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

Good morning, good afternoon, and welcome to our conference call. My name is Sarah Fakih. 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 are Franz-Werner Haas, the Chief Executive Officer of CureVac; and Ulrike Gnad-Vogt, our Interim Chief Development Officer; Mariola Fotin-Mleczek, CureVac's Chief Technology Officer; and Pierre Kemula, Chief Financial Officer, will be available for the Q&A session after the presentation. Please note that this call is being webcast live and will be archived on the Events and 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 views as of today, Thursday, July 1, 2021. 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 from us here at CureVac. Over the last -- past 6 months, we have been conducting a pivotal Phase IIb/III efficacy trial called HERALD study, our first-generation COVID-19 vaccine candidate, CVnCoV. Conducted in 10 countries and across 2 continents in Europe and Latin America, the HERALD study is so far unmatched by similar trials in terms of geographic diversity and even more important in terms of increasingly challenging variant rich environments the vaccine faced. In this highly dynamic variant enrichment and across this broad geography, CVnCoV met this statistical success criteria on the basis of 228 adjudicated cases, including an additional 68 cases compared to predefined 160 cases for final analysis as per trial protocol. Efficacy was calculated to be 53% in the age group of 18 to 60 on the basis of 228 adjudicated cases that met the criteria for analysis inclusion. This was calculated against any severity of the disease and across a total of 15 different virus variants, which in some features 86% variance of concern and variance of interest and 2 additional variants beyond the 13 variants in the second interim analysis. In the same age group and across the same broad range of 15 different variants, protection against moderate to severe disease was calculated at 77%. Full protection was provided against hospitalization or death with 6 cases occurring in the placebo arm and none in the vaccine arm. Efficacy across all age groups amounted to 48%. And please let me -- this was across any severity of disease and in the face of 15 different variants that were detected within the adjudicated cases. The age group of above 60 included 21 cases or approximately 9% of the adjudicated cases. In this predefined group, as per protocol, the data available from these 21 cases did not enable a statistically significant determination of efficacy. We believe CVnCoV is to date the only vaccine, which has been able to show robust protection against moderate to severe disease as well as hospitalization or death, while being challenged with a confirmed spectrum of 15 different virus variants and a placebo-controlled pivotal study. We also believe this data established CVnCoV as an effective vaccine that has the potential to make an important contribution to the continued fight against COVID-19. Now let me hand over to Ulrike, our Interim Chief Development Officer, to walk you through the details of the study set up, the case accrual process and the efficacy analysis within the final analysis.

Thank you, Franz. Please let me start by briefly reminding you on Slide 5 of the highly international scope and the age distribution within the HERALD study. Conducted in 4 countries in Europe and 6 countries in Latin America, HERALD constitutes a multi-variant study with high geographic and ethnic diversity, of the approximately 40,000 trial participants about 25% were recruited in Europe while about 75% were recruited in Latin America, the region which today accounts for approximately 32% of COVID-19 related deaths worldwide. These approximately 40,000 study participants were distributed in 2 predefined age groups. Roughly 5,000 participants or 14% were above the age of 60, while the majority of about 35,000 participants or 87% were between the age of 18 and 60. The mean age of study participants was about 43 years. I'm now on Slide 6 to give you an overview of the COVID-19 case accrual process within the HERALD study according to the study's primary endpoint. This is defined as the occurrence of first episodes of confirmed cases of COVID-19 of any severity. For study protocol, COVID-19 cases are eligible to be included in the vaccine efficacy calculation if they occur at least 15 days after the second vaccination, the earliest time at which the vaccine is considered to be fully protected. PCR-confirmed COVID-19 cases that occur at least 15 days after the second vaccination, additionally undergo a stringent adjudication process, including the exclusion of those confirmed COVID-19 participants who test positively for a prior COVID-19 infection. Since the second interim analysis communicated on June 16 on the basis of 134 adjudicated cases, 94 additional cases have been accrued and adjudicated, resulting in a total of 228 cases used for the final efficacy analysis. Of these 228 COVID-19 cases, 207 cases were detected in participants in the age group of 18 to 60, representing an increase of 88 cases compared to the second interim analysis. 21 cases were detected in participants above the age of 60, representing an increase of 6 cases compared to the second interim analysis. As occurrence of COVID-19 cases needs to be seen in the context of the rapid spread of new virus variant, 204 of the 228 adjudicated cases were sequenced to identify the variant causing each infection. A total of 24 cases could not be sequence due to insufficient sample materials. The next slide is a frequently used slide in our presentation that illustrates the currently estimated variant spread in the 2 study geographies, Latin America and Europe. New virus variants have emerged and spread steadily since the end of 2020 and have all but displaced the original virus strain. As Franz has already highlighted, the dynamic variant background must be considered for the interpretation of the CVnCoV efficacy results. Brands of concern initially included mainly 3 lineages, namely the Alpha strain first detected in the U.K., the Beta strain first detected in South Africa and the Gamma strain first detected in Brazil. This group was recently extended to include the Delta strain first affected in India. Over the past 3 to 4 months, the Delta strain has rapidly spread around the globe and is today estimated to show an approximate 13% prevalence in Latin America and an approximate 26% prevalence in Europe. Also, new variants of interest have been added to the watch list based on genomic properties or other evidence that imply a potential impact on transmissibility, severity and/or immunity. This includes the Lambda strain first detected in Peru and the B.1.621 strain first detected in Colombia. Because of the continuing spread and emergence of new variants, we have conducted comprehensive sequencing analysis to better understand the dynamics of the virus in our trial. Over the next 2 slides, I will go into the details of the unique variant distribution we have detected in the HERALD study. Within the HERALD study, 204 cases for approximately 89% of the 228 adjudicated cases that were used for the final efficacy analysis were sequenced. As said before, 24 cases could not be sequenced due to insufficient sample materials. The strain distribution resulting from the sequencing analysis is illustrated on Slide 8 and provides important context around the CVnCoV efficacy results calculated at final analysis against any severity of disease according to the primary study objectives. Of the 204 sequence adjudicated cases, variants of concerns, including the Alpha, Gamma and Delta strains represent approximately 51%. Variance of interest contributed approximately 35%, including the Lambda or C.37 strain originating from Peru and the B.1.621 strain originating from Colombia. The Lambda variant was previously reported to be responsible for more than 80% of COVID-19 cases in Peru and evidence has become available for high rates of transmission in multiple countries in Latin America. The strain is known to feature 2 critical mutations in the receptor binding motive of the spike protein. As the receptor binding motive is a primary target for neutralizing antibodies, this might potentially allow this variant to evade immunity. Overall, the final efficacy calculation reflects performance against the total of 15 different variants, majority of them known to have mutations concerning increased transmissibility or immune resistance. As shown in the geographic breakdown of the total number of sequence cases, the diversity of variance originates primarily in Latin America, which provides the majority of newly adjudicated cases and contributed overall 155 cases to the 204 sequence cases. In Europe, the 49 cases we observed are strongly dominated by the Alpha strain in accordance with the general virus distribution there. The variant overview provided on Slide 9 further extends the pool of frequent COVID-19 cases recorded in the HERALD study to look at a combined pool of adjudicated and nonadjudicated cases in order to provide a more detailed picture of the variant dynamics within the study. This overview stays on a total of 588 COVID-19 cases, which were accrued and sequenced within the HERALD study irrespective of the formal COVID-19 case adjudication process. This group includes the 204 adjudicated cases as well as 384 nonadjudicated cases, which occurred prior to the 15-day post second vaccination cutoff and therefore, did not qualify for adjudication. While the latter group of cases, therefore, did not contribute to the efficacy calculation. They help to provide a more accurate and extended picture of the circulating virus variances in the study. Overall, 29 different COVID-19 variants were identified which cover all currently designated variants of concern, including the Alpha, Beta, Delta, Epsilon and Gamma strain. Variants of interest, including the Lambda, Yota, Zeta and B.1.621 strain, the B.1.1.519 strain with high prevalence in Mexico and 3 lineages related to the original virus. In accordance with the variant mix in the group of adjudicated cases, severity was again more pronounced in Latin America compared to Europe where the Alpha strain dominates. I'm now on Slide 10 to discuss CVnCoV efficacy data from the final analysis. In the context of 15 different virus variants and in the predefined age group of 18 to 60. CVnCoV exhibited a favorable efficacy of overall 53% against any severity of disease. This includes the occurrence of more than 80% of mild cases, which are characterized by the accounts of at least 1 and not necessarily a respiratory symptom in combination with the positive PCR test. In the same age group, a 77% protection was achieved against moderate to severe disease and full protection was shown against hospitalization or death. Preventing hospitalization of death with a robust and widely variant tested vaccine is an important prerequisite to support the global fight against COVID-19 and the associated burden on health care systems. In the predefined age group above 60, the available data did not enable a statistically significant determination of efficacy. On Slide 11, let me now go a bit more into detail of the efficacy trends we observed in view of selected variants with higher prevalence in the pool of adjudicated and sequence cases. As the HERALD study was not powered to provide a statistically robust efficacy readout of strain, case numbers for the separate variants are too low to calculate statistically robust efficacies or conduct further correlations with specific disease severities. We, therefore, present the efficacy data in this table together with the corresponding case numbers detected in the placebo and vaccine arm as well as the upper and lower limit of the confidence interval to allow for a better assessment of the statistical robustness of efficacy numbers. We were able to assess efficacy trends in the age group of 18 to 60 for the 2 prevalent variants of concern, the Alpha and Gamma variant as well as 2 prevalent variants of interest the Lambda and the Colombia strain. Results shown in this table indicates robust and balanced protection against the separate variant spending a range from 42% observed against the B.1.621 strain originating in Colombia to 67% observed against the Gamma variant. Please remember that these efficacy results are calculated against any severity of disease. I'm now on Slide 12 to remind you again of the safety and reactogenicity profile of CVnCoV on the basis of the first 2,000 participants recruited within the HERALD study. The 2 12-microgram vaccinations of CVnCoV costs are shown to be well tolerated. As previously reported for CVnCoV and in line with other mRNA-based COVID-19 vaccines, the majority of events were mild-to-moderate and accumulated around fatigue, headache, muscle pain, or myalgia and chills and only few fever events were recorded. We were particularly pleased to see that there was no increase in the severity of side effects after the second vaccination compared to the first vaccination. Both reactogenicity profiles are comparable. The data is further stratified according to trial participants between the age of 18 to 60 and participants above the age of 60. As expected, side effects are generally more pronounced, but still in a well-tolerated range within the group of 18- to 60-year-old study participants compared to study participants above the age of 60. Overall, the safety profile is fully in accordance with the safety profile reported for other mRNA-based vaccines and further confirms the safe applicability of CVnCoV. Let me now hand back the call to Franz for a short summary of next steps and key messages.

Thank you, Ulrike. Let me quickly summarize the key messages from the present final analysis and outline the next steps. The readout of the final analysis of the HERALD study confirmed strong public health value of CVnCoV vaccination in the predefined age group of 18 to 60, providing 77% protection against moderate to severe disease and full protection against hospitalization and death. These would be satisfactory numbers when tested against a handful of the currently circulating virus variants. Against the combined simultaneous and unprecedented influence of 15 different variants, including mainly variants of concern and variants of interest is this is truly a major achievement. We remain fully committed to supporting the efforts to end the COVID-19 pandemic, which continues to cause many thousands of deaths each day. We intend to file for regulatory approval, leveraging CVnCoV demonstrated strength against the continuous variant dynamics and in populations where it can provide a great benefit and serve the highest unmet need. We are in a continued and constructive dialogue with the European Medicine Agency, EMA, and data submission process are ongoing. In the meantime, we will further execute on the manufacturing ramp up and build up of our broad European manufacturing network as well as the development of our strong second-generation COVID-19 vaccine candidates which we are codeveloping in partnership with GSK and which we intend to bring into the clinic within the next month. With this, we conclude our presentation and would now like to open the webcast to your questions.

[Operator Instructions] Our first question comes from Umer Raffat with Evercore.

I have 3, if I may. Perhaps, first, I would say we all agree that the study did not achieve the efficacy targets we all had in mind. But I guess what I'm trying to reconcile is the comments you're making around strong public health value proposition from the current data. And what I'm really getting at is if you could walk us through, a, the visibility you have on the regulatory approval; and b, the dollar contracts that you think you basically pretty much have locked in based on the current data that you have. That's first. Secondly, Mariola, we never saw neutralizing antibody titers for patients above 60 years of age in your Phase I data. And now we know in Phase III, there was an imbalance on COVID infections in that age group. There are more infections on 60-plus on vaccine versus not. So I guess, what can we learn from that as it relates to correlator protection? And what can we learn broadly from the younger person data on the correlated protection? Which leads me to my ultimate question, which is the nonhuman primate data for your next-gen vaccine shows the neutralizing titers are 10x higher. But then the mouse data yesterday didn't quite show that. And I'm just trying to reconcile the 2? And when can we have the nonhuman-primate data preview?

Thank you, Umer. First of all, perhaps to start with your first question with regard to the regulatory approval process, which I will lead over to Ulrike to comment. On the contracts, like you mentioned, so we -- as you know, we have got this contract with the EU on 225 million dosages, which has been signed last year. And of course, we are in discussion also with the EU and sharing with them the data, which is going to happen now soon. The data we have been presenting to you. And we clearly see that we are on the road to find a pathway to get approval for what we think there is a public health benefit of the data we are having with all these 15 different variants, which have not been known when we developed the vaccine, and we see this efficacy. And so we are in conversation with them, and we don't have any sign that these contracts are not going to be served and certainly we are producing as we said, to deliver the dosages. On the other hand, certainly, we are in discussion also with other governments, especially in the countries where we have been running the clinical trials, which there are certainly the regulatory authorities also see the data. And as we also think that we can make a difference here for public health interest with our vaccine, we are talking to those as well. So long story short, the one is that we don't have any sign that the agreements we have been signing are going to be terminated, but we will show certainly, especially the EU data, and we are in discussion with other governments there as well. On the regulatory path, Ulrike?

Yes. So we are in dialogue with EMA and remain in the rolling review process and will come -- we work together with EMA on -- based on totality of data on the most appropriate path for approval of our vaccine. So that is work in progress, and we are in close interaction.

However, if I may say, with regard to the timeline, certainly, we cannot say something as we talk now because also we are, as Ulrike was saying, in conversation with the EMA, and we will certainly finalize our clinical trial report and then we are going to discuss with EMA and then certainly, they will take their time, but only they can make an estimate if they have been seen the totality of data here.

Exactly.

Okay. Then maybe on correlated of protection, where we stand here and what can we learn from the data. There's a lot of efforts here to establish this tolerate protection. It's not only our study, but also our organization work and try to compile all the data available, yes, to establish that correlated protection. What is already known. It's difficult to do it on the single subject basis, it's rather per population. And for sure, we hope although our data will kind of contribute to this as well. And therefore, we also will measure antibody titers in the HERALD studies and a huge population, and this is ongoing and yes, it will be also part of our submission of the serological data. In our Phase I, as you mentioned correctly, we didn't include here subjects above 60 years old -- age. And it was done in our Phase II study conducted in Peru and Panama. And we measure here antibody responses also in elderly. This study was blinded for the longer time period. And just recently, the study was unblinded for the analysis, which is still ongoing. And therefore, we will publish and present the data soon. But what I can say that we see antibody titers and elderly, but they are lower, yes, as compared to -- which is also normal as we know that elderly immune system is not efficient as the younger, and this is also true in our study. And we see -- but we see also nice T-cell responders in elderly. So there is immunogenicity observed here. And whether this will explain this cases we see in elderly. We need to see -- I really need to mention that we have really less cases, yes. And therefore -- and majority of them of this 21 is mild, yes. And yes, therefore, it's difficult to comment on moderate severe in this population. And regarding your question, second generation and comparison to first, yes, and we showed in the NHP data twofold increase for the 12 microgram dose. And then in the recently published my data, maybe the difference is not so huge. I think it's due to the dose, yes. So the comparison because it was only 1 dose of 8 microgram, if I'm right. And this can explain that the differences are not so huge as for NHP. NHP data will be published soon. This is a collaboration with Laboratory of Denver. There is a lot of data produced here, and therefore, the manuscript will be very comprehensive is in preparation and publication will come soon.

Our next question comes from Seamus Fernandez with Guggenheim Securities.

This is Evan Wang on for Seamus Fernandez. I have a few questions. First, just want more detail on the regulatory path forward, specifically for the 18 to 60 age population. I know the trial protocol kind of separated overall pop with the secondary endpoint for the elderly population. Can you provide any color on the ongoing discussions there based on this age subset? And if you can provide more detail within that 18 to 60 age fibulation, whether you saw a difference in efficacy across there and whether we may see further stratification based on age. Second, I just wanted more detail on the manufacturing. How many doses have been produced at risk? And what is the interest cost and scale up if authorization is granted. And then third, with the next-gen efforts, I believe this CV2CoV will be using the UTR modifications, but not the modified basis. GSK has described the modified base there. So any ways to accelerate development or run those next-gen vaccines in parallel?

Yes. So on your first question, yes, we are in dialogue with EMA, also about the different age groups. And as we said already, the 18 to 60 years old age group was prespecified per protocol. And we will, of course, also discuss certain option to approve for an age subgroup. I cannot comment on certain substrates at this point in time because they are also case numbers are low and one has to be cautious at this stage to conclude on this data. But of course, we will share all that data with the EMA and discuss the most appropriate path forward.

So perhaps on the manufacturing, I take over. So we have been building up now since a while a pan-European manufacturing network, which is taking over or here in tubing and running what we call GP3 commercial facility, and we are duplicating this quite tremendous oftentimes with Rentschler, Wacker, Silonic, Novartis and to have this capacity. We never stopped with this one, even not ready with the interim data we have been seeing. So it's going full speed that we are producing, which is still the goal that we are producing up to 300 million dosages towards the end of this year. We have to see how many of those dosages can be released then because it's the regulatory part as well because it is part of the dossier as well what we are heading in, certainly with the EMA at the moment. But this is still the goal. And -- it's also providing certainly the manufacturing capacity, which we need for next year. And the same capacity then is needed certainly up to a certain point of time also to produce -- you mentioned it's the CV2CoV. So it's the second generation, what we are developing together with GSK, not only on a monovalent, but also multivalent and perhaps you have seen last week, also GSK had a press conference also mentioning here that it's a combination also blended together with flu based on mRNA. So this is why we need the capacity. Mariola, perhaps you want to take the last one? On chemical modification CV2CoV?

Yes. So our next-generation candidate as we presented here is based on our technology and focus on major nucleotides is optimized backbone and antibody responses, T-cell responses we observed in NHP are absolutely accruing. And therefore, we want really to bring this construct into human and different forms as bivalent vaccines. But optimization never stops, yes. And for sure, we are open and test different kind of optimization and not excluding all the testing of chemical modification. And so it was also in the past, yes. And yes, so far, the data supports our decision to go with the second generation as it is now into the clinic.

Our next question comes from Eun Yang with Jefferies.

So the primary efficacy endpoint of the study is in all age groups, which is about 48% vaccine efficacy missing the 52% or higher efficacy bar in final analysis. And you mentioned -- you continue to mention 18 to 60 group was predefined. But I cannot seem to find that prespecification in your protocol. So is that predefined by EMA before you start the study? Or is this the post-hoc analysis?

Yes. So let me comment on that. So it is not post-hoc. So it was pre-specified in our SAP, and we have also a key secondary efficacy endpoint in the older age group. So that's there, it is mentioned.

Okay. And then another question is, so on the order population, you have more infection cases than placebo. So because of that, do you think that EMA, when they review your application, they would want to see Phase II study data where you had about 270 participants above ages 60. If so, when do you think that data may be available?

This data will be available very soon and also be part of the rolling submission and will be considered also for the evaluation, yes. At EMA, they will evaluate totality of data, which means not only data from HERALD, but also from this trial, which you correctly say included higher percentage of subjects about 60 exactly.

Okay. And then the EMA guidelines for COVID-19 vaccine kind of specified that the lower bound of 95% constant interval should be above 20% preferably 30% or above. So can you talk about your competency in tower in efficacy data points?

Yes. So we have a lower bound of 30%. So we have achieved that criteria for our primary efficacy endpoint, yes. And as you correctly stated, I mean, EMA and there was also a statement from Marco Cavaleri some time ago, will also look really at the totality of data. So they do not give a certain percentage of efficacy like 50% that needs to be met for an approval. Yes. And we think most what is really relevant that we have achieved statistical significance with a lower boundary of above 30%.

Okay. And the last question, and then I'll jump in the queue. So you have agreement with the European Commission to purchase 225 million doses and potential for additional doses. So my understanding is that once it's approved, the European Commission is obligated by 225 million doses. Is there a chance that based on the data they may cancel the order?

Well, we are having very soon a discussion and certainly discussing with the EU commission, but also with the member states because the contract works like that, member states are the recipients of certainly the dosages that we are presenting here the data. And you're right, because we -- these APAs, advanced purchase agreement, is public. And so it's a public knowledge that certainly, if there is approval, the dosages have to be ordered at least we feel now. So we will have these discussions. Certainly, we will present, and that's good because they are our customers to take these dosages to show the data where we think we have not only a second-class vaccine here, but a vaccine in this subgroup rely vaccine, which is also needed from a public health system independently, whether these are -- those of you that are staying in Europe or wherever. So therefore, we are providing this information, and we don't have any sign that this is not going to happen after approval.

Our next question comes from Zhiqiang Shu with Berenberg.

I have a few. First one is I'm trying to understand the delta variants specifically. The -- it's -- in your chart, you showed Delta variant is quite prevalent in the regions that you tested your Phase III. But in the actual cases, it's vary to only 1%. I guess can you provide any color, any hypothesis you may have regarding this disconnect? That's the first question. The second question is around you look -- I think you looked at Slide 11, you looked at efficacy on different variants. I guess have you looked at moderate to severe cases, the efficacy across the Board and also the hospitalization and death, 6 cases, what are the variance in these 6 cases? This is the second question. The third question, I want to also ask about the age stratification. When you submit the application to EMA do you specify that you're looking for 18 to 60? Or you are going after the overall population?

Yes. Maybe on your first question on the Delta variant. So as you correctly stated in our cases, actually, we have just 1% Delta, right? Beneath the timing when this data have been collected. So the data variant is now spreading more and more. But apparently, at the time, yes, when the case occurred there seem -- that was not that prevalent yet. I think that seems to be the most likely explanation for that apparent discrepancy. And EMA, and on your question regarding the age group. So as I said, we are in dialogue with EMA and they will, of course, look at the totality of data. And as of today, we cannot get some comment on the specific age group for the approval or if they will go for an specific approval. As said, we are in dialogue and need all data across all the trials. And your last -- yes, I think that was about the variance that caused the hospitalized to severe cases, the strains. So I need to check back on that. So I do not have this information available.

But fundamentally, when you look at the efficacy across different variants, we -- I think it was actually said in the presentation is that we don't have necessarily the power to draw any conclusions here because the trial was not powered to look at so many different variants initially. So I think it's something that we need to be...

Yes. That is right. So it will not -- we will not have statistically power to conclude any strain specific efficacy in the trial that is very important. Yes, thanks here for making it.

Especially in the moderate to severe.

Yes, exactly.

There is more and more...

There, it is -- numbers get lower and lower, I was very right considered.

And also it's important to see that this overall protection among these 15 different variants is, from our point of view, at least quite significant with 77% in this age group.

Our next question comes from Jonathan Miller with Evercore ISI.

I would love to here -- a couple of things, I guess. When should we expect an update on the full 588 cases that have been accumulated, not just the ones that were adjudicated for the primary endpoint, but all of those cases, including in seropositive at baseline and the ones that accrued before the 15-day window ended? And secondly, are you considering what the pricing dynamics are for your European contract? Would you price materially lower than competitive vaccines, given the data that you've seen thus far?