Hey, good afternoon and welcome to the Barclays Global Healthcare Conference. My name is Carter Gould, Senior Biopharma Analyst here at Barclays. I'm pleased to welcome Vaccitech to the stage. We helped Vaccitech go public early last year, coming up on a year anniversary almost. Joining us is Bill Enright, CEO of Vaccitech. Bill, thank you very much for the time today. Yeah, I appreciate it, Carter. I guess before we launch into Q&A, Bill's gonna use a couple minutes just to kinda set the stage, maybe just give a brief overview on the company and tech, and we'll go from there. Sure. Vaccitech is a clinical stage immunotherapeutics company. We were spun out of the University of Oxford in 2016. It's the same technology behind AstraZeneca's COVID-19 vaccine. It's pretty well validated now. The whole premise behind the company is how can you generate really high levels of T cells that last for a really long time? As we've seen with the COVID-19 vaccine, you know, the mix and match approach seems to work really well at being able to generate those robust immune responses. That was really the premise of the company is starting with one kind of viral vector and then coming in with a different kind of viral vector that gives you the best kind of robust immune response across a large number of therapeutic and vaccine approaches. When you think about the places where you could take that technology, is it strictly just trying to max out that T cell response, or how do you blend that with the sort of functionality of that T cell response? Yeah. It's right now looking at trying to get high magnitude long duration T cell responses in these therapeutic indications. I mean, we're focused on areas where we know T cells are gonna be important. In chronic infectious disease like HBV and HPV, where we know T cells are part of the normal disease curing in you know, when people normally get infected with those viruses. Also in oncology where, you know, in the CAR T space, it's certainly showed us that if you generate a large enough T cell response for a long enough period of time, that you can cure cancer. That's again the premise here. Okay. You guys also did a recent acquisition, not something we see too often with some of the recent IPOs, but kinda complemented your existing tech. Can you maybe just talk about how Avidea fits into the overall portfolio? Avidea is a really interesting additional platform for us. Instead of a viral-based approach, it's a nanoparticle approach, so it's very synergistic, very complementary to what we're doing. I knew the company well. I consulted with them a little bit before joining Vaccitech, so I knew the team. There's good synergies. The two scientific co-founders both spent some time at Oxford as well, in the Jenner Institute where the company was spun out of. They'd actually done some work with our viral-based vectors. Again, this mix and match approach using the nanoparticle plus the viral vector and shown some really good results. We were talking about collaboration. They started. They were in the middle of trying to do a Series A, and one thing led to another. We decided to make this work. Okay. Let's talk about some products. Yeah. Okay. When we think about you guys, we think about that lead effort in HBV. Can we just kinda set the stage, kinda where we are from a with the treatment paradigm today, outline kinda where the unmet need is and where you guys might be able to fit in? Sure. There are about 250 million people chronically infected with hepatitis B around the world. Ninety percent of people that get hepatitis B naturally clear it, but those that don't still a pretty big number, larger than the HCV market. There's no cure, no known cure at this point, so you can control the virus using antivirals like entecavir, tenofovir daily doses, but no cure. Our premise here is, again, if we know that there's a T-cell exhaustion problem in hepatitis B. Remember, checkpoint inhibitors weren't really discovered in oncology, they were discovered in infectious disease. We're combining our immunotherapeutic along with the existing current antiviral therapy together with low dose checkpoint inhibitors. We're using 0.3 mg/ kg instead of 3 mg/ kg. We reported some top-line results in December showing that in baseline antiviral therapy their daily dose, you get a prime of our chimp adenovirus containing the HBV antigens. At 28 days, you get a boost with a different viral vector called MVA with those same antigens in combination with nivo. We saw at the three-month stage, the time point, a overall log reduction in surface antigen, which was better than expected and I think probably the best data that anybody's seen so far with an immunotherapeutic in this space. Okay. When you think about, you know, the targeted level of reduction or the S antigen clearance you need to get to kinda hit that functional cure kind of measure, how do you think about that? You know, or sort of where are we aiming? Well, we're aiming to get rid of surface antigen, right? Take people off of their antivirals and show that the surface antigen level then remains low. That's the goal. You know, this is the first study in this chronically infected patient population. You know, we've got some work to do looking at longevity of that response, looking at potentially repeat dosing, those kind of things. We're also collaborating with Arbutus in looking at the potential addition of siRNA in combination with this regimen as well. That study was announced last year and will get off the ground here in the first half of this year. Okay. Got a lot of different mechanisms in play here. Everybody's trying to sort of get themselves established as the backbone and then play nice with others. Kinda how do you navigate that to make sure that you don't get, you know, relegated? Now clearly I think there is, you know, a decent level of conviction that that S antigen clearance is an immune-mediated event. You know, how do you just ensure you have a kind of a place at the table throughout this process? Well, so far it, you know, nothing alone has worked. Right. Right? You're gonna have to do some combination approach and we've seen that in HIV. We've seen that in HCV. You know, I think that's, you know, if you talk to the thought leaders out there, pretty much people believe that that's gonna be a thing. Immunotherapy is gonna be part of the equation, as you said. Right now we've got the best immunotherapy. You know, if we can continue those data trends, I think that'll, you know, help secure us a spot at the table. Okay. You had the initial phase II data. We still have some more data to come from that study. Can you just kinda outline what's still to come there and when we're gonna see that, those updates? Yeah, I think the next data readout we'll have at EASL in June of this year. We should have some of the six-month data and all of the three-month data at that time. Okay. We'll have the final data set in fourth quarter. You know, based on those, the data at EASL, we're in the process of designing a phase II-B, which we hope to get started in the third quarter as well. Okay. When we think about some of the other combination studies are ongoing, can you just kind of where those are in development and when we're gonna see those kind of get going? The study that I mentioned, the Arbutus study, again, that should kick off in the first half of this year. Those patients will get siRNA and then six months later will get our immunotherapeutic after several siRNA treatments. We should see data sometime towards the middle of next year, I imagine, in that study. I don't think we've guided actually on exactly when those data are coming out. Okay. When we think about the PD-1 component, can you talk for a second just around, like the work to be done to sort of optimize the time and to give that? I know from the IO work and, you know, I guess initially you kinda just leveraged what was done in immuno-oncology in terms of timing, but I don't think there's ever actually been done that empirical work to figure out what's best in infectious disease. No, you're exactly right. It's incredible actually when you look at the literature, how little has been done on the timing. Yeah. You know, despite the large number of clinical studies that have gone on with the checkpoint inhibitors. You know, what we showed at least in this initial read, so we had two different cohorts. One received nivo at the prime and the boost, and then the other received nivo only at the boost. Where we see the dramatic response is when nivo's given only at the boost. There seems to be some interference if you give nivo too soon. Right. That's part of this, the phase II-B will be looking at the timing of nivo and different combinations there. Okay. When we think about that phase II rolling out, then how should we think about the cadence of data that emerges from that over the course of 2023 and beyond? Yeah. The nice thing is these are relatively short trials– Right. From an endpoint perspective. You know, it'll all be dependent on the cadence of recruitment. A large part of that is dependent on, you know, where you're getting this done and patient population. We'll give more guidance on that as we get the trial rolling. When we think about sort of the impacts of COVID in terms of enrollment and how you're thinking about that, at least in the near future where you have some visibility. Yeah. I mean, it's been a challenge, to be honest. You know, we've tried to mitigate as much as possible, so we're in different geographic areas. You know, so far it's been pretty good, where not everybody's been shut down at the same time. We have sites enrolling in Asia, in South Korea and in Taiwan, as well as in the U.K. and in one of the countries that I'm drawing a blank on right now. Yeah, you know, so far not everybody's been shut down at the same time, but it has been challenging to manage that. You know, either getting people into the clinic or on follow-ups, and you know, with restrictions and those kind of things, it's been challenging in a number of ways. Okay. Maybe just last question on HBV. When we start thinking about combining multiple mechanisms from potentially different companies, it does raise the question around affordability, particularly in a disease, you know, which at least, you know, predominantly is not in Western society. How do you think then around sort of, you know, I'm not asking you for your pricing estimates today, but just in terms of, you know, making sure this is, you know, gonna be digestible by different healthcare systems? Yeah, I mean, I think you do kind of the standard analysis, right? You're looking at, you know, what is it costing to treat people right now? We still have 1 million people dying every year from, you know, as it relates to chronic infections with hepatitis B. You're doing those kind of extended return on investment to see where that ends up. Okay. Maybe switching gears to HPV, something where we haven't seen so much data from you yet since the IPO, but was actually one of the opportunities that I think we were even more excited about, when we helped you guys come public. Can you just walk through kind of where we are and that I believe we should be getting some data here in the not too distant future midyear? On the HPV front, you know, this is a disease that impacts a large number of women. We're going after early-stage disease, so CIN 1 and CIN 2. The premise here is, you know, there's a large number of women that go in and they show up positive for persistent HPV infection, but they don't have any signs of dysplasia at this point. Those women are quite uncomfortable knowing that they have a potentially cancerous virus, and they've got to come back pretty much every six months and get rechecked to see if they've started seeing any precancerous lesions. The idea is if we can clear that sooner and get rid of the virus, then you know with a safe and effective vaccine. We're currently enrolling. We showed safety immunogenicity data at IPVC last year with the lead-in phase of that study. The main phase of the study is a dose escalation study that's currently enrolling. We should have efficacy data. There's a planned interim analysis, a six-month time frame of the first 60 patients. That's been delayed a little bit because of the COVID situation, but we're targeting the fourth quarter of this year. Okay. When we think sort of the hurdle for that interim analysis. Yeah. How do you think about that? How are you communicating that to investors? Yeah. We're looking at 50% above baseline. You know, there is, in that patient population, a certain percentage of women will naturally clear the virus. You know, that's why this is a controlled study, and we're looking to get 50% above baseline. We want to be targeting in the 75%-80% clearance range. Okay. Just to come back to the endpoint here, because I think a lot, when we have conversations with investors, there's maybe a lack of familiarity kind of sort of what's the clinical endpoint here? What's the goal clinically? The goal is viral clearance. You're looking at that as the endpoint. Okay. When we think about sort of the different development paths you can take from that point on, can we think about this phase II as in, you know, triggering a phase III? Is there additional, potentially phase II work you might have to do around different patient populations? How do you think about that? Yeah. This is designed actually to move into a phase II/III, so we can expand this study and go directly into that. We've actually gotten the IND approval in the U.S., as part of that plan to move that potentially forward. Obviously, this is gonna be in large part decided by the data and, you know, how this looks. Then we can also, you know, branch into later stage disease and start going after women that already have dysplasias and more on the oncology side. That will likely be a slightly different product. Mm-hmm. Because we're really targeting some of the antigens that are more prevalent in the early-stage disease than in the cancer stuff. When we think about that somewhat earlier stage patient population, to your point, this is a very different field than most, well, certainly more than most oncology products some people are familiar with. And when you think about sort of the clinical hurdle for regulators, and how that may differ geographically, do you have a sense yet on kind of how U.S. versus Europe is thinking about this? Our conversations so far with regulators and payers have been very similar. Okay. in the U.S. and Europe, as far as again looking at viral clearance as being the key endpoint. Yeah. I think, you know, one of the things that I think, you know, really was spelled out to us when we were doing our initial work here is just like, that woman's journey, right, with the repeated visits and the cost and the disruption to her life. You know, have you guys done or is there good kind of pharmacoeconomic work that's, you know, helped put like a price on that to some extent, or just to kind of really underscore it again, like the, you know, the value that something like this could have? Yeah. No, again, it's all a work in process. You know, we've certainly begun that work. Okay, great. Then, why don't we touch first on AZ vaccine and kind of, you know, you guys are entitled to, you know, a royalty there. So how can I frame how you're thinking about the contribution that might bring a, I'm not asking you for AZ guidance, but they've made some comments around kind of, you know, some progress they're making. Yeah. Maybe an update there. Yeah. I mean, from our perspective, we're really looking at this as potential upside. You know, we did a healthy raise last year, with the crossover and then with the IPO. We've got cash runway into the second half of 2024, without any additional revenues. Right. You know, funding our current programs and then looking to add two clinical programs a year. You know, continued growth across these platforms that we have. The AZ revenue, you know, they commented in their third quarter call last year that they'd begun commercial pricing. We had, you know, agreed upfront that they were not gonna charge commercial pricing during the pandemic. We weren't gonna take a royalty during that time period. When they start charging the commercial pricing, then we have the ability to get 1.4% in net sales. Hopefully we'll start seeing some of those royalty revenues this year. But again, it's not in our calculations. Right. As I remember, their 2021 sales were? 2021 sales were $4.1 billion. Yeah. Even if they come down, it still could be– Yeah. a nice chunk of change. At cost. Yeah. Right. Exactly. Certainly would help out. Okay. When we think about the rest of the portfolio, you still have a lot of other stuff going on in oncology, which frankly doesn't get a lot of attention. Can you talk a little bit? Why don't we start off with, like, the lung cancer effort and kind of, you know, where that stands at this point? Sure. The lung cancer program is a program that we are working with Cancer Research UK and the Ludwig Institute for Cancer Research on. Cancer Research UK is actually funding a fairly large phase I/II study. They enrolled the first patient towards the end of last year in that study. That'll be an 80-patient study where 40 people will get standard of care, which is chemo plus checkpoint inhibitor. 40 will get the standard of care plus our immunotherapy. It'll take a little while to enroll that study, but we anticipate at least some interim data in the second half of next year. Okay, great. The prostate cancer. Prostate cancer. That's an you know we had some really promising data in this program. We're using the 5T4 self-antigen in the original studies, and that was done by Adrian Hill, which is one of our scientific cofounders at the University of Oxford. He did a phase I and a phase II study. It showed that you get a 22% response rate when looking at PSA as the endpoint in really late stage prostate cancer patients. It was an open label study, 23 people treated and he had a 22% response rate. If in a similar patient population with just checkpoint inhibitor, you get about a 9% response rate. Right. You know, promising, open label, small numbers. You know, I think the data was promising enough to encourage us to get back into the clinic. We had to go back in and remanufacture. We've decided to add to that construct. Instead of just looking at the 5T4 antigen, we've added three additional antigens into that construct. We should get back into the clinic with that program in the third quarter of this year. Okay. Maybe switching gears to some of the other efforts, MERS, for example, which I think, you know, we've always kind of framed as this potentially very unique and potentially, you know, opportunity that, you know, from a monetization standpoint that's just sort of sitting there waiting. Any updates on that front? I know you guys had a relationship with J&J there, as I recall. Yeah. Yeah. It was through the university and CEPI. Yeah. J&J was also participating in this effort to try and get things through phase II for potential stockpiling. Yeah. I think there's more interest in that vaccine given all what we know about COVID-19 now and the lethality of the MERS. You know, we've got data now in two different phase I studies, one that was done in the U.K., one done in Saudi Arabia, the first vaccine trial done in Saudi Arabia. We're working to move that into phase II. Hopefully that will get going fairly shortly. We're actually talking with regulators here about the potential approval pathway because you know, unlike COVID-19, you know, that's sporadic in outbreaks, you know, kinda like Ebola. It makes it really difficult from an efficacy perspective. You know, initially we were thinking that we need to go down the animal route, and the Animal Rule and Is that still a possibility? It's still a possibility. Okay. We've got some other ideas that we're talking with some of the regulators about as a way to do this. Okay. Cool. We're coming up on the end of time. Bill, thanks very much. Lots to look forward to, particularly on the HPV front this year. Thank you again. Absolutely. Thanks. I appreciate the time, Carter.