You guys are so much better behaved compared to the crowd last week. All right, thank you, everyone, for attending our CMD today. It's a real pleasure to have all of you in the room. I'm Yamin 'Mo' Khan. I'm the CEO of hVIVO, and welcome to our Capital Markets Day. As the world's largest human challenge trial facility, of course, it's not this floor. We're on the 24th and the 25th floor, but Canary Wharf Group have kindly given us this floor to hold this CMD at. This CMD will be webcasted, so I also like to extend my welcome to everyone who's attending this virtually or online, and welcome to this CMD. For those of you who are here in real life, a few housekeeping items. We're not expecting a fire alarm test today. So just so you know, we do have fire marshals on the floor. If you do hear the fire alarm, please use the fire exit just there on the right-hand side. Do not use the lifts. The facilities, the ladies' facilities are just there on the right. For the men's, you have to go right and right again just on the right-hand side. Please turn off your phones. I know you guys are really, really important, but at least for a couple of hours mute your phones or turn them off. That would be great. In the audience today, we've got, I think, around 100 people across from the city, so from analysts, brokers, investors all sorts, which is I mean, it's for little old hVIVO, it's a hell of an achievement that so many of you guys can come out and hear about us. Really kind of really pleased. We did have our official opening day last week. We had just over 100 people attend, and we had attendees from across the big pharma, the biotech, the big global CROs. We also had people from academia, so UCL, for example, Imperial. I think we had people from all over Europe, even from the U.S. and Japan. It was really well attended, and I think people are really excited about the human challenge trial concept, right? So for those of you who don't know what we do, we do a special kind of clinical trial, which is a human challenge trial, where we inoculate people intentionally with the virus to help pharmaceutical companies develop vaccines and antiviral. And if you're interested to get a top-level view, there's a really good article in The Telegraph Saturday magazine, not this Saturday, the Saturday before the second of July, I think. So it's sort of like a five-page follow the volunteer article, which gives you a really good idea. Yesterday, there was something in the Daily Mail, again, talking about FluCamp and how we recruit and treat volunteers. And for those of you who watch Loose Women, they also discussed us. I know some avid Loose Women audience here, so for those of you working from home with a few hours spare, that's something to do. Human challenge trials as a concept has a long history. Back in 1796, a guy called Edward Jenner in Gloucestershire, he inoculated the eight-year-old gardener's son with a virus called Cowpox. So what he noticed was that at the time, Smallpox was prevalent across the area with around one in three people dying from it. And he noticed the milking maids in his farm had bruises on their arms, but none of them got Smallpox. So he surmised that they were getting some sort of infection from the cows that protected them from getting the Smallpox. So he did this very unethical, experiment, basically. So he get this eight-year-old boy, and he injected this boy with the pus from the. I know it's not good, right? With the pus from these milkmaids. And then a week later, he did something worse, which was give this boy smallpox. I mean, remember, smallpox is very dangerous. But thankfully, the kid didn't get smallpox because the cowpox effectively acted as a vaccine, okay? And that's where the word vaccine comes from, vacca, which in Latin means from the milk, right? So that was the first time a human challenge trial was done. But I assure you, they've come a long way with regards to safety and the well-being of the volunteers and so on. But our company also has roots going decades back. So after the Second World War, there was a U.S. military hospital near Salisbury, built by Harvard Medical School, and they donated that hospital to the U.K. government. And the U.K. government decided to open what's called the Common Cold Unit, and their big aim was to basically eradicate the common cold. Of course, I'm sure as you all experienced, the common cold is still around, they weren't able to achieve that mission. But they were able to identify the very first coronavirus back in 1960, which of course is very relevant these days. In 1989, that Common Cold Unit closed its doors for the last time, and one of the leaders of the Common Cold Unit at that time, Professor John Oxford, who was actually here last week at our opening day, he then opened a company called Retroscreen, which was really a laboratory for virology and immunology. We, of course, rebranded Retroscreen into hVIVO, and then a few years later, Open Orphan acquired hVIVO and Venn Life Sciences. And then in 2021, we-- Sorry, yeah, 2021, 2022, we ran the world's first COVID challenge trial. And that was a big turning point for the company, right? Because, you know, before then, you know, human challenge trials were not the mainstream of conducting trials to as for drug development purposes. And the fact that we could run a challenge trial effectively in the middle of a pandemic, I think turned the whole concept around. And we had a significant increase in interest in human challenge trials. I joined in late 2022, late 2021, sorry, and since then, I think we've grown tremendously well, right? We achieved so much. We've done so much. We've revamped our sales strategy. We no longer sell hVIVO as a company. We sell the human challenge trial as a concept because we know that if we're able to convince a client to do a human challenge trial, we will most likely get that work because 90% of the market share is with us. We've changed our operational strategies, whereby we can run multiple challenge trials at the same time, and hopefully, you've seen the positive results of that, not only in just this trading update but also the last couple of years. And that's, that's something we want to continue to build on. So we invested significantly in our headcount. We doubled our permanent headcount over the last two years. We invested in our lab services as well as our technology platform. And as we continue to run these trials, of course, we get more and more demands from our clients. And I think one of our clients asked us to do something we couldn't within the timeframe they wanted it, and they told us to go back and think outside the box and see what you can do. We said, "The only way we can finish your trial to your timelines is that we have to build out a new facility." And they said, "How much?" We gave them a number. It, it was a big number, by the way, right? And they, they said—they agreed. They said, "Fine, go and, and do it." We began to design a new facility where we can accommodate their study and complete that faster. While that, that was in the design phase, we had a second client who said to us they have the intention to do a COVID challenge trial. Now, in our previous facilities, we couldn't do a COVID challenge trial because COVID is a, what's called a Containment Level 3 virus. It means that it require a higher level of pathogen control, infection control, and a CL3 facility has lots of additional requirements. So things like you need to have power redundancies. So in fact, this building has four different power lines coming into it, as well as a generator on the roof. You need to have negative pressure. My colleague, Mel, will describe that in a lot more detail, but it takes a lot more to build a CL3 facility. So we told them, "We don't have a CL3 facility, but we are designing a new facility, and we can redesign that to meet the CL3 requirements," if they were willing to contribute to fund that. And they also agreed. So you can call it luck or good planning, I don't know, what, whatever you want to call it, but effectively, we ended up with 90% of our facility funding available from our clients, and we went out to look for a location. Where do we build this? And our facilities manager came to me and said, "What about Canary Wharf?" And I said, "We're not a bank. You know, why would we go to Canary Wharf?" But then we met with the Canary Wharf Group, and they showed us their ambitions to build the next life sciences hub in this area, and they wanted hVIVO to be, kind of play a key role in that. After talking to them and after some friendly negotiations, they effectively gave us a deal that was too good to refuse, and we began to fit out a facility here. I know you weren't gonna believe this. I'm sure most of you have done some extensions at home and so on, but we finished this project on time and on budget, which is amazing. Within 8 months, we designed it, we planned it, we costed it, we built it, we commissioned it, and it's all fully functional already, except for the CL3 lab, which will be ready in the coming months. At its peak times, we had 185 workers on this facility. We used over 1,000 km of cabling. There's 1000 different monitors on the two floors to track temperature, pressure, force, and so on. So it's a very sophisticated, fit-for-purpose facility that doesn't exist, of this size, doesn't exist anywhere in the world. We also have a BSL-3 lab, which means that we can handle and manage the more contagious pathogens, too. So it's really an amazing facility for us to be able to build our foundations on and for the next step of our growth. ESG also remains a key component for us, and I'm really pleased that Canary Wharf Group also hold that really high in their kind of priorities. For us, we wanted to make sure that we are compliant with our ESG commitment. Two years ago, we established an ESG group that reports to our board, and we've set a baseline of parameters, and we have parameters and KPIs that we measure ourselves against. So things like, you know, we recycle heat, so each floor has heat pads that are used to heat the floor. We got recycling. None of the waste from this goes to any landfill, so we keep a track of that, and I'm sure, if you need any more details on that, we would be more than happy to provide it. We are currently going through an ISO 14001 certification, which is basically a certification for you to have environmental management systems, and that's something we are looking to have in place by the end of this year. So that's kind of the background of the facility. My colleagues will later on come out and give you a little bit more detail on each of the different types of facilities we have with regards to the labs, the clinical side, as well as the recruitment. But I thought I'd take this opportunity to go through some of the top details of our trading update, which we issued. That's a disclaimer. Oh, that's me. So this is our first half 2024 trading update. I mean, we think it's an amazing update for us. We did GBP 35.6 million in revenue. That's a 31% increase year-on-year, and we're able to do this by utilizing the three facilities we had open at the same time during quarter two of this year. So we'll be able to inoculate record number of volunteers and basically drive this revenue. And as I'm sure most of you have worked out, the more revenue we drive, the better our margin are. So this 24% EBITDA margin we're predicting for the first half of this year. Again, an amazing result, and I think that that's something we want to drive to continue to build on that. It's really important that we work, and look, we won't see the full benefits of this facility until 2025 because that'll be the first full year here. Having all the beds on a single floor, I think will make a big difference. GBP 37 million in cash, again, a really good achievement, and this is after a GBP 1.4 million dividend payment. The weighted order book is at GBP 71 million. The interest in human challenge trial services continues to be strong. This is slightly lower than end of last year, but we did recognize a large amount of revenue in the first half of this year. Okay? We also had a small cancellation, which was supposed to go into the second half of the year. But the biggest thing also is that—well, another thing is that the timing of the signing, and this is effectively one contract, okay? So if, if that contract was signed before the thirteenth of June, this order book would have been bigger than it currently is. But for me, what gives me confidence is we have a very good, strong sales pipeline. Our sales teams are working hard to convert them, and that sometimes takes longer than you would want, but that, that's our goal, to continue to build our sales pipeline, and we're adding new challenge agents to our portfolio to continue to build on that. By 2028, by 2028, our target is GBP 100 million. Majority of that will be driven by organic growth, but we do anticipate, M&A activity, before then, and we've estimated around 10%-15% of that revenue coming from M&A assets. So we are currently in the search mode for M&A, and I, and I've spoken openly about this before. You You know, we, we are the only real challenge trial CRO in the world, so for us to acquire somebody, we, we have to be a little bit more imaginative. But we will wait and do the right thing rather rush into something just for the sake of doing an, a, an M&A. Quickly going through the agenda. So this is the agenda for today. As you can see, I'm not going to go through each one, but you have a dot on your badge that should give you an indication of when your tour is, which will take place after the trading update Q&A. So at that point, Stephen Pinkerton, our CEO, will come up and go through a few slides, a bit more color on some of the numbers I've given you, and then we'll have a short Q&A. Following that, you'll be able to go out and visit our lab or get dressed up in a hazmat suit, if you will, and go through our clinic. That's it from me for now. Next, I'd like to introduce you to Alex Mann. Alex has been here how many years? Twenty-five. 25 years. So he's been here for a long time. He's one of the gurus of the human challenge trial industry, and he's helped develop so many of the models we currently have. His scientific expertise is second to none, and, you know, I'd love you guys to pick holes in his presentations if you can. Thank you. Alex. Good morning, everyone. Thank you. Thank you for coming here today, and thanks, Mo, for the introduction. My name is Alex Mann. I'm Senior Director of Clinical Sciences, so my job really is to work with clients to design their studies, so they can get the best out of their products, and also to work with the business development team to get those contracts in the first place. So I've been, as Mo mentioned, I've been here 25 years. And the facility downstairs, which is absolutely wonderful, is vastly different from what I came into in 1999, where it was a spin-out from the Royal London Hospital, and we had a few offices and a laboratory—a couple of laboratories, and that was pretty much it. So where we were back then is when we did do our first quarantine in 2001. This was a flu characterization study. When we did this, we had to find a quarantine, and so we took out a wing of a hotel and built it up over 48 hours into a quarantine unit with all the infection control and everything. So it was a massive enterprise to do that. We only had 12 permanent staff, 15 temporary clinical staff that were working with us, and we would be then camped in for two weeks with these volunteers. We wouldn't leave. Our lives were over for two weeks. And then we would spend 48 hours making the hotel look like what it was before we went there and give it back to the hotel. So that was a massive logistical enterprise, whereas now we have a fixed facility or we had another facility before this, but once you have your own facility with everything under one roof, it's so much easier. We even built a laboratory in the actual car park as well, just so we could get the viruses on the cells quickly. So that was where we came from in 2001 when we started doing challenge studies at hVIVO, formerly Retroscreen. And the majority—Since then, we've probably completed about 80 projects, up to about 80 projects, and by the end of this summer, inoculated around about 5,000. So most of them have been with RSV and influenzas. We've also done, as you can see here, SARS and malaria and rhinovirus as well, but about half have been RSV and about half flu, a little over 2,000 in flu. So flu, since 2001, has remained an unmet medical need. Despite having vaccines, despite having antivirals, seasonal flu still causes significant morbidity and mortality. So generating better vaccines or more improved vaccines, as well as, dealing with viral resistance with some of these drugs, so developing new drugs, has been very important. So as part of that, over the years, we have tried to update our flu viruses, and flu remains a significant problem, and as you'll see, not only seasonal flu but also pandemic flu is a potential concern. So we need to develop these new flu viruses to compensate for that, and we have done so. We've generated several new flu viruses to meet clients' needs. The majority of our new viruses that we manufacture and then characterize and then use for clients are specifically contracts for clients, so it's to meet their particular needs. So there's been quite a few of those that are mentioned here that have been contracted with clients to produce. Others, we have produced a couple of our own to, in order to build those service offering, and we've also expanded to—we had about 10, we've manufactured about 10 new viruses over the last few years. seven—the ones that are most recent in green there. So one of the key things is, is the facility downstairs not only increase, helps us increase the volume of volunteers that we can inoculate per year. It sounds a really weird thing to say, but it does increase significantly how many we can inoculate compared to years and years ago. But it also, we've designed it in such a way that we can actually have other services. So as Mo mentioned earlier on, one of the key things was to make sure that we had a BSL-3 facility. So this is a high containment facility with state-of-the-art airflow, so the. As well as other, other operation, other elements. So this, this allows us both from the quarantine as well as the laboratory side, to do SARS studies and other BSL-3 pathogen studies. Previously, that was more difficult, and we had to use other facilities. So that's one thing that's been built into this. But in addition, we've also looked to expand other services by, through having this new facility, one of which is being able to do bacterial challenge studies and having laboratories to support it. And then also, quite importantly actually, and, and linked back to the pandemic preparedness, is really supporting clients and their products for their indications. So a lot of the time you take a vaccine or a drug to actually just treat yourself and make sure you don't have that severe disease or, or you are resolving that disease quicker. But there's also another element that's come into play a bit more recently, which is transmission blocking. So can I, can I not only treat someone but also stop them from producing as many virus particles and therefore infect less people? So we've built the facility with specific compartmentalization of the air flows to allow us to do these transmission studies. So what that means is, we'd inoculate someone and give someone the virus, and then we put them into contact with, say, five other people that haven't been given the virus, and they will transmit that virus to them in our facility. And the air flows protect our staff as well as the other volunteers from any contamination. So then what we can do is, we can either vaccinate or treat those people and see how much effect that vaccine or the treatment has on transmission blocking. So that's another really important new service offering we have. Just quickly to take a step back to actually say, well, what does What sort of data do we actually produce in those studies? I've got a couple of examples here from RSV on the left and flu on the right. So these are two antiviral studies, and they sort of exemplify a few of the endpoints that we usually include in our studies. So on the left, you've got virology. So this is the amount of virus that the people are producing. So the green line is people who haven't been given the drug. They've been given a placebo. They're producing a very large viral curve there in green, and then the blue and red are those that have been treated with the drug after they've had a confirmed infection. So completely smashing down the virus, working exceptionally well, and that was Enanta's RSV drug. On the right is another type of endpoint, which is the symptom-based endpoints that we developed, because obviously you want to know about disease. This one really here is about the duration of disease. So how long do you have your disease? And here again, this is a flu drug that was given about 24 hours after inoculation, and you see the red line, which is a much shorter duration of symptoms than the blue line there, blue dotted line. So they're just a couple of the endpoints that we use, and they produce extremely clean data that clients can make their decisions on. And so that kind of links, links back to why on earth do clients do these studies with us in the first place? So what's the point? So really, there's a couple of elements. one I just mentioned in terms of the data, it's exceptionally clean. In a quarantine, you don't have the issue of contaminations or community-acquired infections. We're very careful about making sure that people don't bring that into the unit, and then they're in their own rooms, so even in the unlikely event it does happen, they're contained, and it doesn't spread throughout the unit. So that's one element. So it's very clean data. But actually, one of the elements are, because it's clean, they can make decisions quite easily on which dose do they want to go forward with into the field studies, what's the safety like, what's the efficacy like? It helps them also optimize. They can choose which dose they want to take forward to the field studies, and also, either whether it works or it doesn't work, it helps them to de-risk going on into later phase. So if it doesn't work, it's maybe less likely to work in a field study if it hasn't worked in a challenge study, on average. So it helps to de-risk those programs, and it does so for quite a relatively small cost compared to those field studies. So you can do them in small subject numbers, whereas instead of thousands, you're doing tens or hundreds. Much quicker, you're less impacted by seasonal trends, so you could. Again, this is a weird way to say it. You could have a bad flu year, where you don't get much flu that year. That can be a problem for people, vaccine manufacturers, for example. You may have to extend your trial an extra six months. An extra six months to get onto the market can be a significant fund issue. So these studies are done very quickly. We can do them all the way through the year, no seasonal impacts whatsoever. But key elements are a lot of the biotechs come to us less trying to get, say, an uplift or to get attraction of further investment. So either they're attract, they're, excuse me, either pharmaceutical industries are interested in taking them on board or that product on board, or they can get the second round of funding that they needed. So it's really useful to succeed very quickly or fail quickly, so you can pick, you can pick which product you want to take forward. If you've got four products in flu, you can say, "Oh, okay, this one didn't work, this one worked better, so I'll take that one forward." Alternatively, you could try them all in a field study, which would cost a fortune. So all of these elements come together. You'll probably hear a bit later on also other aspects where other aspects of what clients actually are attracted to challenge models, one of which is speeding up the development pathway, and that can sometimes be facilitated by getting efficacy results from our challenge trials, which allow them to talk with the regulators and get fast track and breakthrough status. So that may shorten the back end of their approvals and again, save money overall. So these are just a few elements I just wanted to share with you. Thank you. Thank you, Alex. So next, we have a veteran of the industry. Hopefully, you don't mind me calling you a veteran of the industry. That's great. Stephen qualified from the University of Oxford, he worked in medicine, and then he spent 30 years in pharma industry across a number of companies. There's a long list of who's who, Lederle, Wyeth, Emergent BioSolutions, Sanofi Pasteur, MSD, Pfizer. He has been involved with all sorts of clinical development methods, including human challenge trials. Stephen is currently a consultant with Hurst Grange Associates, and he's here to talk about human challenge trials. Thank you, Stephen. Thank you very much. So he's told you all this. I've been around a long time, a lot of it in the vaccine industry, in clinical development, with a number of different companies, and I've worked at all stages of development, and using all sorts of, of methods, including challenge studies. So, you know, I see their place. So I'm going to tell you, why, why would a company want to do a, a challenge study? Well, of course, we're in Canary Wharf, it's all about the money. And, we know that, vaccine development, like any pharmaceutical development, is very expensive, and it's quite long. And of course, no CEO likes being told they have to wait five years for the results, just put the money in. What the world sees from outside is you announce a program, and you kick it off, and a few years down the line, there'll be a big announcement, hopefully a positive one, possibly, of course, a failure. It's all a bit of a black box for people, to some extent, from outside. But what you see from inside the company or the organization is gate, gate, gate, gate. More and more information needed to justify moving forward. And what you're getting to move it forward is money, and it doesn't matter whether you're inside a big company, where you've got to allocate internal resources and compete with all sorts of other exciting therapeutic areas, or whether you're a biotech, and, you know, you're looking to just keep up to the next time you're going to run out of cash. And what's worse is not only do you have these gates, they get bigger and bigger as you move along. So it gets quite hairy. Now, obviously, there are many other things in investment decisions, but I'm thinking about the information about how the product's going to work. And you can see that there's a gradient, of course, from very simple in-laboratory in vitro methods to tell you what the vaccine is looking like, all the way up through animal studies, human immunology may be very important. And then ultimately, the gold standard really for getting onto the market is an efficacy study. What does the vaccine do in the target population for the disease it's indicated for? And the cost and the confidence in the results moves up as you go through this gradation of different methods. And human challenge models, in my opinion, I don't know if this works or don't know, fits underneath the efficacy study. You don't necessarily know that it's going to be exactly like that because it may be you may be looking at a volunteer population rather than a you know, the actual eventual target population and so on. And it's a slightly unusual situation to be artificially given an infection that may affect the results. Nonetheless, the human challenge model gives you a lot more confidence than many of these other stages of development, and that will really help decide investment, and particularly investment before going in to a very expensive, very demanding efficacy study that will take you several years to get a result. So ideally, that's the place you want to fit this, is early in development, when you. It's not cheap compared to some of the earlier methods, but it's still, you know, a few million GBP compared to tens or hundreds of millions GBP for an efficacy study. I think this has already been mentioned by Alex. Within a challenge study, there are lots of different endpoints, so it's not a simple yes or no answer, which is important, 'cause if it was yes or no, if it's a no, you, what do you do with it? Actually, there's a lot of data in there that gives you an idea whether something, even if you don't get a statistically significant top-line result, you can say, "Has it got something going on in there?" And you can pick it out and try and understand how it's working. I'm not gonna go through all the acronyms. I hate acronyms. I don't know why I've got them in my slide, really. Now I'm gonna give you an example of somewhere where a challenge model could be incredibly useful, and I know there's a lot of interest: flu vaccines. So, the current flu vaccines all work largely by getting an immune response to the hemagglutinin antigen. There's another one in there, neuraminidase, but it's mostly hemagglutinin. And so if we have a new vaccine that's based, you know, may be a new technology, but it's based on getting a response to the hemagglutinin antigen, we've actually got pretty good methods for understanding whether the immune response we're seeing to this new vaccine is going to be useful in the vaccine. But the Holy Grail at the moment is a universal vaccine, a vaccine that's gonna work against all, flu strains, because the hemagglutinin changes for over, over the years. It changes, it evolves. Sometimes there's a big shift to go to a, a completely new strain, like in 2009. But we, we know about the antibody response to that. But for a universal vaccine that's using a different approach that will work against all the A, A, A, hem-- influenza As, and possibly even influenza B and pandemics, we can't use those responses. We don't know what they mean. This is a place where actually showing an effect in a controlled human infection model will give you real confidence to go into spending probably $hundreds of millions and several years doing an efficacy study in the real world. There are regulatory benefits. I think part of the reason they've got me up here is because the benefits of doing a challenge model is; it's not plain and simple. Each time you look at a particular pathogen, particular vaccine, there are slightly different pros and cons, so I want to be clear about that. Often, you know, the people think, well, maybe if you get a positive efficacy result in a challenge, that will help you get approval on the market. Actually, that's not always the case, but it can help you from a regulatory perspective. For example, with the RSV model, I know that several studies have actually been used by manufacturers to get FDA breakthrough status, which gives you certain advantages and speed of moving forward through the regulatory process to get the eventual approval. You know, it may help you by 6 months to a year, but of course, as you all know, six months to a year of getting ahead of your competitors and getting actually sales coming through the door when you've spent probably a decade spending money on development is quite a positive achievement. So it's been useful in these different situations. You can use. I'm used to using challenge models in vaccines, and that probably is their major area of value, I think. But they're also useful in certain other areas. In fact, you saw earlier, Alex showed you, I think it was Alex, showed you a result on a therapeutic and particularly for viruses, but I think there are many other areas. Steve's gonna talk about pneumococcus. I assume you're going to speak about pneumococcus, mention it. There's vaccines, but there is also interest in antimicrobial resistance and different bacterial infections, so people are developing new models to say, can you actually get a quick readout on antibiotics, as well as the antivirals? They may be useful in diagnostic development, and diagnostics are critically important in getting people the right treatment and preventing microbial resistance. And often, what you can do with a diagnostic is actually nest it inside a vaccine or a therapeutic challenge study, so you can actually get multiple things from the same-- I was involved with a challenge model for a viral vaccine, where we were also looking at the use of voice methods for diagnosis. I don't know if that went anywhere, but we were able to nest the study within another study. And finally, I wouldn't rule out the fact that there's a lot of basic biology to be learned from challenge models. And academic units, of course, many of them have their own challenge studies, which are important. And I think there has been at least one major study done by hVIVO, which was funded by a major research organization. Many different areas this could be used. Thank you very much. Thank you very much, Stephen. Next, we have a fireside chat, let's say. So, I'd like to invite Alex and Stephen Lockhart to the panel. We also have a new speaker for us on the channel, Professor Stephen Gordon. If you guys want to sit there, well, I'll introduce Stephen. So Stephen, he's conducted clinical and translation research over the last 30 years in the U.K. and in Africa, and he has a major expertise in pneumococcal challenge models. But he's also worked across many organizations, and one of the key things he's done is the CREATE project, which is a GBP 10 million project aiming at changing clinical research in Africa. He's now the Director of Experimental Medicine at the Infection Innovation Consortium iiCON), near Liverpool. So, I really wanna. I know this is not your area of expertise, but I'm sure all of you want to know about human challenge trials and what is the future for human challenge trials with regards to the industry. So we have somebody very biased from hVIVO, who thinks challenge trials are the only way forward. And then we have somebody from academia, very neutral, you know, looking to see how the academic challenge models can go into helping pharmaceutical companies to develop drugs on a commercial basis. And then, of course, we've got a veteran of the industry. So I, I'd like to open this up to everybody. We have microphones roaming around, so if you put your hand up, please, and introduce yourself and say where you're from, and ask the question. Thank you. That's fine. Coming. Right. It's Robin Davison. I would, I would like to ask if you could basically comment on how you can adapt challenge studies to mimic the sort of pathology in the field. I mean, if you're thinking of. I suppose there's a couple of things I, I was thinking of, like post-exposure therapies, where you might see the patient when their symptoms are at maximum level. Whereas, you know, obviously in the setting you have here, you, you're infecting them and then, you know, you, you might have to sort of adapt for that thing. But also, it also occurred to me that for ones like RSV, most people have been infected with RSV as a child, and the obviously, the market is for neonatal infants, isn't it? How, how do you translate the information you find, the data from the studies you conduct, into the setting where it's obviously by necessity different in the field? Good question. Yes, please. I'm glad you asked it because it's kind of the thing in the room, isn't it? It's t esting healthy young adults is one thing, but where you are in the field is the other. So, my background is I set up a pneumococcal challenge model in Liverpool for a decade, and then I went to Malawi, and I did the same in Malawi for the last eight years. But in answer to your question, first of all, I want to take it in two bits, if you wouldn't mind. The first is the relevance of the exposed person, and the second is the, which you mentioned, is the severity of the disease or, or the clinical stage of the disease. So on the people, I think ethically and in terms of community acceptability, you have to start with the safest possible model you can do, and then you creep towards those at higher risk. So in Liverpool, the people at most high risk of pneumococcal disease are elderly. So having started with young adults, we slowly worked up, so our older volunteers are now over 80 years of age, and people with lung disease. So again, we worked towards people who had mild asthma or chronic asthma. Yeah, so, so you can do it by stages. In Malawi, the people who are most at risk of pneumococcal disease are people living with HIV, and so we've just finished a human challenge study completely safely, with great community acceptability and huge support in people living with HIV. So the answer to your question is it can be done, but not as your first challenge. You start with your safest and then work towards the risk groups. I don't think there was a workshop in Kenya last year. I don't think there is any wish in the community to move to children because of the issue of consent. So I don't think you'll see a child human challenge. I mean, you might be able to work with it, but there was no appetite in the scientific community to take that forward. And then in terms of your question about the point in the disease or the duration, you can run a human challenge model for as long as it's safe, provided it's not severe. So we're working now with the idea of what a TB challenge would look like. Obviously, we don't want people to have frank pulmonary TB, but people could have a chronic skin lesion, and that's been done in leishmaniasis, which is another bug that lives in the skin for a long time. So I think, as with the first answer, you start with the safest, simplest possible model, and then you work towards the thing that is closer to the question you ask. So if you want to keep people in incubation for longer, you can. You can let the disease run longer. I hope that's a help. Thank you. Anybody else have any comment to that? Okay. Hi, James Gerlis from Tellworth. With regard to the acceptability of the human challenge trial and from both an industry and a regulatory perspective, is the, to see a real step change in demand, is the end game acceptability of the result from an efficacy perspective in itself, or is it- is there a big enough opportunity for the, I suppose, the methods from a, ancillary or a supportive perspective, like the breakthrough status you mentioned, Steven? Yes. I think, as Steve was saying, the other Steve was saying, it's about the population that you're in. So there has been a situation where a cholera vaccine was studied in healthy volunteers, and that was considered relevant to travelers because having a drop of cholera on your tongue or down your throat in a model is not dissimilar to how a traveler who has not been pre-exposed to cholera might actually like getting the real disease. Quite different, for example, than cholera in areas where it's endemic, where the pre-exposure is gonna be really very important. And so, yeah, I think the cases where it's gonna be useful on its own for registration are actually quite limited. I think it's mostly useful for, for decision making as you move through development. Does that help, Steve? Did you want to speak on this one? Just to add, that we're conducting a study at the moment called ACHIMA, Advanced CHIM Acceptability, where we're with groups and with individuals exploring what is the limit. And we're particularly asking the community of people living with HIV and the community of people exposed to TB about what would be acceptable and what would be the caveats. So I think it's important to explore with the community ahead of time- Yeah. Exactly as you say, does the ends justify the means, or does the process itself have to have? The answer is both when you're in conversation with people. Just on the regulatory acceptance as well, it's. I guess there's different layers. So one is in terms of for licensure, that's a very specific one just mentioned. But also the other thing is that even if you're getting data, so the FDA, for example, are getting this data, and they're accepting it for breakthrough status or fast-track status. They do like the data. They love the data. It's just, it's only specific situations where they like it for licensure rather than supportive data to support development. So in the land of acronyms, so CHIM, for those of you who don't know, is Challenge Human Infection Model. Controlled. Controlled, sorry. Controlled Human Infection Model. So it's. We love our acronyms, as Steve said. Pardon me. Hi, it's Max Herrmann from Stifel. Just a question on, perhaps beyond the antivirals and more into the sort of, infectious disease models that, obviously Mo's talked about, trying to develop in things like dengue fever and other sort of, mosquito-borne diseases. Kind of interested in how you envisage those studies get, being developed for, for a challenge, study. And then secondly, just in terms of where you, you know, each of you would see the most, need for additional challenge studies in, in different, infectious diseases beyond the ones that, hVIVO are currently focused- It's two questions with mosquitoes and other infectious diseases. But I don't know if you want to have a go or shall I give? Please, start. Yeah. So, yeah, the world's moving t he world is warming up. And so there's gonna be dengue in Cornwall, I would imagine, within some years, or at least the conditions where it could occur. There's no question that the range of mosquito-transmitted disease will expand. There's already a phenomenon called runway malaria, where mosquitoes travel in airplanes, but it's quite rare. But they, the mosquitoes are gonna get there under their own steam. So I think there will be a role for trying to model those diseases. It brings up the same question. It's hugely different whether you travel to an area as a tourist or whether you grew up with that disease. They're entirely different studies. So the malaria study is well. The malaria model is well-established and works well and is being rolled out in Oxford and London, and is now being rolled out in Kenya to try and understand what the two populations do different. In terms of the scope of the studies, they're not that difficult to do. In a facility like this, it would be pretty straightforward to have an insect room, and you infect the insect, and then there's something about the size of a Garmin watch that you put on a volunteer's wrist, and you can just directly observe through the lid how many bites they get. The advantage of that model is you can squash the bug afterwards, so you know whether the bug was infected. You can monitor the volunteer very closely. So logistically, that's not a difficult model to do. Epidemiologically, I think it's an important piece of work that can be done. And then, so there are several centers in the U.K. could already I'm gonna shout for academia, 'cause otherwise, I have to I, I think the discovery has to happen out there in academia, and then when you have something that's got legs and you want to run it at scale and in a reproducible way, then you step into a facility like this. Yeah. Mozzies, definitely. Other diseases, I think we're gonna talk about antimicrobial resistance, is where it's going. It's diseases that have antimicrobial resistance pose a global threat. Doesn't matter where they emerge in the world, they're gonna land up here on airplanes, so. Yeah, with HFEVA, we're very happy to collaborate with academics as well. So you saw, I think, probably dengue on the actual slide earlier on. So that is a collaboration with somebody who's already doing dengue in the U.S. They have restrictions on how quickly they can I mean, the recruitment is usually a bit more difficult in that setting, 'cause, well, it's a lot more difficult because, as you'll hear later on, it's a, it's a different thing, when it's done at commercial scale. But also, the other thing is they, at certain times of the year, they can't do the studies. Over here, we don't have the mosquitoes that transmit it, which- but in addition to that, we also put in layers and layers and layers of containment to avoid any potential transmission outside the unit. So yeah, that's definitely a collaboration with someone who's already done those Dengue studies in the past, so. Looks like we have our first volunteer in Max for our next dengue study. And just so you know, we need a CL3 level facility to run dengue trials. We have that, and we also have to have your lab comply with what's called Schedule 5 standards, which is basically the Met Police coming in and giving approval, the anti-terrorist arm of Met Police coming, giving you approval that, yes, the facility that you have is safe and secure enough to, for you to be able to store and process dengue virus. And they were actually here this morning before you guys arrived, reviewing our CL3 lab. So we are planning the facilities to be ready for a potential dengue trial here. Okay. I think, Melwin, you're- Yeah. I'll come back to you. I won't hang up. Thank you very much. Okay, uh- Melwin Mehta from Sterling Capital Management. I probably have two questions for Professor Stephen and, Mr. Lockhart as well. But, probably both of you can answer both the questions. I'll go one by one. hVIVO has had the success of, receiving FDA approvals already under these challenge studies. How have the regulators now kind of opened the idea, encouraging, whether in Europe or U.S. or Australia, to this whole concept of challenge studies? Do you want to go first? Well, I'm not sure I fully understood the question. I mean, the regulators are very interested in these as methods for understanding what vaccines and therapeutics are actually doing, and like us, interested in the fact that you may move things on faster if you get a useful result. So we find them all extremely interested. Yeah, they're regulators, so we have to be, we have to, you know, we're not looking for a pushover in a regulator. What you're looking for in a regulator really is an intelligent reflection on what the risks and benefits are of moving forward, and obviously, we think very hard about that as well. So you have to take that all into account. But yeah, no, very positive. Did I get your question? Yeah. Can I have a shot? Yeah. So if I can just add something that's not been said, I think probably because of the modesty of some of the presenters, is that the U.K. is a world leader in this, and it's a mile ahead of the U.S.A. Part of the reason for that is that in the U.S.A., the regulation of a human challenge study, the infection itself is regarded as a drug, and that's not very helpful because a bug is not a drug. So the U.K. actually leads the I think it's fair to say, leads the global stage in this style of study. So when your question was put, what do the FDA think of it? That's a particularly interesting group because the EMA, the European Medicines Agency, and the FDA do not see eye to eye necessarily. So, those of us in the game have been at several meetings where the different global regulators are up on the stage and asked exactly, "If we presented you with our data for whatever disease it is, how would you handle it?" So they're getting near to the same place, I think, in vaccine regulation, but they're nowhere near to the same place in allowing the studies. So Europe is going to continue to lead on the studies, and the vaccine regulators are going to use the data similarly, which is exactly as Stephen said, it's a step towards the efficacy trial. Can I add one thing there? Within Europe, I mean, obviously, the U.K. is now outside the EMA. Great shame, but there it is. But the regulation of clinical trials is a national competence. So actually, you find kind of big differences between what's done in different countries. Probably your biggest competitor in Europe is probably in Belgium, isn't it? Because and they're, they're, you know, likewise, they're regulators. And I guess it's partly necessity. You know, if you've got people coming to you with these studies, you have to develop expertise. And so, yeah, the MHRA is particularly knowledgeable. I wouldn't run the FDA down too much. I mean, they've got a lot of very clever people- Yeah. They understand, you know, they understand what's going on, and they do see the value. But I do think, yes, they're slower to get things going really in the U.S. in general than they are in the U.K.. Which is sad for them because a lot of the history of cholera and shigella and other challenge models came from the States. Yes but they kind of lost the plot somewhere on the way. Thank you. And if I may say, in terms of tropical diseases, are you seeing the UN getting involved with funded studies, other corporates kind of seeing that opportunity, especially a whole range? I mean, you already mentioned a few African countries, but how can this be kind of used in those environments? So, so my career has all been in spanning Europe and Africa and trying to work out how the health benefit that we enjoy in Europe can impact in populations in Africa. But, but in a contemporary way, we now are also trying to think, well, how can Africa play its role in, in health impact for the world, or India or Brazil or whatever? So, so it's this business about what's the difference between an endemically exposed population, and can we learn something from that population that will help us either protect our tourists or our forces or our visitors or whoever? Yeah. So thinking as a global village for health is one way. In answer to your question, are people investing in this? Wellcome Trust are investing a huge amount. The last grant was GBP 30 million to the Malawi unit. Outside Wellcome, NIH have invested a large amount through their Walter Reed institutes. I'm struggling to think who else is really investing. Seventeen billion. Oh, Gates. Bill Gates. Yeah, ungratefully, I forgot my first $100,000. Rescued me from academic obscurity. Yeah, so Gates, Gates is very invested in this space. Wellcome- Yes MRC a bit, NIH a lot. Yeah. What about the J&Js, Pfizers of the world? Are they looking at Africa in a new way now? Yes, because some of the vaccines, particularly, the, the one I know about is the pneumococcal vaccine, and we have a problem with serotype three. We have a particular problem with AMR serotype three in Africa, and so we're looking at ways to, you know, test the vaccine. But by doing it in this hopping method, do it first in Europe and then hop to Africa, look at the similarities, look at the differences, and see what we can learn. Thank you. Carol. Julie? Yeah. Hi, Julie Simmonds, Panmure Liberum. I'm just interested in what you're talking about transmission studies and as, as a use of the facility. I'm just wondering about how much they're done currently and how? So yeah, that's a good question. So in terms of transmission studies, so we have performed some transmission studies in the past. They are quite difficult to do. As much as we all get infections, you know, flu, rhinovirus, common cold, RSV during the winter, when you put it into a laboratory setting, it can be quite difficult to transmit, but you can do it. And so we have done that a bit in the past. The unit we specifically got is designed for that. It's not commonly done, I think partly 'cause it's a difficult thing to do, but it is being done more and more in other indications as well. But flu, so the main thing here is that we've designed the facility so it's more We've got a greater chance of being able to transmit. Then combined with our newer viruses, which, some of our more recent flu viruses are really, again, this is weird to say this, they're really good at giving disease. I mean, they give a very high rate of febrile illness, fever, you know, about 50%-60% of people we inoculate, which is really high. So in those type of situations where people are getting really strong disease, we're hoping that they're more likely to transmit to others as well, so the combination of two, the facility and the people. Just a comment on the same question. I'm on the safety board for the whooping cough, pertussis study, and there's been a sub-study done of all the people who share a bedroom with the ones who are inoculated, and there's never been a transmission event. There has never been a transmission event. In our pneumococcal studies, we've also studied the household members and the bedroom-sharing partner of inoculated people, and there's never been a transmission event. So the viruses are quite different, and the other diseases, despite our fear of these diseases, it's actually quite hard to demonstrate transmission. SARS itself, so when we did the SARS study, we found a huge I mean, the titers of the virus, this is, these are in people that really hadn't seen the virus up to that point. They hadn't been vaccinated. It was before vaccinations being going through the whole population of the U.K., and also, they, they had no evidence of immune, They were susceptible, based on their immune system, to the virus. So we inoculated 36, and 18 got infected, and some of them had huge viral loads, really high viral titers in their nose and throat. And then we found that we're looking at sampling the air, the surfaces, and also from breathing into masks, they were also transmitting a huge amount of particles, some more than others. So you may have people that are super spreaders, either due to behavior or due to the combination of behavior and the amount of virus. So yeah, I think SARS is going to be an interesting one to look at as well for transmission blocking, as well as flu and potentially some other organisms. I think the COVID pandemic was a case in point, right? So you had these amazing vaccines, which were, I mean, super effective, to be honest, and took a very short time to get to market, but they don't stop you from becoming infected, right? So not only were you infected, but you're also transmitting that virus to potentially somebody more susceptible to disease. And the goal with the new generation of vaccines that we are seeing from clients is mucosal vaccines, where you either oral or inhaled, and the goal for them is to reduce transmission rates, okay? Because, I mean, just imagine if you had a mucosal vaccine during the pandemic, I don't think you would need a lockdown, okay, or a much shorter lockdown, right? So that's the goal for the next generation of vaccines. We talked to a number of clients who are interested in doing challenge trials with mucosal vaccine, and we think that if we're able to get a transmission model to work, which is, by the way, a very difficult thing to do, just hasn't been done, that that's a huge benefit for a company to go to the different healthcare providers and say, "Not only do we reduce infectivity, but we prevent or reduce transmission." Okay, I think that's a huge advantage for any new product that comes to the market. So that's why we've designed this facility to cater for such events. I mean, the easy one to do, to be honest, it would be Norovirus, right? Mm. Because Norovirus is very easy to spread. Just have a buffet, and off you go, right? So that was the most simplistic one to look at, but there are ways of trying to do transmission studies across different indications. So do you have a question? Yeah. Yes. All right. It's Robin again. I just wondered if I could sort of steer the debate a little bit towards the ethical boundaries and how that, or they feature in the, perhaps the interaction with your clients. I'm just wondering whether, you know, you get asked to do something that you think, "Well, that's something I'm not sure we want to do, or the regulators won't like," because obviously, the regulators also have an input here. Or whether it, you know, in most often, you're trying to persuade your clients to do something which they themselves might feel is, pushing the boundaries of, what might be acceptable ethically, and, you know, you think you can do it, safely, for example. That question for me or the panel? Well, for the three gentlemen as well. Yes, certainly. Yeah, so, I think everyone takes the ethical aspects of this extremely seriously. And for every new pathogen, where people are thinking of a new challenge model I don't like the word challenge; I prefer CHIM, because although no one can remember what it stands for, to me, challenge sounds a little bit aggressive. But anyway, but whenever there's a new pathogen, there's a huge amount of discussion and debate in among public health, academia, and industry people about, you know, what you can and can't do. I mean, I'll give you an example. I've read some papers recently and been talking to people about Zika virus. So, you know, a lot of clients are probably coming to you to speak about. Because of the effects that an infection in pregnancy can have, that's why you want a vaccine, but at the same time, that's why people want to take a challenge model extremely seriously and make sure that you absolutely reduce the risk of such an event happening, because of the study you're doing. So I think it's taken very seriously. Manufacturers want to be seen to be ethical, don't want to push the limits. Companies like hVIVO, certainly, you know, you don't want a disaster on your hands, that would really be a problem. And the academic and public health community likewise, you know, want to take it very seriously. So I think there's so much debate, it's—it would be difficult to get anything done that people would disagree with. Steve? No, I'd agree. I mean, we very carefully look at all our studies. So we, for RSV, for example, I think an earlier question was around in the actual population you want to protect the kids. It does also affect quite significantly older populations with comorbidities, let's say COPD or other cardiovascular diseases and so on. So we wanted to move into the older population with RSV very carefully, and this was with a pharma group as well. And what we did was we very carefully went into that from 60 to 74-year-olds, but were otherwise healthy. They may have some acceptable other diseases that were not chronic and not at a big issue at that time. But the point is, we had also a key opinion leader working with us, a geriatrician, who's working with us to make sure the inclusion criteria into that trial was very carefully controlled, so the risk was mitigated. So in other words, I think as Stephen Gordon was talking about earlier on, was taking steps to take those models a bit further, but within reason, to a point where you're not going to do any severe damage or have some debilitating disease for that volunteer. That's really important that we don't do that. So I think, yeah. So, completely agree with the other speakers, but just two other comments for context. These studies, human infection studies, controlled human infection models, whatever you call them, are much, much, much safer than phase I for a new drug. If you dig through the history, the number of adverse events or that have occurred is tiny compared to phase I drug studies. So, people think it's kind of way out there and risky, it's really safe compared to testing a drug that's never been into a human. So that's just to put it in context. And the second bit is, I don't know if, depends which newspaper you read, but in Alex's COVID study, there was a full-page article of a volunteer being interviewed by the newspaper as to why they took part. And they took part I mean, a lot of you are the same age as me in the room. My kids were really frustrated in COVID that there was nothing they could do to help. You know, they just want us to lock down. Can we not do something to help? And this interview was all about how proud this volunteer was to have actually been able to step forward in a context where this is a, a global pandemic, and there's no treatment, and I have the courage to step forward to try and bring a vaccine to it. So, so, so that's echoed in Malawi. When we went out to ask, "Would you like to do a TB model?" They said, "Now you're talking. You're talking about a disease that we're really interested in. Yeah, this is, this is terrific," you know. So our, our CHIM volunteers want to wear T-shirts that say they've been part of this sort of study. There's a thing about, I'm actually doing something useful, where before I didn't think I had anything to offer to this. Mm-hmm. And then, just lastly, these studies are all ethically regulated, so you have to submit to an ethics committee, and they have to, you have to defend what, why this is a good idea to do that study. So we generally have three levels of supervision. There's the ethics panel in Malawi, there's the National Scientific Committee level, there's the sponsor level, and then there's the Liverpool School also reviews. So we have multiple reviews, and we've never had a study turned down. Leoli? By the way, that volunteer that Stephen talked about, he, he donated his compensation to charity, so he wasn't doing it for money. He was doing it for purely altruistic reason, to help the country to develop the next COVID vaccine. Hi, thanks. Laurie Telvica from Peel Hunt. There have been some recent developments in combination vaccines. I think there was a phase III from Moderna with COVID and influenza. Could you just run us through the mechanisms behind performing a trial for combination vaccines? Thanks. Sure. I can start with that. So combination vaccines, let's just take flu and RSV, just as a simpler one for two seconds, because you don't have to deal with the BSL-3 for a second. But flu and RSV, if you have a combination flu and RSV vaccine, you would tend to We have looked at it in different ways to see if you could vaccinate someone with that combined vaccination, vaccine, then challenge them with one virus, then challenge them with the other one later on. There's pros of that, which is the same people, and you're really looking at those people, how they've developed in their immunity. The downside is, when you in order to get a good model, you need to first screen all your population to make sure that they're susceptible to that virus. If you're now checking that they're susceptible to two viruses, you've now whittled down your number of volunteers to a much smaller number. So actually, sometimes you don't win by doing that. Instead, it's sometimes better to do different arms, a challenge with different viruses. So you'll just do a simpler study design, not a repeat challenge. But it's perfectly feasible to do those type, the COVID, flu one as well. Hi, James from Tellworth again. Just in terms of characterizing the rise in demand for human challenge trials from an academic and an industry perspective, how much of a does it feel like an inflection point at the moment or, you know, maybe post-pandemic? And if so, why do you think that might be? And equally, have there ever been false dawns in terms of when there might have been periods of excitement in the past that haven't quite followed through in a change in trajectory of demand? I think 20 years ago, we were faced with a lot of hostility, and I think largely that has gone away. People are reassured by the safety and by the intention of the scientific community. So the sort of, if you like, the suspicion has gone away. You must have been exposed to this as well. I think- The suspicion has gone away. Are we at an inflection? I, I think we're at a point of serious consideration. That slide you showed, where does it fit in the pathway? But that's becoming much more closely defined. Yeah. So Yeah, I was thinking of it from slightly different areas as well. So in the U.S., I think flu challenge has stalled for a little while as well. And so we were doing flu challenges in the early years, and ethics regulators were very supportive. They were proof of concept studies. They weren't for licensure. These were supportive to help people make decisions about their platform. And so from that perspective, we didn't see much resistance there. But in terms of more generally more acceptance among the community, so from regulatory, just generally more acceptance, 100% it's changing. It's definitely an inflection. I think a lot of the efforts from Wellcome and others to push the challenge models as well and their value add, and the safety profile that we've shown with the challenge agents, I think is definitely helping as well. So I think the history goes back quite a long way- Mm. Because regulation and the way we do clinical trials has evolved a lot in the last 40 or 50 years. And I think what's happening with controlled human infection models or challenge studies is kind of following on from that. So clinical trials now, ethics committees are absolutely required, and we do everything by the book. We're very careful about the risk benefit. Well, if you don't know that there's yet a benefit to a particular product, then all you have to worry about is risk. You're trying to show the benefit. So yeah, those things are all taken extremely seriously now compared to the way they were. I would say just before I joined the industry, these things were all still evolving. You know, GCP and so on was kind of new, and so challenge studies have benefited from that newer way of thinking. I say newer to me at my age, but the U.S. had a history with challenge models being done in incarcerated prisoners. I mean, it was still voluntary, but it was a horrible situation, and that really brought the whole thing into disrepute. And there were also, you know, the issues in the U.S. with untreated syphilis infections and so on in the past, that really put the brakes on a lot of this thinking. And I think in Europe, yeah, pretty much in Europe, obviously, since, forget the war. But since then, you know, things have been taken rather differently from the way they'd evolved in the U.S., and that's perhaps why we've got an advantage over the U.S. now, because they had that history that was so negative about infectious experiments. But there's also a thing that delay in getting a product to license kills products, so, and it killed the vaccine industry completely, and it may kill the antibiotic industry yet. I mean, yeah, unless there's a way of getting through the delays that you referred to in your talk, there aren't gonna be new products, and so this offers an alternative to a five-year, 50,000 people clinical trial. So it's kind of, I think people are testing how bright is this light? Mm. And the more- Right. The more products that get to market that have been through the challenge model in whatever indication, I think that will also give momentum to it as well. I think that would definitely be helpful. Great. I think that was a really interesting, really informative session. So I'd like to thank Steve, and Steven, and Alex for the presentation. To my surprise, we're on time, so we're punctual. Very good, guys. Thank you very much. So we'll now take a 15-minute break. Following that, some of my colleagues will go through some of the key aspects and the features of this wonderful facility. So if we could, if I could ask all of you to reconvene at 11:40, that would be great. Thank you. All right, guys, thank you very much for coming back so promptly. Really appreciate it. So we have a full session in the next, what? An hour or so. We'll go through some of the features of the facilities, and we'll have different department heads going through their own areas. So the first, I would like to invite Melanie Smy th, the happiest person in the company. She's been here for a couple of years, and she manages our clinical site, both this one here, downstairs, the quarantine facility, as well as the Plumbers Row screening facility and the one in Manchester. She's got extensive experience in nursing, as well as in the private healthcare. For those of you who are going to the tour later on at the quarantine facility, you'll meet her again, because she will be hosting that. So Mel, come on board. Thank you. Thank you. Good morning. Is it still morning? Yes, good morning. As Mo said, I'm Mel, and I run clinical operations here at hVIVO, so I look after the screening facilities, as he said, London and Manchester, and also our fantastic custom-built unit, which hopefully you'll come and tour later on. I've just got a few slides for you today. I'm gonna give you a brief overview of the floor plan of the unit, just show you the rough layout. I'm then gonna talk about some of the changes, which a couple of my colleagues have alluded to, that allow us to handle the Group Three pathogens. Then I'm gonna talk about some of the operational improvements we've seen since we've moved into the new build. The first thing is the floor plan. I've put a little key here, just to help with ease. The easiest way to think of the unit when you're looking at it visually is almost like two Cs. So the top C is rooms 1 to 25, and then around the bottom there, 26 to 50. There are 36 outside rooms and 14 internal rooms. The corridors, for anyone that's visited our previous sites, the space is a huge difference. The corridors are just under a meter larger than our previous facility, and each of the individual quarantine rooms is two square meters larger than our previous facility. Because the staff and the clinical staff were involved in the building of this unit, we've actually custom-built it to our needs. So some of the things that were sticking points in the previous site, we've ironed them out for the new build. So a couple of the things which I'll show you on the tour, we've built, for example, small alcoves in the walls for the crash trolley, so still accessible, but off the floor of the main operating area. We've also built it with a design that everything's doubled. So again, on the unit and the tours, you'll see it, but we have kind of two nurses stations, which you can see there. We have two pneumatic chutes for transportation of samples, double ice machine, double tissue weighing machine. And what this does for us is it allows us to be agile with our clients. So we can do one 150-bed unit if you want. We can fill 25, we can do 24, we can run multiple at the same time. Each of the individual rooms is its own negative pressure. So technically, if you wanted to, although I wouldn't do it, you could have 50 different viruses in this unit safely. The big change for me as a nurse in this unit is that the kitchen's on our floor. Sounds so simple, but actually, our volunteers get good quality, homemade food, and it's straight onto the floor. So in our previous build, the kitchen was on the ground floor. The unit was either on the second floor of the same building or across the road, whereas now it literally comes down into the air lock below it and straight into the unit. So these little changes have made it better for the volunteers and the staff. A couple of the things here, which we've alluded to previously, allow us to handle the Group T hree pathogens. So in our previous site, we could only handle, I think, up to Group Two. The main change is each of the individual rooms is built to hospital isolation standards, so each of the rooms within the air extraction has a HEPA filter to remove all bacteria and all viruses from the air. The HEPA filter or air handling system, I should say, maintains negative pressure in each room at about -15. So this allows, when you open the door for a few seconds, to maintain negative pressure and maintain containment. The air changes in the room, so the actual entire air of each individual 50-bed room changes eight-10 times an hour. And it also has its own failover system, 'cause obviously, I guess most people's concern is a breach of containment. The air handling unit, if it was to fail, actually has its own failover system, and backup fans will kick in to maintain containment of any viruses we handle. And something that Mo mentioned earlier is our backup power. So obviously, again, containment and power, we can't lose it. So this entire building is actually connected to two separate power stations via four lines. So if for some reason one of the four lines was to disconnect, there's an automatic switchover to one of the other three with no loss of power. And then, heaven forbid, both power stations were to go down, we actually have backup generators on the roof, which again, will do the entire building with no effort and no loss of power. Consolidation of our units was quite a big thing for me 'cause it was better optimization and better use of our staff and our resources. So for anyone new who knew what we were like back in early 2023, we had the Whitechapel facility, which was a three -floor hotel, and it had a seven-bed unit, six-bed unit, six-bed unit, each on a different floor. Very difficult to staff. We then had the QMB facility based in the university, and that was a really nice 24-bed unit, but again, across the road from the Whitechapel Hotel. So we were constantly using staff, myself, and labs to move samples across roads, up and down floors, into different labs. Now, what we've got is everything on the one site. So you have all fit We actually have more beds. So we had 43 inpatient beds. We now have 50 inpatient beds. So we're actually getting more utilization and more use of the facility with the same headcount. So we've gone from 43 inpatient to 50 and 10 outpatient to 14 outpatient with no change in headcount. And also, again, we're saving two members of staff each day that we're running high levels of samples. So it's quite a lot of operational efficiency in the move. A couple of things, again, as a nurse that we wanted to put in, the two-way call bell system, it sounds really easy. You think, well, everyone has a call bell system. You need to remember when you're working with pathogens, you're in full PPE to enter that room. So if you're a volunteer and you ring the buzzer 'cause you want a bottle of water, I would have to put on full PPE, respirator hood, the full machine, just to enter to ask you what you want, and then have to come out, don and doff the PPE, clean up to go and get the water, to come back, to scrub in, to give you it. This actually works like a phone system. So when you initially buzz, I can actually answer and say, "It's Mel. Hi, what do you need?" "Oh, can you just grab me a bottle of water?" "No problem." So we've actually cut our PPE use right down. So our PPE and respirator hood use is dropped. We're also getting faster communication, so actually, volunteers aren't waiting for us to scrub in, so they're getting that instant response, "Hey, it's Mel. I'm just about to come in. Can I get you something?" And also, it works out better for the staff in general. It's just a, I'm very happy we've got it. And then the second thing, which I guess is a lab and Mel thing, is the pneumatic chute, which is a savior. So previously, when I mentioned we were moving between the three floors and the two sites, we'd be physically handling samples in appropriate containers to the lab. This could take up to seven-eight minutes. If you're doing a PK day, where rapid blood tests every five, 10 minutes on every volunteer, it's doable, but it's very difficult. The pneumatic chute allows us to move the same samples in 30 seconds. So already we've got that agility, we can do more samples, we can process better, we're not using the runners to do simple tasks. Participant comfort was also a big thing, so a lot of money and revenue goes into getting these funnels and getting these people to take part in marketing, and it's a huge bundle of work. We want them to, when they get in the room and they meet me, to stay. We don't want them to go. What we've done is spent a lot of time and effort on making the rooms bespoke and really homely. Hopefully, you'll see that when you come round. Each room has its own individual air conditioning unit, so within a certain level, you can alter the temperature of your room. We've given everyone a large screen TV and a PS5, so they've got some things to do, keep them occupied. We've also went above and beyond with hospital-grade furniture, but still antibacterial and still fashionable. So basically, it still complies with infection control, but actually, it doesn't feel like you're in a quarantine unit. And I don't know if any of you know this, most NHS mattresses are only designed for about two nights of sleep. So you wouldn't want to sleep there for a week to 10 days. Some viruses, it's two weeks. So actually, again, we spent a lot of time and effort finding mattresses that are comfortable but still comply with emergency situations and also infection control. And again, I alluded to the food earlier, but food's a huge part of, of what we do. If you're in a room and you're getting tests done and you're feeling a little tired and a little mopey, what have you got to look forward to? Food. So actually, the food's amazing. We have an app that they use. They can order their breakfast, lunch, dinner, snacks, whatever they want, within reason, and it will be delivered to their door. And I added this. This was from Sohail, so thank you, Sohail. "The thing that I liked about this FluC amp trial," so this was somebody that's done one in Canary Wharf, "is that there were a lot of improvements since my last trial at QMB." So already, the volunteers, the information, I mean, we've only been open a few months, is starting to trickle in that they're seeing the improvement, and that means a lot to me. And another thing, which for me is a huge part of my what I do, is staff well-being and retention. Staff is an expensive commodity. We try and keep our bank-to-perm split roughly 70-30, so we've got that agility, but also we want to keep our staff highly trained, highly engaged, and present. So we've actually worked hard to build this team that we've got. The effort we've put in really to the welfare space here, these people are here for 13 hours a day, so we've put a lot of effort into here. You can see there's a little foosball table, there's drinks, coffee, cereals, that kind of thing. And you can see the team here. This was the picture they sent me on the day that we opened, which was really nice. I'll keep that forever. But this is a huge part of what we do, because actually, retention, or poor retention, is a profit loss for me. So actually, keeping staff happy, engaged, and wanting to work for us is a huge part of what I do. That's all from me, and feel free to ask me any questions on the tour later. Thank you. You should appreciate Mel. She has delayed her flight to the Open because of you guys, so bear that in mind. Next talk we have is on our FluCamp. The FluCamp is the brand we use to recruit our patients, which I'm sure everyone knows is the single biggest challenge for all clinical research. Sohail Nawaz took over our patient recruitment arm of FluCamp around two years ago. And he has experience with big pharma, biotechs, and consumer-directed engagement systems and operations, and he's come here, and he's basically overhauled our system of FluCamp. So he's gonna tell you more about that. Thank you. Just check it's morning still as well. So good morning, everyone. So, as Mo said, my name's Sohail, and I head up the patient volunteer enrollment team, and I'm gonna spend a little bit of time talking to you about FluCamp, which, as Mo touched on, is our recruitment arm within hVIVO. Now, it's a brand that's been used to recruit for over 25 years, so it has a lot of awareness, recognition, but most importantly, trust with our volunteers, that it's a brand that they can recognize with. And I joined the company just over two years ago, I was given a very clear mandate, that as our trials grew in size, and also grew in complexity, that we really did need to think about how we recruit volunteers into our trials. One of the things that Mo failed to mention at the time was, of course, that when you think about the viruses that we utilize, 85% of volunteers will instantly be non-suitable, won't be suitable for this trial, so they'll already be ineligible. Then, when you add in other layers of medical history reviews, because we really are looking for that small grain of sand in this big picture, 99% of volunteers will not be suitable. So we really do need to think about how we can recruit volunteers. That meant we don't just think, change things around the edges. We had to fundamentally change our recruitment strategy. So looking at the people we have, looking at the processes, but also in terms of technology. And technology plays a big part in everything that we do, and I'll touch on that later on as well. So in terms of the team that we have within FluCamp, there's about a team of around 100 individuals that we can call upon to help us and support us, all with a single goal of enrolling volunteers onto our trials. And there are three key strategies or stages within a volunteer's journey to be enrolled into a trial. First is recruitment. So this is where we do all our marketing, our creatives. We work with digital agencies and partners. We also now work with our volunteers to create our materials. And we have two dedicated individuals, a marketing manager and a marketing executive that takes care of that. We spend a lot of money on online social media advertising, so we also have an individual who looks after all the comments that come on. I think we all are probably used to social media or looking at reviews, but not many companies invest in actually the comments. And we've taken a quite an active role that actually we're able to support our volunteers and guide them where, and signpost them where they can get more information. That's the recruitment side. We then look at the enrollment, and one of the first decisions I took when I came onto this company, it was to bring our contact center back in-house. It's such an important part of our journey, or the volunteer's journey, that we wanted to bring that control and that quality back in-house. So every Our contact center is a hVIVO, they're all hVIVO employees. We're able to give them the right level of training, the right level of support, and we have an operations manager that looks after that. We also have an individual within the enrollment team that works closely with clients and our internal teams to develop an individualized recruitment plan. So, for example, Alex mentioned about a trial where we were looking at a particular type of group, so potentially elderly patients or elderly volunteers. I shouldn't call them volunteers, but patients. And we knew that using social media, for example, wasn't gonna be appropriate, so we had to think about different strategy in terms of how we can recruit. So that individual works quite closely with clients and internal teams, but they also give a regular update in terms of how we're performing and course-correcting as needed along the journey. One of the other things I'm very proud of is that we have a payment coordinator sitting in the team. Now, within the industry, it's probably the norm that in terms of paying volunteers or patients, it can be quite a slow process. I think one of our companies that we visited told us that they can do things within three weeks, we can pay them within three weeks. We can do it within 24 to 48 hours, and we're quite proud of the strategy and the systems that we have in place. So that's the enrollment, and then right at the end, of course, as Mel touched on and Mo mentioned as well, we have our two screening facilities, one in London, Plumbers Row, and the other in central Manchester. And this is where we bring volunteers in to do the initial screen, where we take their blood test and do their consent, and if they're then suitable, we then bring them in for a full health check before they're enrolled onto a study. And that's the team at the end there. One of the key things that we have is that we have a generic screening protocol for asthmatics and healthy volunteers, which allows us to recruit and screen volunteers throughout. What it does is allows us to speed up study timelines or recruitment timelines because we already have a bank of volunteers that we can then leverage and enroll into study, rather than wait for an official approval and then bring them on to study. So it's quite a unique capability that we have within FluCamp and hVIVO. We screen five days a week. Our capacity is around 1,000, but of course, we can change that higher and lower as needed, so we can work on the weekends, or we can do extended hours. We've done weekends in the past and able to do more than 1,000 as required. When you think about the volunteer journey, and I touched on this earlier, you know, the funnel that we have to do, and this is a 2023, there are various areas or touch points where a volunteer can fall out. What we don't want to do is bring volunteers in for tele-screening, which can be quite an expensive, not only in terms of internal resource, but also the effort that goes in. So we want to make sure that only those volunteers that are invited are the ones that have the highest chance of success. But of course, that means we're ruling out quite a lot of volunteers who apply. We then have our serology results, and as I touched on medical history, that takes out a huge batch of volunteers. So really, in 2023, when you look at the numbers, of all the leads and the volunteers that we engage with, 0.5% of volunteers made it onto a clinical trial. So that's the numbers that we're dealing with. Recruitment generally is about 30%-40% of a, a clinical trial's budget, and we also know that the number one reason for clinical trials to go over budget or to be delayed tends to be around recruitment. So clearly, we have to be very careful in terms of how we manage that and, and manage our resources, but also in terms of volunteers. And we leverage various tools. One is around strict control in terms of our invites, but we also do real-time analytics, looking at how our funnels are performing, and if there's any course correction required, we're able to quickly do that as well. Okay, so in terms of our database, so bearing in mind the funnel that I shared, traditional kind of recruitment strategies and organisations that you might engage with will be very keen to tell you about how big the database is, that we've got millions of patients or volunteers in the database. From our perspective, we only want to talk about those volunteers who are actually engaged and motivated to be a part of a trial. So I'm very pleased to tell you that we actually just took out 500,000 volunteers out of our database because they were no longer engaged, they were no longer motivated to be part of a trial. But what we do have is over 300,000 volunteers sitting in the database who applied for a trial and are keen to work with FluCamp or get onto a clinical trial. And of those, you can see the breakdown, over 200,000 are healthy, just under 80,000 asthmatics, and 40,000 what I term as special populations. Now, we don't do trials in patients, but we do get volunteers and patients applying to be a part of FluCamp, and they currently sit within our database. Now, we do do regular engagements with these volunteers, we do keep doing regular outreach, and we know from our own consent engagement that we have, that 40%-50% maintain the database. So we're maintaining that and removing any of those that don't want to be a part of the trials anymore. Something I'm very pleased to announce is that we're looking to. What do we do with all these volunteers? And we're going to be launching FluCamp as a service model. What this means is that we're going to be launching our volunteer database with other organizations, other CROs, other pharmaceutical companies. As I touched on earlier, the number one reason for delay tends to be recruitment challenge, and we know that. I'm not just saying this 'cause it's me, but we know that we're a market leader in recruitment. We know that the number of volunteers that we get through the door, in terms of our space online, it is the number one. So we know that we can recruit quite quickly and efficiently, and plus, we have this valuable database of engaged volunteers. One of the other things that we've also have is a loyal volunteer community. We have volunteer ambassadors that now work with us to create materials, which is more of a peer-to-peer engagement rather than driven by a company. We see huge uptake with the volunteers in terms of enrolling, applying, and of course, entering into our database. If I could just give you a figure from January of this year, 135 videos that were released into the online space were all done by our volunteer ambassadors, and only four of those were from FluCamp. So that's where we actually drove the video, and 131 were driven by our volunteer ambassadors. In terms of this as a service model, we want to also talk about the end-to-end service. We've got key partnerships in place. So for example, this part, one of the partnerships gives us access to 7 million patient database. But one of the other things that we did recently was sign a contract with Uber Health. We're all used to Uber. We use it to get from point A to point B. But Uber recently launched Uber Health, which is a service that allows patient transportation. So when we think about the future, 30% of volunteers tend to drop out in the long-term follow-up. This is where we can book in transportation six months in advance, but we can also monitor that journey. So we know if we need to have a team on standby in the clinic. For example, we're going to be doing a field study soon. We can have a team waiting on standby when the volunteer enters the unit because we can see their journey being mapped. And finally, in terms of technology, we've invested quite heavily. We will continue to invest quite heavily to really leverage automation. Just with the numbers and the sheer volumes that we deal with, as much as automation we can plug in, will help us in terms of managing our resources. And finally, what I'd like to touch on is that we're going to be launching FluCamp Portal. So this is gonna give access to our clients, and our partners, access to our database. So they'll be able to search real-time in terms of the volunteers and the patients that we have and be able to, engage with us, to engage those volunteers, to help them and support them with a clinical trial. We will be doing a tiered recruitment offering. Clearly, we recognize the different shapes and sizes of CROs and partners, so there will be three kind of layers that they can engage with. I'm very pleased to say that we just recently completed a contract with another CRO, a global CRO, who came to us because they were struggling to recruit for volunteers with quite a difficult patient population, recruit population. They wanted 50 referrals, and we were engaged with them, we understood their needs, we did a database search, and we were able to give the referrals within four weeks. It could have been sooner. We wanted to take a pause in the middle to engage and make sure that we were giving them the right leads and the right contacts. I think personally, we could have done that within two to three weeks, just with the database that we had and the quality of the leads that we were able to send over to them. This, of course, is now. We are talking to the company now in terms of the next step. So can we move it to the advanced and to the premium model as well? So just to leave you with some numbers, and these are from January to June 2024. So this year, with those videos that I mentioned, we had 16 million views online of the volunteer ambassador videos. We had 500,000 unique visitors to our website, and we hit a new milestone and a record with 18,000 applications in a single month of May of this year. And some of the other stats you see typically, we do around 17,000-18,000 screens per year. And this year, so far, we've already done at the end of June, 10,000. So we're on track to get to hit another milestone in terms of the number of screens we've done in a single year. Now, I'm hoping this works. What I wanted to do is just show you a video of a volunteer who came to our quarantine and, of course, made a video. Now, we vet the videos in the sense that they don't talk about trials, they don't talk about anything to do with the clinical trial, because that's, of course, protected data. They can talk about the experiences, that peer-to-peer engagement. So I hope this is gonna work. GBP 3,000 of FluCamp. Quarantine, day six. Today was another early start for some tests before I had my first decaf tea of the day. They've also provided me with plenty of other hot drink options, including mint, chamomile, fruit, and decaf coffee. Then I got myself ready for the day. After missing such nice weather at the weekend, I was kind of pleased to see the rain this morning. Today's breakfast of choice was a sausage and egg muffin and some overnight oats. Lots of you've been asking me whether you can work remotely whilst you're here, and the answer is yes. The nurses don't need you for much during the day, so you've basically got the freedom to do whatever you want to fill your time. I went for a baked potato with beans and cheese for lunch today, which was really good. I also started running low on snacks, so asked one of the nurses for a packet of crisps, and they really delivered. I was given popcorn, mini cheddars, lentil crisps, biscuits, cookies, and blackcurrant juice. A bit later on, another nurse bought me an ice pack face mask, some baby wipes, and some throat sweets, just in case I started to feel unwell in the night. This evening's dinner was spicy noodles with chicken thighs and a strawberry cheesecake for dessert. It's probably been my favorite meal so far. Stay tuned this week for more quarantine content, and feel free to use my referral code below if you decide to apply for FluC amp. As Mel mentioned, our volunteers tend to like their food, so as you can see. But this is a video that got 1.9 million views online. And again, as I say, it's that peer-to-peer engagement. Thank you very much. The line for FluCamp starts here, okay? Okay, next we have a double act. We got our two leaders from our lab. We have Marianne and Alison. Marianne joined here in 2012, and she's the associate director of our Laboratory Operations. Alison has been here since 2002, almost as long as Alex, and she's also the director of Laboratory Project Operations. All right. So my name is Marianne. I'm responsible for operational delivery within Labs, and today I'm going to tell you all about our amazing new facility just a few floor downstairs. So, our previous facility, since 2011, really, we haven't really have had any change in terms of lab space. Between now and then, obviously, the business has grown significantly, meaning that what we can do at our previous facility is pretty much servicing the clinical challenge, and we don't really have room for expansion. We can't push the water any further than we had. So yeah, just servicing the challenge that is. Our new labs here at Canary Wharf, we have been able to design them with the help of our architect teams, obviously, and we've been able to incorporate some new fancy little features just to make the best use out of the space and drive some efficiencies as well. In terms of capacity, we tripled the capacity compared to what we had before. Our labs are CAP-accredited, sorry, that's College of American Pathologists. We are also working towards gaining some UKAS accreditation, and our labs are MHRA inspected as well. So this is just an overview of the new facility. So there's five areas of main focus that we'll be diving into. So in green, you've got our Category Three lab, in blue, our processing and virology laboratory, in pink, our cell culture, in orange, our molecular facility, and then in gray/black, some flexible lab space. So we'll be diving into each of this area a little bit more. So starting first by our Category Level Three lab. So this lab is going to enable us to work with, agent Group Three pathogens such as SARS-CoV-2, dengue, and some potential bird flu strains as well. So this is something that's completely new to us. In the past, we have worked, at Cat Three level, obviously, but we had a lab that we rented from a third party, from a third party, excuse me. This time, we're going to have full of, full ownerships of this facility. We're actually in the process of recruiting a manager to take care of this area. And the fact that it's managed by hVIVO means we'll be in charge of the maintenance schedule, making sure that doesn't clash with our ongoing studies, for example, and also work to our hVIVO standard in terms of quality, so our own code of practice, rather than being sort of imposed somewhere else's. So lots of changes for us. Moving on to our processing and virology lab. So in this lab, we've got a tripling in capacity, and that's mainly due to the design of the lab. It's big, you'll see downstairs when you come. It's very open space. We've streamlined the workflows, and we've added some new features, such as a little hatch. So between this lab and the cell culture lab, we've got this hatch, so operators don't have to take their PPE off, walk in the corridor, go and collect their plates, do the same thing again, put their PPE back on, and then start working. They can just grab them from the hatch without having to change. We also have, as Matt mentioned before, a pneumatic tube system to dispatch the samples. So there are three dispatch points upstairs from us on the unit, all coming directly into the lab in one single location. So these features have allowed us to increase our efficiencies or do more with the same amount of staff, for example, as well as increasing our quality, not only for samples, but also for data. The cell culture and molecular laboratories, for both these spaces, we are doubling our capacity, so we've got lots of room for expansion. So as I mentioned before, this is very different to what we had at our previous facility, where literally we ran out of space completely. There, we've got lots of capacity to take on some different studies, lab-only studies, so supporting field studies, for example, or whatever they might be. So if we take the cell culture lab, for example, in our previous facility, we just had one pretty small lab. Now we've got three different rooms, so one dedicated for preparation and then two even cleaner rooms for actual, for the culturing of the cells, and they've got two more safety cabinets in each in total, so we can do a lot more. And then finally, one of the most interesting feature of our new space. This is our flexible laboratories, we call it. So something we couldn't do before was send out some proposals for potential contracts that are out of our current core competencies, such as, for example, some bacterial work. We couldn't do that because we just physically didn't have the space at our previous facility. This lab is allowing us to bid for this kind of work, because should we land such a study, which we're really hoping we will, we can transform this lab. So currently, it's an overflow space, but that could really easily be converted into whatever we need it to be. So for bacterial, allergy, or whatever else. That's really interesting. So that's it from me. I'll be handing over to my colleague, Ally, for the rest of our presentation. Thank you. Okay, so, following on from the overview of our exciting new state-of-the-art laboratory facility, the next question will be: what does the future hold for hLab? So I just have a couple of slides here to basically talk you through our vision. So for several years now, hLab has been at physical capacity at our current laboratory facility. We've been busy delivering clinical laboratory support for our human challenge trials. We often receive numerous requests from clients asking if we can help support them with their field trials, and this move to Canary Wharf will now be in a position to support more clients in this area of work that will sit alongside our existing services. So with this in mind, this seems like the perfect time to launch our goal for hLab to be known as a leader in clinical laboratory support and specifically targeting year-on-year revenue growth in this area. To help us achieve our aim of this standalone business offering, which will be separate from our current hVIVO services, we are introducing a number of new initiatives to bring awareness to the hLab brand. Next month, we'll be launching a dedicated website for hLab that will showcase the services that we can offer. Also, as part of the launch, we will be targeting a number of conferences that hLab will have a presence at going forward. The first of these ones will be the World Vaccine Conference, sorry, Congress in October of this year. So the increase in capacity that Marianne talked us through, along with the dedicated specialty suites, will allow us not only to expand our assay portfolio, but also the breadth of the pathogens that we can work with. We have plans underway to develop and validate a number of assays for a variety of the Group three hazard pathogens, and also to introduce laboratory services for bacterial studies. In addition, we are launching a biospecimen services that will provide clients with prospective samples that they can use for their own early-stage research. The increase in capacity also presents us with the opportunity to fully review all of our current systems, and we'll be looking to introduce automation in areas such as cell culture, which has traditionally been quite a manual process, and also we'll be reviewing our current automation and looking where we can improve and expand upon that in areas such as our PCR. These updates to the technology will be able to streamline our workflows and further increase throughput and capacity. The final step in that process will be to look at establishing the seamless interaction between our LIMS systems in the laboratory and our eSource systems, which is the patient management. So with regards to our assay portfolio, it's worth mentioning here that hLab-only business isn't something that's new to hVIVO. In fact, the company started out with this as our main service offering, and it has continued along in the background where it has been feasible. So at present, most of our clients in hLab come to us at the challenge model stage, and well, as I mentioned, we'll continue to do that work. It will enable us to work with clients much earlier on in the drug development process, supporting their field trials, which adds the benefit of continuity for our clients and also for the assays to be used similar in the field trials to what they are in the challenge model. So we currently have a number of serology, PCR, and infectivity assays set up for our challenge models. Over the last six months, we've been performing additional validations to make sure that these are suitable for the field trial model. In addition, we're continuing to develop new assays for hMPV and SARS Omicron and on the right-hand side, are options that we'll be able to develop in the future. We're currently at the scoping stage for many of these viruses, but these kind of list the key ones that we get a lot of inquiries about from clients. The expansion will also allow us to offer more of our PBMC processing services that we do on a bespoke level for our clients, additional biomarkers, and obviously, the provision of clinical trial kits. So, yep, that was my final point on that, and I'm looking forward to lots of exciting times ahead for hLab. Thank you. Thank you, Marianne, and thank you, Ali. Next, we have Eglė Pavydė. Egle joined the company around two years ago. She's our business director for Europe and Asia Pacific. She's had great success in bringing more awareness and more business from Europe as well as the Asia Pacific. She's got a number of years' experience in BD, including at a CRO called Biomapas. And I'd like to welcome her to talk to you guys about hVIVO. Hi, everyone. Nice to be here in front of you today. So I would like to start my presentation of talking a little bit of recent trends in the industry because I think we can be a world leader in human challenge, but if no one needs human challenge studies, you know, why to be a leader there? But we see that actually from the trends that are happening, we are really addressing most of those. So I would like to start with RNA virus vaccines, which are in the core focus, I would say, of development as well as treatments, and this includes influenza, RSV, and SARS-CoV-2, which are our core models right now. Also, we see zoonotic diseases, so those diseases which are transferred from animal into human, and we all know that we had the COVID pandemic happening in a way like that. There is now a lot of talks in conferences about avian flu, and in general, when we speak about the next pandemic, all the scientists in conferences, they are talking when it's gonna happen and not if it's gonna happen. So that's a definite. And right now, the two core targets are avian flu and influenza H5N1. Then we have climate change, which I think was also mentioned during the fireside chat today, when we have dengue, Zika, malaria, and those diseases are moving upwards, and it's becoming not only the tropical area diseases, but the problem for everyone. Therefore, we see more, more opportunities coming our way, especially for dengue. And then we have AI all the time everywhere in our lives. It's also in infectious disease research, when we talk about, finding the new targets in, treatments or viruses, but also doing the surveillance for the disease and predicting outbreaks. COVID-19 is here to stay. I think now it's clear for everyone, and I'm really happy that quite recently we signed a contract for further development of our Omicron model, and if this model is successfully placed, which I believe will happen, then we have some studies lined up moving forward for Omicron. And then we have next-generation mucosal vaccine. So when we are talking about vaccines, everyone is looking for breadth and for longevity of vaccines, the protection, so mucosal vaccines is something that is really in core focus for that right now. When we look at the market, it's really growing, so we don't see, like, some kind of decrease in clinical research in infectious diseases after the pandemic stopped. And what we really see that there is a huge increase in the funding from academic and nonprofit organizations, and these organizations are such as BARDA, Bill & Melinda Gates Foundation, Wellcome Trust, and CEPI. We see the numbers here. Those are, of course, invested over a period of time, but this is a good sign for, for everyone, for the biotechs especially. But we also see the industry investing still and more in infectious diseases such as Novo Nordisk, Pfizer, and BioNTech. When we speak about hVIVO, so we are, and we will be end-to-end human challenge trial service provider, but we also want to address more needs of our clients and go with them through a longer way in their development. So this includes patient recruitment services that, my colleague just talked about, the analytical lab services, specifically in infectious disease and respiratory diseases, and the clinical site services. So we want to move even beyond that. Right now, we are recruiting loads of healthy volunteers, but we also want to do patient studies. We already have experience in asthma, so infectious disease and respiratory diseases will definitely be something that we will be mainly focusing on. But here on the slide, you see the experience of our investigators, of our medics in the team, so they have a way broader experience. This means that we can run studies in other indications as well. A good example, I think, is a recently announced phase II-B field study, where we were selected as a single site in the U.K. We will be recruiting 1,000 volunteers, and I think you can see that there is already a big difference between what is recruited in human challenge studies and what is recruited in a field study. This will be done within an eight-week period towards the end of this year. We want to expand further our outpatient unit in Plumbers Row, and we are increasing the capacity of recruiting 100-200 volunteers per week. For that, we have different collaboration models. So what we can do is run a full-scope phase II study if it's within our capacity, or act as a full-service CRO. We also can act as a site in a phase II, phase III study, which is a good case study here on the slide, and what Sohail told about standalone recruitment services with subjects referral. When I'm mentioning those other things that we are doing as part of human challenge studies, I cannot skip to mention Venn Life Sciences, which is actually involved. This is our subsidiary, which is involved in all the backend services that we do. So medical writing of protocols for our studies, also data management and statistics. But they lead the journey of drug development of the clients from the very early stage, from the discovery to non-clinical, so animal research, and then moving to phase I. They are also expanding their capabilities in various ways, and I think right now we have much better collaboration with them, and we are working as a single large team. The last slide is a bit on our pipeline. So I think we are still predominantly having most of our pipeline coming from U.S. and Europe, but also the Asia-Pacific piece is growing in that regard. I think a very good example how Asians plan their studies was from one of the recent calls with a client. I was asking them: "So how likely that you are going to do a human challenge study?" And the response was: "If it's on our slides, we are doing it." So that is a very good way to show how Asians plan a bit differently, and they don't approach you if it's, if it's not in your plans. Then the distribution between the biotech and pharma, so we have more opportunities coming from biotech, but you have to understand that, of course, pharma has the big money, so more of those pharma opportunities are those which are materializing in the end. And when we look at the pipeline distribution between challenge and non-challenge, I was thinking about it yesterday, and I thought it's a good parallel, like, from what we had before and what we have right now in this unit, like flying with a plane. Before, hVIVO was only onboarding the business class passengers, which were paying huge amounts of money, and we were putting the luggage on the economy class seats. Right now, we want to onboard more of those field studies, which will definitely be lower in budgets, but then with the efficiency that we have right now, we can do way more for our clients. I think from the model perspective, we don't have one single model dominating, which again helps us distribute work more efficiently, distribute the recruitment more efficiently, and have different viruses in our portfolio. This is all I want to tell you today. Thank you. Thank you, Eglė. Okay, our final presentation is a brief overview of our trading update. Steve Pinkerton, our CFO, he's been with us since 2016, and he took on the role of the CFO in October 2022. So Steve, welcome. Thank you. Thank you, everyone, and, I hope you've, you've seen some of the management team, presenting today, and I do have to thank them for making my, my life so much easier because these results are pretty decent, as I'm sure you all agree. So it's much easier to explain and to walk through. I'm not sure how it works. This is, Right. So just touching on revenue, I think Mo's already alluded to the fact that we have accelerated, some project work, mainly because we were contracted by the clients to do so. They want to hit certain timelines, and we are working to deliver this, across those timelines, to meet those timelines across three different facilities. No small feat. But some of the interesting facts behind that is, we have done a record number of. Much easier to look from down here, isn't it? A record number of volunteers inoculated, 56% more. And if we'd had Canary Wharf at the first of January, we would have been able to do it all in Canary Wharf facilities. We wouldn't have had to do the other three facilities, but because we're transitioning, we needed those three facilities to deliver on. I think the other thing to mention is that, the challenge revenue per volunteer has increased, and some of this is mix, some of this has got to do with pricing. We are always updating our prices with new information. My team, the team, fully appreciate the number of metrics that we look at on a monthly basis. We go into grand, grand detail on all the metrics that we look at to enhance and to track how we're performing, both on our costs and on our revenues. So the other very important fact, to deliver this volume of work, we need a number of, you know, we need a high order book, and we started off the year with a very strong order book, and we have six studies in quarantine, across five different viruses. That makes recruitment and getting volunteers through the system to deliver that revenue much faster. Venn Life Sciences hasn't had a significant impact on revenue year on year, mainly because the exchange rate has gone adverse to them. But if you looked at the local currency rate, they have grown 10%. So a solid performance, and we're looking to do more on that side of things. Just to go back a little bit to the acceleration of client facilities, I know everybody's going to ask, well, how we've recognized the accelerating, accelerating fees that we've received from our clients to build Canary Wharf. We recognized some of it in 2024, 2023, and the rest of it is being recognized in 2024. So we will maintain our GBP 62 million full-year revenue guidance, and it's, you know, we're reaffirming it, and yeah, after a strong H1. EBITDA it, you know, we've had a significant improvement in volume. That means greater utilization across the staff and across the facilities. And actually, some of the interesting metrics about this is that I've highlighted that we, our volunteers grew by 56% year-on-year. Advertising, if I compare the advertising cost for H1 versus the advertising for 2023 versus H1 cost for advertising in 2024, it was flat, no increase. So, you know, we did a, you know, Sohail and his team have done a fantastic job in recruiting volunteers. So this is where some of the margin is coming through, and recruitment is our highest margin contributor to our EBITDA. Not in absolute terms, but in percentage terms. The highest margin is delivered by clinical operations and then laboratory work. So it, but just gives you a sense of where the money is coming from and how we are able to leverage our facilities and our work. The So one's just got to understand that this EBITDA is stated after running three different facilities, having overlapping costs. We are manufacturing new virus challenge agents. We've manufactured an H3N2. We're finishing off an RSV, new RSV, virus because Memphis has run out. We're just finishing it off at the moment, so we need to replace those viruses, and so that is also included in the EBITDA margin. So it really gives you a sense of, you know, next year, we'll get a real sense of what we can deliver, being all in one facility, but it's looking positive. And I'm glad you've all interpreted the guidance over here was full year EBITDA margin at the end of the mar-, at the upper end of market expectations pretty well. So thank you for that. Last bit on cash. Yes, it's up GBP 37 million, up from last year, but from December, it was GBP 37 million as well. So a couple of points to highlight here is, at December, client-held cash was GBP 16 million. So the underlying cash that we owned, that we could do what we'd like with, was GBP 20-21 million. At the end of June, client-held cash is GBP 7 million. We own GBP 30 million of that cash. Okay? So we don't see an increase from December to half year, and that's mainly because we've delivered the work, we've accelerated the work, so we've hit a lot of milestones, and it is for one of our big pharma clients, and they pay 60 days. And because we've hit a number of milestones since April, 'cause they've been in the unit in April, we've hit those milestones, and the cash is still coming through. So there's a bit of a delay, and unusually, we have a much higher increase in trade receivables. So that's what's holding back the cash, but it's just a timing issue. It's no issues other than that. Apart from that, then the last thing is, obviously, we signed a deal early in mid-June, and they still got the. Well, their booking fees and their startup fees were received in July. So it's a bit of a timing issue, but we're more than happy with that. So that's, I think that's enough on cash. Just only to highlight, there's no debt, and there's obviously with GBP 30 million pound, GBP 37 million pounds worth of cash in the books. And, that's it. We're open for questions, I think. Thank you, Stephen. Thank you, everyone. So, we are a little bit short of time, but happy to take two or three questions from the audience on the trading update. Oh, yeah. Laurie Telvica from Peel Hunt. So there was a brief mention about the field studies costing less than the challenge studies. Could you talk a bit more about the potential margins and costs associated with field in comparison to challenge? Thank you. So challenge trials, I mean, we talked about this, but we're a 90% market shareholder, and it's a very kind of scientific expertise you require, as well as the facility to run. So that is a relatively high-margin business. But field studies are much more simpler to do. There's the market is much bigger, but there's the number of suppliers is huge and lot of competition. So we expect to see a lower margin on the bids that go out with regards to that. But because we're able to leverage our current facilities as well as our resources to deliver those studies, we expect to see a better margin on delivery. So this will be our first major trial that we will be running in Plumbers Row. We anticipate we'll deliver similar margin to what we achieve with a challenge trial by utilizing those kind of, those synergies. Anyone else? Very quiet bunch of analysts. Great. Thank you very much. All right. Thank you. So I'm just gonna close out now. T eenage years. I have a teenage daughter, so I know what that means. We're still looking to find our place in the world. I think we, as a challenge trial industry, you know, there's a lot of good data coming out from it, but there isn't, we haven't reached the critical mass, I think, of the data that really puts challenge trials on the map with regards to the clinical development plan that the industry produces. I think over the last 18 months or so, the first time we've seen companies coming to us with their full development plans from phase I to phase IV and saying, "We have a challenge trial in our plans." Historically, that never happened. We have always had to go out to the market and convince clients to come to us and do the challenge trials, and that is something shifting. So but I don't think we reached our inflection point. But this facility, this milestone, is probably one of the biggest things we've achieved in the company's history. So I do wanna take this opportunity to thank all the employees, current employees, past employees, our board, of course, our customers, investors, supporters, academic partners, I think most importantly for me, the volunteers. Okay? I mean, without the volunteers, you can't develop drugs. I mean, something people don't always kinda remember. We need healthy volunteers and patients to volunteer for clinical trials to be able to help develop new drugs, and that's really key. You will have seen already from several conversations, we use the influence of the volunteer's well-being in the design of the facility. When you go downstairs and you have a tour, have a look, you know, you'll be able to see that for yourself. I want to thank everyone today for all the presenters for doing a great job, for the panel, for some stimulating discussion, and thank you all for attending this. At this time, we will be saying goodbye to our online virtual attendees, soon coming towards the end of the webcast. But the people online will have the opportunity to go on a virtual tour through the link that should be on your screen. So thank you to all the virtual attendees.