Great. Thanks for joining us for the next session. I'm Matthew Harrison, one of the biotech analysts here at Morgan Stanley. Very pleased to have Vaccitech with us here. Quickly, before we get started, I need to read a disclosure statement. Please note that all important disclosures, including personal holdings disclosures and Morgan Stanley disclosures, appear on the Morgan Stanley public website at morganstanley.com/researchdisclosures. Bill, I thought we'd start off maybe with sort of a broader program before we go into each of the programs that you've got in the clinic. I think through COVID, everybody's gotten familiar a little bit with ChAdOx. Maybe you could talk about ChAdOx-MVA and sort of the basis for the company here, and why you think that's a good platform to generate therapeutic vaccines. Yeah. Thanks, man. Thanks for having us. The ChAdOx-MVA platform was developed at the University of Oxford at the Jenner Institute. The rationale there is we know adenovirus generates the highest levels of CD8 positive T cells of any technology platform out there, bar none. That we can stimulate that even further by coming back with a heterologous prime boost, so a different vector other than an adenovirus. MVA, through a lot of trial and tribulation at the Jenner, was found to be the platform that worked best. We're really technology agnostic, to be honest. This is the platform, the combination of viral vectors that is giving us the highest levels of CD8 positive T cells for the longest duration of time. We know from work that others have done in chronic infectious disease and through the CAR T space, that high levels of, and long duration of CD8 positive T cells can be important in certain disease areas. You're on mute, Matt. Sorry. Appreciate that. Thank you. Look, I guess the place to start after that is, if you know that, how'd you pick the targets? Why is the pipeline set up the way it is? Just give us a little bit of insight there, and then we can obviously go through the programs. Yeah. Again, very consistent with what I was explaining before. We went after targets where we believe that T cells are going to have an impact, particularly CD8 positive T cells. We're looking at chronic infectious disease like Hepatitis B and human papillomavirus, where we believe those will be important in the cure because that's how those diseases are cured naturally. We knew through the natural clearance that occurs in a small portion of patients in HBV, in a larger proportion of patients in HBV, it's all done through the T cell mechanism. In oncology, very similar. There's a lot of work being done to show that T cells are important in the clearance of cancer. Okay. Okay, great. Actually, one more question I think before we go into pipeline specifics. I think investors have seen over the last 10, 15 years, a variety of therapeutic vaccine platforms. In general, the data and the potential of those platforms really haven't delivered. Maybe just, I guess, give people a little bit of context of why you think that's not going to be the case here. Obviously, you pointed to the level of T cell generation that you have, but maybe other points would just be helpful. The three areas where we think we have differentiation is in the ultimate magnitude of the T cell response. We know magnitude is important. If you look at CAR T stuff, if you don't give enough CAR Ts, you don't get a response. If you increase the amount of CAR Ts, you do get a response. You also want that to be long duration. What we're seeing is levels of anywhere from 2- 6,000 spots per million in an ELISpot assay. Two years out, we're still seeing levels that are above the peak of any other technology platform out there. It's really a significant increase in the magnitude and the duration of the response. By every measure that we've been able to look at, we also saw that these responses are polyfunctional. They're doing what they're supposed to be doing. They're actually recognizing and killing the infected cells or the mutated cells in the case of oncology. That's what gives us the hope that this is going to be successful. Also companies like Inovio have kind of showed that in HBV, for instance, they get some efficacy. Maybe not sufficient for commercial activity, but that they are seeing some efficacies even at a much lower level of CD8 T cell response. We think we can improve on that and thereby increase the efficacy. Okay. Okay, perfect. Great. Maybe we should start with HBV, mainly because that's the nearest term readout here. I guess maybe give people a sense of the kind of data we should expect to get here at the end of the year, and also broadly how you think this is going to fit into this sort of treatment landscape for HBV, which continues to emerge, I guess, is the way to put it. I think this year we'll have data, we'll have safety and immunogenicity studies. Safety and immunogenicity data. We've got two studies ongoing right now, VTP-300 and HBV002, which is a phase I/II. The VTP-300 is in healthies and in chronic patients, but it's only being treated with ChAdOx. It was really designed as a safety study, since this is first in humans, also looking at cross-reactivity, because our construct was designed as a genotype C specific construct. We want to look at cross-reactivity across other genotypes. Genotype C is the most prevalent genotype found in the world, a lot of it in Asia, in Eastern Europe, which is consistent with where a lot of the chronic HBV infections are as well. Those are data that we expect to come out here in the fourth quarter of this year. In the 1st quarter of next year, we'll be able to add in some of the efficacy data around surface antigen reduction. As I mentioned, this is genotype C specific, the phase II trial's being run in Taiwan and South Korea as well as the U.K. We hope to get more genotype C specific patients in that patient population, and then look for, at again, at this stage, we're looking for biological activity here. If we get a 0.5 log to 1 log reduction in surface antigen in these patients, that's a good start given that we're doing a single prime and boost. I think most thought leaders in this space, as you mentioned, it's evolving, but I think most people think that a multifaceted approach is going to be necessary. We're combining our prime boost. Patients are already getting antivirals, the tenofovir, entecavir, to keep the DNA load low. We come in and stimulate the T cell response. We know in HBV that T cell exhaustion is a problem. We're also combining with low-dose checkpoint inhibitors to try and deal with that T cell exhaustion as well. Okay. Okay, great. As we think about the data we're going to get at the end of this year, obviously, we got a little bit of look at safety, a little bit of look at immunogenicity. How much do you think that gives people a view on, obviously what they care about, which is surface antigen data in the first quarter? Or do you think there's not a significant read-through there? Yeah, I think we don't know enough information at this point to know how much read-through there's going to be, Matt, to be candid. We're looking to see whether we can get, again, we can demonstrate that we can get high levels of the T cell response. We know that's going to be knocked down somewhat in the chronic Hepatitis B patients. We still want to see a response. It's a response to the antigens that we're using. We're using surface antigen core and polymerase as the antigens there. We want to make sure that we're seeing read-through on all of those antigens in both the healthies and the chronics. Okay. You mentioned half a log to a log. Maybe just give people a little bit more context in terms of why that's the threshold you guys are looking for in terms of a good data set. This is a first-in-man study. We want to be careful as far as dosing goes. You're trying to kill liver cells that are infected with Hepatitis B. If you go too aggressively, you may have other issues with killing too much of the liver at once, for instance. We want to do this in a controlled way, make sure that the product is safe, and then look at other dosing regimens coming back with a repeat dose. We've shown that we can boost with multiple doses of MVA, so you can go ChAdOx, MVA, MVA. You can go ChAdOx, MVA, ChAdOx, MVA. We don't know what the right dosing regimen is at this time. We hope to at least have some level of biological activity in this first study. Okay. Got it. I think maybe the context then is we should think of that more as the minimum level of biological activity for you guys to proceed to then optimize the dosing regimen? Exactly. Okay. Exactly. In combination with that, we've announced a collaboration with Arbutus because, again, we don't know whether the prime boost in combination with checkpoint is going to be enough. We announced a collaboration with Arbutus, where we're going to add in siRNA as well, another direct-acting antiviral, to see whether or not that's necessary or that'll be helpful. Okay. Maybe ultimately, just for context, what do you guys see as ultimately what you need here in terms of the optimum regimen? Is the idea to get people off of antivirals and have them have an effective cure? What exactly are you looking for in terms of the ultimate profile? Yeah. The ultimate profile is a functional cure. I think from the regulatory perspective, what we'd like to see is taking people off their antivirals and six months later, still having surface antigen reduction. Okay. Perfect. Good. We'll look forward to that data then to get our first look on that program. Second thing is, you talked about HBV. Obviously, we do have, as you pointed to, we have some proof of concept with others in the field here. Maybe I guess first question is, why do you think you can do better or how are you differentiated versus what we're seeing out there? Maybe we can talk about the trial. Yeah. I think a couple of key ways we're differentiated here. Obviously I'm going to sound like a broken record, but it's the magnitude and the duration of the T cell response. I think that's one way we're differentiated. In this case, we're also differentiated because we're going after early-stage disease. There's a significant number of women out there who get diagnosed with persistent HBV infections and they have no dysplasia, no lesions. They're basically told to go home and wait and come back in 6 months or 1 year. You're infected with an oncogenic virus. You may develop cancer, so get checked at a regular basis, and if you develop cancer, we're going to cut it out. The premise here is why wait? Why not treat them and then clear the virus so that they don't end up getting cancer? Coming in and looking at early-stage disease allows us then to actually get a breadth of antigen responses. When you're looking at the oncogenic indications in HPV, people are primarily focused on using E6 and E7, which are the antigens that are highly expressed in cancer. We can go back and look at E1 through E7, and so we get a much broader breadth of antigens. Also we're targeting a much broader breadth of genotypes of HPV too. We're looking at five different genotypes where the majority of folks are focused on HPV 16 and 18, which are about 70% of the oncogenic indications. Okay. Good. That's helpful. You obviously have an initial study running there. What level of evidence can we expect to get out of that study, and what's your goal to be able to see there? In this study, we're looking for HBV clearance as the obviously the secondary endpoint. Primary endpoint in this first in-man study is safety. As the first secondary endpoint is HBV clearance as measured by Quantitative PCR. There's a percentage of women who clear naturally, again, through a T-cell mechanism. We want to get a 50% increase above that natural clearance. Okay. Is the study, just for everybody's benefit, is the study powered enough to be able to statistically demonstrate that, or are we just going to be looking at trends in this sort of initial population? It'll be trends in this initial population, where it's 105 people that will be included in this study. You should be able to see reasonable responses. Okay. Great. I guess 1 other thing, because you pointed out the other constructs that people have used have a different group of antigens and different group of overall subset of patients that they're looking at, and you're looking at a much broader subset. I assume the natural T cell clearing in that group also looks different. Maybe just give people a context so they can sort of rightly think about when you say a 50% improvement, what that actually looks like. Yeah. I think in natural clearance rates, we are expecting somewhere in the 30%-50% range. Our target is 75%-80% clearance. Okay. Great. Good. I guess second question then is, let's say you can see that trend here. How quickly can you move on this program? It sounds like maybe you don't have to do potentially the same kind of dosing work that you might have to do in HBV, or combination work. Maybe just help us think about the path forward. This trial was actually designed so that we can step it right up into a phase IIb and expand the trial into additional locations and increase the number of enrollees in the study. We'll move pretty much right into that phase IIb study. Okay. Great. Good. Maybe here we should talk about some of the other work you're doing on, I guess prostate is probably really the next thing to discuss. I guess maybe the context that I would give is obviously as we think about vaccines, viruses, there's some proof of concept. Cancer vaccines, we've had even more trouble with. Maybe talk to us about why prostate seems to be a good place to start in terms of solid tumors, and how investors should just think about the kind of data you can generate there. It's interesting. I don't know that I would've started in prostate if I was designed de novo. When Vaccitech was spun out of Oxford, Professor Adrian Hill, one of our scientific founders, had received some EU grant funding and had already started these studies. It was a legacy product that we showed last year had some pretty promising results. Professor Hill did a phase I and a phase II study using 5T4 as a self-antigen. The phase I study was in pretty early-stage patients, so it was before prostatectomy, and he showed that, in fact, you can induce a robust T-cell response even against a self-antigen using this technology platform, which really isn't easy to do. It's about 10-fold less than we see against non-self-antigens, but you still see a pretty robust response. Then post-prostatectomy showed that the T-cells actually were infiltrating the tumor. Took this into a phase II study in late stage metastatic prostate-resistant cancer patients and showed an increase over checkpoint inhibitor alone in those patients. We've got about a 23% response rate when measuring PSA as the primary endpoint. A greater than 50% reduction in PSA was the endpoint that was measured. It was an open-label study, and it was done in 23 people, so not trying to over-interpret those data. The KOLs and the PI that were involved here were sufficiently impressed with the data that they thought we should follow this up with a controlled study. That's what we're working to do. Because we had to remanufacture drug here to run this controlled study, we actually decided to add additional antigens into the construct. In addition to 5T4, we've got three additional antigens that will be added into the construct, and that will get back into the clinic in the first half of next year. Okay. Great. I guess one of the other things that's maybe just helpful to talk about is you obviously have rights or potential royalty interest in a variety of infectious disease vaccines too. Maybe just for everybody's benefit, just walk us through sort of what's going on there and if there are any key things that people should be looking at in terms of development of those vaccines. Yeah. Again, we are much more therapeutically focused, but the technology platform is really flexible and in ChAdOx alone, as is seen from the COVID-19 vaccine, generates a very robust antibody response as well. We moved really quickly to move forward that COVID-19 vaccine that we eventually out-licensed to AstraZeneca through a deal with the University of Oxford. As part of that, we get about 1.4% of net sales on the COVID-19 vaccine when AstraZeneca starts their commercial pricing. We agreed upfront that we weren't going to take a profit on royalties during this pandemic phase. When they start charging commercial pricing, then we have access to royalties. We have exclusive rights for all the things that we have in development and then non-exclusive rights for anything new in infectious disease and exclusive rights to all of oncology for this technology platform. Anything new that comes along, new emerging infectious diseases, we have rights to move that forward, and we've shown that we can do that pretty quickly. Okay. Great. Good. Maybe we should also just touch on, since you're a new company, where you are in terms of cash, what sort of runway people can expect, and what exact milestones that can get you through? Sure. Yuri, do you want me to go on? Yeah, definitely. Matthew, we are at slightly below $240 million of cash right now, which is pretty much exactly as we expected during our IPO process. No surprises over here. Where we expected the cash to be, we think the cash runway at least till H1 2024. H1 2024, it's actually a relatively pessimistic forecast, based on the no revenue, no cash revenue coming into the company, which is, as you can imagine, pretty gray sky scenario. Okay. From this standpoint, we believe we are fully funded for these three years and can progress all our existing programs and add new programs as well. Okay, great. Perfect. Bill, maybe in the last couple of minutes, we should just also touch on, you have a variety of earlier-stage programs that you're thinking about, 400, 500, 600. May be good to just touch on people and give people a little bit of a taste of what comes next in the pipeline. We're actually kind of working through that. One of the programs we didn't talk about is we have a lung cancer program as well that we're collaborating with Cancer Research UK. They're actually funding and sponsoring a pretty large phase I, II study that'll be in the clinic later this year as well, and in non-small cell lung cancer. We're looking at where it makes sense to move these things forward. Obviously, some virally induced cancers come to mind, such as EBV. That's a pretty interesting target for us, some different oncology indications. There's a number of other chronic infectious diseases that are also of interest that we have some early work going on in. Okay. Great. Well, both of you, Thanks for being here. Appreciate it. Thanks for the good broad overview of the programs and look forward to the data coming in later this year and early next year. Matt, thanks for having us. Really appreciate the opportunity. Thank you.