 So good morning, good afternoon, good evening, colleagues. Following the sobering comments from Padma and Ben, this is, I suspect, a timely presentation to have. And hopefully you'll be all a little bit more optimistic at the end of this. So when I was looking back at my notes, the last time we talked about vaccines was in January this year. And a lot has happened in that space. A lot of development work, but probably the most significant one is that a fairly large number of Illry staff and CGIR staff have actually had their first COVID-19 vaccine shot. Unfortunately, we can't add this to that group, the Ethiopian group, but as they are very well aware, senior management have been making all sorts of arrangements, trying to secure and procure vaccines for the other's campus as well. So that's been a positive move forward, although there's still a long way to go. So what I thought I would do today is to give an update on COVID vaccines. Although we already have some, there are many more that are in the pipeline. Unfortunately, as we're aware, there's a supply problem in terms of the current vaccines, but we've also finally reached a stage where there's a lot of comparative data now coming out at the end of phase three trials, talking about vaccine performance, also talking about the immune responses to the various vaccines. And so there's a lot more information to present. And I also finally want to end up talking about a couple of in-house tests that we've developed at Illry to support COVID laboratory research and Anna will talk at the end of this about one of the newer ones. So as I said, we'll divide this into three sections. I'll talk about vaccines, vaccines applied, then move over into vaccine performance and then end with in-house tests. Now, I hope that you will be able to recall the earlier presentations that I've made so that you can follow some of the designs and the details and I'll try and remind you of what, as we go along. So next slide, please. So the COVID vaccine research is still a very fluid landscape. There are a remarkable 102 vaccine trials that are going on in clinical development. So if you remember, this means that there are 102 efforts going on in humans. There are 185 vaccines still in pre-clinical development. So that means basically still laboratory work or animal experiments going on. And the table below points shows you a breakdown of those 102 trials that are going on in clinical development. This we've lost you. Yeah, I got muted by the host. Oh, okay. Where did- I didn't like what you were saying. Obviously, I might as well stop talking now. Where did you lose me from? You were just referring to this table of the 102. You have that sub-unit on this table. Okay, great. Thanks, Jimmy. So the table below here breaks down the 102 trials that are going on in clinical development into the various platforms. And as you can see, the number one that's up in that list is protein-based sub-unit vaccines that are coming up that are still being trialed. There are also other types of platforms that are being used. So the viral-vected ones that we've talked about before DNA-based vaccines inactivated SARS-CoV-2 viruses and then the RNA viruses. And you've got another bunch of different types of platforms that are being trialed, but in much lower numbers. On the right-hand side, if you look at the phase two trials, there are 34 vaccines that are in phase two trials. So that means in humans that are being used to look at the immunogenicity. And there are remarkable 30 trials in phase three. So this means looking at the efficacy in humans with respect to the vaccines that are being used or being developed, I should say. Now, obviously not all efforts have been successful and four have been abandoned. Now, as we go on, unfortunately running phase three trials will become more challenging. And the reason for this is because if you think about it, we have a lot more people now who have recovered from infection, vaccines are being rolled out. And so finding populations to work with is going to become much more difficult. And in fact, what might end up happening is we may start to see a possibility of controlled human infection trials, which I had mentioned in one of my previous presentations. So next please. So one of the vaccine efforts that I thought I would highlight, no, please go back. So one of the vaccine efforts which is in preclinical development, which I thought I would highlight, which might not tickle, but would be of interest, is actually based on Newcastle disease virus. So I'm sure most of you or at least those of you who work in poultry will have heard about Newcastle disease and there's an attenuated vaccine that's used in poultry. Well, that virus is now being manipulated to be able to use it as a vaccine as the adenovirus vaccines have been used. And one of the advantages here if this works is that it could actually be produced in eggs like the influenza vaccines. And so production becomes much of a less constraint if this Newcastle disease virus vaccine works. I thought it was an interesting example of an agricultural virus being now used for human vaccine development work. So next slide, please. So this lists the current vaccines that WHO has listed in their emergency use. And there are six of them which are listed on the left hand side. That's Pfizer and Moderna, which are the mRNA vaccines. AstraZeneca and Johnson and Johnson which are the adenovirus vaccines. And then Sinofarm and Sinovac which are the inactivated viral vaccines. And the importance for having emergency use listing is that these vaccines then become available through the COVAX facility. And I've mentioned the COVAX facility previously. This is the facility that's designed to try to roll out vaccines particularly to low and middle income countries to get at least 30% of the population that are vaccinated so that they can get over the acute phase of the disease when it occurs there. Now the Novavax vaccine which is the leading protein based vaccine. This is now in a pre-submission meeting that's been going into WHO. Now the six that are listed here are not the only vaccines that are being used. There are actually 16 that are being used. So for example, we've talked about the Sputnik vaccine previously. And there are other vaccines that are being used but these have not been listed yet by WHO. And so officially they're not available through COVAX. And what's interesting is that we know that SARS-CoV-2 can get into animals. For example, in mink and in cats there've been infections in tigers unfortunately death of zoo animals. And so vaccines are now being used or have been developed for use in animals. And these are vaccines coming out from the Russian labs as well as Zoetis is now getting into this space. So next slide please. So in total as Jimmy showed in the earlier statistics about 2.1 billion doses of vaccines have actually been administered. And this map here shows where most of those vaccines have been used. And this is starting from December last year. And unfortunately, as you can see that the rollout in low and middle income countries has been very poor and less than 1% of these vaccines that have been actually administered have been utilized in sub-Saharan Africa, for example. So next slide please. So this led to the WHO director general making a statement about the shocking global disparity in vaccine use. And if you remember previously we talked about the vaccine nationalism, vaccine hoarding whatever you want to call it which led to construction of the COVAX facility. And COVAX has now constituted a task to look at the supply chain and manufacturing aspects of the vaccines to see if this could be used to enhance the supply. So the COVAX task force has developed three work streams an immediate one that's looking at partnerships to enhance input supplies, looking at restrictions in trade and then enhancing the fill and finish matching which is basically taking a vaccine that's produced by somebody else and then bottling it. And then in the medium term, they're looking at how to create global manufacturing capacities, utilize existing capacities and develop regulatory and manufacturing workforces. And in the long that expanding capacities in manufacturing capacities in low and middle income countries. Now on the right hand side you can see who the major players are in that. And the WHO and Bill and Melinda Gates Foundation, CEPI, GAVI, UNICEF are all involved in this. And next slide. An interesting development that's coming out of the WHO is to create an mRNA manufacturing training facility. So these you remember, the Pfizer and Moderna vaccines are kind of the leading mRNA vaccines. And what they want to do is to constitute a hub and training for production in low and middle income countries. And this just shows you the timeline and vision that they have for this. And what's interesting is that this facility will not just be obviously for COVID vaccines, but it would be designed then to be able to also make flu vaccines and other types of vaccines that would be required in low and middle income countries. Next slide please. So if we go back to the challenges in increasing the supply of vaccines that this has been broken down and into four major categories. The first one is just to improve the flow of raw materials to sites of manufacture. And one of the issues is that there are trade barriers on specialized equipment, reagents, production capacity. And we've heard also in fact of trade barriers being imposed by countries, basically to prevent their own manufacturing capacities. The second one is that there is a need to harmonize regulatory processes across different countries. So at the moment, as we know, many countries require local studies and local compliance to be carried out before vaccines can be start to be used. And the third is expanding manufacturing capacity, as we've just discussed, especially in developing countries. And the problem here involved technology transfer, installing, upgrading manufacturing plants and also the people capacity. They're not enough expertise for people on the ground and actually making clean rooms is one of the most difficult components that needs to be taken into account. And finally is establishing the supply chain intermediary so that there's a global matching of demand and supply. It's amazing, apparently, how difficult this is. We should ask Andreas about this purchasing issues, timelines and there's a requirement for over a hundred components that go into the manufacturing of these vaccines. So the supply chain issues are massive. So next slide, please. So one of the problems that still contributes towards these issues is that we still don't know enough about scale up of the current vaccines that are being used. You remember we said that mRNA vaccines have never been used before. So there are very few contract manufacturing organizations for this. And although Pfizer has been carrying out multi-site upgrades and actually subcontracting to those who can help them. So for example, Novartis, Lonza, Catalan, who are manufacturing facilities. This is always something that's still being learned. Now there's a new company that's come on the horizon called CureVac from Germany. It's another German company that's been making mRNA vaccines and their vaccine now only needs 12 micrograms of mRNA per dose. So where is the Moderna vaccine and the Pfizer vaccine use 100 and 300 micrograms? So per gram of mRNA, you can see that the CureVac vaccines would go much longer way. And so we're hoping that the CureVac vaccines will come online fairly quickly. Now, unfortunately, the adenovirus vaccines are difficult to scale up reliably. So there's batch to batch variation. And these are looking at 10,000 liter, 20,000 liter fermentation processes. And even the companies are struggling to have reproducibility in terms of the virus that can be recovered from their systems. Now AstraZeneca has 15 manufacturing sites, sorry, 25 sites in 15 countries. And this doesn't include the efforts from the Syram Institute of India. Now Janssen has now got help from Merck, the emergent biological E to help produce vaccines. And Sputnik now is apparently looking at manufacturing in 10 different countries. Now the recombinant proteins, when they come online, as we've talked about earlier, protein-based vaccines have been in use much longer. So there's a much more know-how and scale up of protein-based vaccines. But these will need adjuvants. And so there's a concern that adjuvants may become the limiting factor when protein vaccines come to sight. But then again, people are looking at how to scale this up. So the vaccine landscape is going to look quite different over the next few years. And one of the important things to keep in mind is that all of the current vaccines are under emergency use authorization. Now it's quite likely that the Pfizer and the Moderna vaccines will get FDA approval for general use. Now what that means then is that these companies can actually start their own campaigns. They no longer are bound by the emergency use. They can start their own direct marketing to consumers. They can start advertising. They can start changing their prices. They can start doing all sorts of things. And so this is potentially an area of concern that I thought would be something to earmark. We don't know what the impact of that will have on the general supply and cost structures and also how they then start using these vaccines. Okay, so next slide please. So that was a brief update on the vaccines in the supply chain issues and those in the pipeline. I wanna turn now briefly to talking about the comparative data. There's enough data now that's come out from all of the phase three trials. And if you concentrate on the left-hand side of this figure, what you can see is that the vaccine efficacies and which are shown in the red dots here and the pink lines identify confidence intervals. You can see that the vaccine efficacy rates go from 95% right down to 50%. And the WHO requirement was for 50% efficacy. So you can see that by the Pfizer, Moderna, Sputnik, Novavax, they're all at the upper end. Sinovac, which is an inactivated virus vaccine. The AstraZeneca is kind of in the middle. But next slide please, next rather. What's remarkable is that despite this range of different efficacy against disease, they all protect against severe disease, right? To 100% all of them. So although you have a huge range in efficacy, they all protect against severe disease. And that's the key metric that we're looking at because it prevents hospitalization. It prevents stresses from the medical services and also protects against death. So they don't all protect against mild disease. Now we've heard about the emergence of variants. The data so far looks like there is sufficient protection against variants. And as we get to know more about the immune responses that are generated by these vaccines, it's this data is feeding back towards developing better vaccines for the future use and also diagnostics. One key factor that still remains to be identified is the duration of immunity. We don't know how long this immunity is going to last and the requirement for booster doses. So next slide. Now because of one of the supply chain issues, people started wondering about mix and max vaccinations. And there's now data coming up to show that this clearly works. Now, most of the vaccines that are being used require two shots. So that's a prime and a boost, but that is two shots of the same vaccine. So the Pfizer, Moderna, AstraZeneca, these are two shots of the same vaccine. Immunity starts to kick in under the first shot, but it's then maximum after the second shot. Now, in immunological terms, it's been known for a while that if you do what's called a heterologous prime and boost, so this is the mix and match. So these are two shots with different vaccines. So for example, AstraZeneca first and then Pfizer. Well, what's been shown now is that there's a superior antibody response from an AstraZeneca first Pfizer second compared to two AstraZanicas, for example. However, one of the downsides is that there may be more minor side effects that have been noticed in this, but there's pretty solid evidence now coming up from this. So from the immunologists are not kind of surprised by this, but it's good to have a confirmation of this from in the scientific field. Now, while the mix and match vaccinations might work, obviously the companies are not particularly thrilled by this approach because it reduces their sales. And so we'll have to see now what happens in the future with respect to whether this starts to become a recommended use of vaccines or not. And the next slide here shows some really nice, exciting data. If you remember very early on, we talked about the importance of an antibody response and an antibody response that neutralizes the virus from causing an infection. So this now is a really nice study coming out from Australia which uses modeling as well as their approaches that they've been used in influenza studies and showing that there's a very nice correlation between the neutralization activity and protective efficacy. Now, unfortunately, this is a science paper and they've used the scientific names of the vaccines. And so on the right-hand side there, I've just listed a key which breaks down what those mean. So right at the top end of the curve, you've got the Moderna, Novavax and Pfizer vaccines. And then it comes down all the way down to the Coronavax or Sinovac vaccine. And in the middle of that, you've got convalescent. So these are people who've recovered from COVID and apologies for the typo over there. So this is the antibody response in people who've recovered from infection. And as you see, they fall very nicely in this curve showing that they will also have protection against viral infections in the future. So what this means is there are lots of, I should add that there are several caveats to this study because the study took data coming out of phase three trials and so they've had to do a lot of normalization of that data. But even then it's a striking correlation. But what this really does show is that antibody responses could be used as an additional tool in trying to predict vaccine efficacies, improve vaccine design, and then also perhaps eventually in terms of trying to see whether there is enough immunity that's left in a population that's been either vaccinated or those that might require booster doses. Because as you can see here, not everybody reacts equally to the vaccines. Hence you've got these long whiskers here as are shown in here. So this also highlights the need for standardization of assays across different efforts to be able to interpret data appropriately. So the next slide. So WHO continues to play a big role in all of this obviously. And just yesterday there was a WHO webinar which talked about how they were gonna be coordinating the global response to the variants. So this is taking a leaf out of what WHO does for the influenza seasonal vaccines. And so they will be playing a major role in the identification and characterization of the variants. They've recently come out with the new nomenclature for variants. I see that David has picked up on this. So for example, they're no longer being called from the geographical isolates where they were first seen but they're now being given Greek alphabet numbers. So for example, the Delta variant is the one that was first identified in India but they're now being called the Delta variant. So WHO has now constituted various task forces that will look at the variants, what are the possibilities of these variants breaking through vaccines, the need for modifying vaccines. And there were a number of producers of vaccines who were talking at this webinar and what they're doing in terms of preparedness in case variant vaccines are needed as well. That is not the case at the moment but should the need arise, the industry is gearing up towards how to respond to vaccine failures due to variants. Okay, so now moving into the last part of this presentation and that's just talking, next slide please. Talking about some of the in-house assays that we've developed. And as you're aware, we've repurposed ill-re-facilities and expertise to support the SARS-CoV-2 lab research. Next slide please. And in particular, we've been supporting the Ministry of Health, the government of Kenya here, carrying out PCR test diagnostic testing and more recently doing next generation sequencing and genomic surveillance, identifying SARS-CoV-2 variants. And here I really have to thank and point out the huge role that the PCR diagnostic team and sequencing teams have played in allowing us to support the Kenyan government in this fashion. And I think Sam Oyola and Edward O'Coth also deserve a special mention because they've been facilitating not just the interaction with the Kenyan government but also leading some of the lab work that's being undertaken here. And of course a lot of this work was feasible because of financial support from BMZ. And the CRP livestock.