS outbreaks do we need to have how many MERS how many? Public health infectious disease outbreaks on a global scale Do we need to experience before we recognize that we can't have an Ectopic response we have to have a sustained commitment and we have to stick with it Even when whatever the precipitating problem was goes away to me That's in a sense the ultimate poignancy and I really share with you your final remarks about now We need to lean into the future here Create new new avenues new tools new partnerships to be able to sustain this effort over the long run Because I don't want to have to sit on a panel like this again as much as I've enjoyed it Thank you. Thank you so much Julia. It's very eloquent. We're here at Malpani MSF Thanks very much, and I really appreciate being invited to join this panel today Doctors outboarders in medicine so frontier has been responding to this outbreak Really since the start and raising the alarm and looking for more resources, especially in terms of teams and infrastructure Very early on we also realize as we often do with many of the emergencies We're responding to that. We simply do not have the tools we need whether we talk of vaccines or drugs or diagnostics So we've taken a very pragmatic approach to try to really deal with this outbreak in a way that our health care workers More who have died in this and in any other response that MSF has given before as well as affected communities can get the best outcomes So just quickly to talk about some of the things that MSF is doing These are the trials we are going to be launching at least two of the trials before Christmas this year for some of the drugs that Tony had put on his slides, and that's for Pava Piravir and Brindisapavir And we also are going to run a third trial using convalescent plasma And our criteria very much was simply based on whatever safety and efficacy data we had As well as simply having a supply available And that certainly has excluded use of some of the monoclonal antibodies and especially ZMAP since there's not a lot of supply One thing that I've been especially involved in is some of the safeguarding of access issues That we consider very important both in terms of the immediate term And ensuring that we can use these drugs also for emergency or compassionate use for other patients outside of the trial Since we certainly don't want to have differential outcomes for patients that are either within a trial or just are simply in the community We certainly are also concerned about the medium term access issues in terms of if a trial is proven to be successful That we can continue to ensure that there's supply available to the patients if this outbreak indeed continues As Julie is noting and certainly we're also very concerned about the long-term access issues in terms of registration of these products in terms of adequate supply In terms of the affordability of these products and the management of intellectual property And this is especially important because as Julie was noting This is unfortunately something that's going to keep coming back and we are not sure as an organization in the future All of these other responders will be there But it will simply be MSF in these communities that will have to respond and we will need access to these products in the future So we need to take steps now to ensure that we can safeguard long-term access In terms of vaccines again very early on alongside others in the global health community We very much were thinking about the importance of vaccination potentially to turn the tide of the Ebola outbreak and have been engaged in pragmatic advocacy really to pull out all the stops in terms of Really accelerating the trials and also in terms of accelerating the production Recognizing that both for the companies and for donors that this would entail certain risks to be taken in the short-term and in the medium term So we've certainly tried to take a very pragmatic approach to that And we really do welcome the commitments that have been made at Gabi Although we do have some short-term concerns. I guess in terms of the let's say structure that's been put forward one is certainly around The potentially the price of the vaccines which has not been specified actually in the strategy that has been put forward It's been left to be very vague And to the extent that we think these vaccines should be available very close to their marginal cost is something that we hope Gabi can achieve Related to that is certainly that we would like to avoid overpayments for these vaccines There is a lot of contributions that the companies are making there's also a lot of contributions that governments are making To actually help to pay for these vaccines and we certainly support direct compensation for the investments companies are making In so far than that we can ensure that the vaccines are available at its marginal cost And we should also remember that there are other incentives that are being introduced to potentially reward companies for development of these vaccines including the priority review voucher in the United States which can be a very important sum of money to encourage companies to develop vaccines or drugs against specific neglected diseases and Congresses just amended the legislation to include Ebola So these are all very important incentives But we need to be sure in terms of how this funding is being provided to make sure it's well coordinated as we're Have been discussing and the last issue certainly about equitable distribution We do see that we are moving towards industrial scale production for a lot of these vaccines But in the shorter or medium term there will be some problems in terms of providing adequate supply and to the extent that we Discover these vaccines are safe and effective We want to make sure that they are prioritized for the affected communities. We know that there'll be other interests in terms of Securing supply let's say potentially for developed countries But there's also issues in terms of how do you manage the distribution between different affected communities? And we hope the WHO is able to take a central role As an organization we are considering developing a clinical trial in Guinea with government of Norway and other partners That we hope we can get off the ground by next March Moving now into issues around second-generation products, which we think is very important I'm certainly in terms of vaccines. We would like to see a future vaccine to be more thermostable This is a challenge for MSF for many of the products that the companies on this Stage are currently selling to us and that we are often unable to deliver them in very remote settings because we simply cannot Move them out of the cold chain and to a controlled temperature chain So we hope a future vaccine is able to address some of those issues In terms of drugs and with the monoclonal antibodies we do think they show a lot of promise and there's a lot of interest in MSF to use these drugs We are concerned over potentially the use of biological samples from affected populations in order to develop these products It's potentially a concern that has arisen for us internally So we simply want to ensure that if materials are being used from affected countries that Various concerns around access are triggered in terms of managing the supply And of course we want to ensure that there's affordability these products and that they're available again in a sufficient supply for the affected countries And it's just perhaps to end on some remarks and just to note also that for monoclonal antibodies actually the the US has Expanded the orphan tax drug credit to include the development of these monoclonal antibodies which pays for 50% of the clinical trial cost But doesn't actually safeguard any of the access issues which we're concerned upon so demanding That there should be affordable that they should be available in sufficient supply That's also a concern we have with the prior to review voucher and really with all of the funding that's being provided It seems like none of that is being tied to actually ensuring access which really matters for our organization Because in the long term ultimately we're going to be responsible for acquiring those products and using them in the field for our patients Just to end in terms of some additional thoughts I mean three lessons for us certainly in responding to this outbreak in terms of the drugs and vaccines One is certainly about the the challenge we continue to have and really insisting on the importance of access Whether we're talking about the shorter medium term or long term that funding that governments are providing need to be linked to these access issues our clinical trial partners often Are not as familiar with these issues because it's not the course to think about these issues in clinical trials And it's not normal actually for MSF to be engaged in clinical trials But this is front and center for us as an operational organization. That's in the field trying to deliver Treatments in the long term. So there's certainly a lot of challenges there to normalize this more in clinical development I think now and in the future a second thing is certainly around transparency, especially a funding There's a lot of money that's being put towards this and that's important to move sort of from the famine to feast But we think that we need to understand better how this funding is being spent What conditions are attached to it and how it all works together and certainly that's especially important for the US government Which is offering so much money from different sources towards the response before which there's often not a lot of clarity for us as an organization The last issue I noticed simply this issue of the failure of our system of research and development I work for an entity called the axis campaign which our organization launched in 1999 because we were concerned that our system of research and development Does not ensure that drugs and vaccines are affordable that they're suited to the conditions in which we work and that they simply do not exist And that is what this outbreak represents to us It is simply we are faced with the same situation We had 15 years ago and this systemic failure is something we all own as a global community And it is something which we have still not responded to when you look at the the vaccine the VSV vaccine Which mark has now? Licensed in that was developed by the Canadian government Many years ago and was licensed actually to a small manufacturer for $200,000 Canadian dollars to which nothing was done then for a long period of time until this current outbreak that is a failure When I hear comments Unfortunately of saying that this is an opportunity cost or this was not expected as business as usual that confirms our concerns Ebola is a concern for us It is a public health problem and it needs to be front and center We need to have new incentives that try to prioritize these diseases there They should not be seen as opportunity costs They need to be seen front and center as part of our global response and as our system of innovation And that is really what's required to have changes in the future This is an emergency, but so are other things. So is drug resistant TV. So is basic antibiotic resistance So is a range of 17 other neglected diseases and all of these merit our attention But they require new ways of thinking and new ways of research and development And it's only if we can find new ways to actually develop drugs and vaccines Are we going to prevent being on these panels in the future because we are going to continue to face these challenges and as an Operational organization, we're going to have to continue to respond and put our staff and to see effective communities Suffering so greatly as they have in this outbreak. Thank you. Thank you very much for you It's it's really striking how much soul-searching and introspection This crisis has stirred and how much efforts at innovation and changing Business practices and and modes of operation how much all of you have been stretched in this period to do things that are outside the normal pattern There's three issues. I'd like to quickly touch on and then open to the audience One is the question of how these trials can be best carried forward. There is a debate going on now there there would be in an ideal situation as an obvious preference for the classic randomized trial Approach double-blind trial And that will be attempted in in in many in many settings as we go forward There's uncertainty though that we know the risk environment is complicated We know the operational environment is complicated We know that the acceptance by communities is very fundamental in being able to move forward with trials And so it seems to me that as we're entering 2015 with expanded multiple expanded trials That this unresolved debate around how do you operate with greatest adherence to principles of safety and efficacy While being pragmatic and adaptive to a highly challenging and highly urgent environment How is that likely to play through it? It's an honest and open set of challenges for which I don't know that there's any immediate and clear answer But it would be useful to hear from all of you how you anticipate Navigating the environment and moving forward Tony. Do you want to say a few words about that so? First of all when you do when you're dealing with trials There is the balance as I said in my brief opening remarks about trying to get a product that potentially is Going to be beneficial to people as quickly as you can While making sure it is beneficial or not harmful and that's really the fundamental rationale for a randomized control placebo double-blind trial I Think that that can only be done With complete buy-in by the people involved and those responsible for them, which is the reason why We're now in our fourth visit to Liberia in discussion with the Liberian health authorities About the feasibility and the advisability or not and the decision is or as opposed to or not to do a randomized control trial fully being aware that the advantage of doing a placebo control trial where not every single person gets the product is That from the standpoint of proving efficacy or not It is really the only surefire way of doing that. You can have other trials You can have cluster randomization. You could have step wedge, which are actually okay But they're much less stringent from the standpoint of getting the data the advantage of the other trials is that You can get everybody will ultimately get the vaccine So if it works, that's good The other trial the randomized trial you can probably get an answer of efficacy more quickly Once you get the efficacy you're going to distribute that vaccine to everybody and anybody who might benefit from it So there's the balance that ultimately if it works Everyone is going to get that's the You know the framework Then you look at the advantages and the disadvantages if in fact you're Distributing a vaccine before you know it works the advantage is that if it does work you get it to people quickly The disadvantage is that you may not ever prove that it does work So when we're going to be sitting on this panel with the inevitable next outbreak We will not know if we have a vaccine that works That's the that's the problem the issue with a randomized controlled placebo trial is that some people are not getting it right away And there is this absolute Understandable desire that if something is is going to be beneficial get it to there quickly as possible I gave and I'll Just finish with this because it's very important. I mentioned this at another seminar we had here about the issue of the difference between Therapies that you make readily available for which I was the champion of during the HIV AIDS versus a vaccine that you don't know works and There's a big difference there because in what you're giving it to people who are perfectly normal and others you're giving it to people who have a terrible illness and The thing that I will never forget as I mentioned that people may have heard of this is that we had a vaccine For HIV that looked really good in an animal model it passed phase one was really safe No Prohibitive adverse events and even went into phase 2a and Looked good. So the decision was that if you look at Ebola as dramatic as it is Seven eight thousand people have died from Ebola over the last four days 16,000 people have died from AIDS So you could have made the argument as soon as you had that safety data in the HIV trial Give it to everybody who needs it because it's a terrible catastrophic pandemic The only trouble is in the randomized control Double-blind trial we found out that there was a 41 percent increased risk of getting HIV infected if you were vaccinated with the vaccine and it had nothing to do with behavioral Changes it had to do with the vaccine So that's one of the reasons why when you're dealing with giving something to someone who is an otherwise Normal person even though they're at great risk Seriously balance and I don't know Steve what the right answer is But I do know that you at least need to seriously consider the pros and the cons and that Consideration has to be with the people in the country who are going to be involved with the vaccine And if they don't want it, they shouldn't get it They should get whatever trial they feel is appropriate for them. So we're in a negotiation We're balancing out. Yes, the urgency the operational environment the demands from the community and the leadership Itself and that is all to be determined as far as the mix of tools and approaches Would you like to say something? Yeah, I think I I'm very supportive of the view that Tony is Expressing and I'd like to add two dimensions to it Malaria kills between 12 and 18,000 children every hour and We need to be very cognizant of the proportionality as we're talking about a very important point regarding Ebola is In January February March April The world doesn't have enough vaccine dose to immunize everybody and the issue of having people at risk who are Normal subjects but are at risk of acquiring Ebola Will exist outside of the clinical trial design? This is not a situation where we could potentially Immunize the whole population even if you wanted we couldn't so there will be people who participate into the trial and people who don't and I think the ethical question on Keeping people away from a vaccine that could have protected them Could be extended to the overall population for me. It's one of the reasons why I'm saying, you know pragmatically. There's nothing else we can do then Providing this vaccine to a smaller proportion of the population But of course engaging explaining and having the agreement is absolutely paramount It's also the reason why we are not favoring any one of the trial designs that are being put forward And we're working very hard to make vaccine available for all of them. We don't know which one we will I do have a concern if you look at what's happening in Liberia that had we introduced the vaccine a month ago We would be thinking that the decrease in Events now is related to the vaccine when it's related to all the things and therefore we wouldn't know We actually would think the vaccine work, but we wouldn't know and we may be wrong For the future so I Think we need to be have a very balanced Very participative very open But also scientifically sound discussion around this You know, this is really hard and I I just want to jump in here with the perspective because I completely agree with Tony And I think Participatory is is the concept that needs to be emphasized. It's one thing to sit You know in a corporate headquarters and think we know the best way forward is a completely different thing to have a Conversation with the people who are on the front line or the people who are in the affected countries who see medicine Very differently than we do and have a whole different cultural context in which they make decisions So that participatory element is is really important and probably the thing that worries me is That even if we knew the vaccine work will people take it That's a problem that we see with vaccines that have been around for as long as bolio vaccine has been around We have this incredible vaccine hesitancy and when the diseases as frightening as Ebola is I think it's going to be very difficult To help a population have trust and confidence in the product So the more participatory the decision process the more transparent we all are I think the better likelihood We are to bring whatever we can find that's helpful to actually be at the front line where people need it No, I fully concur. I think the major changes has been said is Will it be an accepted by local population not only having authorization of local ethical committees But really getting the acceptance of the people That that participate to the trial and being well prepared that if issues are wise during the trial That there will be a better case is anyway that it has been it can be approached in a very objective way And you can avoid mass history that would start Accusing the vaccine or sort of whatever. So I do think that the social thinking around how to involve the such a population and The work of any of when issues do arise will be very important to make this trial successful One thing that I would like to add to that for a vaccine who comes a few months later is on how we will go later on Demonstrating for the later vaccines whether there's a fixie or not whether we will have to go to randomized trials again, which When there's an effective vaccine becomes even more controversial Although whether we should really start looking into him logical bridging Combined with non-economic data or whatever there's certainly a discussion that we will soon need to have Rohit MSF is of all the organizations here is the one with the deepest on the ground close in extended contact and knowledge How to how to and I'm sure you're pulled in in divergent directions in terms of this issue around ethics and trials Community relationships, how do you see this? Well, I mean the basic summary is what others are saying, which is it is about community engagement and community acceptance And we are built basically on that basis. So that's just part of the DNA of the organization It's not something just to be said. We haven't finished. I believe now the trial design for the vaccines We have made a decision for our trials on drugs not to introduce randomized trials It's it simply was a decision that was taken very early on in the organization That this was something as a medical provider that we would be unable to do and we are instead relying on again on approaches That have been criticized elsewhere to look instead at the historic Trends and in some of these communities in terms of what has been the outcomes in terms of mortality rates And there is an understanding of the shortcomings, but it also is a medical provider. It is And again, it's because it is new for us to be engaged in trials We simply do not feel that we would be able to engage in a randomized controlled trial for the drugs But again for vaccines. I believe there are discussions of ways of trying to and again for drugs because there's no equal place There's reasons in which you know, right? So Steve Again the point you made is an excellent point There is a big difference and I people should need to understand that between a drug for someone who's sick Versus a vaccine so there's no criticism of Design of trials that can be anything from adaptive trial to the any kind of trial you need to really Do what's acceptable and what you feel is the best. So there's there's no space between us on that now one of the issues that has surfaced in this period is Coordination how to make sense how to track and coordinate efforts Gavi the vaccine Alliance took this step last week when its board met to to put itself forward I'd like to ask Natasha bill of Moira From Gavi to just say a few words. There's a microphone right here around How does this step help put in place mechanisms that build confidence around the? Coordinated effort looking forward Sure explain a bit about that. I will do my best, but thank you Steve for hosting this panel, and it's a you know Terrific group of people that are really in the middle of all of this right now So it's great to be here. So just to give everyone a little bit of background in September Our executive committee of the board asked the secretary to basically look at ways that Gavi could potentially have a role in in the Ebola outbreak and in the crisis and Basically over the last two months. There has been a tremendous amount of work that has been done Over this period a lot of work with all of the people on the panel and pretty much every stakeholder that's involved in this process and that all came to a point at our board last Thursday where The board discussed the idea of what that role would be and the decision was a Couple of things the first was that everybody is related is this a funding envelope of up to 300 million dollars The procurement of an Ebola vaccine once it's been deemed safe and effective by the WHO And then there's also another 90 million up to a 90 million dollar envelope for two purposes One is around the rollout of a vaccine once it becomes available and then the other piece Is around recovery of immunization systems? I think everybody is aware that especially in the three countries that have been affected Immunization systems have been decimated a huge reduction in immunization and When the time is right these countries are going to have to rebuild and we are going to be part of that solution for them I think it's very important for people to understand I think some people here know that we are just weeks away from our second replenishment which is Not about Ebola The number that we are looking for is seven and a half billion dollars and that was well before This crisis hit so the numbers that we're talking about for Ebola are in addition to What we're looking for replenishment. I think it's very important to know that that funding is additive and not part of You know our regular critical immunization work You know what we are doing as far as next steps I mean we literally just made this decision four days ago But the work has already started to really get ourselves in place to be ready When a vaccine comes about so four work streams have been created around the the areas of the board decisions so procurement rollout Future outbreak and the recovery of the system. So we're really working to ensure that These pieces are all set So that when a vaccine becomes available We are We're prepared to roll it out and as far as the recovery piece goes as I said I think countries are still in process of figuring out what they need to do and we're putting ourselves together So that when countries are ready to start rebuilding that we are really there to support it And you know as far as I mean we play Oh, I think what has happened in the last two months really shows the important role that Gaby has around immunizations But also around strengthening health systems around immunization And we're a small piece, but I think you know just kind of going back to what everybody said But in particular Dr. Gerberding around partnership, you know, we will play a certain role In the vaccine process, but it in order to ensure that it's really getting to the people That need it, you know, if we will rely on our partners on the ground Along with all of the other folks that are part of this process Thank you very much Natasha There seem to be a pretty strong consensus among the speakers that Future business needs to be done on a different basis And that part of this introspection process is Looking ahead with that in mind Could we get a little more particular around a little more concrete into what actually Would you see as the essential changes? in Practices in coordinating mechanisms in planning and creating incentives Julie Well one thing I think we would all agree on is that companies crave predictability So we we'd like to have the confidence that if we start something we can Move it to its completion We'd like to have the confidence that if for example We have a governor government partnership that that partnership is good to the duration of whatever it is that we're trying to do And not something that's going to go away with the next election or the next sequestration or the next to You know challenging circumstances in anybody's government So I think that's one aspect of it is the kind of the confidence that if we're going to make an investment in a Partnership that the partnership can hold and I think we have good examples where that's happened So I think Barda has come through on its commitments and I'm not Criticizing any way. I'm just saying that that that is a necessary component of this I actually think all of us would benefit from a public that is more informed and more reliably Informed about why these kinds of investments are important You know, we just heard Gavi say that we have a pledging conference and people need to Commit governments need to commit donors need to commit and in order for that to happen Publix have to really understand what is the value proposition that we're creating and why is it important to to vaccinate and what? What is the benefit that not only the children or Adolescents who are benefiting from immunization or in the case of Ebola all the people who benefit What's the benefit to the to the people who don't have affordable access? But what is the advantage to the rest of us? And I think it's important that we not be shy from the fact that vaccines and vaccination is an important public health good And the commons that sharing that good has become very global and we're only in a one One traveler away from a threat in our own Neighborhood if we don't do a good job assuring affordable access to the whole community But I think in terms of how we develop pipelines of vaccines One of the areas for opportunity that that we're exploring not just in the context of Ebola But for many of the others so-called neglected diseases are hard to find Treatments and vaccines for diseases is the pre-competitive collaboration. They're increasingly very interesting places where companies can come together and work on projects bring different ideas together long before there's a product or a Candidate target so that we kind of can share in our own intellectual capabilities But also partner with the people in academia or in other kinds of companies and nonprofit organizations to bring the best ideas forward Long before we are targeting a product and for neglected diseases That's probably really the only way to harvest that intellectual competency and and expedite. It's useful Progression, why don't we hear from the other two in the industry representatives on what we're hearing from industry here And then something that our company is extremely committed to From our track record as you know, we have some very specific ideas around what we should do going forward Because there's there are the vaccines that exist But there are those that don't those that exist I think all the companies have approaches to ensure access and obviously Gavi is playing a fundamental role in providing that predictability and that Sustainability that allows for very low prices to be Available for for access in the least developed world. I think the challenge actually is how do incentivize innovation and very high risk Investments to go into areas of diseases that may or may not someday come and The key elements as we live it through and every time there was an outbreak we did is speed And volume And frankly in all the outbreaks that have or pandemic that have Scares that occurred. We are very fortunate that none of them actually Turned out to be one. So we actually don't know whether we're prepared or not So we need to be very careful as as a society to To be much more prepared frankly. So the way we look at it is that at least as vaccine is concerned is That vaccines work through what I would call platform technology if I take any one of the vaccines we have seen there The chimpanzee or the human adenovirus or the VSV virus or RNA as for adjuvants There there is a great technology that can be used to make many different vaccines and In fact, we can predict with reasonable accuracy, but not like Which vector which technology which platform may be best suited to what kind of pathogen? So our recommendation is actually to Create an organization and exactly how we can organize it and how we should fund it and Participate to it is open for debate, but create an organization that is going to identify four five or six such platform and prepare them for scalability to To gain that speed of reaction And actually also use them to build vaccines for the predictably possible outbreaks and Have those vaccines available But but also when we haven't predicted the pathogen that the this scalability as I call it Is built into the platform so you can go actually really very fast So these collaborations would be a new this is to be a new a grand collaboration of a kind that you're talking about in which Different industrial Interests would would be sharing in this potentially it can also be frankly it can be competitive or pre-competitive Both models are possible. There are very significant synergies between The way you design and develop a vaccine for Ebola and the way you design and develop a vaccine for another disease. That's more Commercially relevant to sustain a business that takes the risk of innovation like the vaccine industry does And you know the knowledge you generate from one can serve the other and vice versa But I think there is there is a need for concerted efforts and Organization that's dedicated to this because the other point is Is the following I'd like to say the following if I may one of the one of the points in this particular Situation is that if a company didn't care about Ebola nobody talk about them There are vaccine companies that are not doing anything for the Ebola vaccine We need to be careful that those who actually have made the commitment outside of any form of financial or any otherwise contribution from anybody To commit their resources to do that to make these vaccines to discover them develop them Manufacture that made them available take all the risks that are taken Are not those that are? Pointed at I think that's the first big picture context That we need to do and need not forget Because what's very important is that these type of commitment to public health To global health for our social responsibility has to be sustained in the world we live in in the world We live in enormous investments are made in R&D 90% of those investment in many cases fail and in some cases they succeed and we need to be able to Sustain that innovation engine I think I think we need to have the I would say the courage at the same time to say we need to be a sustainable business and at the same time We will commit outside of any condition whenever public health needed to do it That's what the company should do and freckles. That's what our company is doing every time And we have the opportunity to do it and what we're proposing is to do it on a grand scale for many many more Pathogens than we are Thank you. Yeah, I think it's an excellent idea that Once you go into details will need a lot of more discussion But certainly I think both companies are quite similar in terms of corporate Responsibility social responsibility thinking we do have a dedicated public health group Which actually is tasked to really do its R&D? Only on those type of projects the only thing is you have to keep it in balance with the total Portfolio because you just can't afford to have too many of them But certainly also there we were looking into working together with a network of of partners being companies or being Institutes in the pre-competitive area, but so I do think that part of the future is there part of the future I think Reference was made to to the the problem with antibiotics and multi-resistance Is also that the society need to start thinking differently on how Drug-specific antibiotics are being compensated for because it's clear that in the normal price setting it just Does not work You really need to look into other ways of incentivizing not to make them usually expensive, but that the overall effort in some way is being Taken into account such that progress can be made in that field. Thank you. I'm gonna turn to Rohit and then Tony and then we're gonna open for questions and comments Rohit on this question of what needs to change Tony So a few thoughts we recognize the efforts that companies are making right now and we certainly appreciate that But if you take the example of GSK's vaccine that was only Acquired because you purchased the company called Ocaros and that was for another vaccine And unfortunately this was just sort of included in the package and sort of sat within the company So we recognize the steps that have been taken now But and of course a lot of the other vaccines the VSV vaccine was actually Developed by the government of Canada through public funding and it was already shown activity through their efforts And there simply was nothing to be done There it's just to take a step back I mean the big picture about this is we only have one system of innovation today That's the patent-based system innovation And that is something which all of these companies have pushed quite aggressively for over the decades and have globalized in the 1990s And so in a sense you own the system of innovation This is what you asked for and this is what we have today And that is what we are actually having to deal with every day in the field and that is one of the symptoms or Basically the results is what we see with the Ebola outbreak today and people can dispute that but this is something and again Your companies today are still pushing now for higher and higher levels of intellectual property protection that we think are only deepening the problems We're seeing around the world instead of actually solving them Now in terms of the suggestions of things such as product development partnerships Or platforms, I mean this was already something that has been introduced actually now almost 15 years ago Our organization launched one of the first product development partnership in in 2000 the drugs for neglected diseases initiative We still pay for about 25 percent of its operating costs So while we don't necessarily disagree with looking for these solutions to potentially develop technologies or platforms For us, it's really more of the same There already is a lot of product development partnerships out there and all we are seeing today is we're adding more and more of them Sort of paper over the cracks that we're seeing in our system of research and development What we have been doing over the last decade is working at the World Health Organization in Ellsworth to document the systemic failures We see in research and development and the World Health Organization has come out with two Comprehensive reports on this issue that show the extent to which our patent system is not developing drugs and vaccines and diagnostics That are needed in developing countries and they have developed a range of recommendations to try to break this Debate between innovation and access to ensure that we can have the public health tools that we need to respond to Emergencies like this and the everyday problems we see in developing countries today And there's a range of recommendations that talk about new models of innovation that move outside of the patent system That seek to de-link the cost of research and development from the product price so that we can actually Focus on actual public health needs to develop public health goods Which is essentially what we're doing here today with the Ebola vaccine through substantial public investments through Procurement mechanisms being put for by Gavi. We are essentially Developing these vaccines through new models of research and development. We're just doing it through a sort of I guess Random and sort of step-wise process But unfortunately a lot of people in industry have been fighting against these new models of research and development Because they challenge our existing system of R&D and we have been continuing to advocate for this because we are concerned about the long-term impacts We have already seen some success in the vaccine space actually with the meningitis A vaccine Which was developed through a collaboration of the serum Institute the National Institutes of Health with financing from various partners that Develop an effective second-generation meningitis A vaccine at 50 cents a dose that essentially De-link the cost of R&D from the product price So this can be done and we think it can be done in other areas Our concern though is that the solutions that are coming out are just more of the same the United States It's completing negotiations of the Trans-Pacific Partnership Agreement at this time That simply seeks to introduce the highest levels of intellectual property protection in the Asia Pacific region and eventually around the world And none of that will deal with these problems. We simply will have more of the same problems and and to end again We do think that these new models are not just free Bola. They're not just for neglected diseases They can be for very basic things such as antibiotics We basically have the United States saying that we cannot rely on industry with current models of innovation to develop the antibiotics We need even in our hospitals today and we're going to need new models of innovation and substantial new forms of funding We simply think that this can be applied on a much broader scale And it's necessary not only for people here in the United States But around the world because otherwise we're just going to continue to face these problems But we need new ways of thinking it's not just going to be the solutions We've used over the last decade because they're not getting the job done. Thank you Tony What needs to change so Steve first of all the comments of my colleagues on the panel are all Right on and I agree completely with what people have said So I'm just maybe make one or two very brief comments that is in a different area Fully knowing that I think what they said is probably the most important thing and it's two things and it has to do with something that we've been dealing with some time and that is the issue of changing in the sense of Making sure that we pay attention To something that has been started some time ago that has recently been crystallized in what has been called the global health security agenda in other words to try and develop some sort of an infrastructure in the developing world So that when you go in to a country for one reason or other you leave some sustainable Infrastructure that could be intellectual or could be physical mostly Intellectual and training so that the countries involved if we had had Some sort of a of an infrastructure available in the Guinea, Liberia Sierra Leone area when the first cases came out to be able to do the kind of identification and Isolation and contact tracing we may not have had an outbreak as explosive as it was. It's very interesting. We've learned We've had PEPFAR now since 2003 and PEPFAR has not only had a major impact on HIV but has also left in countries an extraordinary infrastructure of people committed to the health of that nation that has now transcended HIV in a way that involves a variety of other diseases maternal health child health Vaccinations for individuals measles programs, etc We really need to pay attention to that because I have Extraordinary respect and admiration for the courageous and amazing things that met sans-saint-frontier it does But the cavalry can't keep coming in at every single time because they only have a limited amount of resources to do that So we need to start developing some ingrown groups that can do that The other thing is just I couldn't help but but think when you were talking about I We all said it but I I know Julie said it right off that these are surprises that are not Surprises and if you want change we've got to get the mindset to realize that Outbreaks actually occur and when you're in dealing with an infectious diseases, you should be expecting them I couldn't help as we were talking thinking that some of you may have seen Years ago that HBO series a band of brothers When the hundred and first airborne was going into best on as the army was Retreating and the guys in the army was saying in the regular army was saying why are you going in there? You're going to get surrounded and he looked at him the major from the from the hundred and first and said But we're paratroopers. We're supposed to be surrounded So it's the same thing with infectious diseases You should expect that they're going to be outbreaks and they shouldn't be surprises I'll leave you with that That's very a very good image Let's open for some Comments and questions will take three or four to time sir down here in front Please identify yourself and please be brief. There's a microphone there. Yes. Thank you very much My name is dr. Benjamin O'Herry. I am the owner of first consultants medical center in Lagos, Nigeria We were the ones that jumped on the first and the last Ebola grenade Now Thank you, I wanted to raise the issue That I think is very important going forward here is the issue of Stigma now I Have Come here because of What lies ahead? In a country of 160 million people 18 people were infected 12 were from my hospital now it have survived and They've been declared that their serum Has the antibodies But they're still suffering from stigma now in a country and in a continent and in a zone where 70 to 90 percent of The people get their healthcare from the private people How are we going to be able to introduce this? when right now the practice is Stop the fever If you have a fever at the gate, you don't come into the hospital So how are we going to be able to convince them because I heard a Comment about participatory because it means that you have to really Go in there and talk to the people and get to know how to overcome their fears which We now know as the stigma Thank you. Thank you. Let's take a few additional Comments and questions right here sir My name is Wayne Pambianke. I tip my hat to all of you I think you've done a marvelous job from the beginnings of this outbreak to testing vaccines and drugs starting next month is really quite miraculous one observation that strikes me given the number of Patients and the deaths if I understood some of the earlier slides only two drugs are being tested It seems to me in this country alone There must be many candidate drugs and I wonder how the funnel got that narrow Thank you. There's a gentleman right behind you there Yeah, Ken my record Roldax Eight years ago the international Red Cross warned about the development of biological weapons that could target people based on Genotype for instance race of the 16 White or yellow people who have contracted Ebola all have survived except an elderly Spanish priest So all the people who've died of Ebola are black Does that mortality distinction in addition to the off-the-chart number of infections and deaths that have occurred? Suggests that the West Africa Ebola variant maybe a weaponized version of the virus Okay, let's take one other is there any other Right here, sir. We'll come to you in a moment in the second round. Yes. Thank you Again, I commend the effort here. I'm Greg Glenn. I'm the head of R&D at Nova Vax We're a recombinant vaccine company and I think the you know the efforts commendable And I don't want to put any potholes in the way I think you were we should do what you're doing I think the companies have mobilized in a tremendous way cooperatively I would point out that these are vectors and so we're very focused on just vector technology and we know There are limitations. They haven't really worked in other settings. They have pre-existing immunity They developed very low immunity to the target antigen So and we have non-human primate data So I think that that's the bet and I believe a plan B Should be at the forefront for a for a second kind of vaccine because there is some chance That when we come to phase two, we'll look at this and say I don't know if that's something we want to push forward into phase three So I appreciate, you know comments on you know, the long-term plan B sounds like it's being discussed Is there a short-term backup plan? Thank you. So we have a question around overcoming fears and stigma Question around is it only two drugs in development question around differentiation between black versus white versus us based for Africa population is this weapon weaponizable and Then they appeal around plan B. Is should there be should there be a formal plan B put forward right now? Would like to jump in and pick off whatever piece of those You care to yes y'all With regard to overcoming the stigma We certainly don't have a panacea solution to that but the point was raised earlier that People who are organizing such a study really need to have a lot of attention to specifically this aspect Reminds me that we did trials with a cellular pertussis in Senegal in the 90s and we really had studied nurses who went into the Compounds and actually really took that time to tell to the people about the vaccine and Certainly was not your objective to have the vaccination done that day So it really takes a lot of time of Explaining and discussing such that you really get the trust of the people and get people on board So I do think that socializing with the vaccine and what a transfer is an important aspect that all Study teams that will be in place will need to take into account monster So we should engage but we shouldn't underestimate how much of a challenge Because there is there is There's a stigma of having fever because it could be a baller that has so many implication on the social tissue that For instance, if anyone of the vaccines induces fever after immunization exactly how The community will react to that It's something that we really need we really need to Be on the ground and we need to absolutely work hand in hand with the local health authorities and community and investigators to make sure there isn't actually an Unpredictable and predicted the reaction that can be extremely detrimental to the introduction of the vaccine or to the conduct of a clinical trial It is a significant concern and I think the larger the population we immunize The more concerned there will be to that there will be timely Association between events that are not related to the vaccine and the immunization So very very important very important issue I was going to address a second point I just wanted to add if you study the history of infectious diseases whether you're talking about smallpox playing Pandemic flu. It's a history of stigma. I mean, it's an inevitable Complication of the fear that outbreaks in in gate So we would be very naive to think that isn't going to be a major challenge in the situation that we're facing here Maybe not worse than it is anywhere else. I remember during SARS people didn't eat in Chinese restaurants in Toronto So, you know, we even highly educated people are vulnerable to that kind of irrational Irrational response to a threat and we know that we don't have an easy solution But one really important aspect of it at least in my experience has been finding the local people who are trusted and Help them understand the whole situation so that they can speak on behalf of their own communities and Try to generate a little critical mass of trust at least. Did you get to complete your thought on that? Yes Stigma is also seen in the United States I don't know some of you may have seen one of the television shows they had of all of the Ebola survivors one of whom I took care of Nina So I know her very well and they were asking are you being embraced or is there a segment? They said it's like almost maybe 60 40 60 percent of the people embrace them and 40 percent of the people Stay away from them and one of the and I won't mention his name But one of the ebola survivors made the point that it's very easy for him to get a table in a restaurant now So it's not just in Nigeria Right maybe a couple points on stigma I mean certainly that's some people may have seen in the news Some of the treatment of returning volunteers for doctors up orders back into the United States Was a really big concern for us and certainly that we need to be able to encourage people to really make these sacrifices to go in the field It is important to note also that a lot of the staff that we have going including some of my colleagues who normally do advocacy On the other issues we work on are now in local communities and three and all the affected countries Really working on very local communications on the ground and these are the resources that I think people don't see in the Organizations that are in the field, but they are doing very hard work with people in the local community Are on the front line really trying to communicate what the virus is about how to respond to it and to reduce the stigma and I think To the extent that this is so focused on the medical aspects It really sort of loses sight of the fact that that is where you can get the empowerment of local communities Just note also on the idea simply that this is not going to be enough as an organization We are doing a lot around trials But we have not stopped our very urgent calls for more teams more infrastructure to go into the field and not simply for Governments to offer funding in response to the outbreak we and certainly I'm glad that there will be a separate discussion on diagnostics because we do think and alongside vaccines That really is going to be critical for turning around the future You're on Yes, I'm on this question around the pipeline of drugs and testing. Yeah. Yeah, it's just that we were only sorry testing out to At the outset plus convalescent plasma again because of the concerns of supply There are others that we are looking at that Dr. Fauci put up and there are is in consideration also some repurposed drugs To the extent that there's supply and that there's obviously very good safety data So there are going to be others that are used and I believe there are other trials that are using other drugs on this question around survivability and Numbers in the United States too many confounding factors because if you look at the quote white people who were infected a Substantial proportion of them were it were a fact to the United States where they got intensive care and that doesn't mean that the physicians in West Africa aren't as good as the physicians here But they you have one or two physicians taking care of 30 patients Whereas there we had when we were taking care of Nina We had like seven of us at one time taking care So I think the survival of people when you're in intensive care and you're monitoring your electrolytes and you have IV Central lines makes a big difference. I don't think that that's race I think that just happens to be the distribution of people who are error-backed And on plan B, I think you know, it's a point I was making last week at the NIH Which is it's absolutely key that all the vaccine candidates are progressed we don't know which is the better vaccine and We don't know that we have enough vaccine of any one vaccine Urgently enough depending on how the situation unfolds and evolves. So we need we we need to pursue all of them And we need to help each other Thank you That's a very very nice way to draw things to a close here. We're at the end of our time This has been an exceptionally rich and informed discussion. I thank all of you and Natasha Thank you for joining us and weighing in on behalf of Gavi Tony Julie Monsef, Johann Rohit Thank you so much for the all of the