Good day, and thank you for standing by. Welcome to the Valneva report VLA2001 Cov-Compare topline results. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press Star and One on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press Star Zero. I would now like to hand the conference over to your speaker today, Thomas Lingelbach, CEO of Valneva. Please go ahead. Thank you, and good day to everyone. Very warm welcome to our webcast, related to our exciting VLA2001 Cov-Compare top-line results. On today's call, I am being accompanied by the trial's chief investigator, Adam Finn, Professor of Paediatrics at the University of Bristol. Thanks a lot for making time for that, Adam. Much appreciated. You know that Valneva's VLA2001 vaccine candidate is the only inactivated whole-virus vaccine candidate against COVID in development in Europe today. It is intended for active immunization of at-risk populations to prevent carriage and symptomatic infection with COVID-19 during the ongoing pandemic and potentially later for routine vaccination, including addressing new variants. We have leveraged our existing manufacturing platform that we developed for our inactivated whole-virus vaccine, IXIARO, a vaccine against Japanese encephalitis. We have applied this proven inactivated whole-virus approach, coupled with a modern adjuvant, a toll-like agonist, namely Dynavax's adjuvant CpG 1018, which is known to bias the immune response towards TH1 and which has been approved already in Europe and the U.S. as part of HEPLISAV-B. You know that today's results follow the phase I/II clinical results that we reported back in April 2001. Since that time, we have already initiated rolling submission to MHRA. We commenced that in August this year. We have initiated also extensions of the ongoing studies, both the phase I/II study as well as the study 301. That's the one we are going to talk about today, as well as a study in New Zealand in elderly. With that, I would like to hand over to Adam, to take us from slide eight, please. Thank you, Thomas. Welcome, everyone. An exciting day for us, seeing these results come through. Just like to summarize for you a little bit about this study. This was a randomized observer blind controlled immunogenicity study comparing the Valneva vaccine to the authorized Oxford-AstraZeneca ChAdOx vaccine or AZD1222. The eventual design involved randomizing people over the age of 30 years, with an open label group under the age of 30, just over 1,000 people. The over 30s were randomized 2: 1 to receive either two doses of the VLA2001, the Valneva vaccine, or two doses of the Oxford-AstraZeneca vaccine, both spaced four weeks apart. There were three main aims of this study. One was to look at the superiority in terms of functional antibody, geometric mean titer of virus-neutralizing antibody using the same assay in Public Health England lab at Porton Down that had been used for the AstraZeneca development program. Looking at those titers two weeks after the second dose. It was also predefined that we would look at non-inferiority in terms of seroconversion rate. Of course, a major objective here was to look at the safety of the vaccine tolerability and any adverse events. Can I have the next slide, please? Just focusing on the tolerability and safety aspects of the study. The rates overall of adverse event reporting were extremely high, as you expect in these studies, as picking up all reports in all subjects of any events of any sort. You can see that those rates were as we expect in studies of this kind, extremely high. However, it is notable that if you compare the 30 years and older age group who were randomized, there is a 10% difference in the overall AE rates between the VLA vaccine, which is just under 89% overall, whereas the AstraZeneca rate was 98%. If you focus down a little bit more closely on the specific reactions that we associate with vaccines. First of all, solicited injection site reactions, things like tenderness, pain at the site of injection. There was a statistically highly significantly lower rate in the Valneva vaccine of 73.2% compared to 91.1% in the Oxford group. Although we're not presenting on this slide, this was very largely reflected in the first dose, where, as you may be aware, the AstraZeneca vaccine is actually significantly more reactogenic than it is after the second dose. In terms of systemic reactions, in particular things like fever and malaise, there was, again, a statistically significantly lower rate in the Valneva vaccine of 70% versus 91% in the AstraZeneca group. Again, highly significant. In terms of unsolicited adverse events, those are things that just show up, not particularly being asked for, the rates were very comparable between the two, very slightly higher, and significantly higher for the Oxford-AstraZeneca. Importantly, there were very, very small numbers of unsolicited serious adverse events actually for both vaccines in the study. None of the unsolicited serious adverse events were felt to have been related to the vaccine. Overall, the majority of these adverse events were mild or moderate, and we really didn't see serious problems at all for either arm. Next slide, please. Overall, the conclusion on safety side is that this vaccine was extremely well-tolerated across the age groups. The younger age group, the under 30s, there were around about 1,000 of those, showed rather similar safety profiles. As we expect with these vaccines, the rates were overall slightly higher in the younger age group than in the older age group, but not significantly so. A pattern that we would expect and very similar low reactogenicity for this vaccine. In terms of helping this vaccine towards authorization, it was clear that the tolerability profile was actually more favorable compared to the already authorized AstraZeneca vector vaccine in people aged over 30. I'm going to hand back to Thomas now, who I think is going to tell you more in detail about the immunogenicity results. Thanks. Many thanks. If you look at page 11, we come now to the two co-primary endpoints around immunogenicity, we will start, of course, with neutralizing antibody levels, as measured with MNA50, wild type measurement against the neutralizing antibodies. Here, we see a statistically significantly better level of GMTs neutralizing antibodies. The ratio, in between AZD1222 and VLA2001, as defined in the study protocol, is 1.39 in favor of VLA2001. This, of course, is a pretty convincing level of neutralizing antibodies. Also on the Valneva side, significantly higher than what we saw in the phase I/II study where we had a shorter interval in between the first and the second dose. If we look at the second co-primary endpoint, namely the seroconversion, with regards to the neutralizing antibodies, you essentially see that the seroconversion reached for both vaccines above 95%. The objective was non-inferiority on seroconversion. With levels above 95%, we do not even need to do a non-inferiority statistical analysis because it's obvious that most participants seroconverted based on a four-fold rise against baseline, which is another very convincing and very good result. Basically, the trial met, therefore, its co-primary immunogenicity endpoints at two weeks after the second vaccination, meaning day 43, in adults aged 30 years and above. We showed superiority in terms of geometric mean titers for neutralizing antibodies as measured by live virus micro-neutralization assay. As I mentioned, GMT ratio 1.39, with GMTs for VLA2001 above 800. It demonstrated non-inferiority in terms of seroconversion rates, as mentioned before. It's also quite important and remarkable for an inactivated vaccine that 74.3% of the study subset in the VLA2001 group had T cells that were reactive against peptide pools spanning the full length S protein, and we showed T-cell immunity against the S, M, and N protein. When we look at the overall clinical data conclusions, which are summarized on page 15 of the presentation, one more time, we demonstrated superiority on geometric mean titers for neutralizing antibodies, non-inferiority in terms of seroconversion rates. This means together with the safety profile that was reported by Adam, we met all the key criteria that we had to meet for this pivotal study, according to a protocol agreed with the authorities, both from an MHRA as well as from an EMA perspective. It is also of note that the occurrence of COVID-19 cases and this was an exploratory endpoint, was similar between the treatment groups in the participants 30 years and above. However, the complete absence of any severe COVID-19 cases may suggest that both vaccines used in the study prevented severe COVID-19 caused by the circulating variants, which at the time was predominantly Delta. I mentioned already the T-cell response is specifically encouraging and showed really a broad antigen-specific interferon gamma producing T-cell reactivity against S, N, and M proteins. When we look a little bit at the ongoing trials and what we have planned thus far, I mentioned already that we have started the extension for booster on the studies VLA2001-201. This is the phase I/II study. Here we take a 6-month follow-up check for boosters, and this is already ongoing. We have also started to enroll the sentinel subjects for our adolescent extension. Here we are targeting more than 600 in the age group of 12-17. We have fully recruited already the elderly arm of our study, VLA2001-304, which is being conducted in New Zealand, with more than 300 aged 55 and above. Because we want to see also the results in this age group, given that we had only a very few subjects above 55 in the study 301, given the rate of vaccination at the time in the U.K. Going forward, what we would like to do is to extend the ongoing study 301, the one we are reporting about today for booster. Here we are targeting approximately 400 people. Of course, pediatric. We think that our vaccine may be particularly important for the pediatric population. Therefore, we want to start a dedicated pediatric trial in the age group of two to 11 as quickly as possible. Of course, the key question is how can our vaccine booster people who have been primed with all different kind of vaccines and people who need a booster. Basically after 6+ months and at a low level of antibodies at the time. This is a study that we have currently in our design in the make, but it's certainly something that we are planning for 2022. In terms of route to licensure, we have already started, as I mentioned at the beginning, the rolling submission with the MHRA, which commenced in August. We expect final submission to MHRA for November. We may potentially get an initial approval by the end of this year from the MHRA. We have the pre-submission discussions with EMA ongoing, and plan to initiate submissions there ASAP. I talked already about the elderly participants in the study VLA2001-304 to collect the additional data for the EMA package. As mentioned at the beginning, all Cov-Compare endpoints have, of course, also been aligned with the EMA as well. Overall, of course, as you can appreciate, we are extremely pleased with the results. It confirms what we had envisaged for this vaccine. We will go full steam ahead with the necessary submissions and hope that we can still make a positive contribution to the ongoing pandemic, and probably even a solution for people who have been reluctant to get vaccinated with novel technologies thus far. On that basis, let me close the presentation and open it up for questions. As a reminder, please press star and one on your telephone if you wish to ask a question. To cancel your request, please press hash key. We will now take our first question from the line of Maury Raycroft from Jefferies. Please go ahead. Your line is open. Hi. Congrats on the update today, and thank you for taking my questions. First question, just around next steps on the regulatory side. I guess, can you provide any more specifics on timeline for getting feedback from the EMA? Will you include any booster data, whether that's from the COV-BOOST or from your own internal study in that filing? We will not include the further data for the current package that we will submit to the authorities. We hope that we will be able to flank it with a set of first booster data from the study 201. All the rest will come later. Got it. Okay. For timeline for getting some additional clarity from EMA on the regulatory side, or potentially even from a contract with the EC, is there anything additional you guys can say about that at this point? Well, you addressed two questions. Let me start probably with the first one. On EMA, we would like to start the rolling submission process really very soon. We are waiting for one or two formalistic steps here, but this should not take a long time. We really expect this, as I said, very soon. On the EC deal, you know that we reported earlier that we are in active discussions with EC, which I can confirm today. I hope that the positive data will create a further positive momentum in hopefully closing a deal with EC quickly so that we can supply product quickly, because the longer a potential contract will take, the longer it will also take to actually supply products. Got it. Okay. That's helpful. Maybe last question from me and I'll hop back in the queue. You said there were no severe COVID-19 cases, but just checking if you can say anything about the hospitalization rates between the two arms of the study. None. Great. Okay. Thanks for taking my questions. We will now take our next question from the line of Jean-Jacques Le Fur from Oddo BHF. Please go ahead. Your line is open. Good afternoon, also great congratulation for these results. I have three questions. The first one is, do you intend to file in other countries than EU and U.K. with this existing phase III results? The second question is regarding the EC deal, do you need to have the EMA approval before signing such deal with the European Commission? My third question is, what could explain that the occurrence of COVID-19 cases was the same for both vaccines, despite the superiority of VLA regarding neutralizing antibodies? Thank you. Well, okay. What was the first question again? The second question was EC deal. Do you intend- The other territories, yeah. in other countries than EU and U.K.? Yeah. The answer is yes. We have already initiated discussions with other countries, including other regulatory bodies, e.g., in Asia. Yeah, at this point in time, we do not expect that the EMA approval of the vaccine would be a condition precedent for the execution of an EC deal. On the last question, I probably defer to Adam. Sure. Maybe Adam, you want to say a few words to the third question about COVID cases? Yeah. Sure. I'd be glad to. I think this is a very important question and an important concept to get across, because it's easy to make the assumption that somehow increased immunogenicity equates to increased efficacy, and that simply isn't the case. When it comes to antibody responses to vaccines, the amount of antibody you need for protection is essentially enough. If you've got enough antibodies, you really won't drive up your efficacy any further by generating more. I think, therefore, people need to very much avoid falling into the trap of looking at immunogenicity of the various vaccines and somehow assuming that more immunogenicity is necessarily better. It's simply not going to be as straightforward as that. What we're, I think, observing in this study is that both vaccines are highly effective, particularly against severe disease. What we've been able to demonstrate is a significantly superior immune response from which we can infer that in terms of protection, the Valneva vaccine will be at least as good, if not better, than the AstraZeneca vaccine. At least when it comes to antibody responses. Of course, we've also looked at T-cell responses here, and that's another story. We've got broader T-cell responses to a wider range of antigens, and time will tell how important that may be in terms of preserving effectiveness as the virus evolves. Thank you. Many thanks. Thank you for your question. The next question from Samir Devani. Please go ahead. Your line is open. Hi, everyone. Thanks for taking my questions. Congrats on the data. I've got a couple. I know Thomas, you mentioned that the seroconversion rates are very high, so partly irrelevant, but you presented per-protocol data. I just wanted to confirm that on the ITT, that it was still non-inferior to the AZ vaccine. That's the first question. Perhaps just in terms of COVID cases, I appreciate there's no severe cases, but could you just tell us what number of cases there were in each group? Thanks very much. Basically, yes. To your first question, yes, I confirm that for IMM, ITT. To your second question, we cannot at this point in time. We are still in the process of reviewing the COVID-19 cases in detail, especially with regards to mild versus moderate. There are still a few confirmations outstanding, and that's why we haven't reported those numbers yet. What we said already earlier is that the overall number of COVID-19 cases were equal in the two groups. Okay, that's great. Just perhaps one extra question just on the adolescent data in 301. When can we expect to see that data? Early next year. Early next year. If it goes well. Okay, that's great. Great. Congratulations. Thanks. Thank you so much, Samir. Any further questions? The next question came from the line, Max Herrmann. Please go ahead. Your line is open. Great. Thanks very much for taking my questions. Congratulations on the data today. Three, if I may. Firstly, just whether you looked at any neutralizing antibodies on the N or M protein, whether you've got broader potential coverage against the virus beyond the spike protein. That's the first question. Second is, with regards to the other inactivated viruses. Obviously, there are a few Chinese-based vaccines that have been commercialized in other markets. I wonder what the safety profile of those has been with regards to conditions like myocarditis and the stroke that has been seen in some very rare cases. Whether there are other kind of very infrequent safety concerns from the inactivated viruses that have maybe been commercialized. Finally, just have you got a feel for what GMT titers are required for protection? I appreciate that it's hard to know whether you need the T-cell response and a combination or what, but just to get an idea whether by getting higher titers, you may be getting a better coverage in the sort of outliers in the bell-shaped curve, as it were. Let me probably try an attempt on the first question, and then I hand over to Adam, who may want to give a bit more flavor to the others more broadly. First of all, we have not looked yet into all those details around N and M, for example. When you look at the, for example, IGGs across the different groups, we are let's say, give or take 10%, 15% higher in the Valneva group as compared to the Astra group, whereas we are neutralizing antibodies 40% higher, right? Of course, the IGG measures against the S protein only. When you see neutralizing antibodies, there might be neutralizing antibodies against other regions like M and N. This is just an hypothesis at this point in time, but might well be that there are other things that contribute. Let me hand over to Adam for his views and also for the other topics. Adam, if I may. Sure. Really interesting questions. I think the general immunological consensus on B-cell responses is that anti-spike functional antibodies are really what are likely to turn out to matter, both because the S protein essentially decorates the outside of the virus and because of its functional role in binding to the ACE2 receptor. I think the expectations of there being important functional anti-N or even anti-M antibodies are low, even though we do see anti-N antibodies post-infection, so they are induced by infection. I don't think I've got very high hopes that will be a major advantage of this vaccine or other inactivated whole virion vaccines. That's in contrast to the T-cell responses, where, of course, the intra-viral antigens may well be very functional when it comes to attracting cytotoxic T-cells to kill virus-infected cells. I think the breadth of T-cell response may well turn out to be important vis-a-vis S protein only vaccines. In terms of the other inactivated vaccines, there are three that I'm aware of. There are from China, CoronaVac from Sinovac and Sinopharm. Also there's perhaps slightly more close to this vaccine, the vaccine generated, produced by Bharat in India, which has a different cell-like receptor adjuvant in it. The data that we've seen in WHO, where I sit in the working group for SAGE, from those three vaccines have not showed up any of these rare side effects. These studies are of the same order of magnitude as the efficacy studies for the vector vaccines and the mRNA vaccines, which, of course, didn't show those very rare side effects either. These vaccines have been really quite widely deployed, Bharat in India and the Chinese vaccines all over the world, but not in places where there are really high-quality reporting systems in place that we could count on to show us if these rare events were occurring. With that proviso, they have been given to many millions of people, particularly in Latin America and Asia, and we've not heard any reports of such side effects, so encouraging in a limited kind of way. On the question about how many antibodies do you need, well, Oxford have come up with a paper that describe a putative, at least population applicable, correlative protection, which was around the level that we reported in this study for that vaccine. We don't really have a convincing individual correlate of protection at this point that we can point to and say, "Person X is now safe from serious infections." At least in terms of comparing the efficacy of the vaccines and the overall GMTs, it does look as though there's a threshold around the 500 mark on the assay that's being used by Public Health England. It does get very difficult if you then start looking at other assay systems that have been used, particularly for other vaccines that have not been tested in the U.K., like the Pfizer vaccine, because these assays can't really be compared with each other. They're methodologically distinct. I hope that's helpful. Yeah, very helpful. Thank you. We will now take our next question from the line of Seamus Fernandez from Guggenheim. Please go ahead. Your line is open. Great. Thanks, congrats on the data. Just a couple of quick questions. Can you guys update us on how far out these patients are being followed? Just, I know that the threshold is one factor, but there's also the diminution of effect or the loss of immunogenicity that's in the press quite a bit and is viewed to be an important factor. Just wondering when we might have more information on the durability of the immune response. Second question is on the older patient population. We cannot hear you anymore. I think we lost the end of the second question about the older patient population. Yeah, I think we lost the second part. Thomas, do you want to go ahead and follow up? Yeah. Hello? Hello? Can you repeat your question, please? Yep. The second question was on the older population, and it was specifically around, is this predominantly just going to be a booster-based population for the older elderly population, from your perspective, as you plan to study that group? The last question is just on supply. How are you guys estimating available supply potential in 2022? How could that evolve going forward into 2023 and beyond? Yeah. I think we will certainly follow study subjects up. I think the next visit is planned for day 71. Is it correct, Adam? I think. Yes, I think so. Yep. We will follow up study subjects to look at antibody persistence over time. That's clear. With regards to the elderly, the elderly study in New Zealand is specifically designed to address primary immunization of elderly. This means, also we are allowing seropositives, but we are primarily looking into seronegatives, in the elderly population, which is going to support the label claim above 55 years with the EMA. With regards to supply, this is always the same, right? We need to understand demand with supply. We have created a quite significant manufacturing capacity in the U.K., or we are about to build significant manufacturing capacity in the U.K. Of course, this needs to be reviewed as part of the U.K. government's termination of the supply contract. We have also a partner within our existing manufacturing network with whom we are working on COVID-19. I would say we have built optionality, and we have built scalability, and now it is all about understanding the demand for that vaccine. It's fair to say that we will be able to respond to the demand that we're going to see. Just as a question, the importance of the selection of the right adjuvant in this case certainly seems to be quite important. How do you think that can impact, in particular, the older population as you look at relative comparisons in the New Zealand study? Thanks. Interesting one. Do you want to take it, Adam? Well, yes, it is interesting and hard to predict. I think this adjuvant is certainly doing well so far in terms of what we were hoping, both in terms of B cell responses and actually T cell responses. So far so good. I think it's a bit hard to predict exactly how well that will be carried up into the elderly. We've certainly seen with other adjuvants in recent years that there is the potential to induce immunogenicity in the elderly using adjuvants which is very encouraging as a matter of principle. We really will have to now see, and we'll look with great interest to see what the responses look like in these 300 odd subjects that have been immunized in New Zealand. Thanks. Great. If you don't mind, I had one follow-up final question. Any updates on the U.K. contract at all, or is that sort of in active discussions and there's no update at this time? No update at this time. Great. Thanks so much. We will now take our next question from the line of Greg Skibinsky from Goldman Sachs. Please go ahead. Hey, good morning, good afternoon. Thanks for taking my questions, and congratulations on the data. Thanks, Seamus, for stealing my last question. I've got three still, if you don't mind. First, just if you could share some more details around the comments around the final assay validation, and I guess what really I'm asking about is the level of risk that the results that you're sharing today may change, whether it's minimally or meaningfully. That's my first question. My second question has to do with the COV-BOOST study and if there are any updates there, how should we think about the potential outcomes there and what the implications for Valneva might be. My third question has to do with maybe it goes back to the demand-supply topic, but it's really more about your own internal supply and just in the context of there being concerns on a more global basis on supply chain issues. I wouldn't expect it to apply to Valneva, but I just wanted to confirm that. Thanks. Greg, thanks for your question. Let me start with the first one. You've seen the disclaimer on the slide, right? The final assay validation which of course is required for the final CSR submission is still ongoing. We need, as part of this final validation step, to verify the integrity of the VLA2001-301 data which has to do with validation of electronic systems. We do not expect this to be a major technical or scientific risk, but it's something that needs to be completed, and we are working in close partnership with Public Health England to conclude also this last and final step. When it comes to actually the second question that you raised on COV-BOOST. Thus far, no data has been published on COV-BOOST. COV-BOOST is a study where many vaccines have been used at a very early booster time point. I think people have been boostered in between 2.5-3 months after primary immunization by either Pfizer-BioNTech or AstraZeneca. No matter what the outcome will be we do not currently contemplate that it will play a role in our submission process especially given that we will need to generate our own booster data, and we will need to generate booster data in real booster settings, meaning settings where people don't have antibodies anymore and are in need of a booster. That's all I can say on COV-BOOST at this point in time. The third question was around. Just Yes, that. Supply chain. Yeah. Go ahead. Thomas, it was the third question around supply chain issues and whether that was a potential problem. Yeah, I know. From the- Yeah. I thought I had answered already the supply-demand question, Greg, in the previous answer. Nothing more to add to what I said. We have our partners. We do not expect that we see any further shortages. We hope to be able to supply according to demand. That's all I can say at this point in time. Yeah. Thanks. As a reminder, please press star and one on your telephone if you wish to ask a question. It seems that there are no further questions. Are there any further questions? There are no further questions coming through. Please go ahead. If there are no further questions, I would like to thank you all for your attendance today. I would like to specifically thank all trial investigators as well as all trial participants and collaborators, especially the National Institute for Health and Care Research and the clinical teams within the NHS research centers as well as Public Health England. Very warm thanks to you, Adam, for making time today but also for your very pivotal role as Principal Investigator of the study. Thank you so much. Thank you, Thomas, and thanks for the questions. More than welcome. Have a good day, everyone. This concludes today's conference call. Thank you for participating. You may all disconnect.