Well, thank you very much everyone for coming to this Capital Markets Day. I think it's going to be a very interesting, compelling day. It gives us an opportunity to highlight the evolution of hVIVO from a human challenge trial niche CRO to a full service, end-to-end, clinical drug development platform. Over the last 18 months, we have fundamentally reshaped the company. 2025 was a challenging year in some ways, but in other ways, I feel we have a much more broader, diversified service offerings for the company to our clients. This morning, you'll hear from our leadership team to go through some of the key changes and describe the new service lines we're offering right now. Also you will hear from a number of external speakers. I'm very pleased that we've got a really compelling lineup of speakers today. We'll have people from across academia, the investor community, pharma and biotech, and they will showcase some of the projects that we have run, are running, and also hopefully give you an overview of what the market stands at the moment. In the afternoon, we will also focus on some of the other. Sorry. In the second session after break, we will also focus on some of the other key areas, such as respiratory and cardiometabolic research. We'll finish off with a panel between a biotech and a pharma who both came to the conclusion that hVIVO was their partner of choice for their drug development. Be interesting to hear their decision-making process and why they both selected us as a drug development partner. After lunch, you'll have the opportunity to have a tour of the quarantine facility as well as the laboratory. If you haven't signed up yet, I'm sure there will be spaces. If you could let one of our staff members know, we can put you on the list and take you throughout what I think is an amazing facility. I am biased, of course. You'll hear this term a lot today, a new model for integrated early drug development. By integrated, it means that we do all the work in-house, so without third parties. We have full accountability on what we deliver on those aspects. Early drug development means phase I and phase II, including preclinical as well. We do, of course, run phase III clinical trials. We finished or are currently ongoing with the phase III work with Cidara, now Merck. We're also, of course, I'm sure most of you are aware, are planning, are in the process of building up to run ILiAD's phase III human challenge trial. Those are clinical sites activity, not full CRO services. When I was telling my daughter, my teenage daughter, that I was going to describe the company to people today, she said, "How long is your talk?" I said, "15 minutes." She goes, "That's way too long." I said, "How long should it be?" She goes, "30 seconds." I'm going to do my best in 30 seconds to basically give you a holistic point of view of what you expect to hear today. The key message is that hVIVO has evolved from a niche human challenge trial into a differentiated, fully integrated, early-stage drug development partner. Differentiated means that we have key USPs that no other CROs in our sector size has. For example, we have a genetic screening protocol. We have one of the largest clinical trial participant databases. We have over 200 beds in two different countries. We own our own laboratory. We own our clinical sites. These are aspects of what we have in-house right now that most of the CROs do not possess. Fully integrated. We have four service lines, so we can offer those services to customers as four standalone service lines or one fully integrated platform where we can take a customer from the beginning of the journey in preclinical all the way to phase II, phase III, and hopefully Rick from Decoy Therapeutics will give you a little bit more color on that. That's the TikTok generation summary. You can leave if your attention span doesn't go any further. For those of you with long attention spans, of course, this evolution of hVIVO means that we now to reset the investment pace. Why are we different? 2025, candidly, was a difficult year. The macroeconomic headwinds, I think, were suffered by many companies in our sector, and the vaccine field especially had a challenging year. I believe we came through that year even stronger. We diversified, we've acquired, we've integrated, and I think we now have an offering that is second to none in the industry. That diversification is already delivering. We now already have contracts in place for services that we didn't offer 18 months ago, and that's a key part of our growth strategy. The human challenge trial business is also seeing a pickup. We've signed three human challenge trial contracts already this year, and we have seen real good activity and momentum in the infectious disease market already, and Mario from RA Capital will highlight more on that in a little while. 2026, of course, we're very guided towards a high single-digit growth and where we have contracts in place, we have a very strong momentum in our pipeline, and we expect to deliver this year. That basically means we have a much more stronger investment case. I think the one key message again really is that we have multiple ways to win now. Whereas historically we were only reliant on human challenge trials, we have much more diversity in getting our message across. This pie chart shows you how we have diversified through our revenue base across the different service lines. The numbers for 2024, 2025 are actual numbers on revenue generated across the four service lines. You can see 2026 forecast is more diversified than ever. Of course, this is partly due to the cancellations in 2025, but also due to the growth in the other three service lines. That growth will continue, as we are able to effectively expand our target market because we're able to reach clients at different stages of the clinical development process. When it comes to capital allocation, we remain fairly disciplined. It's key for us that we don't stretch too much. Our first key priority for growth is organic. We've already seen this. For example, we've added new equipment to our laboratory capability, which Chris will talk about. We've expanded our challenge models, which Andrew will talk about later on. This is our core aim is to grow organically, we will also be open to further bolt-on acquisition that enhance and fill the gaps that we may currently have. Of course, return to shareholders when appropriate. We will be looking for M&A assets going forward, they have to be a right fit for us, both scientifically, also in the right clinical space. If it gives us an ability to expand our therapeutic areas, great, or geographic presence, that's also a good asset. The one key factor we want to keep is that it must give us the capability to cross-sell to our current services. CRS has given us that. Customers from CRS, for example, are now able to take advantage of the hVIVO services and expand what offerings we have with them. We've shown with CRS and CryoStore that we can acquire, we can integrate, and we can make those acquisitions profitable as we expect both CryoStore and CRS to be profitable this year. What we will not do, as I mentioned earlier, is we will not stretch too much. We will not have huge debts and go for non-adjacent services. That's a key strategy for us as we move forward inorganically. When it comes to future projections on some of the key numbers, I think our medium-term target really is to continue to grow our revenue base by 10%-15%, expand our EBITDA margins. Our goal really is to get to 15%-20%. That will, of course, depend on the revenue mix from the different service lines, and that's something we're currently looking at. Expand our cash conversions and continue to improve our book-to-bill. This year, as I mentioned already, our sales has been going really strong, our pipeline remains second to none. One question you have to ask really is why are we doing this? Is there a real market gap for the new hVIVO? Okay, that's key. If you look at the current, the way the drugs are developed. To get to phase II, it costs around $200 million. It takes around six years. Majority of drugs fail at the phase II to phase III stage. Phase II is the really key stage for any biotech to really get a good valuation. That's where you show first signal of efficacy. 80% of the trials are delayed due to enrollment issues. That's one of the key things we offer is commitment to patient enrollment. In a phase II, you typically need to outsource to a CRO and laboratory, multiple sites, a patient recruitment company, and so on. That fragmented outsourcing model really increases inefficiencies, hampers quality, and also makes studies last longer. Our offering is that through our scientific and medical and clinical consulting, we can help clients design the right protocol for their needs so they get the data that they need to get to the next stage. That integrated tech-enabled one platform offering means that on a single contract, you can go from preclinical all the way to end of phase II. One single contract. Every party working from preclinical to phase II is under our umbrella. We are fully accountable to the customers. I don't know many of you have CRO experience, but some of the sponsors will know the number of times the CRO says, "We are doing our best, but the sites are not recruiting." No one is taking accountability for the delivery. We own our own sites, we will take full accountability of delivery of our study on time basis. To help the client to get to a no-go decision much sooner, much faster, much cheaper. At the end of the day, the whole goal of the community really is to get medicines to patients faster, and that's the role we want to play. If we look at it simply, human challenge trials is a unique way to show efficacy really fast. We're trying to do the same thing with other indications. Effectively speed up the process going from preclinical, first in human, to proof of concept. That's key for us. We are doing this right now for respiratory and for cardiometabolic, but there is an opportunity for us to continue to expand those therapeutic areas into other primary care indications. I'm not going to go through this in detail because my colleagues following on from me will talk about this in a little bit more detail. The key message really is that we have four verticals, you can take each one of these service lines as a single service offering, and we have one horizontal. In other words, you can have a client from the beginning all the way to the end working through the system of the four service lines. At the bottom half of the slides, it shows you where our service offering is based on the clinical development stage across the program. What we now have is multiple entry points. Historically, for example, all human challenge trials, with the exception of what ILiAD has said, had been phase II. That's it. We only had customers who were ready for phase II. Now we have a much more broader target base. Effectively, our TAM expands significantly. How this sits is really interesting. Our consulting team, of course, a very experienced team. Katsu here will talk about some of their expertise and experience. For us, I see that almost as a lead generator for the follow-on activities we run. The CMC, the PK work that the team does means that those clients, as they move through phase I, phase II, can increase the business in the other service lines as we move forward. The human clinical trials with the acquisition of CRS and cardiometabolic research, I think everyone here in this room knows how much obesity is increasing, and every other company is trying to get in this area. The fact that we got one of the European leader, KOLs, on board means that we can really work hard, and we are doing really good work right now with some key obesity leaders in the field. The other thing, the uplift from CRS means that historically, CRS used to outsource a lot of their work because they didn't offer the full service in-house. Now, being part of the hVIVO family, we can keep more work in-house. The value of a single contract suddenly increases on a single sale. The human challenge trial business, hopefully, I don't have to say a lot to you on that. We are the world leader. We continue to drive that effort forward. Andrew will talk a lot about that. One key thing I think is important that you're seeing this vaccine, anti-vaccine sentiment in the field. You've seen increase in infection rates across the board. What we've seen is there's an uptick in antiviral research. Two of the three challenge trials we've signed this year have been in the antiviral scheme. For us, if you can't prevent it, you have to treat it, and that's what we're here for. Finally, the lab business. When hVIVO originally started as Retroscreen, it was a laboratory company. During its evolution to human challenge trials, it basically catered for only in-house work. Since 2024, we've relaunched laboratory as a standalone business. It is beginning to do really well. There is one error here on this slide. The cardiometabolic research market is GBP 64 billion, not GBP 64 million. Just a small error. My final slide really is to show you what does the market look like as we go forward. On the left-hand side, you can see a chart in the early stage clinical development market, where we sit and how that's increasing around at a 9% CAGR across the board. The pharma companies are coming up a huge issue. There's a GBP 300 billion patent cliff in the next five years. They have to get new assets into their pipeline. Okay? They also have a lot of cash. Okay? They can wait and pay a higher amount for de-risked assets. They're basically waiting for biotech companies to do phase I and phase II, get proof of concept before they're really impressed. You see a lot more late-stage buyouts in the market at the moment. For us, this means that biotechs have to do this work themselves now. Okay? For biotechs, time is money. Time is everything. Okay? The fact that our model can deliver phase I, phase II together is really key. There are not many companies out there that can do healthy volunteer studies and then shift into patient studies at the same time. We have that capability because we do have a database of healthy volunteers and patients. Speed does matter for these kind of companies. This is a real key that our proposal to do combo, phase I, phase II trial, I think will have a significant interest, especially in the biotech markets. The investment we have made in building a system under FluCamp and now a similar brand in Germany to develop patient recruitment capability, I think is going to be key for us. Okay? There are more and more clinical trials done now than ever before. These trials have eligibility criteria, which makes it harder and harder to find the right patient for the right trial. This challenge will continue to get harder. Okay? I believe our use of AI in the platform we're using in the patient recruitment aspect, I think will be key driver for us. Trials are more complex than ever before. Clients want to measure 101 different things in a given trial. Our scientific and our clinical expertise we have, I think in-house, is really key. There are experts in the room, and to be honest, without them, we would be nowhere. I do thank for their experience and expertise. What I will do next is to introduce four people to talk about the four service lines. Katsu will be talking about our consulting service line. Mel will talk about clinical trials, Chris will talk about our lab, and Andrew will talk about CSO. Thank you very much. Good morning. My name is Katsuhiro Mihara. Thanks for your introduction. I'm delighted to talk about hVIVO consultancy business in the next five minutes. This is a snapshot of early development journey. As Mo talked about, historically, hVIVO has focused on clinical stage activity, like stage 3 here. As you can see, development starts much, much earlier. Our engagement with the sponsor actually starts at the moment of candidate selection, where sponsor's primary interest is whether or not their development regulatory strategy are solid, robust for their success. Our role here, stage 1, is strategic consulting, defining, rationalizing the strategy for sponsors. Also help develop the strategy for startup company for their fundraising support. Next step is CMC and non-clinical, where sponsor will face an important decision point, which is a vendor selection for manufacturing and GLP tox animal studies. This is a costly decision point with high risk. Based on recent FDA metric, 75% of the drug non-approval is because of CMC manufacturing quality issue. It's really important, essential to have the right vendor from the start, especially for the manufacturing vendor. Our expert will define and identify the best matching vendor for sponsors, balancing the technical, scientific, cost, and timeline. In the development, sponsor will face issues, but we steadily troubleshoot them to maintain the clinical entry timeline, but also budget in control. Next step is clinical. We will support the designing of the trial, but also translation of the dose from pre-clinical to clinical. We hand over project to clinical trial service of hVIVO for the trial execution. I'm really excited to talk about our recent collaboration initiated with the Decoy Therapeutics. CEO Rick Pierce is also here today, who is really developing the innovative drug in a very effective way. I'm very impressed. Our collaboration begin from the actually rationalization of the clinical dose for the phase I trial. Collaboration will continue to the clinical state of the collaboration. Next to dose, we also support regulatory support, consultancy support. The development being highly complicated, sponsor will face issues, borderline matters, which may require some deviation from regulatory standards. This can happen in the drug development. Those need to be really properly discussed with the regulator. Experts have a strong expertise in the regulatory interaction, knowing exactly how to formulate question, also how to present data effectively to the regulator. Lastly, in collaboration with the laboratory service of hVIVO, also support the biomarker bioanalysis strategy. The key message here for the consultancy business is that we drive early engagement. The sponsor unlocking the potential value creation for the company. How do we actually contribute a long-term value creation for the company? First item we already talk about is early engagement, stepping into a strategic stage early. Secondly, we have trusted expertise. Our sponsors are coming back to us repeatedly for support. One typical example is the venture capital investor collaboration. Over decade of years, we have been collaborating with several renowned venture capital investor for their asset evaluation, like Jude Asians. They come back to us because they trust our expertise, also commitment and dedication. Third aspect is that long-term relationship. Our consulting does not stop at phase I, but will continue phase II proof of concept and phase III, positioning hVIVO a long-term strategic partner for sponsor. All of these aspects will help create more opportunity across the trial service, challenge study, and also laboratory service, leading to the sustained revenue creation for the entire hVIVO company. Thanks for your time. The speaker is Mel. Perfect. Good morning, everyone. My name is Mel, and I'm here to talk about the hVIVO clinical services arm. I guess I wouldn't be a very good site director if I didn't immediately acknowledge the massive increase in capacity. We now have over 200 beds dotted into four clinical facilities here in purple that you can see. We also have our additional sites in white, which do our consultancy, our biometry, and our biobank services. I made this slide to really show you the true breadth of service that we can offer to our clients. Really the end-to-end vision. Somebody can come to us with an idea and inspiration, and we can bring it into reality. I've deliberately highlighted the purple box because these are things that are unique to hVIVO. First of all, our genetic screening process. We actually genetically screen volunteers and patients throughout the year, despite site activity, to build this incredible participant database. At present, between U.K. and Germany, we have over 400,000 participants ready and waiting to take part in our research. Most CROs, larger CROs, will rent sites when they want to deliver a study, so they'll hire a small facility or a couple of small facilities. As Mo has alluded to, we wholly own all of our clinical facilities. This gives us continuity in our delivery and also continuity, for me, importantly, in our quality of data. This is to give you a visual of the two databases. Obviously, FluCamp has been going quite a long time. Thank you, Soheil. The U.K. database is on the top, and this is our German database on the bottom. The text at the left was really to show you where I felt the benefits of the integration. Our German colleagues have actually had a very successful GP networking community event. They've had great attendance. We are bringing that to London, and we're very excited to bring that to London. We're also enjoying their expertise, thank you, Thomas, in cardiometabolic and renal, and we are integrating all of our systems. Most of them are already done. We've integrated our FluCamp databases, we've integrated our IT systems, our quality management systems, and also our financial systems. We're well on the way. My last two slides were really just to show you our diversification beyond challenge. This slide's about London specifically. In September 2024, we made the jump and thought, "Let's do more outpatient, more traditional style studies." Since late 2024, we have contracted and delivered seven studies, which is actually incredible. We are well known for our respiratory work, but we've started to branch into more severe asthma or complicated recruitment asthma like eosinophilic. We've also had great success with our older populations in recruiting for those studies, and we've proven that we can deliver large volume in a short period of time. This is my favorite bit because this is 2026 and beyond. What next? Where do we go? For me, it's taking the learnings from Germany and diversifying and pushing forward. We are in the final stages of discussions for studies for COPD, type 2 diabetes, high blood pressure, and obesity. Very exciting stuff. To finish, I would like to talk about our German colleagues, obviously way above us in numbers with regard to this type of study. They've delivered a whopping 114 studies since 2020, which is incredible. They also have very unique partnerships with Europe's largest university hospital, UKSH. They're going to continue with the stuff they're really good at. They are key leaders in these areas, they're going to carry on with the cardiometabolic. In 2026 and beyond, this is studies they do, but they're advancing and progressing them. Moving more into drug-drug interaction work, bioequivalence work, and progressive liver disease. I think to conclude, I just wanted to say, for me as site director, the integration has brought together our expertise, our capabilities. We're now able to finally deliver multi-site studies across the U.K. and Europe, we're well-placed to expand in the future geographically within Europe and beyond. Very exciting. Thank you. Good morning, everybody. Hopefully, you can hear me. I know I've got some vertically challenged colleagues, so hopefully the microphone on the jacket is compensating us up. I'm Chris Forsdyke. I head up the hVIVO Laboratory Services Group at hVIVO, over the next few minutes, I'd like to tell you a little bit more about how we are well-positioned in the current outsourcing market, how we continue to invest and drive to solutions-based approaches technically to our clients, and also from a future-looking growth perspective, how we can certainly tap into and drive the integration and the adjacencies to where we operate at this moment in time. First, a few kind of details, I guess, around the numbers in the market. Hopefully, everybody's aware that the global outsourcing market for bioanalytical services is a multibillion-dollar industry, projections from various sources predict that that is going to continue to grow fairly extensively in the high single digit, maybe even the low double digits, over the next four or five years. On top of what is good growth, there is obviously the continued expectation from clients that we have a growing complexity of needs analytically, that needs to be derived from samples and projects that we work with. There's a demand for first-time right data electronically delivered to influence real-time decisions, either at the manufacturing or the clinical phases of those particular projects. hVIVO really over a number of years have obviously invested in not just the platforms and the science, but also the engineering and the facilities that we operate in. We have a number of advantages and differentiators really at this moment in time, ranging from the well-engineered bio-safety level 2 and 3 facilities that we have that often have a relatively high cost of entry for potential clients. Therefore, it becomes more economically savvy to outsource that type of work. We've obviously got a lot of assay development expertise that have been built up over decades of working on the human challenge trials amongst other kind of projects. That integration of the clinical knowledge with the laboratory knowledge is obviously something that you can't really kind of monetize or kind of qualify, but brings a lot of value and added momentum to what we can offer. Obviously associated with that as well, the dedicated scientific project management overlaying what really is a wide diversity of laboratory capabilities that we have established, ranging from virology through all the techniques and platforms that you see there through to cell-based assays. Effectively supporting sponsors from assay development, through clinical trial execution, and regulatory submission using robust regulatory platforms, and ultimately the data that we provide as primary or exploratory endpoints. I won't go into too much detail on this particular slide, but this really sort of signifies the transition that we are making with our investments as well to transition from more of a transactional laboratory partner to more of a solutions-based partner. If we look at the 2025, 2026 investments, especially in the molecular biology space, we are now able to offer our clients and potential clients a whole series of solutions tailored to really the requirements of either the preclinical or the clinical projects from rapid PCR testing through whole genome and variant analysis using next-generation sequencing. Then really kind of multiplexing at the molecular level, driving automation to obviously increase throughput and robustness, and effectively being able to offer clients much more information from decreasing sample volumes, which are obviously expensive to generate from either the clinical or pre-clinical aims. One example I will pick out from that slide is the diagram or the picture second from the left, which is our next-generation sequencing platform, something that we have traditionally outsourced over recent years, that we invested in at the end of 2025 and brought in-house expertise alongside that in early 2026. Already we're seeing a very healthy backlog within that NGS space to the point where that instrumentation and the investment has effectively paid for itself through the work that we've already conducted in the first half of this year, in combination with a backlog through the remainder of this year and into 2027 projects as well. Effectively, our next phase of laboratory growth for the standalone work, in addition obviously to supporting the hVIVO portfolio, will focus on continued investment in terms of automation and making sure that we have the latest equipment from a regulatory perspective to serve the client base that we're interacting with. Also on the IT front, we continue to invest and drive our introduction of our laboratory information system, which is our journey really to go from a paper environment to a paperless environment, and really being able to deliver data to our clients in real time for real-time decision making. Skipping over to the right-hand side, again, we have a great opportunity to continue to tap into the analytical requirements of the growing hVIVO clinical operations, not just in infectious disease, but also with our Germany colleagues in that phase I space. Really expanding because a lot of the platforms and capabilities that we have overlay into different areas of drug development and making sure that we actively pursue our pre-clinical aims, so that, again, in line with what Mo presented earlier on, we have a full spectrum of discovery pre-clinical through clinical development of laboratory services. With that, I will hand over to Andrew to take us through the human challenge. Thank you. Good morning, everybody. I'm really delighted to have the opportunity today to actually update you on some of the advancements we've made in our human challenge business. We're really proud, actually, the fact that we are externally recognized as being the world leader in developing and delivering commercial human challenge studies. That is really after a lot of decades of working in this space. Over two decades of working in challenge studies, we now have done 81 different challenge studies. We've inoculated over 5,000 participants, which is a really large number for challenge studies. Importantly, we have 13 distinct different challenge models. To deliver this takes a really big and specialized infrastructure. Mel's already talked to us about her clinical sites, and of course, that in terms of the challenge studies is a 50-bed unit, which comprises the en suite rooms, which are so critical for that infection control you need to be able to do these studies. Encompassing on that, of course, you can't deliver these studies without the great recruitment team and of course, laboratories. Really what I'm saying is, just like Mo was pointing out, that we have four independent service lines that can contract separately. Actually, human challenge studies has always encompassed all of those different aspects. Scientific consultancy is absolutely critical. These are very niche studies, and they take a great understanding of the pathogens and the nuances of working with challenge studies to be able to develop them and work with our customers. Of course, the clinical trial side, which is not only the site, but actually the recruitment, the medical writing, and the stats team. All of that comes together to be able to deliver that trial. We're really proud of the fact that we do all of our own laboratory work on this as well. We believe this is really important for not only absolutely the accuracy, but also making sure the integrity of the work and the quality of the work that we deliver is really key. Because if you've got your own laboratory, you're analyzing that data, you're constantly reviewing that data and improving that data and making sure the models are the best that they can be. Why do our customers want to do challenge studies in the first place? Mo mentioned in the beginning in his talk about how important it is about speed of delivery and understanding whether the product is efficacious or not. Just as important to be able to kill a product early as it is to be able to get that data early and prove that it's working, so you can go back to the drawing board or develop it faster. Bringing a drug to market quickly, it really does save money, time, and helps lives faster. We've had a look back and what we're able to demonstrate is from the point of signing a clinical trial agreement, we can get proof of concept data within 12 months. The beauty of challenge studies is we can give them a fixed cost and a fixed budget and deliver on that. Compare that to a traditional field trial, those studies can take really a number of years. If there's low circulating viruses going on, you then have to extend, do more sites, or perhaps even go to different hemispheres to get the data. Challenge studies, one site, deliver it, get your data within 12 months. If you look at that and compare it to field studies, we've demonstrated it can be up to three and a half times faster in getting the data, which is really, really powerful. Mo also mentioned about the vaccine industry struggling over the last 18 months. We've seen that a little bit in the challenge studies. We do have some vaccine contracts. Also what we've seen is that as some funding has stopped in some vaccine areas, actually that's produced opportunities because there's the same amount of money out there going around in infectious disease. What we're seeing is where it used to be split between antivirals and vaccines, actually now the proportion has now shifted, and we've seen a much larger influx going into antivirals. That's really been reflected in actually the contracts which we've signed in the last 18 months, because now we're signing more antiviral contracts in the human challenge business than we are vaccines. You can see there's still the same amount of money going around there. It just shifts between antivirals to vaccines over the different dynamics over the different years. I would like to now update you on what we've been doing on investing further and making sure we maintain that world-leading position. We've been investing on developing new challenge models and attracting new business into hVIVO by having different pathogens, therefore able to test different products and get efficacy for different vaccines and antivirals. Really importantly, over 50% of the substantial cost that it takes to bring a new model to market has actually been covered by collaboration agreements with our clients. We've been working very collaboratively with that to bring not just models that we think will be good, but actually models that our customers want, and therefore entered collaboration agreements. We've been able to develop seven new models in the last two years alone, and this has given us really a world-leading portfolio. I want to just highlight a couple of those. hMPV, RSV B, and influenza B, we're the only commercial center globally that has these models. This really gives us a nice niche to bring in and attract business on that. Not only have we developed challenge agents which are unique, we've actually also refreshed some of our well-known challenge agents in the influenza and RSV space. What that's done is actually we've been able to improve the infection rates and really enhance those models. Even those workhorses that have been delivering for us in the last two decades have actually now improved models and actually even more attractive to our clients to use them. I just want to leave you with a little bit of a case study, because I think this is a really powerful message actually. We often talk about clinical trials, but why do we do clinical trials? We do clinical trials to have a real-world impact, I think the RSV vaccine is a really excellent case study for that. Going back a couple of decades, hVIVO, we developed the RSV challenge model vaccinations against RSV have long been seen by the industry as a really challenging, difficult area, there's a whole succession of actually failures to produce the vaccines that are efficacious. It was seen as a risky area by biotech and pharma. Using a challenge study to look at the efficacy of those new products was really key for a de-risking tool. When there was a new development for the so-called Pre-F vaccines, which describes how they're actually working, they were tested in the challenge model, that was the world's first time we've been able to demonstrate that an RSV vaccine can be efficacious against this difficult, high-burden disease. On the back of that data, that really encouraged investment into this space by those companies, they got fast-track status with the regulators really then speeded through straight into phase III pivotal trials. Now of course, we have those RSV vaccines. They're being used the last few years, just in the news only about a month ago, you may have seen it actually, this is an example from the BBC, where they looked back at not just clinical trial data, but this is looking back at real-world data. What they've been able to see is since the rollout of these RSV vaccines, 80% less hospitalizations of babies into the hospitals because of RSV. That's a really dramatic real-world impact from that maternal vaccination, which we're proud to have played our part in. Thank you. Okay. I think we need to change the slides, hopefully. Hopefully that was a quick rapid tour of our service lines. My colleagues will be here for the rest of the day, if you have any questions, please feel free to corner them and ask them as many questions as you like. The goal for today really was to have our external partners and customers talk about hVIVO human challenge trials and the market. The first one to come up is Mario Barro. Mario is a quirky character. When I told him I wanted to ask him to present here, I proposed the title of the presentation, he said, "You can have whatever title you like, I'm going to do the same presentation." Independently, whatever I said. Mario is head of infectious diseases at RA Capital. He has been heavily involved in the decision-making process of which companies RA Capital invests in. He's been on the advisory scientific boards and the boards of Vaxess, Curevo, which recently got acquired by Eli Lilly, Icosavax, which was acquired by AstraZeneca, Cidara, which was acquired by Merck. He's a good man to follow if I was you guys. He has a long history in the industry with Sanofi Pasteur. He also worked with BARDA for a long time, I'm really pleased that he's here to present to you on the infectious disease market. Thank you, Mario. Let me see if I can dominate this or not. Okay. When I was asked to come here and present, one of the things that motivated me to come was because at RA, we care a lot about the execution of the work. It's not only about the investment. We don't take on a company and invest in a company and let them alone. We have a pretty strong group of people who are guiding and helping the company through the process. I think that it's a duty for us to also come and support one of the leaders in the industry on clinical trials. Coming to here is not only out of knowing Mo and knowing the team here, but also it's almost like a duty for us to come and support the great work that you guys are doing here. For those who don't know RA, we've been around for about 22, 23 years, give or take. We are in Boston. We are an investment firm. A few investment firms that work across the whole space and on the biotech industry, but also we do invest from early. We can create a company, we can seed a company, we can take on a new asset and start from zero, and we can also invest in the public market. Everything in between is also part of the field of investment for RA. Right now we have about $15 billion under management for the company. I'm continuing growing. I started about five years ago, we were at $8 billion at that time. Beside RA, we also have a team, and it's called RA Ventures or RAVen for short. I am a partner for RAVen is the group of people who are crazy enough to start from zero. This is a group of individuals who has been around, have done it more than one time, and they do know how to create a company. They do know how to find an asset that can rapidly become valuable and can go from the seed stage to a Series A and beyond. The beauty of the RAVen incubator is that they also come together with a bunch of capabilities that we have built during the last five years since I started there. Now we have a clinical group called Blackbird. We have an AI group also supporting the organization. We have financial support. We have people who can help us being the CFO for our companies, and also we have bio-market and other capabilities inside of the RAVen team. As part of that RAVen team, about four years ago, we founded this company, GVAX. It's just bringing as an example, but also because it's part of my blood and tears every day, and I'm the CEO of this company. RAVen funded the company about four years ago. We started with a collaboration with an academic in Indiana University. I spent two years working with him in his laboratory, then from there integrated a whole dataset and brought a team together in Philadelphia. Now they're working for the last two years getting ready to jump into the clinic next year. This is a unique platform. We are working on a new type of vaccine for children and adults which is going to actually drive a strong mucosal immunity, something that has been lacking for some of the vaccine targets that we have out there, particularly for gastrointestinal diseases like norovirus. Like Mo said, we definitely have an infectious disease team that's been strong for the last five years. We have put our thoughts into investment, and those investment has become a success. Some of those are like you see the one has the green light there. The green logos are companies that have graduated, like we used to say inside of RA. Curevo was just recently bought by Eli Lilly. Curevo is actually developing a next-generation shingles vaccine, a less reactogenic shingles vaccine, and it also can improve the access to this important vaccine, given that there's only one in the market. The Cidara example, and I'll talk about this in a little bit, but it's another company that graduated. It got bought by Merck end of last year. Vaxcyte is one of the examples of a company that we successfully took it through an IPO, and now it's a public company, and it's still part of our portfolio. Icosavax was bought by AstraZeneca about maybe two years and a half ago, and they were developing an RSV, hMPV, PIV vaccine. We have other companies in the portfolio. Norvink, I'm going to talk about Norvink a little bit in a couple of slides. Then ILiAD, who Keith is over here somewhere, the CEO of the company, Keith. We invested on ILiAD, and we're very proud of that investment because it's going to be a really important vaccine. This is my hammer and nail slide. At the bottom left, it's like if we solve everything on infectious diseases, how much money we make, right? This is all the nails put together, and we can make a-- There's a lot of potential revenue there. That means that there is a lot of nails you have to decide which one you're going to work on. The hammers pieces is all the different thing that we can use to hit on those nails. On the prophylactic side, there's a bunch of technologies out there that we've been looking at, and similar on the therapeutics. I think that there's a lot of opportunities. It's important to have a vision around infectious diseases, and this is one of the things that RA cares a lot. We have this view on the investment. Usually, we call it-- We promote internally inside of RA Capital the question, what are the problem that you're trying to solve? Right? What is the vision that you have for each of the different problems? I think in infectious diseases, we have spent about five years doing that, and now we have not only a portfolio of companies that we can invest but also a portfolio of ideas on where we would like to invest in the future, and that make us pretty much ready to jump into that type of opportunity. This doesn't come without challenges, right? You don't invest in infectious diseases in 24 hours. You have to go through multiple challenges. There are challenges for prophylactic in development and also challenges for therapeutic. All of those challenges have way to get mitigated. We look for a way to mitigate those challenges by looking at the story, at the science, what is out there for each of these different opportunities. I'm not going to recite the slide for you guys, but it's just to make sure you see that we have been able to differentiate what is in each of the different space and what is important to look at for each of those. The other thing is, another reason why I'm bringing this slide is because we're going to talk about the controlled human infection model here, and that CHIM model is what solve one of the multiple challenges that I have highlighted here for you. There are common challenges, and that's maybe more important to pause here because it's a shorter slide where I can spend more time on it. On the commercial side, on the reimbursement risk for infectious diseases, it's a challenge, yeah, because if you're talking about vaccine and there's not a right reimbursement at the end of your development or an antibiotic is a better example, probably. Investment there has become more and more difficult. We look at government guidance for this. We try to also educate the government, educate people around us to make sure that the right economics and the right value from what we're developing is being taken in account. In the case of Cidara, for example, we almost maybe, probably a month or two months before the acquisition, we published a large article with a full description of what was the actual value of the Cidara molecule for human health and the public health. That actually was quite important in the acquisition process and the valuation of the company and make the whole things really progress fast. There's also regulatory uncertainty and endpoints that we need to take care of when you're talking about infectious diseases, both for prophylactic or therapeutic. Of course, working with the FDA pretty closely and other regulatory agencies is quite important here. The epidemiology uncertainty is also one of the things where the FDA play a huge role because it's hard sometimes to run clinical trial when you don't know when people are going to get infected. Corrina is going to be talking about her work during the Cidara time, and timelines matters a lot when you're running an efficacy study for influenza. This not only happen for flu, but happen for multiple other diseases. You're going to try to do something now for COVID, when we don't understand still yet the whole seasonality of the virus. It's becoming more and more complex. For CureVac, we were developing a shingles vaccine, you don't have an attack rate. You just have a shingles disease and people that you don't know when this is going to happen, the trial length can be very long. Getting this down to the very good execution for this type of trial is going to be very important. There's something that Mo mentioned. There's an anti-vaccine sentiment out there and anti-science sentiment, we are really fighting that through communication and making sure that people understand the value of what we do every day. The human challenge has a really important role in how we look into infectious disease opportunity for investment. I put there and highlighted the four main reason why the CHIM model for investors. It de-risks the efficacy of anything that we are evaluating very early. If you think about a vaccine development or an antiviral or anything like that, there's no biomarker in place of any particular guidance to tell us if this is going to work or not, it takes all the way to phase III to understand if the investment is right. It's very capital heavy, you have to have a lot of patience. You have something that in phase II give you guidance about that, you would value that significantly. It does enable you to do a face-to-face comparison with the standard of care, which is for people who are developing and brave enough to develop things that are going to be better than instead of develop things that are just going to be first. It allow you to get that data early and also have that communication with the regulators so you can actually put in place potential new type of labels in your product. It generate correlate protection for data that you can then use in a larger phase III trial, and it also derisk your phase III trial design if you have that correlate protection as well. For some development, like ILiAD, you can get an FDA to agree that this is a recognizable path for approval. This is not the first time. It was used before for flu vaccine, not as a full recognizable path for approval. What ILiAD is doing is pretty unique. When we take a look at the human challenge data, we look for validated models. We look for things that have been used before or has been at least done in comparison with a standard of care as well. We want to see some sort of a regulatory buy-in into the study. Definitely a study that has not been put in front of regulators and don't have feedback, we don't value that data that much. There's been some cases of, for example, HSV vaccines that were done outside of the FDA regulation, that those studies were really complicated to evaluate. Durability of the challenge, that's also important. We also care about the opportunity to take a look at the data, not for somebody who was immunized, for example, and then he needed the challenge, but also something that has to do with. It gives you some idea about the durability of the immune response. We're looking at data with ILiAD as well. The mechanistic richness of the human challenge is very important because there's a lot of data points that come out that study that can actually inform us moving forward into phase III. This is the Cidara example that I brought here. This is a very busy slide that we put together at RA when we were trying to present our story of Cidara to the LPs this year. We have our LP day about a month and a half ago, and we presented the whole story in one slide. I just want you to focus on the GBP 240 million pipe and licensing of the product because this was a product that was in J&J, in Johnson & Johnson hands, that they divested. We put it back into Cidara for development, and I will let Corrina take care of it. You know what happened after that. Before that happened, we had to make the decision of putting this amount of money in an investment, and a lot of the data came through that human challenge data that hVIVO did for the Cidara molecule. It tells you a lot about how much we value that data set. This is the data set that we took a look at it, and when we were investing, and you can tell clearly, between the placebo and the J&J molecule, there was a significant difference on protection. Out of the human challenge, we went from, it was about 50%-60% protection rate, which was very close to what we observed in the real-world evidence out of the performer for multiple antivirals against flu and vaccines against flu, and this is what give us conviction to move forward on the investment in addition to our evaluation. This was quite critical. Just want to mention to you that we just finished an investment on a company. The former name was Pneumagen here in St Andrews. The investment also came out of a human challenge data set that was performed here at hVIVO. They show for this molecule, which is basically a nasal spray that can actually block the entry of the viruses through your nose, a significant amount of protection if you compare against placebo for that molecule. We're going to start working with the new name of the company. It's going to be Norvink because they are north from here, and they're also in St Andrews. We're about to announce that probably today or tomorrow, the investment. From ILiAD, and Keith's going to be here, so he can explain in more detail, but ILiAD is going to be developing their best-in-class vaccine for pertussis protection, and the human challenge is going to be critical for their development. Just want to close by telling you that those are some of the examples, but there's more things that can be done, and this is a list of viruses or infectious diseases that can be developed forward using human challenge. I'm just going to focus on norovirus because it was not mentioned before. It's a very important infectious diseases. You guys have seen the news on people getting infected in cruises and things like that, but it's been all over the place lately. It's very difficult to develop the vaccine, and human challenge, it probably is going to do wonders to support development. Probably a well-controlled infectious disease model. We don't have that yet. With that, I'm going to end my presentation. Thank you. Thank you, Mario. It's a much better sales presentation than I've ever given for Human Geneplex. Unpaid. I've not paid him a penny. I bought him dinner, that was it. Nothing else. Next speaker is Dr. Keith Rubin. Dr. Keith Rubin spent a lot of time in medical practice before he moved into industry, where he founded Seedlings Life Science Ventures, a small group where they invented some medical patent technologies, and then moved on to found ILiAD, where he's still the CEO, and he has this lifelong drive to get a pertussis vaccine to patients as fast as he can. I'd like to welcome Keith. Thank you. Thanks, Mo, and thanks for including ILiAD in today's meeting. It's been also great to spend some time with the team just in person. These are great folks, very committed and very serious about what they're doing. It's great to be here. ILiAD was founded in 2012 and has, from day one, had a very simple mission, and that is to eradicate pertussis disease all over the world. Very laser-focused on that from the very beginning. What I'd like to do, if I could, is show you. Let's go to the next slide, please. All right. I will talk to myself. Thank you, Fam. What we're going to see, we were trying this this morning. We'll see if technically it works, but I wanted you to have a sense of why do we care about solving this problem? This is really what it's about. Let's see if it works. We don't have the visual, but maybe we can throw the video up. It doesn't have to sync, but maybe we could just run that slide. Okay. There we go. Maybe we could put the sound on. The baby can't breathe because the airway is constricted. It's brutal. You can imagine just seeing that video. It's really hard to watch, and that's for a baby that you don't even know. Imagine it's somebody that you love and you care about. What is unfortunate, beyond just this one case, is that by CDC estimates, you have 160,000 children dying of this every year around the world, and you have 20 million plus cases to varying degrees. That's more than 400 children dying every day from this disease, more than 50,000 cases every day of kids going through that. It's just awful. That's what we're trying to solve. What is all this about? It's about stopping that and all the misery and suffering that goes along with it. Whooping cough is, we've had it for hundreds of years. We've had vaccines for 100 years, yet they never seem to stop this problem of a cycle where every few years you get these really bad outbreaks. In 2024, these are just a bunch of press releases and newspaper articles and media just showing how tough this was in just recently, 2024. Highest cases in decades all over the world, in Europe, U.S. and China, Australia, South America, all over the world. Maybe the most in resource-constrained countries in Africa, Southeast Asia. Huge global problem, not talked about enough. This is what we're trying to solve. 2024, we have an outbreak. Again, vaccines for 100 years. What is the problem? There was an older vaccine called the whole cell vaccine, that was used for many decades. The problem is that it had a fair number of side effects, like high fevers and seizures. In the early '80s, the pharmaceutical companies, starting in Japan tried to figure out, can we make something that works but it's safer? They came up with something called the acellular pertussis vaccine, that's pretty much the vaccine in most developed nations now. In the more resource-constrained countries, they still use the older vaccine. The vaccine that, again, is used extensively throughout the developed world is this acellular vaccine. That's the current vaccine, it has two major problems. One, it's not very durable. You get your vaccine, but it doesn't last that long. Two, it provides immunity below the neck, protecting the lungs for a limited period of time, but it doesn't provide mucosal immunity. Okay, why does that matter? It matters because that's where the bug lives. It lives in the upper respiratory tract of humans. You can force it to live in an animal, but that's not natural. Those are experiments that we do. Naturally, the humans are the host, it's the upper respiratory tract, the nose and nasal passages, it doesn't live very long on a desktop. The problem with the current vaccines is you never get rid of the reservoir. 4-8% of people walk around with this bug in their nose at any given time. Very likely that some of us in this room have this bug in our nose. You say, "Well, we feel fine. What's the problem?" The problem is that is the route by which you ultimately get the disease. You get it in your nose, then it distributes toxins through the body, that's how you get disease. The other thing that's critically important is that that is the primary way that it gets to that young infant. What do I mean? If you have a newborn in your house, they're one week old. Okay, they're two weeks old, now you're going to have the family over and friends over. If Uncle Joe or Aunt Mary are having a bad cough and a bad cold, you say, "Please stay at home. Don't come over. Come back when you feel well." Okay, fine. The problem is that all the other folks at the house may be carrying the bug, and they don't know it. For every one person who's diagnosed with whooping cough, there's somewhere between 100 and 1,000 that walk around with this bug in their nose. Why is that important? It's because when the family member who has the bug in their nose and they don't know it, picks up that little baby and say, "You're such a cute baby," boom, you get transmission. That is the primary way, and this has been carefully studied in papers by, for example, by Scarpino and Althaus, but that's the primary way that these young babies get exposed. Okay. From day one when we started ILiAD, the idea was, "Hey, let's try to figure out how to stop those bugs from living in the nose." This is the solution that we've been working on now for about 14 years. It was developed at the Institut Pasteur by Camille Locht and Nathalie Mielcarek. They've been working on it for about 20 years. This is not immediate gratification. As Mario said, it takes patience and a lot of work, and a lot of people to progress something like this to public health, to improve public health. It's a spray. On the left, it's just a little syringe and a tip called a vaccinator, and you just spray it in the nose. You can see a little plume. This is a young man, a boy, getting vaccinated. That's it. Simple spray, one shot, done. This is how it works. You get your spray in your nose. That's the first panel. It's live, and it's attenuated. It's a weakened form of the natural bug. It colonizes, and your immune system naturally then gets rid of it. By doing that, you then get protection not just below your neck, like the previous vaccines we've had for 100 years, but you also get great mucosal immunity. By the way, if you get over whooping cough, and you don't die from it, you get great immunity above the neck and below the neck. The folks at the Institut Pasteur, when they were developing this vaccine, they were trying to mirror that. "Hey, let's try to get the immunity from a natural infection, but not the toxicity and the pathology of the natural virulent bug." Now we've done six clinical studies, including four phase II studies, where we've shown just that. So far, this vaccine looks very promising that in a safe and effective way, we can induce this kind of mucosal immunity and systemic immunity, not just below the neck, but also above the neck. If that works, then you have the opportunity to really ultimately eradicate this disease. That would be an amazing contribution to public health, and it's what we're working towards. Let's just look at some quick data. We won't get into too many details. The vertical axis, the y-axis there, are the number of bugs in the nose, and the x-axis, the horizontal axis, those are three different vaccines. What do we do? We vaccinate the individual. In this case, these were baboons, non-human primates. We vaccinate them compared to a placebo. Then a couple of months later, we challenge them. We spray the virulent bug in the nose and see what occurs. Of course, we know that the current vaccine will stop disease in the short term, and so does BPZE1. When you look at the nose and nasal passages of, well, how many bugs are there after you spray that challenge and you sample, you wash the nose, and you sample the nose, how many bugs are in the nose? The first blue bar, I don't know if it shows up as blue, but it's the far left tall one. That's the current pertussis vaccine in the baboon model. Again, you vaccinate with the current vaccine, you a couple of months later challenge those baboons. You spray the bug in their nose, that virulent form of Bordetella pertussis, then you sample the nose after that. This is the number of bugs, that tall line or bar, or the number of bugs till you clear the infection. The one in the middle, the gray shorter bar, that's the old vaccine that is still used again in certain developing countries. On the far right is BPZE1. What we showed, this was shortly after we licensed the vaccine in 2013, we did this experiment. It was published in The Journal of Infectious Diseases. We showed that compared to the old vaccine and the current vaccine, we had more than 99% reduction in bugs in the nose after the challenge. This gave us a lot of confidence that this vaccine could work. It's really energizing. This is the first thing we did after we licensed it. Okay. How did we do in humans? The next study, there were a few clinical studies in between, the next study that we did where we did a challenge study, again, vaccinating with the current vaccine, vaccinating with BPZE1, those were the two groups, waiting a couple of months, then spraying an attenuated form, a weakened form, which in fact was BPZE1, which is the challenge agent we used. Then again, sampling the nose after that challenge. How many bugs are in the nose? Again, in this case, the y-axis, the vertical axis, are the percentage of people who had gotten vaccinated, challenged, and who had bugs in their nose or not. You see that in the BPZE1 group, 90% were protected, as opposed to the current vaccine, which had 70% colonization. You say, "Well, 30% seem to be protected." That's going to be a nuance because if you looked at their baseline antibodies, they probably had had some exposure to the bug. The bug naturally circulates, this bacteria, Bordetella pertussis. Again, what was striking is that BPZE1 did such a great job at protecting against these colonization. We published this in The Lancet in 2023. Okay. That's an attenuated challenge, not the virulent challenge. How about the real bug in humans? How does that work, and how are we doing with that? What was developed, and Diane is here, Diane Gbesemete, who will be on the panel in a moment. She and Robert Read at Southampton started working on a model back in 2017, and they put together the PERISCOPE Consortium, which was funded by pharmaceutical companies like GSK and Sanofi and the Gates Foundation and the European Union. It was a real effort to try to figure out how are we going to get new pertussis vaccines, because it's really tricky to do a field study with pertussis. You don't know exactly when the outbreak will be, where it will be. They started working on this challenge model, and they've been incredibly successful. Thank you, because that's allowed us to be able to do our work, and it's the work we're going to be doing for our pivotal study. Why do we need to use a challenge model? Again, you don't know where pertussis is going to show up. It's episodic. You don't know where it's going to be, when. By having a challenge model, you can really control those variables, and therefore you can accelerate the development of vaccines and have really precise data. It also ultimately allows you to have fewer participants in this study, which also greatly reduces the cost of being able to do these studies. With respect to who are in these challenge studies, they're healthy participants, and they're given antibiotics at the end of the challenge so that they don't go to disease. We're mindful of that. Of course, safety is job one. There was an effort to try to figure out, well, what does this model look like? Without going into the details, there was just a lot of work done over a lot of years to develop a model that was robust, where you could show a distinction between the vaccine that you're trying to assess and approved and either a placebo or the current vaccine. How did we do in that model when we, again, vaccinated with our vaccine, vaccinated with a placebo, waited a couple of months, challenged, and then sampled the nose and nasal passages of those human participants in this clinical trial? Again, something that looks very much like the baboon. We showed a 99% reduction in the bugs in the nose compared to the placebo. The vaccine that we're developing, BPZE1, looks really promising to solve this major public health problem. As has been alluded to this morning, you need also regulatory clarity on, hey, can you use this model? Can't you? In 2022, BPZE1 was fast-tracked, and as part of fast track, it basically means you are working to address an unmet medical need, which is the case. Again, we've had vaccines for pertussis for 100 years. We still see all these outbreaks. It's still a major public health problem. In 2025, we had a couple meetings with the FDA, including a type C meeting, and they then gave us the green light to use a human-controlled infection model, this challenge model. That is what we're going to be doing later this year with hVIVO, and it really paved the way for that partnership. We won't go into details on this, but big picture, that study, this pivotal study we're going to do, this phase III study, we're going to vaccinate a group with our vaccine. We're going to vaccinate another group with the current standard of care, the acellular Tdap vaccine. We're going to wait 12 months. This is for the primary endpoint. Those folks will live their life. 12 months later, they'll come back in. We'll spray the virulent bug in their nose, and then we will sample their nose after certain time points, and we're going to look to see, does BPZE1, as we've seen now in mice and baboons and our other human data, does it bring down the number of bugs in the nose in terms of the individuals? Are we able to see that differentiation between our vaccine and the current vaccine? We'll also look at data at 3 months, so we'll be looking at both 3-month and 12-month data. That's the pivotal study that we'll be doing with hVIVO. Why hVIVO? Top 3 things, experience, experience. This is a very thoughtful and knowledgeable organization, and there's not another challenge site in the world that has done as many challenge studies, which is huge. The other is that they're able to bring participants into the trial recruitment, which is not a trivial matter. It's a really important part of the process. They also have these purposefully built facilities and a challenge unit. They've also integrated, as you know, these very important clinical and laboratory capabilities, and we've been spending probably a year or so now with the lab team, have done a superb job getting basically ready for the trial. There's a lot of work that goes on before you actually start a study like this, and for more than a year, we've been doing that work, and it has been exceptional, including starting from zero and being able to measure these colony-forming units, CFUs, the bugs in the nose, and actually being able to measure that and test that, and they came up to speed remarkably quickly and highly effectively. We're really appreciative of that. If this study is successful, we have the vaccine that literally every single person on Earth could benefit from. We're very grateful for the partnership, and we're really excited about getting this study going, and God willing, we'll have the vaccine that we can deliver to public health as quickly, safely, and effectively as possible. Thanks for having us. Thank you, Keith, for that. I think Keith's presentation really is a timely manner why we do what we do. I think even our own mission statement is to help bring medicines to patients faster. We did this with the RSV vaccine that Andrew talked about that's currently reducing hospitalizations in babies against RSV to less than 80%. Hopefully, together with ILiAD, we hopefully get the ILiAD vaccine to market and to patients as soon as we can. Our final talk before the break is a really good transition from talking just about human challenge trials, but how hVIVO is helping customers not only do human challenge trials but get to phase II and phase III. It will be conducted by Corrina Pavetto, who has a long history, over 15 years with BARDA, working with their influenza vaccine and antiviral program, providing regulatory and clinical development oversight. She then went to the dark side, the industry side. Mario persuaded her to join Cidara to basically spearhead the Cidara program in influenza. I think she was a key driver, key component of getting that program conducted before its final exit to Merck. Corrina. Good morning, everyone. It is such a privilege to be here to really talk about Cidara and the collaboration with hVIVO. It has been an exciting 18 months. I am currently now working in the private sector, helping other companies. No longer working on this project. I left Merck in April. I will advance here. I am just going to give a brief background on Cidara, how it all started, where we got to this, then highlight our collaboration with hVIVO. Really, I joined Cidara in May shortly after they got the acquisition back from J&J, thanks to RA Capital and their investment. I basically called up Mo and I said, "Look, I took on this job. I think that there's going to be a great partnership for hVIVO." I know they had worked previously with the Cidara team in the challenge trial, the challenge trials, as you'll hear, are a real good initial footprint into later phase. They had worked with the team on the virology. I said, "It makes sense for you to really partner with me to get this program done." We had a very aggressive timeline. I joined the company in May, we ran our phase II trials in the field before the influenza season that fall. Really, I can highlight here that hVIVO is really a great team. I think you'll hear that throughout the day. They have excellent scientific backgrounds. They were a true partner with us. We would call them up and ask them for regulatory advice, virology advice, they were always there to really meet our needs, really a huge part of the success of the Cidara story. Just a little bit about CD388. CD388 is an antiviral linked to an Fc human antibody component, it was really developed to protect against influenza. It's a one-dose, single-dose given close to the influenza season that really provides protection for the whole year. It was developed originally by Les Tari, who was part of the research team in Cidara, then they co-developed it with Janssen starting in 2021. After the acquisition, J&J decided to exit infectious disease. The RA team, led by Mario, really said, "This is a great asset. Let's get it back." The Cidara team were able to acquire it back in April. It was a very aggressive thing, as Mario highlighted. They actually divested one of their assets that they had got approved and brought this asset into the company, pivoted from. They had an early oncology program, but really all hands on deck for the infectious disease program. It was a very rapid startup. Anyone that's worked in the influenza space, you're fighting the seasonality of it. If you don't get this product into patients in the clinical trial before the influenza season, it really blows your whole study, and that has happened in the past. We were really careful to make sure that we got this product into the clinical trial and started dosing in September, finished in early December, just in time for the flu season to hit the U.S. and the U.K. Just to really highlight the fact that hVIVO has really been our partner. They worked on the early challenge studies with the team, with J&J. We moved quickly into this phase II rapid enrollment, and they also are part of the ongoing phase III, and really led to the acquisition by Merck at the beginning of this year. The deal was done in January of 2026. Talk a little bit about the phase II trial. Moving from the human challenge into the phase III was a way that we could really de-risk and plan for a really good phase II trial, given the way they operated with the phase I/II-A challenge trial, the way that we were able to swab and follow cases in the phase II-B trial, and it really kind of accelerated our development and enabled a readout after the season in May of 2025. Talk about the phase II-B trial. What it was, it was over 5,000 unvaccinated healthy subjects were enrolled in the U.S. and a large contingency in the U.K. Over 800 subjects were randomized, and we were looking at 3 different dose levels. It was really pivotal for this trial to be done right, to be able to select a dose to go into our phase III program. The hVIVO site was kind of added as a last-minute kind of de-risking situation. In flu trials, the season can be different in the Northern Hemisphere. Europe could have a strong season, the U.S. could not, have a weak season, and it was really important for us to have a good, robust flu season in order to collect cases to measure the effectiveness of our product. We added the U.K. site kind of as a risk mitigation strategy, and they were able to enroll over 833 people for us in that trial. A large part of our sample, and I think we actually got 10 or 11 cases from the trial to add to our efficacy endpoint. Just to really highlight, we quickly moved from the results for this trial. We did an interim analysis in May. We actually had the data in June, We kind of de-risked the situation by having a type C meeting with the FDA in May of 2025 ahead of data to really get buy-in to what our phase III program would look like. We really had the summer to have our regulatory discussions so that we could move into the pivotal phase III trial, and that started in September of 2025, shortly after data readout from phase II. Anyone who's been in this phase, it's really hard to move quickly from a phase II trial into a pivotal single phase III trial, and we really were able to do that because of the partnerships with our vendors, and hVIVO was a key of that. Really like I said, they enrolled a robust dataset for us in six weeks, faster than any of the U.S. sites, which was pretty remarkable. The biggest, I think, benefit of hVIVO is really hLAB. Anyone that's run influenza trials knows that the testing is very vital in importance. hVIVO and hLAB are really our central virology program. They did all the testing for the primary endpoint for all the sites in the trial, and they were extremely fast with their turnaround. This was our primary endpoint, so we really needed that data as soon as possible in order to achieve the outcome. They also helped us with the integration with the U.S. sites, with sample collection, and making sure everyone was doing the methodology was correct, and Andrew and his team helped us with the required FDA virology plans. It was just a great fit for the program. In addition to being a clinical site, a specialized laboratory testing, we also called on hVIVO to really help us with our global regulatory strategy. Cidara was a very small company, 40 people. We had two regulatory people, 10 people in our clinical group, and we were so focused on the U.S. market that we didn't really have time to look ex-U.S., and it was one of the things that potential investors or potential acquirers really wanted us to focus on a global strategy. We used their regulatory consulting group to really help us do a lay of the land of a global plan as well. We not only used them for the clinical conduct, the lab, and the regulatory consultant. They really were a strategic fit in the whole adjunct group of Cidara. I think I covered this. Again, I think one of the key benefits for us is they really were supplemental to hVIVO. hVIVO was really supplemental to the Cidara group. They really helped us with the Venn Life Sciences, with the regulatory strategy, but they were also our partners. They would review documents beforehand, help us in startup. I know my team really valued their input in helping us stay on track. I just want to highlight the team here. This really was the dream team. Some of these are still currently at Merck working on the project, but I really want to highlight the Chief Medical Officer, Nicole Davarpanah, who was not an ID physician. She was actually an oncologist, but she quickly became ID, and her and I worked conjointly with the groups listed here, and we just feel so fortunate to be part of that, and thankful for the partnership at hVIVO. Thank you, Corrina. I think what Cidara achieves is pretty amazing, but I think the key for me, really, is the speed at which they moved, and they've managed to get to proof of concept in such a short timeframe, and now Merck & Co. is the middle of running a large global phase III program. Thank you for that. It highlights the fact that our human talent product diversification, that we moved into having the other service lines also contribute towards the success of this product. When Keith was talking about the setting up of the model and the METATASIS and the PERISCOPE study, that was Diane and her colleague Robert Read's work on that. We're delighted to have her join us with the rest of the panel that you've already met. We've already been focusing on a couple of key case studies in the last session, with Cidara, of course, and ILiAD. We're going to continue this panel focusing around there, actually we want to broaden out that discussion a little bit longer than that as well. Looking into a little bit more detail about what it takes operationally to deliver these studies, as well as what type of products get invested, and have a little bit more of a deep dive. We have some key questions focused on the expertise of our panel here, and then we'll open it up to the audience after a short while. Please do think of some good questions to ask these guys who've given up their time to join you today. I think let's start right at the beginning, actually. Of course, you can't do any of these studies without getting some funding involved, because of course, these are expensive trials to conduct. I think that brings us nicely onto Mario, who's in investments for RA Capital, of course. I wonder if you can give us a flavor of what type of products are getting investment nowadays, and then we can bring that onto challenge studies a little later. Let's start there. What sort of products attract you when you're looking at investment cases? Right. This is a loaded question, okay? Because the answer is never we want to invest on flu, or we want to invest on RSV vaccines, or on this particular indication. The approach is a little more different. We look into the whole field of infectious disease. Usually, the team talk with between 100 to 150 companies every year that come to RA to introduce us to what they're doing and why they're doing what they're doing on infectious diseases. There's a lot of people out there investing their time and their money and their life on trying to get a new approach. Our role, the first and foremost role, is to try to understand why they're so invested on something like that. Because when you get a CEO that comes to you, even if it's the craziest idea, it's like imagine, it is important to understand why this person is so excited about this. That's the first thing we do, and then we try to understand the science. We at RA are fortunate that we started the company by building this TechAtlas team, who is a large number of researchers and analysts that have been looking into the biotech industry for many, many years, and the whole knowledge is now accumulated after 20 years of RA being around, and that help us evaluate the potential of that investment. Infectious disease has their own challenges because and this is why about five years ago, Peter wanted to create a vaccine team. The first domain-focused team in RA that was created was the vaccine team, and that was created five years ago because of those specific challenge that we have around developing a vaccine or infectious disease indication. That is basically the crux of the process. We take each company that come to us very serious. Nobody is left behind, and nobody leave the interaction with RA without our best thoughts on what they're doing. Even if we don't believe in what they're doing, what we tell them, and we tell them why that is not going to work. Specifically, we look for a lot of indication that give us confidence whether or not we should invest or not. I think this is where your model or all the work that you guys do in clinical development is very precious for us. And during my presentation today, I tried to synthesize as much as I could. What is our view on the control of human infectious disease model? Right? It give us a lot of confidence, particularly if it was well done, particularly if the model is well developed and mature. I think one of the biggest challenge for the model is to get to that point. Get to the point when everybody have confidence on the model. Not only investor, but also regulators as well. And scientific confidence, right? The flu, for example, the flu model. When I started back in the day in BARDA, talking about several years ago now. We mentioned the human challenge model, and many people say, "Oh, that's not going to work. We're not going to be able to use this." And it's been a process for the community to further develop that model. We actually funded at the NIH to actually develop the model. We put GBP 40 million on Vaxart back in the day when they had their human challenge. They performed one of the largest human challenge that we had ever performed for flu, and the development of their vaccine. It is a combination of effort. You need government support, academic support. You need people like you guys who has make it into a professional setting where you can come here and you can have a serious conversation about how to do a human challenge study. All this add. When we come to review the data, we take all of that in account. It is important to fund studies where standard of cares is participating in the study, so we can actually understand how the human challenge model perform for things that are already approved. There is nothing approved, and it's a little bit more difficult, but it can be better than me. We can do something different. You can enroll people who are already immune to, and that has been going through the disease, and then you know that they're going to be protected. You can do more other things. Definitely it's going to be important in the future. I think that also the collecting the right data set out of those human challenge studies is also critical. I mentioned that today as well. Don't know if that answered your question, but I think this is where we stand. It's not the solution. I don't want to tell you guys that everything's going to go through a human challenge, but it's an important piece in the solution for us to accelerate and get conviction that a particular indication is going to work. Yeah, you raise a good point there, because it's not just about developing any model. The model's got to be relevant, and it's got to actually have endpoints which can translate to those later field studies. If it's set up and really not delivering that, so giving a very artificial read, then it really belittles the usage. I think people think you can just set up a model, and it's always going to work, actually, but it does take a lot of understanding about how these models work and actually really thinking about where is this product going next, and then to try and implement that in the challenge study design. That's what we try to do very extensively at hVIVO, but I think it's sometimes lost on sponsors. They just want a quick gain from it, but actually you can do so much more if the challenge model really reflects real-world data. I think that brings us nicely onto the pertussis, because of course, that's exactly what you guys have developed and what you've really set out to try and do from the beginning. Perhaps we start that journey with yourself, Diane, because of course you set out the model with the Southampton group, with Rob Read there. You're the PI on that study. We saw that really impactful video that Keith showed there, and I wonder if you can put in your words what was the problem you were trying to solve, and what was your thinking when you set out that model, and what were the challenges you had on that? As you've said, the reason we set up these models, the reason we do this research and all of this hard work is to answer a clinical question and to solve a clinical problem. Our group in Southampton, as part of the wider PERISCOPE Consortium, there was an increasing recognition that pertussis, while reasonably well controlled initially by the vaccines that there were available, remained and was increasingly becoming a public health threat. Yeah. We were seeing pictures like the videos, like the baby that we saw there. That was a really powerful image. I'm a pediatrician myself. That's my clinical background, and I'm very aware of and have experienced the awful disease that pertussis is and the awful impact it has on babies, on families. Seeing those numbers of cases increasing year-on-year as the vaccines have changed. We had to change, as you mentioned, from the whole cell vaccine to the acellular vaccine, and since then we've seen that gradual increase in cases, the number of outbreaks and resurgences in disease every few years, and we're going to see that increasing and carrying on over the next however long until we have a new, more effective vaccine in place, as a larger proportion of the population have only ever seen acellular, so the acellular vaccine. At the moment, it's about the age of 22, anybody under that age in the U.K., maybe slightly different in other countries. They'll only ever have seen the acellular vaccine. As that increases, as time goes on, we're going to see more and more of these resurgences, larger outbreaks, and that's exactly the problem that we were trying to address. There were lots of different studies involved within the PERISCOPE Consortium. We in Southampton were particularly interested in developing a model, not just of looking at disease, but looking at that asymptomatic colonization, looking at that carriage of bacteria that could then be transmitted on to more vulnerable people, because that's really the key to eradicating pertussis altogether. That's just not possible in a field study, because as we've already talked about, it's very sporadic, it's difficult to diagnose, and it would take a huge number of people. It's just completely logistically impossible to do a study with the number of cases that we have at the moment. Yeah To look even at disease. To look at preventing colonization, that asymptomatic carriage, there is no other way of doing it other than with a controlled human infection model. That's what we were setting out to try and do. I think you've really highlighted a key area there, because Mario was talking about making sure that the models show what you'd need to show to have confidence in these products in the filter. Actually, this is a really key difference between this model and a lot of other models. A lot of other models are looking at the disease, because often the disease is really what they're trying to prevent. Actually, what's really impressive about what you're trying to do, Keith, at ILiAD, is that you're going one step further, and it's a big giant step. You're not just trying to protect that individual, you're trying to protect them from transmitting that pathogen to somebody else. The relevant question here for that really holy grail of the goal there is the colonization. Can you stop someone actually having it and not just the disease? This also brings us on to safety, of course, because we don't want to cause that horrific thing on our volunteers on these studies. It's a nice combination of making sure we're doing these in a safe way, but actually we're not progressing to disease in this because we're treating with antibiotics. Actually, that's important because it's not the disease that's the key factor. You're trying to look at can you prevent colonization, which is so much more important in terms of global health. Keith, I wonder if you can add any more comments onto that about your views of this early stage development. Well, the first thing I want to make sure I underscore is that while colonization and the prevention of colonization is a key differentiation between what BPZE1, our vaccine, at least in mice and baboons and humans so far is able to accomplish compared to the current vaccines. We are also very focused on preventing disease, and in the same way that we have this great data on prevention of colonizing infections, we have great data in at least mice and baboons in terms of protecting against the disease as well, and we'll be doing more of that work as part of our pivotal study. Just to be clear, We think we can do as well and probably better in terms of durability. We certainly have preclinical data suggest that. As it relates to disease, of course, colonization and prevention and ultimately getting transmission down is fundamental. To be able to do that, as Diane said, to do this in a field study would take probably hundreds of thousands of people and exactly when. It would just be not feasible, frankly, as people at the FDA have said. It's just not feasible. Having a human challenge model is really remarkable. We were asked by regulatory agencies in 2015, "You guys should do a human challenge study because it's so difficult to do a field study." We said, "Well, that would be nice, but one doesn't exist." Now we're going to develop the vaccine and the model. I think in order to get things done, you sort of have to stand for something. We were focused on the vaccine itself, but we're so grateful that all the work that you and Rob and all the team at Southampton and all the partners in PERISCOPE did to get this model, bring it to life, and that was hard work because it has a lot of different components to it. These things are not trivial, and I would hope someday that we do a good job of sort of as a community of biotechs and pharmas and all that, getting the rest of the world to understand how tough this stuff is. It is really difficult. It is a lot of sleepless nights about making this decision or that. It takes a tremendous amount of time and energy and effort. I really respect and appreciate what you and Rob and the team at Southampton did, and that has allowed us to be able to leverage that and utilize that, and now to be able to partner with hVIVO to be able to conduct that for our pivotal study, it's really extraordinary, and also very fortunate that the work was done initially. You raise a key aspect there, because I think that it turns on its head about what the normal paradigm is, because you mentioned that the regulators raised challenge studies to you, and it's normally completely reverse to that. It's normally the sponsors going to the regulators saying, "Can we accept a challenge study on this?" It's really reassuring to see that there are examples where the regulators do recognize that there are certain scenarios where it's just not feasible to do these studies. I was wondering what other aspects do you think about the design of this pivotal phase III study? Do you think what made it so attractive for the regulators to agree to use a challenge study for your pivotal authorization, do you think it is because it is comparing against a standard of care, or is it the durability that you mentioned, or what do you think is the key factor for that? Well, I think in terms of durability, we won't learn that from this. That is once the vaccine is sort of out there. We will have to be doing that work. We have a lot of preclinical work that really supports that, but ultimately, we are going to have to prove that over time. In terms of the differentiation from the current standard of care and really getting at the heart of the problem, which is folks in this room likely have this bacteria in the nose, and we need to get at that reservoir and protect against that. That is the way from a public health standpoint, if we look at other examples in history, like the Haemophilus influenzae b vaccine, that is how you get it from X number of cases down to basically zero. We do feel ultimately that if we get it right, we can eradicate this disease from human beings on Earth. That is a great thing to work for. That is a great thing to work for. Of course, all the team at ILiAD have worked so hard on making sure that phase III protocol is designed very carefully to deliver exactly what you need it to deliver. With clinical protocols, they cannot convey everything. I wonder, Diane, from a practicing clinician's perspective, what sort of hands-on experience can that give to this, and the importance of that when we are designing these studies that you just cannot capture in a clinical protocol? Of course, in the delivery of this, we will be collaborating with yourself, and we really value that at hVIVO, collaborating with hands-on physicians who have experienced this and are working with this day in, day out, and that we believe helps our practice and helps to be more relevant and more safe as well. I wonder from your perspective about what that perspective is. I think one of the key most important things in delivering a model like this has to be participant safety. We've talked about the fact this is a colonization asymptomatic model where we're aiming not to cause illness, but the reality is we're giving an organism that has the potential to cause significant illness, and we absolutely need to avoid that. Part of delivering the study is really careful safety monitoring of participants going through the study and making sure that any sign that we are in fact causing disease or symptoms is picked up really quickly and is acted on really quickly. That's absolutely vital. Of course, what we don't want to do is pick up people with a bit of a cold or hay fever or anything else that might mimic those symptoms and inadvertently take them out of the study and therefore kind of reducing the scientific integrity of the study. It really is a careful balance to get right. Yeah. Protocols, guidelines, and sort of clinical decision tools that might be within a protocol are really important. They're really helpful, and they help to sort of keep that approach consistent across potentially different sites, but different investigators, and across the study, and that's really important. It doesn't replace clinical judgment and being able to assess those different factors, the variability- between different participants who don't fit in a neat box, they don't necessarily follow exactly what you expect them to do. That clinical judgment in making those difficult decisions is absolutely vital. Yeah. Hand in hand, obviously, with what's written in the paper. Yeah, absolutely. I think those who are looking from afar don't always appreciate that depth, that's really critical for safety. Safety is always our first concern for any clinical trial, but none more so than when you're actually giving them the pathogen that you're trying to test. Corrina, let's switch tacks a little bit because we've discussed a lot about the Pertussis setup, that challenge model. I'm keen to hear your perspectives on that early-stage study you did for the challenge study, how you feel that was important in taking that further. I know you touched on that in your talk, if you can elaborate a little bit further. Sure. I think it's important, influenza is well-characterized, I think, in the challenge model, you guys have the benefit of doing several trials in that. I really think it was that early kind of proof of concept because after you establish safety in phase I, you go to these proof of concepts. While the challenge trial is an investment, it's not nearly as expensive as a field trial to really look. I think it was important, really, for Cidara to look at the different doses in the challenge trial for them, have that data set. Obviously, that was a big catalyst. If Janssen would've stayed in the ID space, they were planning a huge phase II global trial with a significant capital expenditure based on that limited data from the CHIM. I think that that's an important inflection point when you're moving into larger phase trials. I also think the challenge model gives you the opportunity to really plan out how you want the challenge model to your sampling times, what it's going to look like. I think the challenge is really to be able to have the data in the challenge model to really extrapolate to success in the field trial, and that hasn't always been the case. Yeah In the influenza area. I think that's kind of maybe why there's been a negative connotation for flu challenge trials. I feel like, with the expertise at hVIVO and your experience in influenza in particular, it was a well-thought-out challenge trial. Sampling times were extrapolated into field and larger trials. Then having the breadth of knowledge from having you guys do the assays and the virology part of it translated easily into a successful field trial. Yeah. Thank you. That makes sense. Mario, from an investment perspective, of course, there was a challenge study from Cidara, then moved on into the phase II. Clearly, both of those aspects would've been important for an investment case. I wonder if you can share a few words about how you think, from an investor, was that sort of challenge trial viewed? Because as Corrina pointed out, I think something which not everyone does, but I think was important in this is they didn't just look at single efficacy, but actually tried to understand from a dose relationship what was the best dose to try and de-risk. Was that an important aspect? Yeah. When we look at the data from CD388 from Cidara, one of the fellows that worked with me, Tom Thomas, who's now at Arrecabida, he went to another venture group to an analyst, he's doing very well there. He did an extensive amount of evaluation of all the human challenge data that has been published before the CD388 data was out there. Then we did an across-the-board comparison with all the efficacy data that was available for not only flu vaccine, but also antivirals. That created a mesh of intersection of data sets, of human challenge data set, and efficacy data set that allow us to understand and interpret that CD388 data that we were evaluating, right? I think that for pertussis, for example, the fact that the model was developed before we're getting on to this phase III trial is what the FDA is going to look into it. To make sure that the interpretation of the data is correct, okay. I think that we're looking forward to get the same type of data set from other indications. You talk about RSV, for example. We talk about hMPV. This type of data set, I know it's going to be an investment from your end, but this is what is going to actually elevate the value of that. Yeah Human challenge data to the next level. There are more tools right now because you can do AI work as you do the human challenge data. You get the human challenge data, you can actually try. There's some people talking about way to connect real-world data with human challenge data. There's way to improve the interpretation of the human challenge. The other point that we don't talk a lot is about the things that don't work when you put it. Yeah In human challenge, that's also equally important because. That's a good point. Everyone assumes everyone always shows efficacy, but it's not the case, is it, of course. In flu, a good example was for a while, there was this disease enhancement question that we have with antibodies that people were trying to develop for flu. Human challenge was also fundamentally important to trying to understand if we can actually move certain antibodies into phase III, because you can interpret the human challenge data into some sort of enhanced disease model as well. There is the value when you get good data, but there's also a huge value when you get negative data. Yeah. Then you stop development. You stop draining your capital into something that is not going to work. Yeah, absolutely. as well. I think you touched on the fact there that challenge studies, because they're in a quarantine, you get the whole time course of the data, you get such breadth of data that you can really add to the scientific community that knowledge, because you can study so much more things than just the efficacy of the product. Actually really learn a lot about the disease as well, particularly in those early stages developing of the model, like Diane, when you're setting up the pertussis model. Of course, then you come to doing a phase III, and that's a whole different ball game altogether, isn't it? The phase III that you're designing right now is over 500 participants, that's a very large undertaking. I wonder if you can give us a little bit of perspective about what it does take to set up and deliver such a large challenge study like that. Yeah. Thank you, Andrew. It takes a lot of work and a lot of time, and a dedicated team that really cares, because there are many decisions that go into these, and you never know which decision is the most critical one. Things get sorted through very carefully and regularly. Then, of course, choosing where we're going to do the work and with whom we're going to do the work outside of our organization is also quite critical. On that front, we're very focused on experience and facilities, and the discipline to execute, which is really fundamental, and that's why we obviously came to hVIVO. There was a lot of thinking before we Yeah chose hVIVO. It's a tremendous responsibility, both to the investors who, as Mario mentioned, RA has invested in ILiAD, which we're extremely grateful for. They did a lot of hard work, and they obviously are very thoughtful about how they conduct their investment decisions. Therefore, we feel a tremendous responsibility also to make sure that we're good stewards, right? Because this money is coming to us, it's not going somewhere else. We need to make sure that we have done everything in our power to optimize the outcome. You can never guarantee the outcome. You have to do the study and see what it shows. Yeah. You can think very carefully, you can be measured about your decision-making, you can choose great partners, be very thoughtful about every step, that's what we try to do. We feel tremendous responsibility to do it to the best we can. It's about eliminating all those other variables, isn't it? Making sure it runs as smooth as possible so you can interpret the data. Corrina, you're a clin op specialist, I was wondering how you would go about this, you seeing any challenges with doing something at such a large scale as this? Yeah. I think it's right just building on what Keith said. I really do. The scientific expertise that you guys provide, the company expertise, I feel like one size doesn't fit all, too. Yeah. I think you really need to take your time and plan out your challenge trial and your other trials very well. I think it takes a lot of brainpower and teamwork to really figure out what is best for individual products. Thank you. I would like to thank our panel, really what I want to do now is just open up to see if you have got any questions from the audience for anyone on our panel, please. There is a gentleman there, Andrew. Over here, please. Hi there. Just a quick question, thinking about the RSV vaccines that you mentioned earlier. One of the key issues that Pfizer and GSK are having at the moment from a commercials perspective is these vaccines are quite effective over multi seasons, and finding the optimal time for revaccinating. Yeah. Human challenge trial data is obviously used by developers to make that go, no-go decision. It's hopefully, in the case of ILiAD, going to be used by regulators to make an approval decision. Do you think there is scope for human challenge trial data and studies to be conducted in a way that informs payer decisions and vaccine recommendations? Yeah, that's a good question. Always when we design these challenge studies, we've got the end game in mind. They are trying to look for that core, are they efficacious or not? There's a limit to the questions you can answer with one clinical study. Typically, you can't answer all questions in one study. The first question is trying to look at that efficacy. After that, it is about durability, i.e., how long do these stay viable for before you have to revaccinate? That is a difficult question. You can design challenge studies like that to look at it and, for example, giving the vaccine at different time points ahead of when you actually challenge the participants. To some ways, you can never completely mirror what needs to happen into the later-stage field trials, which is why they're very complementary, they're not going to answer all questions. Particularly with that RSV vaccine, it's targeted largely at pregnant mothers, of course, we wouldn't give a pregnant mother necessarily the actual pathogen from a safety perspective. You do still need these later stage field trials to answer those questions. What the challenge studies can do is that they will accelerate getting that product out and being used. Once they're being used by then hundreds of thousands of people, sometimes millions of people, then you get that rich real-world data to then look at the next generation of those vaccines. The important point is you've already got something which is working at that point in time. You're already saving lives. It's now a question of how can you improve upon that? Anybody else on the panel got anything to say? No, I think you're right. Any other questions? One thing that I want to make sure that we highlight is we call it human challenge, but we also call it controlled human infection model. It's a very controlled environment. Yeah. We understand the infection model. We understand how people react to it. This is all the work that you guys see with pertussis is one critical example. For people who are not an expert on the space, just highlight how much effort it goes into the point when you have the model, and you understand the model, and it's safe, and you can use it in people. Then you can actually get the data when you apply the vaccine or you apply the antiviral or the antimicrobial. There's a history on how we do these type of things from the '70s when the first human challenge model were developed for flu, and the malaria models were developed by Walter Reed in Bethesda. The field has gone through many, many years of research to get to this point and being able to call a control a human infection model. Absolutely. I think there's a question on that third row there. Thanks. Mike Mitchell from Cavendish. I think it's been alluded to in the discussion already, hVIVO clearly represents and delivers very significant capabilities, perhaps this is directed to Keith and Corrina. If you imagined a world without hVIVO, heaven forbid, how would you go about replicating the expertise, the capacity, the capabilities, the advisory? How would you think about managing your respective development campaigns that you've spoken about this morning? Would it be so critical that you're actually considering and revising the viability of those development campaigns? Is it possible to think about trying to involve or invoke a wider spectrum of suppliers? It might not be one company, it might be another. Is that even possible? Corrina, do you want to start? Yeah. I'm not sure I really understand. Can you repeat the question? In a life without hVIVO, how would you? Without hVIVO? Yeah. How would you go about that? How would I have done this without hVIVO? Obviously, they're world-renowned in the challenge space, I don't think that we would've been able to have done a challenge trial to the same caliber, right? For the field trials, it would've been interesting. We probably would've just stayed in the U.S. and not had the U.K. contingency. I think we would move forward kind of U.S.-focused alone, doing a large field trial in the U.S. and not had the U.K. kind of risk mitigation without hVIVO. We also had other collaborating partners too, so we probably would've leaned on other CROs. Parexel was our CRO partner in the U.S. that managed the U.S. sites for us, and they did a really good job. I think the virology piece is difficult because I don't think there is a first-rate virology lab, and definitely not in the U.S. The other partners ex-U.S. really are not of the caliber of this group. I think the virology would've been hard. It was very nice to have the virology done in the challenge phase II and then phase III, just the continuity of the testing and making sure everyone was doing the swabbing properly and things like that. That was key for the thing. I think it would've been challenging. Yeah. Keith? I apologize, I couldn't quite hear the question. In a life without hVIVO, how would you go about trying to deliver your pertussis challenge study? Would you have to get multiple other partners, or what would that look like, do you think? Or would that even be possible? Part of the issue is just the sheer size of the study. Obviously we spent a lot of time with the FDA and MHRA and other regulatory agencies to make sure that we're conducting a study that's actually going to be able to lead to registration and approval of the vaccine. So I'm not aware of another organization that could handle a challenge study of this size, and so it would be difficult. We would ultimately find a way because that's how it is at ILiAD. In terms of sort of the straightforwardness of it or the ability to execute at a level that we feel very confident about is much more efficient with hVIVO, and at the end of the day, it wasn't a hard decision where to go. Thank you. One last question if there's any. In the front. Mic for friend's coming. Obviously. Hi. Rick Pierce from Decoy. Really excited to see the readout at some point down the road here. How big a trial size, because you're actually doing a registration study, obviously you can get the N should be pretty good with your numbers. You could do a relatively small trial. What did the agency ultimately ask for in terms of a safety database and the sort of the standard things that they look for, and how do you address that? Yeah. Thank you for asking the question. In terms of safety, it's obviously fundamental, and it's been touched on here. We're quite focused on that, and as Diane said, we're exposing an individual to a virulent organism. Safety is always at the top of our list. There's a lot of careful thinking there. We actually have a dedicated safety lead within the company, and we of course have the PERISCOPE data that we built upon, and there are data safety monitoring teams that do our work. We have a very carefully developed infection control measures, and then there are all the interactions with the regulatory agencies. It's a back and forth. "Well, what about this? How about that? What do you think? Hey, you should be thinking about this." It's a very thoughtfully measured process to get there, and ultimately picking the right partner to execute is also part of the safety. Getting back to the substance of your question, our safety study is going to be 6,000 individuals, which will be 3,000 adults and 3,000 pediatrics. The focus of the hVIVO study is an efficacy study in preventing this primary endpoint of colonization after 12 months. Of course, we're always looking for any safety signals, and again, have data safety monitoring board. It's always job one. We're very focused on that. Ultimately, we will be doing a separate study in the future that will be a dedicated safety study. I think that comes back to the first question there that one study can't typically answer all questions, that the benefit of a challenge is that you directly inoculate them, so you need relatively small numbers to get the efficacy. That means it's not the large enough data set to give you the safety data, hence you got to run the separate safety study. With the safety study, you know you can do that in time because you're not worried about what's going on with the disease in the community, because you're just looking at the response to the vaccine. This goes hand in hand and really helps your clinical development. With that, I'd really like- At what point do you have phase III, phase IV? Like when It's definitely phase III because you still need the safety from the phase III. Yeah. Yeah. Yeah. Really like to now give a round of applause for the panelists, and thank you very much for that. Thank you, Andrew, and all the panelists for an engaging discussion. We can now pivot from human challenge trials to talk about some of the new areas. The first one is respiratory which will be covered by Alex Mann. Alex Mann is one of our Senior Director scientists. He's been with us for over 25 years. Has got a huge amount of experience in human challenge trials, both in infectious diseases and also in respiratory. The last couple of years, he's been heading up our respiratory franchise, especially focusing on non-human challenge trials in asthma and COPD. Alex. Okay. Hello, good morning. My name's Alex Mann. I'm Senior Director of Clinical Science here at hVIVO, and I've got the pleasure to touch on really how we're expanding from a very well-established viral disease models, our challenge models, into respiratory like asthma and COPD. The first question that really springs to mind is why respiratory in the first place? Why expand into that? It really boils down to several core elements. One is there's a very high prevalence of asthma and COPD in the community, both in the U.K. as well as globally. Alongside that, despite some really wonderful therapies that have come through in biologics and inhalers that are on the markets, there still remains a significant population within those diseases that are not properly well controlled and still exacerbate on a yearly basis. There's an unmet need, and that will be more discussed by Prof. Richard Russell shortly. It seemed like a really natural progression for hVIVO to move into this because we've been working for 20, 30 years in respiratory viral diseases like flu, RSV, SARS, and so on, and rhinovirus in healthy adults, but also in asthma as well. We've been building the infrastructure over time to really develop from the infectious disease side, and that is also ready, and you'll see the lovely facilities later. It's also ready for airway disease studies as well. Alongside that comes all the expertise that's been built up over time with those respiratory challenges as well. Really, with all the challenges that are going on with clinical trials, and I'll touch on that in a second, we really feel there's an opportunity to really accelerate the recruitment and delivery for the clients. Some of those challenges, I've listed a few just here. There are others, but a key element of some of the challenges that trial sites do sometimes find is that asthma and COPD isn't necessarily a simple disease. It's quite a complex disease. If you have an asthma patient or a COPD patient in front of you need to understand what type of asthma have they got, what type of COPD have they got. Have they got type 2 inflammation, high or low? Therefore, when you have a trial with inclusion/exclusion criteria that are focused on the mode of action of that drug, they want this specific population or this specific population. You need to really characterize your patients to understand that. That's really key in terms of onboarding them into those trials and recruiting strongly and recruiting on time. There tends to be a bit of a lack or limited availability of inpatient facilities. Also sites that can perform trials 24/7. Monday to Sunday, evenings, weekends, Christmas if need be. The point is, we can work all the time on these trials. There is very limited availability of those facilities. Then lastly, and this more relates to the challenge studies, there are also limited tools to de-risk the early respiratory development pathway, and we'll touch on that secondly. Taking all the challenges but also the opportunities, how are we looking to really differentiate ourselves from others, specifically adding value? A key element there is to actually enroll and recruit the patients much quicker, reliably, and have a really big pool of patients that can be onboarded quickly. They're very happy to be in trials, and they're ready to go. We do this in several ways. Firstly, we've got to identify those patients. We've got a lovely recruitment team, a nice engine that's been optimized over 20 odd years, focusing on healthy adults, but also asthmatics as well. That really does recruit from the whole of the nation rather than just locally. That can be turned towards specific asthma patient populations. To date, we've got about 80 odd thousand in our database that have identified of having asthma and COPD. They may not have it, but they identify themselves as having asthma and COPD. We then bring them in to properly characterize and establish, do they have that disease? What is their disease like? These are a range of assessments you can see here that we perform on a daily basis. Also some assessments that are very specialized that we can perform with our key collaborators at King's Centre for Lung Health, like the bronchoscopy and imaging. In addition, we collaborate with them on a lovely longitudinal asthma and COPD cohort that really characterizes them well and keeps them engaged over time. With all of the infrastructure developments, we've got the inpatient facility, which you'll see, with all the capabilities that we developed and with the KOL collaborators such as King's. We really feel that when we get these challenge studies that can be used for asthma and COPD, we can deliver extremely strongly. How are we rolling this out? We've already started. We've been working in asthma for quite some time. There's over 100 clinical studies that are active in phase I, II, III in adults and over 130 in COPD, so there's definitely an opportunity to get onto these trials. We have been with asthma. We've been performing multiple phase I, II, III studies to date and also challenge studies. COPD is coming a little bit behind that and progressing really well. We expect in the next year and a half or so to be progressing into new services. The focus there is on new services, onboarding new clients. We open ourselves up for new opportunities in other respiratory indications or related indications like allergies and bronchiectasis, and we will develop our capabilities to be able to respond to those interests. The real thing at the moment is we're getting a huge amount of interest in asthma and COPD rhinovirus challenges. With everything we put in place, I think we can deliver very strongly. Thank you very much. I'd just like to introduce. That's actually in the wrong order. I think just get the other slide up, please. We're just going to introduce Professor Richard Russell from King's Centre for Lung Health. He is a collaborator with Professor Mona Bafadhel on longitudinal study and also otherwise, but also he's the chair of the British Thoracic Society, head of department, Peter Gorer Department of Immunobiology and Professor of Respiratory Medicine at King's Centre for Lung Health. Thanks, Alex. It's great to be here today, and it's somewhat outside of my comfort zone a little bit, and I wondered whether I was a kind of sacrificial lamb, perhaps, in this way. I do have colleagues here, which is great. It's a really important thing, and actually understanding how academia works with companies like hVIVO and then about what we're trying to do delivering. Seeing the passion in delivering these drugs to change people's lives, and that's what we're really talking about, and that's why we clinical academics enjoy this work and do this work because that's what it's all about. Seeing others that have the same passion and desire as us is really important and keeps us going. Can we move forward? That's my King's slide. We'll see. I'm going to reiterate and focus a little bit on what Alex has said. I think we'll move forward. There we go. I am going to talk particularly about what about respiratory health, what is important in respiratory health at the moment, why now, and obviously what hVIVO and King's have got to offer together in a sense. Alex has already mentioned, I will try and put some numbers on this for you, I am sorry to say that respiratory medicine is often ignored, often not picked up on. COVID was a respiratory illness, I am sorry to say that we did not maximize that benefit that came from COVID. We missed that opportunity. Right now, respiratory disease is a massive problem. Growing respiratory disease burden affecting hundreds of millions globally. What does that mean? China. How many people got COPD in China? 400 million. Okay? 400 million. Over 200 million have been diagnosed, they have declared it to be one of their five health priorities for the next 10 years. They are taking this seriously. U.K., 3 million. U.K., four and a half million people with asthma and increasing. This is a big burden, 25% of the people admitted to hospital with exacerbations of COPD, which has a 15% mortality rate, are under 65. This is not a problem of old men who smoked all their lives. It is a problem of real people. This is something which we really need to get across. There is a massive opportunity gap because of under-investment. I work with cardiologists very closely at the moment. They are very effective. They are very aggressive. They do not like each other very much, I would not go for a drink with them. They are really effective at changing the world. They have been very good, they say to me, "You know what? You have got an opportunity in respiratory because you have got headroom, because you are so bad that you can get things better." We cannot do that anymore because we have got smaller and smaller benefits. Drugs work already. It is really hard for them to then find new things which make a difference. That is an important thing. We are under-invested, there is opportunity now for new investment to leverage those numbers games. Things are changing, we are playing catch-up. Precision treatments are now real and live. Biologic therapies in asthma are life-changing. If any of you are on them, you will know this. The right phenotype of person, which is identified by simple tests, changes their lives when you start them on biologic therapy. The first biologic therapy for COPD has been approved in the U.K. by NICE a couple of months ago, the second one is about to be approved. I was lucky enough to lead both of those presentations. It is a huge opportunity now going forwards, our technology is actually relatively simple. The identification of the problems are relatively simple. We just need to make it happen as well as develop new treatments that will change the trajectory of our patients. I am excited by the possibilities in the U.K. because we have a very strong ecosystem already for being rapid with our commercial outcomes. The government are about to announce, I do not think it is quite secret, that the Office for Life Sciences are investing a matched GBP 75 million investment that will prioritize respiratory medicine and respiratory innovations. There is a drive to this underneath by the government. For example, next week there is another big opportunity with the U.K. government working with AstraZeneca and also working with the Chinese government in trying to do joint respiratory research, which again, I think just shows the commitment to what is going on here going forwards. The clinical need here is absolutely massive. Probably more than one third of you in this room will die of a respiratory illness. Pneumonia very often due to chronic disease and stuff, but other things as well. Mark my words, not that I am much of a doom merchant, but the next pandemic is inevitable and is coming, and I hope we are prepared and respiratory medicine is in a better place to optimize what we get out of it. These impacts are understood very much by the hVIVO team. Alex has been fantastic working with us at King's Centre for Lung Health and King's College in understanding that. The burden economically is enormous, GBP 11 billion a year in the U.K., with hospital admissions and long-term management being absolutely the drivers of that. I spoke to our national clinical director about what he wants to achieve with biologics and COPD. He said, "Just cut down one admission to hospital." That is what we need to show. That is the burden, that is the problem we have at the moment. As I mentioned, the prevalence of these key conditions are absolutely going forwards. As you have heard from Alex, hVIVO are the leaders. We are the leaders in understanding the impact of asthma. Their asthma cohort is unique and the largest in the country, and that is really powerful. We have got opportunities now in how we can do this better, both with better diagnosis and then earlier treatment. For example, the biologics in COPD, people think, "Oh, they are not going to work in COPD because it is a smoking disease." It is a chronic disease where people's lungs are exhausted. To a degree, that is true. Why would a biologic therapy ever work on somebody who has got very severely damaged lungs with emphysema? The studies interestingly show that actually, if you look at the people who are a little bit further upstream, a bit earlier, you actually do see clinical benefits with the latest large GSK study showing a 10%-12% response in the people with more damaged lungs, with a 35% response in the people who have got earlier disease. We need to be doing more studies to look at that and actually taking those opportunities to actually intervene. That will be disease modification, really. As I have said, respiratory disease is a healthcare priority for the government. The three policy shifts that we have got in the U.K. help us. The drive from treatment to prevention, the drive from hospital to community, the drive from analog to digital. All of those things are actually mapped very closely to where respiratory patients are and how we can manage them and how we can research them. This is another piece that I think we need to build in, respiratory patients are unheard. They are unheard because often they are deprived, both from a healthcare point of view and economically. The government have a priority to sort that deprivation out, and we can tap into that from an equality point of view as well. I tried to put some money on this and to actually understand and speak some of your language a little bit. The therapeutic global market is growing massively from GBP 100 billion to GBP 245 billion in the next 10 years. There's no doubt about that, and that's about prevalence. These people are already baked into the system. As I mentioned, China is the epicenter of an epidemic of COPD and is taking this very seriously. They're putting their money where their mouth is. The biologics are expanding faster than ever. We've got two. We're about to have three with a new drug reading out, there's probably two others which are also going to read out very soon this year, which I think will be positive, including new indications for treatment as well, which is important for current therapies. We have new innovations coming with oral and also inhaled treatments, which will change the way in which we can give medication. At the moment, some of these biologics are either intravenous, one or two, but also are subcutaneous. As I mentioned already, the idea of personalized medicine is clearly going to transform what we do with giving the right patient the right treatment which suits them. Not difficult to do. Our technology is simple, but actually it works very well. This will improve outcomes, and it will make sure that we are cost-effective with what we're doing. Why is the U.K. a good place to do respiratory research and a good place for research? Well, we are lucky in the U.K. having such good primary care data. We are the strongest country in the world with U.K. COPD databases, there's another data, commercial database as well, such that we have integrated data sets. We are used as the test bed for that by the whole world. That allows us to do large-scale data collection as well and make changes. A study I was partly involved with, which was understanding the impact of cardiovascular disease and COPD together, enabled us to look at over 8 million patients in a six-month period to then form a firm and absolutely clear, indisputable answer about the impact of these diseases together. As I've mentioned, the government is investing in this now and is supporting this. The Health Minister who resigned two weeks ago, Sajid Javid, was extremely supportive. We are now engaging with the new health ministers to try and make sure that this agenda is being driven forward. I've got no doubt with the big pharma companies that we have in the U.K., GSK and AZ particularly, having massive legacy in respiratory medicine and being extremely committed to the future of respiratory medicine, not just in the U.K. but also globally. We have a collaborative research culture, you heard already, between academia, you've had examples of this already, with target identification between industry and in healthcare providers. As you know, healthcare trusts are being driven and measured according to their research output as well as their clinical outputs as well, which is very exciting. Of course, we have a reasonably advanced, not always very helpful, regulatory framework. I think we've forgotten some of the outcomes from COVID, but we are getting better again at doing that to reduce risk. Why King's Centre for Lung Health and King's and hVIVO? Well, we're actually close together. We're inspiring each other. We have an integrated research and clinical practice. We go in the King's Centre from pharmacology, from target identification, through to molecule development, through to clinical trials. We do basic research as well as trials, and actually working together with hVIVO in the trial world is going to be a great future for us. We have this multidisciplinary expertise. I am head of an immunology department, and bringing immunology, which is the future of where we need to go for disease modification, is critical, as well as engineering clinical trials, as I mentioned already. That, again, partnership with hVIVO enables clear material transfer and to really get the most from our samples, and that's going to work both ways, I hope, with what hVIVO plans going forwards. Can we access patients? Yes. South London is diverse. South London is large. South London is often untapped. We have a research network forming now, which enables us to not only access asthma, but also COPD and other diseases in this whole area. We are looking at a population of around 3 to 5 million people, which will give us access, again, to many thousands of potential patients. Our patients always say yes to research, there's no question, because they want change. Of course, we need to be able to translate and scale up. Working with hVIVO, as you already heard, enables this to happen, creating, for me, a virtual cycle that we see. In summary, to emphasize those points, there is a massive unmet need. It is relatively under-researched, under-resourced, but is now an increasing burden on the world. There's no doubt about the potential for market growth. It is happening, driven by biologics, precision medicine. Not difficult medicine, just precise. The environment is good in the U.K., with strong healthcare infrastructure, policy support. Yeah, there's some challenges. Yeah, there's regulation. Yes, there's NICE, but NICE is softening. Finally, we have a great opportunity locally through partnership from King's Centre for Lung Health, King's College London, with hVIVO to really enable rapid, and speed is important, rapid development of really good studies which answer clear questions and then deliver translational outcomes. This is me as a scientist, wanting to answer important scientific questions as well, to get the best that we can out of every single piece of information for patients. Thank you for your attention, and I hope that's been helpful to just contextualize where we are in respiratory in South London. Thank you. Richard is a little modest. He's one of the key leaders globally in his field. He's the chair of the British Thoracic Society, he has a lot more influence and leadership than he's willing to say himself, I'm going to say it on his own behalf. Thank you for giving us your time and talking on respiratory. We're now going to move into cardiometabolic drug development. If we can have the next one. I can have the next slide. This will be presented by our colleague, Dr. Thomas Forst. Thomas Forst is a key opinion leader endocrinologist. He's been with CRS for around eight years. He has a long tenure in medical practice. He also worked at Eli Lilly through different stages of development of several endocrinology products. He currently has relationship with majority of the big pharma that work in this area. Novo, Lilly, AZ. He actually sits on the scientific advisory board of AZ. He just returned from the American Diabetes Association Conference, which took place in the last couple of days. He may be a little bit jet lagged, but coming up, Thomas Forst. Mo, thank you very much for this very nice introduction, but at the very end, I'm a medical scientist and a trialist. That's what I am. Coming to this cardiometabolic area, we are talking more or less about obesity. As Mo mentioned, I've just returned from the ADA meeting in New Orleans, I guess more than half of the presentations over there have been presentations about new drugs for the treatment of obesity and of the obesity-related disorders. This is more or less what we are talking about is the metabolic syndrome. The metabolic syndrome, which is driven by insulin resistance, by fatty liver disease, MASLD, how we call it today. It's lipid disorders, it's hypertension, it's inflammation, which plays an increasing role in this metabolic diseases and in some cases, in around 20% of cases, it's also associated by type 2 diabetes. Why is this so important? Because this drives morbidity and mortality of these patients, this is cardiovascular disease. Three out of four patients with obesity and type 2 diabetes die from cardiovascular disease or from stroke. It's also heart failure. It's also orthopedic complications. It's cancer. For example, colon cancer is much, much more often in obese or type 2 diabetic patients. Breast cancer is much more often in obese or diabetic patients and much more often in this kind of insulin resistance. We have sleep apnea, which is more often, and at the end, also these inflammatory diseases like psoriasis. You all know obesity is rapidly increasing all over the world, we expect within the next years that more than 50% of the world's population will be overweight or obese. In Europe, we have the situation that two out of three children in the age of 14 years is already at least overweight. We will have a big market coming up. We have these new drugs and more and more new drugs are coming up the road for the treatment of obesity. This grows, of course, the CRO market. This, of course, increases the number of trials, early phase trials, but also late phase trials within the next couple of years. This is why we believe it's a nice place for us to even grow hVIVO and increase the activity and the business of hVIVO. What you see over here are a couple of companies which have these drugs in late stage development in phase II, in late phase II or phase III. With a lot of these drugs, we have a very close relationship. This is Boehringer Ingelheim, of course. We will talk about that in a minute. It's also Lilly, it's also Novo Nordisk, it's Roche. I just met at the ADA with Structure Therapeutics. I'm really happy that they will also come to us and run a couple of study with us in Europe within the next couple of months. They have not done it before. They have mainly had their development in the U.S. up to now, but they will come to Europe. That's something which is pretty clear. This is just the top of the iceberg. You see over here, these are a lot of companies or a lot of companies which have drugs in the development for obesity or of these obesity-related complications like fatty liver disease, but also like cancers and cardiovascular disease or heart failure, which will be treated in studies, at least, with these new drugs, which originally have been developed for the treatment of obesity or even for control of glucose levels. If you look at this cake, at this moment in time, Germany and the U.K. runs around one fourth of these trials in Europe. We are really convinced that now together with hVIVO and the German sites, we will be able to increase this part of the cake within the next couple of years. You see what is here is what is required. If you want to run these kinds of studies, you need a lot of assessments you have to bring in place to offer the companies things in the early development. It's very, very important in this drug development process that we will have an early proof of the concept. An early proof of efficacy of this kind of drugs or even an early proof of failure of these drugs to invest money in the correct way. We have established a lot of this, let's say, pharmacodynamic measures to measure obesity, to measure the distribution of body fat, and this is an important point, but also to measure the relative relationship in between adipose tissue and muscle tissue in our patients during treatment with these weight reducing or weight controlling drugs. We also have to measure energy expenditure. You see all the drugs we have in place at this moment in time trigger weight loss by reducing appetite and increasing satiety. We will see new drugs now which also increase energy expenditure. We have drugs in development and in clinical studies which will improve the relationship in between adipose tissue and muscle tissue, which is a very important point. For all of that, we are very well settled to offer our customers the investigations which are needed to get this kind of proof. I just said already, I just returned from the American Diabetes Association, and there we have seen one of our last studies be published, which we have done with a couple of companies. This is ACHIEVE-2 trial where we have been involved, and this was published on Monday? Yes, on Monday evening, we are very proud that we are part of this publication. In the last year, we wrote an article, a review article, about the role of this kind of incretins in the treatment of obesity, but also in the treatment of obesity related complications, which I already mentioned. Again, I'm very proud that this is one of the top viewed articles in Diabetes, Obesity and Metabolism. This is something we try to do very often also to get a view on us that we are one of these most experienced companies or CROs in the development of these kind of drugs. What is our goal? You see at this time, I think we are one of the most successful CROs in this area, the 5 successful CROs in this area over the world. We want to expand our experience. We want to expand our offers to customers in obesity and metabolic disease to become the number one within the next years. We want to expand what we have already built up in our site in Mannheim, which is our leading site in cardiometabolic, to London, so that we can offer this kind of trials not only in Germany, but also here in the U.K. We will increase our patient recruitment capabilities. You have seen that there is a huge database here in London, in the U.K., from these activities. It's much less in Germany in the cardiometabolic area. This is an investment we are doing and to creating even a broader database and to deliver for these lots of studies coming up the road. We will broaden our opportunities to offer this kind of investigations, which become more and more important in the obesity trials. You see, a couple of years ago, it was nice to measure BMI and body weight. These times are gone. We have to measure much more, like I already addressed, like fat distribution, like muscle, like energy expenditure, like fatty liver disease, like whatever, like heart failure and measuring heart ejection rates and things like that. We want to bring closer the consulting work, which is done in preclinical stage with our clinical experience, so that we can bring much closer the link in between preclinical assessments and then the move over to the bedside, coming to the clinical parts. We can grow the demand from obesity and next generation cardiometabolic therapeutics significantly. I believe this will become a very important part of the business within hVIVO beside that what has done in the past with these challenging studies. I think this is a market which is really at the beginning. Coming back from the ADA, I have seen so much drugs over there. Dual agonist, triple agonist, quadruple agonist, these small molecules now working as a GLP-1 analog, but we will see dual oral molecules, triple oral molecules. This is something which is going on, and this will keep us busy for the next 2 decades. I'm absolutely convinced about that. Thank you very much. Thank you, Thomas. It's difficult not to be impressed by Thomas' experience and expertise and relationship with several big pharma and biotechs who are working in the cardiometabolic diseases. Really, I'm proud to have him on board as one of the key team members in the company and heading up the cardiometabolic franchise. I'm pleased to tell you the next is the last session, the final session of today for you. We wanted to discuss between different stakeholders of why they chose hVIVO as their partner. We thought the best way to bring that to life is to ask a CEO from a biotech company and an outsourcing person from a big pharma to discuss how they came to the same decision in selecting hVIVO as their partner. I'd like to welcome Rick Pierce, CEO and co-founder of Decoy Therapeutics. He's been with Decoy for around eight years, but he's a serial biotech executive, a really big name around the Boston, Cambridge scene. Every time I speak to him, he gives me new names to speak to. He has a hell of a network across the board. Konstantinos, I'm really going to slaughter this surname, unfortunately. Synodinos. I'm sorry, Konstantinos. He's a procurement executive for over 20 years, with 17 years in the pharmaceutical industry. He's currently responsible for around half a billion dollars worth of outsourcing at Boehringer Ingelheim. Thank you, and good luck. Thank you very much, Mo. We will discuss a little bit around about this early clinical developments and why to choose hVIVO. One thing I wanted to start with, is it different, or what are your needs when you come over from the preclinical stage to the clinical stage, and what is a reason for you to decide or to choose for a CRO or a site? Maybe Rick, you start. Thank you all, thank you, Mo, for the invitation to come, and it's been wonderful to be able to spend a little time with the hVIVO team again on this visit. I think listening to today's program really helped inculcate in me why we chose hVIVO, and we've known the hVIVO team for, I think, four or five years almost. We met them at BIO several years back and have watched the growth of the company. Clearly, I'm from Cambridge, Massachusetts. We're an AI machine learning company that is spun out of MIT, focused on developing in the next two years, we will bring two drugs into the clinic using human clinical trials, the challenge studies, as our path. Integrated preclinical phase I, phase II, almost identical molecules, but we make what are called designable multi-antivirals. One drug can hit multiple viruses and multiple viral families and be able to treat many people around the world. Big scale, huge. We are focused on speed using AI, our investors expect that we can deliver the same kind of speed in the clinic, and hVIVO can help us do that. As you heard today from Andrew, the speed at which you can bring a drug through phase I, phase II, and demonstrate proof of efficacy before you go spend money to do that 6,000-patient study, which we will have to do if we're going to do a big study, as Cidara has shown. Two words came to my mind, and it was global nexus. You've become, at hVIVO, over the four or five years that we've watched, you've become the global nexus for human challenge studies. You are the best in the world. If we believe we have two drugs that we'll bring in the clinic that will cover 75% of respiratory viruses. They also will treat things like Nipah and Hendra and very obscure global public health issues in India and China and other places. These drugs are going to be big scale. You have to have the best rigor. We wanted to start very early from the beginning, from the preclinical, working with Katsu and the team at Venn in working our program and looking at our protocols and CMC and all the things that can trip you up that can really make or break a great clinical program. Being able to execute that with enormous speed. It's amazing to listen to your story from Cidara and having watched it from the sidelines. It's really an impressive story. What was all behind that was the hVIVO team. It was not hard for us as we looked at the landscape, and we talked to some of the world's biggest and obviously very good at what they do, but you didn't have the confidence interval that they could work with an 11-person company, not 40, with 11 half-time consultants. We will grow. I don't know if we'll get to 40, but we'll grow pretty quick. You need to have people you can trust and people that have the expertise and people like yourself and people like Andrew. When Mario Barro looks at your company and says, "They're using the right people out of these. Do they have the right drugs? We'll see." I think investors do want, they're investors in the room, you want to see that the companies that you're working with understand what they're doing, are working with the best people they can possibly work with, to de-risk those programs as much as possible. That's why we chose hVIVO. Thank you very much, Rick. This is from the view of a smaller biotech company, and it's from the view, especially with regard to more of these challenge trials. Now, Konstantinos, you are representing a big pharmaceutical company, one of the big leaders in the world. You also worked a lot with us also in other indications. What is your view on the importance of your partner CRO? We work a lot with you on the cardio, renal, and metabolic areas, and inflammation as well. We have a different setup. We choose our partners based on long-term relationships, and we choose them based on their therapeutic area experience, disease area experience, their capabilities in recruiting and retaining through the process of the phase I, the patient or the healthy volunteer into the study. We're making sure that we working directly with the CRUs, rather than having the middleman, which is usually a big CRO that then will go and outsource to a smaller CRU. We like to do that direct approach because we value the connection and the science that the investigators are bringing to the company. We have long-lasting relationship, and we feel that the team is an extension of our clinical teams in that sense. On top of that, I think, moving away from the phase I and towards the proof of concept, which then involves arms with patients and so on. It is important for us that we get that powerful recruitment and retention ability of CRS and hVIVO. Being able to do a multi-site, multi-country setup, is very important for us. Using the much faster timelines of MHRA in kicking off a study and then expanding those studies in Europe through the German sites is also a very interesting aspect for us. You said something which is, I think, very important, and this is a little bit different from that what we see in late-stage clinical development. When we come in in these early stages, we become a part of your team. Exactly. Have a very close relationship. For example, we have once weekly team meetings with your team and our team to see how things are going on. I think that was very nicely said from you. We are becoming a part of you during these kind of trials. There's one other point which I think is changing very quickly. In former times, we have done these classical phase I studies in the healthy volunteers, much later, we moved over to the patient studies in phase II and phase III then. I think this is a little bit changing. We see much faster or smaller classical phase I programs, which are already combined with early involvement in patients. What do you think? Is this something which is more the future of clinical trials? Yeah. Rick? I want to say one comment, and that is, I said to Mo and Andrew, I think back around Easter time when I was here, that if we do our job right, we could easily become hVIVO's biggest repeat customer because what we do is create molecules really quickly. We will prove them out using integrated phase I, phase II-A human challenge studies. That idea of being able to work within a single ecosystem with an integrated team that you know, not running to some large CRO here and trying to find this site and that site and manage all that. I've been there, done that before, with another company that we ended up selling to Pfizer. The idea of being able to work with a team, a small team that you know, and being able to take your drug through the paces, preclinical phase I rapidly into the challenge study. You see one of the smartest fund managers in the world sitting in the room, supporting hVIVO. There's a reason why they're doing that. They're doing the same thing in China. Mario didn't talk about China, but they're doing very quick trials in other areas. I think there is a huge opportunity for us, selfishly, as a company, to work in this ecosystem because it is really well set up and really well planned out. Your MHRA is very receptive. I think EMA is very receptive, and unfortunately, my country is not. We've seen a lot of disruption. RA has been very helpful in terms of trying to promote science. We've had science effectively deeply damaged, I think, in our ecosystem, and it's very bad. It's our job. That's why I'm here, because I think that the right time, right place to be doing our work with hVIVO in London, in Germany, integrating. Ultimately, my last company, we did our work reference country U.K., launched in Europe, sold the company after filing an IND or an NDA in the U.S. We were bought out by Hospira, now global drug marketed globally by Pfizer. It's a playbook that I'm comfortable with, and it's a regulatory group that seems to be more with it right now than around. Yes. Konstantinos, when we move faster from the healthy volunteer into the real patient populations to see if the drugs are safe in the patient populations, but also to get an early indication of the efficacy of the drug, how important is it for you that you have a CRO, which has, of course, a lot experience in running clinical trials, but which has also the medical expertise in that indication and the access to these patient populations? Exactly as you explained. We see more of those combined umbrella plans, as we call them, when you get through the MAD stage and you add a patient arm. It is important that this travels seamlessly from one cohort to the other. The knowledge that you bring from testing it to the healthy volunteers into the first patient population is very important. It creates a risk-free transition. Combined with the fact that there is a very robust recruiting and retention policy and understanding on a multi-country and multi-site setup, I think that combination is what we're looking for. It answers, basically, your question, I think. Yeah. I think it's also a big advantage if you move. If I may. Yeah. It's also the combination of having that trust in the exchange of science that help us work with you in building the trial setup. That kind of consultation process when we're coming and we're talking about the trial setup and what is feasible at the end of the day in terms of going forward with these trials. Yeah. I think it's also a big advantage if you move from the healthy volunteers to the first patients, that if the team has already the experience from the phase I, which have seen which side effects are over there. Exactly. Have already some experience in healthy volunteers and know the drug. It's a big advantage also for the patients. Exactly. You also see that on the later stages when we're on a phase III and we're going back to you to do a bioequivalence. Right Determine the different dosing regimens or different delivery methods, basically, because this is where the experience lies. Yeah. That makes the whole process risk-free and faster as well. It advances it also in terms of speed. Yeah. What we see very often, if a big company like yours comes to us, you have a lot of specialists in this area. You have already very nice developed protocols, this is sometimes very different when we come to smaller companies where we do not have this clinical experience. How important is it for you, Rick, that you come to a CRO where you have specialists which can advise you in coming up to these clinical trials? Well, I think we enjoy a little bit of being a fast follower, and having the models built, tested, and the understanding. We're able to, I think, leverage that all that's gone before us. I think that's why we're here and not working at Carolina or one of the other places, Duke. I think there are other people that can do challenge studies, or Johns Hopkins University, or whatever. They're much easier for me to get to, but they're not the best, and they haven't done You've done more human trial studies than anybody else in the challenge study world, and you have the understanding of the models and the patients. Having the medical directors and the people, the clinical site managers watching, understanding, and having been in the site. I spent 15 years in investment banking. I looked at tons of companies, 300 companies a year. I looked at their clinical programs, I looked at where they did their stuff. We would go visit sites. We would go visit manufacturing places as a part of our diligence. I can tell you, I've spent time looking at this site, and it's really impressive. To have your lab literally like you put your samples in and you see- Wow, it goes through. Exactly, yeah Bam, it's going. I've never seen anything like it. It was like kind of a James Bond movie. It's quite impressive, isn't it? Yeah. Thank you very much. Yeah. We only have a few minutes left. Are there question or comments from the auditorium? Kas Blokla. Yeah, sure. I'm curious about Oh, thank you. One thing that I'm always curious about this whole idea of using wearables to measure data, like the Oura Ring or the watch. Is there anything that you have thought about? Because you have the challenge unit, you have people who are getting infected or treated, that you can actually bring some of that information into this other area that is going to be growing in the future, when people are going to start trying to monitor their health more and more through different wearables, and can you use that then later on in development? We're talking about wearables, right? Yes, wearable. I think in the early clinical phases, it's not really a trend right now, because you usually go through that process of setting up and doing that investment of setting up a wearable when you're usually on a phase III study. That can change, of course, but so far, the trend that I've seen is that those are usually happening on the later stages. Sorry, just to jump in there, to answer from an infectious disease and from a challenge perspective. We have included some wearables for SARS, for example, our challenge to look at whether we can use it in a prognostic, diagnostic way. There are different technologies there, look at cough, for example, that can monitor. In an inpatient setting, you can use some of these devices that you usually use for just night bedside table, you can actually use 24/7 and quantify cough more accurately, for example. That can potentially help with, if you're interested in cough, pertussis obviously is more on the carriage. There was discussions around monitoring cough and whether that could be an endpoint within that. Yeah, there's certainly some possibilities for including them. Where we do that in a large stage is when we monitor glucose monitoring, for example. This is a good example. It's very common in clinical studies, but I agree with Konstantinos, it's more in the later stages where we have that. It's a standard in the meantime. You're from Boston, you probably know WHOOP. They were able to predict a day or two before that you were going to get sick or whatever. It would be really interesting to see whether they would be interested in doing some kind of. They don't have the FDA clearance, but still, you might know who your placebo group is, or it could be kind of interesting. Placebos are sometimes very effective, as we have learned. Quite. Yeah. If you don't have other comments or answers, I think then we are coming to the end, and I want to thank you, Konstantinos, to thank you, Rick, for this panel discussion, and Mo, I give it back to you. Okay. Thank you everyone for a great panel session. Before I come to a final closing, I'm open to any questions anyone may have for myself, any of the speakers today, or any of our leadership teams. Thank you. Good afternoon. It's Miles Dixon from Peel Hunt. Can I ask the question about, not just to you, Mo, but to all of the speakers today, particularly around the U.S. and the rhetoric that we've seen coming out from 2025, that's damaged so badly. I think I heard anti-science earlier on. Clearly, we're in a mode that I think you've been very clear that 2025 was difficult from that perspective on a kind of order book basis. It feels that it's very quickly changing, and I wonder if I could ask a broad question to the speakers today about how they feel that dynamic is changing. Are people starting to look through it, or is there fundamental change in the industry around the language that we use and just getting back to business? I have an opinion on America, but I would love to get an opinion from the Americans on America. Yeah. The question was, how much damage does the anti-science sentiment coming out of the U.S. has caused long term, or do we think we're through it and things are improving? What happened is policemen showed up, and he was brought out of the Congress. This is unbelievable what's going on there. Now the ADA excuses that this happened at the meeting. It's unbelievable. Do you guys want to say anything? I didn't. Okay. I think it's difficult to qualify the impact. It would take time to see what is going to be the negative impact of things that happen is that, for sure, we've seen agencies in the NIH, people with a lot of experience not being able to do their work. What I can tell you is that at least from our RA point of view and my personal views, it's just to put out there the science that we believe in it. We have written several articles on vaccines, on infectious diseases, on the importance of the work that we do not only in the web, but we also have spoken in places and supported people who are fighting for science in U.S. I think that what matters the most is not to try to understand how bad it's going to be, but it matters the most to continuing and communicating to people how relevant is the work that we do for everybody. I think that's been the RA way to approach the problem. We've seen that pharma, it remained committed to science. We're seeing investment, we're seeing acquisition, we're seeing further commitment on the science. We've seen Sanofi just having review investment on science. They got a new CEO that is coming as well to the company with a new vision for the company. We're seeing that Eli Lilly acquiring three vaccine companies in one go. This is totally unusual. Those are the big guys. I think that there is compensation going on because science has been always something that people evaluated and everywhere. It's going to take time, but it's going to be hard to tell you how much damage. The most important thing is just to think about how much we can do to prevent that from happening. Okay. I would just add to that is I sit on a board of the Canadian Entrepreneurs in New England, and I have a board member who's Polack, who's one of the SVPs at Moderna, who runs about $1 billion of Moderna's British, Canadian, and Australian vaccine businesses. I think at the end of the day, people, they do vote, and their gas prices are higher. Their healthcare is not as good as it was. I think people are getting a little fed up that they can't get a vaccine, or the freedom to do things is being taken away. Hopefully people come with the midterm elections. Hopefully, we'll see some change there. I think if we don't, that could just sort of impact even further. I agree there seem to be winds of change where vaccines are sort of coming back. They were really pushed pretty hard. You see Moderna sort of has come back a bit, and they're certainly active in the space. I think we're contrarians. I've always been a bit of a contrarian in my life and gone against the sort of conventional wisdom, and oftentimes, it pays off pretty handsomely. We've actually seen a little bit of an uptick in the antiviral space, I think, as a result of the anti-vax movement, but I think that's not a good thing. I think you want to have a good balance. I would leave this audience, this is your time. You've got a great opportunity. hVIVO has a tremendous opportunity to grow their business because I think a lot of American companies are going to be coming, and they want a regulatory environment that is much more predictable, and we don't have that right now. Keith? I'm not sure I have much to add with respect to the sort of more global U.S. environment. I don't spend a lot of time working on that. I can tell you at the grassroots level with respect to our company, we've had terrific interactions with the FDA. They've been very responsive, very thoughtful, very detail-oriented, and at least the machinery of the operation at that level is functioning quite well from our experience. Just to add that to the discussion. Look, from my point of view, most Americans are as frustrated with this anti-science sentiment as we are here in the U.K. I think we say, "Oh, it's an American thing," but I don't think it's an American thing. It's a very small group of people, I would say. I think one of the leaders in RA Capital wrote a huge blog about the anti-science sentiment. Even I think the CEO of Pfizer, he had changed his view on what the administration is doing and saying about vaccines. I think things are changing, I think. We've seen Eli Lilly just acquired three companies in ID space. They must see a future. It's not good news, but the increase in incidence of these infection rates across different indications, I think is almost a proof that vaccines do work. In 1796, we proved vaccine worked a long, long time ago. It suddenly just doesn't disappear, that that science is no longer solid. I think it's a short-term thing, not a long-term thing, and I think the pressure now being created by the science community, I think the World Vaccine Congress, I think Andrew Pollard stood up, and he gave a very emotional speech about the importance of science and doing good work to make sure we prevent these communicable diseases. I'm optimistic for the future. Neil Keegan at Sanger's. Mo, I hope you're sitting down because I'm going to give you a positive vibe. Wow. One aspect of the FDA is that they're looking to bring drugs quicker and faster, and that plays into the HCT environment. Outside the U.S., there's tremendous amounts of money going into private companies across Europe and indeed the U.K. The science is stellar. The constant theme from your speakers has been of the unmet need, which is huge and growing. The 400 million COPD patients in China, et cetera. Do you see a positive outlook on this, and are you directing the business to look less to the West, and particularly the United States, and more to the East and addressing those opportunities, and maybe even closer to home in the U.K. and Europe? I think we're well-placed, and the U.S. can sometimes blind us to the opportunity, in my view. You are right. I think there's opportunities in both, right? I think as Rick mentioned, we've seen interest from U.S. biotech companies who have historically run their trials in the U.S., because of the unpredictability of interaction with the FDA, and it's exactly to what Keith points out, it's the inconsistency. One company has amazing experience interacting with the FDA, whereas someone else, we're talking to a client that have been talking to the FDA for almost two years to get approval guarantee, and they haven't been able to. Whereas Keith's team has been very successful in that. I think there is that inconsistency, which pushes a lot of these biotech companies into Europe and to Australia and so on. That's one. You're right. The huge increase in especially Chinese biotech industry and the amount of money going in there means that eventually, I know Richard is in China every other day, he tells me, eventually, those companies will come to Europe to run bridging trials or trials in European Caucasian patient population, and that's one of the areas we are looking at as we move forward. Absolutely, we think that is a growing market, and we can address some of that. Sorry, a bit of a continuation on that question. Do you think the business as it is with beds and recruitment services in Europe only, there's enough of an opportunity for you to grow there, or do you think there will be a point where you need to be physically present in North America or China? In the medium term, I think Europe is sufficient because there are many other countries. Spain, for example, is the number 1 country when it comes to number of clinical trials done in Europe. There's obviously some openings there. Long term, I think U.S. is somewhere we want to look at. In China, it's an interesting place to run trials in country because at the moment at least, you run a study in China, you have to effectively do a bridging trial outside of China in Caucasian patient population. Having presence in both countries, I think I'm not sure is ideal, but I think attracting those customers to run their trials in Europe, which I think will be a need eventually, that's our key medium-term goal. I think long term, we don't want to be an ICON or a PPD and so on. We want to focus on this early-stage clinical development. I think we have a model where we will insist on running clinical trials at our own facilities rather than contracting to multiple sites and having no control or accountability of the delivery. I think that's going to be our differentiator, and we want to double down on that. We talked about the COPD, I think Richard mentioned about this precision medicine. One of the key consequences of that is the eligibility criteria of which patients can take part in those trials. It shrinks. That means it's really hard to find patients that fit that protocol. You have to do a lot more screening, have a much bigger database of patients to find the number of patients that will go into that protocol. I think that's one of the key strengths we have by building the platform of the number of patients we have in the database, it means we can fill those very niche patient population protocols. Anyone else? Hi. Christian Glennie with Stifel. Maybe for Mario, sort of two-part, I guess just your evolution or thoughts about how you see challenge trials as part of drug development as you reflect on your time in this space, and has that changed? Have you always been pretty positive on it, or has it been an evolution of that to this point now? For example, you have this investment in ILiAD and a phase III. The second one is, I think you mentioned challenge trials is an important part, but it is not always what you go for. I guess, what are the scenarios in which you would not use challenge trials? On the assumption that it was a good model. Say there was a good model there, but maybe you still would not use a challenge trial in this scenario. Is it about the rates of infection that you can get in the field and things like that? What is the scenario in which you would not use a challenge trial? Thanks. Let me think for a second. I think in terms of scenarios. May I stand up? Of course. It is a free country. Good point. I just didn't. You're so shiny over there, so I want to get under that studio thunder. The one question was about the scenarios for the use of human challenge. I can give you an example, which might not be generic, right? Something that is closer to me right now, which is the norovirus space, right? I'm the CEO of GVAX. We're trying to develop a vaccine to protect people against norovirus infection. The virus is very hard to grow. It doesn't grow in cell culture. It's unpredictable when you see an outbreak. It doesn't have the seasonality of flu. When there is an outbreak, there's an outbreak. You're like, "Oh, Jesus, I should be there with my vaccine." Where they couldn't run my clinical trial and on that site, right? In flu, there is also a humongous amount of experience, right? When Corrina was running the clinical trial for the Cidara, she knew what clinical sites she was going to use because those are clinical sites that have been running flu efficacy study for years and years. There you go. If I can do my phase II study and a human challenge study, the well-controlled challenge study for norovirus that can give me a guidance of whether or not my vaccine works, that would be pretty much very significant because then, number one, you know what the strain you're selecting for your vaccine, is it going to protect people? What kind of protection you expect to do? Does that kind of guide you through your phase III? Look at the Clostridioides difficile development, right? Clostridioides difficile, Pfizer had to go back and re-design the endpoints for their vaccine because the vaccine actually works, but for any specific number of endpoints. You had to rerun a whole phase III study just because you mess up with the selection of the endpoint, not because the vaccine is not working. In norovirus, I'm afraid of not knowing that. If I had a little bit of an indication of how this is going to work in my phase III study, I would definitely pay for a well-controlled human infection model that tell me about that. Unfortunately, the human models that we have so far are very difficult also. They don't work that well. I'm looking forward to see that type of development. hMPV is another one. Is that you have the RSV seasonality, the hMPV seasonality. We think that we know that, but we don't know that that well. PIV is the same thing. There's areas where you can actually get a lot of data ahead of time, right, on this type of indication. What was the other question? Well, the question was more if there was a really good model that existed, say in RSV, we know that, and flu, you might still not choose to do a. What's the scenario in which you wouldn't decide? Is there any scenario in which you wouldn't decide to do a. Right challenge trial if there's a good model existing? Right. I've seen data. I'll give you an example. The use for vaccine for flu, there was this large movement many years ago to develop a universal flu vaccine using vaccine that, I'm going to go a little bit technical here, that goes into inducing immune response against the stalk of the HA and not the head of the HA, which is a more common space that all the flu viruses have. When we look at some of the human challenge data, it actually shows that it might not work, and then you lose your intentionality to actually invest in that type of development. There have been cases where the data from human challenges actually guide you to not do the investment. Back in the norovirus space, Vaxart published their human challenge data. Vaxart is a public company. We didn't see any change on the market value of that organization because their human challenge data was not robust enough. Either because the human challenge, the model is not well-developed, let's go back to having a well-developed model, or because the vaccine really doesn't work well, or because the human challenge didn't respond to the question that investors wanted to have because it was an old virus, for example, that they were using, not a virus that was currently circulating. Who cares if you can protect against something that was circulating 20 years ago, right? There's so many pieces of information that you can get out of this that if you know how to deconstruct the data correctly and put it in the view of what is happening right now in the infectious disease space, it help you to actually move forward with one investment or not, right? Right. The other part was your evolution of your views of human challenge trials generally, has it always something you've always believed in from many years ago, or has it been an evolution of the value of a challenge trial? I think that couple of things that I have evolved into that is to understand I'm not a clinician, I'm not a doctor. I have a PhD in microbiology. It took me a time to understand, through my friends and my colleagues who are clinicians, and really understand the nature of the disease, how well I should interpret the clinical endpoints that are used in human challenge versus what really happened in real world. I think this is when I had the stronger evolution in my thinking. How when you work with animals and you're a pre-clinical guy, like I used to be, you're very black and white, right? You immunize the animal to use, or you infect them, they die, right? That's very black and white. Going into the clinic with a human challenge and understanding those clinical endpoints, it took me a while to understand that and appreciate better human models that represent better the endpoints that you see in the clinic, and also understand better the data that I was getting out of those human challenges. It goes without saying that this is why we call it controlled infectious disease model. They have to be well controlled. We need to understand. I spent many years with working with NIH and Mount Sinai and the clinical side there at the NIH, understanding how the flu model for infectious disease work in a challenged setting, and trying to understand the interpretation of the data, because, of course, you never let people get infected all the way to their lungs like it happened with the real flu, because then that's something that you want not to happen. It's an upper respiratory infection model, interpretation of that data. I think that this is where I have evolved more on my thinking around the human challenge data setting. I would say secondary, no less important is all this idea, and I don't know yet where we're going to go with that, this whole biomarker idea that we can collect from the human challenge data. Yeah. Thank you, Mario. Any other questions? If I could just add to that from a perspective that we see, because we're talking to a lot of our potential clients, and actually they come in groups. When there's a new technology developed, could be an academic paper, for example, could be like the new RSV vaccines with the pre-F. You see, when you've got something new like that happen, the first person that does it has set a benchmark, you see others wanting to copy that because they want to understand in a very quick way with the challenge data, okay, how does mine compare to theirs? You see for the first few, people are very keen, you almost create another group of challenge studies because people then want to copy, they actually come to us and say, "I want that study to be done exactly the same way because I need to want to compare my data." You get to a point where that technology has advanced so much that one of the first players has gone into phase III, they're getting quite close to market authorization, at that point, it's now a real race to market. Someone then new coming in, to your point then, as they would then have confidence that that mechanism of action does work because many people have proven it in the challenge beforehand, and that's a scenario where they then just jump straight to the phase III to try and catch up. To start with, it creates a glut of business. When it's proven success, it goes forward. You wait for the next development for a next type of product to come through. You see the same glut. We've seen this in flu, we've seen this in RSV. This tends to be what happens. Great. Thank you, Andrew. Anyone else? Ready for lunch, I assume. Final closing. I wanted to kind of just bring to life what we did with Cidara in the first instance with case studies. Corrina did an amazing job at describing what we'd done. I want to see, kind of illustrate what we've done and what we're hopefully going to do in the future. With Cidara, we obviously then ran the human challenge trial. In most cases, this would've been our end of interaction with that particular customer. We would do the human challenge trial. Then we basically stop that. That relationship would stop. The client would continue with third party CROs. Because of the fact that we launched our lab and clinical site capabilities in 2024, we were able to continue that relationship with Cidara to run their phase II study as a clinical site, recruiting almost 20% of the patients globally, as well as acting as the central virology lab for the primary endpoints in the clinical trial. Not only that, we then also progressed to being a clinical site for the phase III study and also continuing the central lab duties across the globe for what now is Merck. That effectively some of this data at least was part of the package that the reason why Merck acquired Cidara. The key fact for you, especially for the numbers guys, is that if you look at the total portfolio of the work, only 30% of the revenue from this client, from this program, was in the human challenge trial. Two-thirds of revenue we generated on this program was non-challenge trial revenue. I think that's a sign for me that we are diversified. When I say we have multiple ways to win, this is what I'm referring to, that human challenge trial in itself isn't the end for us. It's part of a journey where we go from preclinical phase I, phase II, and the lab work and the phase III clinical site work we're doing. Then, of course, we're hoping, hopefully with the help of Rick, we want to replicate this. Even at an early stage, right? We're not starting this interaction at a human challenge trial stage. We actually already have signed a consulting agreement with Rick and his team, and Katsu and the team are now working on helping Rick and his team on the CMC work, on the preclinical work, putting together the regulatory package, and hopefully with some success and some funding raised. That's why he's sitting next to Mario, by the way. With some funding raised, they can progress into phase I and then to phase II, and then hopefully into phase III using the lab and site capabilities. This is what— When I say end-to-end platform, this is what it's all about. I think this shows highlights in real life with people sitting in the room, okay, we have already done it and who are planning to do it with us. I think that's something I think is crucial and key message for this kind of investment committee investment day. Finally, the investment case. Most of you have probably heard me say this to death before, but the key things I want to highlight is we are differentiated in the sense that we have a high hurdle to entry. Human challenge trials, I think we've spoken about the number of trials, the amount of data we have, experience, expertise, the people, the facilities is second to none. The diversification, it says implemented, but hopefully this is a journey, right? This is the start of the implementation. We will continue to diversify further into other areas. We're looking at diversifying organically within, but also through acquisition into other therapeutic areas and geographic regions. The key differentiator. As we grow, of course, it becomes harder for one to be differentiated from the masses, but we want to make sure that we are different. The screening protocol, the participant database we have, the fact that we own our own laboratories, our own clinical sites, I think makes us really different to the masses of CROs out there trying to go into the same space. We have a loyal customer base, we work with very small biotech companies all the way to the biggest pharma companies in the world. I think that's really key for us. The majority of those customers are repeat customers, whether they're in human challenge trials or whether they're in phase I and phase II. That is because of our teams, our people, because when our project teams work with customers, it's always the people who create the relationships and help bond and get the repeat business. I think that's kudos to those teams that we work with. The other key thing is because of our ability to sell so many services, I expect our size of a single contract to be bigger now because we can do more in-house rather than using third-party external partners and outsourcing some of the smaller work. Part of that, we're already seeing signed contracts as well as new proposals coming in. This is, I think, an attractive valuation point. Of course, I would say that, but most of the analysts also agree with me. I think considering our path and where we are and the road view we have right now going forward with some of the contracts we've signed, I mean, I do believe the ILiAD project is a precedent for us, not just because it's the largest contract we've signed, thank you, Keith, but also it's the first phase III respiratory. It sets a precedent, the fact that other companies can follow this path that ILiAD have blazed through in talking to the regulators and saying, "For this indication, it's almost impossible to run a trial, a phase III trial. Can we run a human challenge trial as a phase III pivotal trial leading to at some point use that data for licensing purposes?" I think that's a key point. This is a bigger precedent rather than just the largest contract to opening up new markets, new indications for us and also for the whole human challenge trial community. The market outlook. I think all the numbers point to the fact that things are improving. Every analyst I speak saying 2025 was better than 2024, 2026 is better than 2025. I'm not saying we're back to the boom years, but there's more M&A activity, there's more IPOs, more funding raised. All that points to a really good point for us. The fact that the patent cliff of GBP 300 billion we're talking about over the next five years, the pharma having a lot of money buying assets, as they just said, biotechs having to do their own phase I, phase II, really increasing the market. The big thing with the small biotechs, no offense, Konstantinos, they make quick decisions straight away, right? With BI, I mean, it takes them six months to qualify a new vendor. With Rick, it's one phone call, right? Get it done, right? I think those biotech can move fast and get these projects onto our books straight away. I love the fact that we're in cardiometabolic diseases. That's a huge area for us. It's not just about the operational capability and having the number of patients in your database, but the scientific knowledge that Thomas and the team bring to our clients, I think is key. With that, I think I want to thank you, everyone. I want to thank you to the team who have arranged all this. There's too many names to mention. I don't want to say a name because I'll miss somebody, but you know who you are. It takes a lot of work to put this together. I'd like to thank all the internal speakers who've done an amazing job in highlighting our capabilities. The goal today was really not to have our internal leadership team to talk about hVIVO. It's to get external people. The group of external speakers, I'm sure you agree, was second to none. I'd like to thank you all for coming, especially for those of you who have escaped the Trump administration to come over here for a few days, and be here. Really, really pleased that you've taken time out of your busy schedules, especially Keith, who came in at the last minute as a replacement for his chief medical officer, who unfortunately couldn't attend. Thank you, all of you, and thank you for all the audience for coming.