CureVac N.V. (CVAC) Earnings Call Transcript & Summary

Greetings. Welcome to CureVac's Preliminary Phase I Data from Joint COVID-19 and Flu mRNA Vaccine Development Program. This time all participant are in listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions]. Please note this conference is being recorded. At this time, I'll now turn the conference over to Sarah Fakih, Vice President, Corporate Communications and Investor Relations. Ms. Fakih, you may now begin.

Thank you. Good morning, good afternoon, and welcome to our conference call. My name is Sarah Fakih, and I'm the Vice President of Corporate Communications and Investor Relations at CureVac. Please let me introduce today's speakers. On the call with me from CureVac are Franz-Werner-Haas, our Chief Executive Officer; and Ulrike Gnad-Vogt, our Interim Chief Development Officer. Please note that this call is being webcast live and will be archived on the Events & Presentations section under Investor Relations on our website. Before we begin, a few forward-looking statements. The discussion and responses to your questions on this call reflect management's view as of today, Friday, January 6, 2023. We will be making statements and providing responses to your questions that state our intentions, beliefs, expectations or predictions of the future. These constitute forward-looking statements for the purpose of the Safe Harbor provisions. These statements involve risks and uncertainties that could cause actual results to differ materially from those projected. CureVac disclaims any intention or obligation to revise any forward-looking statements. For more information, please refer to our filings with the U.S. Securities and Exchange Commission. I will now turn the call over to Franz.

Thank you, Sarah. Ladies and gentlemen, a warm welcome to this conference call and a very happy new year from all of us here at CureVac. As highlighted during our Q3 earnings call in November last year, 2022 was a highly productive year for CureVac. We have fundamentally transformed our organization and grown our operational bandwidth. Most importantly, we have broadened our proprietary technology platform and extended our robust product development pipeline, two core competencies that were accompanied by the robust expansion of our large GMP manufacturing capacity. At the core of this transformation, we have initiated and executed on our broad clinical development programs in COVID-19 and seasonal flu in collaboration with our partner, GSK. Both programs are based on CureVac's proprietary second-generation mRNA backbone designed and developed to achieve improved mRNA translation as well as stronger and earlier immune responses at low doses. These 2 programs are driven by a broad and unrestricted technology approach covering unmodified and modified mRNA as well as monovalent and multivalent formats. Our goal is to select the best-performing candidates for the next stage of clinical development in both indications. The positive clinical data demonstrated to date and described in today's press release as well as presented within this webcast have enabled us to make this selection. It is important to stress that the early results from the Phase I studies are not derived from a formal interim analysis. They are preliminary based on a limited number of participants prior to database lock and not yet complete, which means they remain subject to change. Nevertheless, we consider these preliminary data to date meaningful enough to draw 3 main conclusions with regard to the potential of our technology platform. First, the preliminary data clearly validate CureVac's mRNA technology platform led by our second-generation mRNA backbone. Our platform has demonstrated its potential to provide vaccine candidates that, as of today, appear to be in line with currently licensed vaccines for COVID-19 and flu in terms of reactogenicity and immunogenicity. Second, the broad and unrestricted technology approach we took with our second-generation backbone candidates enabled us to select modified mRNA as the best-performing technology for prophylactic vaccines in both indications. Correspondingly, we will enter the next stages of clinical development with modified candidates in COVID-19 as well as in flu. Third, clinical development of product candidates in both indications will continue in 2023 this year with bespoke candidates designed with current state-of-the-art vaccine formats and tailored to public health needs. In COVID-19, we expect to advance candidates that encode relevant variants in a mono and/or bivalent format to match the current standard of care. In flu, we expect to advance a multivalent candidate. As our modified candidates will form the basis of our continued clinical developments, we will focus on these data during this webcast. On Slide 5, let me briefly remind you of the 4 Phase I dose escalation trials that are the basis for the vaccine development programs that we are jointly conducting with GSK. For COVID-19, on the left, the tested candidates include CV-0501, a monovalent modified candidate and coding the Omicron variant, BA.1; and CV2CoV, a monovalent unmodified candidate encoding the original or wild-type virus. For flu on the right, we are testing flu SV-mRNA, a monovalent modified candidate expressing the H1N1 hemagglutinin antigen, a subtype of influenza A and CVS QIV, a multivalent unmodified candidate addressing relevant antigens of 4 different influenza strains. All 4 candidates are being tested in a one-shot booster setup. I will now hand over to Ulrike to walk you through selected preliminary data on reactogenicity and immunogenicity profiles for the modified vaccine candidates.

Thank you, Franz. Good morning and good afternoon to everyone on the call. On Slide 6, I would like to start with an overview of the preliminary reactogenicity data available from our jointly developed COVID-19 program. The illustrated data represents solicited adverse events in younger adults within 7 days after the boost of vaccination. As Franz has already said, our studies are characterized by a broad and unrestricted technology approach covering unmodified and modified mRNA. In the figure on the left, you can see the comparison of our second-generation unmodified construct, CV2CoV, with our second-generation modified construct, CV0501, at a 12-microgram dose level. Please note that this qualitative comparison is based on 2 separate studies. The comparison shows that the change from unmodified to modified mRNA results in pronounced differences leading to substantially lower reactogenicity for CV-0501 as a dose. The 2 figures on the right further illustrates the full CV-0501 dose escalation ranging from 12 to up to 200 micrograms in younger adults, age 18 to 64 years and older adults aged greater or equal to 65 years. The data demonstrate that for younger adults CV-0501 reactogenicity remains acceptable from 12 to 100 micrograms with only 1 systemic Grade 3 adverse events at 100 micrograms, which was reported as a headache. At the highest dose of 200 micrograms, 2 local Grade 3 adverse events occurred, both reported as redness at the injection site. In older adults, 1 systemic Grade 3 event occurred reported as a headache in the [indiscernible] microgram dose form. The profiles illustrate that the lower reactogenicity of modified mRNA allows access to a much broader dose range compared to unmodified mRNA. On Slide 7, let me move on to the preliminary immunogenicity data with a focus on the modified second-generation mRNA backbone construct, CV0501. Shown here are the available geometric mean titers or GMT of neutralizing antibodies induced by CV-0501 in younger adults as a function of dose against the Omicron BA.1 variant for which it encodes. The orange bar represents antibody titers before the booster vaccination, and the blue bars represent antibody titers either on day 15 or on day 29 after the booster vaccination. Due to a later start of recruitment for the older diagnosed groups, the corresponding data readout are currently being finalized and will be available for next COVID-19 program data reporting. GMTs were measured with pseudovirus neutralization assay. Across the display dose levels of 12, 25 and 50 micrograms on day 15 and at 12 micrograms from day 29, CV0501 induced a substantial antibody increase from free to cause those titers. This antibody boost is further quantified for each dose group as the ratio of post- to pre-boost titers. This so called geometric mean increase or GMI is indicated above the orange and blue bars. It represents the most meaningful metric to assess the potential of CV0501 as a booster vaccine against the tested variant. Depending on the dose and day, the GMI ranges between 6.8 and a 9-fold increase of antibody titer. On Slide 8, you can see the corresponding graphs at those time points in the younger adult dose group, looking at pre- and post-neutralizing antibody titers elicited by CV0501 against the SARS-CoV-2 wild type. To the left of those figures, the data was extended to allow for comparison with antibody levels elicited by our second-generation unmodified vaccine candidate, CV2CoV, which encodes for the wild-type. The CV2CoV titers at 12 micrograms were taken from its separate Phase I study. All of these data do not represent a direct head-to-head comparison within the same trial antibody titers as those candidates were measured using the same assay to allow for a high-level qualitative comparison. Despite encoding the Omicron variant, CV0501 was able to strongly boost neutralizing antibody titers against the wild type, demonstrating substantial cross neutralization at about 2x higher compared to CV2CoV on day 15 and about 1.6x higher on day 29. The fact that pre- and post-boost neutralizing antibody titers are markedly higher against the wild types and BA.1 across all dose groups can most likely be attributed to the generally higher prevalence of wild-type pre-immunity in the study population, which has been primed with licensed wild-type vaccines. Boosting of a higher pre-immunity is expected to lead to generally higher neutralizing antibody titers. The geometric mean increases show that CV0501, it uses booster activity against the wild type in the range of 3.3 to 5x depending on dose ending. In summary, the preliminary reactogenicity and immunogenicity data available from our COVID-19 program supports the selection of the modified mRNA technology as the best-performing technology. The second-generation modified construct, CV0501, was shown to be well tolerated within a much broader applicable dose range compared to the unmodified second-generation mRNA backbone construct. So far, a small number of Grade 3 adverse events occurred at 100 and 200 micrograms in younger adults and 1.3 events at 50 micrograms in older adults. All of them occurred well above immunogenic dose levels. In younger adults, CV0501 induced substantial antibody responses even at the lowest dose of 12 micrograms with strong cross-neutralization against the wild type. Overall, the use of modified mRNA in CV0501 enabled better reactogenicity profile, which was accompanied by stronger immunogenicity. Let us now move on to our flu vaccine development program. Starting again with the available preliminary reactogenicity data, Slide 9 displays on the left, the reactogenicity profile of flu SV-mRNA, the monovalent construct encoding a hemagglutinin antigen using modified mRNA. Flu SV mRNA was tested in the dose range of 2 micrograms to 54 micrograms, which escalated to almost double the highest dose compared to the unmodified CVS-QIV candidate, which was tested between 3 micrograms to 28 micrograms. The flu SV-mRNA dose range takes into account that the candidate is a monovalent construct. Correspondingly, the applied doses reflect doses for a single mRNA construct, which would later be multiplied for a state-of-the-art multivalent flu vaccine. The total mRNA content of such a multivalent flu vaccine could potentially range up to 200 micrograms, the upper limit of the dose range in the complementary ongoing study of the modified COVID-19 candidate, CV0501. Shown on the right is again the reactogenicity data for CV0501 to allow for comparison of those constructs using modified mRNA. We have refrained from comparing the flu SV-mRNA reactogenicity profile to the profile of our unmodified flu candidate CVS-QIV in this webcast. In contrast to flu SV-mRNA, CVS-QIV is a multivalent construct encoding a number of relevant targets covering for different flu strength. We previously reported early reactogenicity data of CVS-QIV in the dose range of 3 to 28 micrograms. The data supported a benign profile across all tested doses. This trend has not changed. Moving on to the available preliminary immunogenicity data for flu SV-mRNA on Slide 10. We are looking at the ratio of post- to pre-boost geometric mean hemagglutinin and inhibition antibody titers to determine the geometric mean increase. Data is shown for younger adults in the range of 18 to 45 years. Within the study, immunogenicity of flu SV-mRNA was assessed in parallel to a licensed quadrivalent flu vaccine comparator shown as the orange bar to the right. You can see that flu SV-mRNA achieved comparable antibody increases to the licensed vaccine, boosting geometric mean titers at least about 14-fold beginning at the lowest dose of 2 micrograms. Due to a later start of recruitment for the older adult dose groups, the corresponding data readout are currently being finalized and will be available for the next flu program data reporting. On Slide 11, you can see post vaccination hemagglutination inhibition antibody titers in younger adults in those groups of 2 to 36 micrograms. Antibody titers were adjusted for prior infection, age, and pre-boost titers. According to the geometric mean increases, the modified flu SV-mRNA achieved numerically higher GMT than the license comparator across all dose levels. At the dose level of 18 micrograms, GMT was more than 3x the GMT of the license comparator. On Slide 12, I would like to complete discussion of the available immunogenicity data for flu in younger adults with a graph of the seroconversion rates. The consistently higher antibody titers across all doses resulted in seroconversion rates that are also substantially higher for our modified mRNA candidate. In summary, the preliminary reactogenicity and immunogenicity data available from our flu program further support the modified mRNA technology as a selected technology for ongoing clinical development. The monovalent flu SV-mRNA was generally well tolerated across all tested dose groups and successfully boosted antibody titers against the matching flu strain. Preliminary immunogenicity data showed that flu SV-mRNA antibody titer were in line with the license comparator vaccine beginning at the lowest tested dose of 2 micrograms. With this, let me hand back the call to Franz for a summary of today's key messages and an outline of what is next.

Thank you, Ulrike. Let me quickly highlight the key takeaways from today's presentation. The preliminary data we have presented today provide a strong proof of our technology for our proprietary mRNA platform and prophylactic vaccines. This proof of technology needs to be seen in the context of a fundamental transformation of our organization in 2022 which has enabled significant expansion of our operational bandwidth. This covers our demonstrated core competencies in mRNA technology as well as product development pipeline, complemented by our scalable manufacturing. With today's manufacturing setup and ongoing expansion into large-scale production with GMP IV, we will be able to supply clinical trials or commercial efforts seamlessly and mostly autonomously. Manufacturing will be a key success factor moving forward. Together with GSK, we plan to advance candidates in COVID-19 and flu in 2023. For COVID-19, candidates will encode relevant variance in mono and/or bivalent format to match the current standard of care. The Phase II study is expected to start later in 2023. For clinical development in flu, we plan to advance a multivalent candidate targeting all 4 flu strains recommended by the WHO. A Phase I/II study for multivalent vaccine candidate is expected to start around mid-2023. We also expect our second-generation mRNA backbone to drive forward our cutting-edge genomics and bioinformatics platform in the oncology area in which we have already announced the scheduled start of 2 clinical trials this year. In 2023, we thereby anticipate starting another 4 clinical trials to advance promising product candidates in prophylactic vaccines and to kick off clinical developments in oncology. We feel very energized by these positive preliminary data presented today. They demonstrate our commitment to the promise of mRNA and the potential of our proprietary technology platform. With strong focus and the ability to transform in 2023, CureVac worked hard and delivered its plans in 2022 to go forward. With this, I conclude our presentation and would now like to open the webcast for your questions.

Thank you. [Operator Instructions]. One moment please while we poll for questions. [Operator Instructions] Thank you. Our first question will be coming from the line of Ellie Merle with UBS.

Congrats on the data. Maybe just looking forward beyond quadrivalent and flu as well as thinking about the combinability of COVID and flu vaccine into, say, a single shot. Can you, one, comment on the ability of your modified mRNA platform to be able to do this? And then second, talk about your thoughts on this from a commercial perspective in terms of your perspective and the outlook on the potential for say, combination vaccines as well as also in flu adding additional antigens.

Well, perhaps to start -- thank you very much, Ellie, for the question. Perhaps I'll start with the latter one. I will lead over to Ulrike talking about the platform with the regard to the modification. With regard to the commercial attractiveness, certainly, it's a bit too early to say. Certainly, the goal is, at the end, what the entire field is trying to do is to use the mRNA platform, which is very versatile, and you can combine. And very important here, you can produce rather fast, which is where you're coming closer to the peak season of flu. So that's the idea and also with the multivalency to work with. The -- certainly, by that, you can attract the market because the idea is to get a higher efficacy to be proven then in the next clinical trials. With regard to the commercial attractiveness, flu market is defined. How this will play out at the end of the day for mRNA, we will see. There's not much more we can say at the moment.

Yes. Maybe to comment on our second question. So -- and we were able to show that with our second-generation mRNA backbone and the modification of such backbone, we can achieve an excellent balance of high immunogenicity and low reactogenicity that also enables multivalent vaccine. And I think this strongly support our platform approach as basis for clinical development of vaccine. I'm not sure I understand your second question about the flu vaccine.

The second one is just on your thoughts on the commercial potential. I think you guys commented.

Great.

Thank you.

Our next question is from the line of Umer Raffat with Evercore ISI.

I have several today, if I may. First, just trying to understand the timing of the disclosure. I feel like it was still half baked. A lot more data was still sort of coming up, for example, the older patients, the Part B of the trial, et cetera. So I'm curious how you guys thought about sort of going forward with the disclosure because it seems like there's a lot more coming. Secondly, there does appear to be a little bit of inverted dose response on both on the COVID side and flu side, and I'm curious why that is? Or is that just variability based on smaller data sets? But I'd be curious how you think about that. Third, I feel like the single most important thing I was focused on was the spread, meaning the dots for each patient on those titers because that was really the issue on the unmodified construct where 20% to 30% of patients were just too low. And I'm curious what the spread looks like. I know you showed all the averages. And then finally, for flu, what was the comparator? What specific construct was used as comparator?

Thank you, Umer, for the great questions. So I mean, with the third question you have been raising this combined with the first question. So the -- you talked about the limitation of our CVnCoV, which was the first product. candidate we had where certainly the reactogenicity was a limiting factor to go higher with the dose, and then seen certainly the efficacy there as well the various neutralizing titers immunogenicity. And therefore, on the basis of these preliminary data, what we see now is exactly where we say this is material, what we see. And therefore, we have been urged to go out and say, okay, this is what our technology platform is doing. What we are showing you to and have been showing you today is telling you something about the functioning and the working of our mRNA technology, not that much with regards to what are the next steps in product development which will come soon when we have got the final readout of the data. But what we see right now is exactly what you've been saying, the limiting factors in the first place in the first product candidate, which we certainly overcome on the basis of these limited data, what we see is certainly working on the different fields, so by broadening this technology platform. And this is very exciting, on the second-generation backbone on these different kind of construct. And therefore, we have been running these programs, these 4, in order to find out, okay, what is the next logical step built on this technology platform, what we see now on the data and what it means transferred into the next product development, also what Ellie was asking before, what are the next steps in flu combo with COVID. This is to be seen on the final readout on the data. So there is more to come. You're absolutely right. Lead, over to you.

Yes. And you're, of course, correct. This is a Phase I with a small numbers. But I think the data clearly show the improved reactogenicity profile of our modified candidate compared to our former candidates. You can see that we can dose up to 200 micrograms without any major reactogenicity issue. So I think here, I'm convinced these data really validate this approach for further studies.

And with regard to the comparator, I think this was the last question. We cannot say, but it's an approved well-known flu vaccine.

Our next question is from the line of Roy Buchanan with JMP Securities.

Just a couple more. I guess, any thoughts on how this data compares to what Moderna presented last year? Is it basically in line, any caveats that we should be aware of? And sorry if I missed it, but going forward, which doses are you going to take going forward? Are you going to use multiple doses in the Phase II? Or is it going to be a single dose? And that's for both flu and COVID.

Yes. So first of all, I mean, there was no direct comparison in these trials with the license comparator, and we cannot comment, therefore, on comparison to any licensed vaccines. What was the second part of the question?

Just which doses are going forward? Is it a single dose? Are you going to try multiple doses in Phase II?

This is currently under discussion. So the Phase II design is being developed together with our partner, GSK, it's too early to disclose.

And therefore, we have to see -- this is what I tried to say earlier, we have to see the final data here. Again, this is really about the technology platform is working and improved significantly. How this now compares to other mRNA vaccines approved or in the clinic, certainly, one has to look up to publicly available data, but this was not done in the same trial. So therefore, to say fairly, scientifically accurate to say, okay, this is how it compares, you should have done it in the same trial, which certainly then in the product development, most probably this is what you have to do. But this is what we will come later on when it goes about -- when it comes to both the product development and the next steps.

Okay. Great. I guess I'll throw in one more. You said for the COVID vaccine, you're going to go forward with this current standard of care. And I guess at this point, it means BA.4, BA.5, but those strains are pretty much irrelevant in the U.S. at this point, depending on where you are, I guess. If there's not an approved or authorized XBB vaccine, for example, later in the year, how do you guys think about which strain you develop going forward?

The current standard of care is bivalent BA.4/BA.5 plus wild type. We are, therefore, planning to include a bivalent BA.4/BA.5 plus wild-type candidate to validate our current findings with a direct comparison to a licensed vaccine. Data from, let's say, the 2 trials hand-in-hand with the evolving landscape will inform the next steps.

And as you certainly can see that this is exactly where RNA is so interesting for these kind of developments is there are new strains and you will -- we will see, we will all see how this epidemiology will develop. And what the next clinical trials will be, which has then certainly also a regulatory aspect where the regulatory authorities are closely involved. But this again, these thoughts, we will then more broadly comment when we have got the final data, then of course, together with GSK.

The next question is from the line of Evan Wang with Guggenheim Securities.