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

Thank you. Good morning, good afternoon, and welcome to our conference call. My name is Sarah Fakih, and I'm the Vice President, Investor Relations and Corporate Communications at CureVac. Please let me introduce today's speaker. On the call with me from CureVac are Franz-Werner Haas, the Chief Executive Officer of CureVac; Pierre Kemula, our Chief Financial Officer; and Klaus Edvardsen, Chief Development Officer of CureVac. From GSK, we are joined today by Rino Rappuoli, Head of Vaccines R&D. 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, Tuesday, October 12, 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, and welcome Rino Rappuoli, who we are happy to have participated in our call today from GSK Vaccine's headquarters in Belgium. The global fight against SARS-CoV-2 continues. However, the situation has changed considerably. Since the fight against COVID-19 began, licensed efficacious first-generation vaccines have become available, which have successfully helped to manage the initial peak demand to rapidly prime vaccinate unprecedentedly large populations. While the pandemic is still ongoing, the benefits of these vaccination efforts are easy to observe. Globally, COVID-19 cases and deaths reported [ weakened ] as the WHO continued to decline after reaching an interim peak earlier this year as a result of the rapid spread of the Delta variant. Today, a wind down -- a downward trend in weekly COVID-19 cases can be observed continuously, dropping from a mid-August peak of more than 4.5 million new cases per week and about 68,000 deaths to about 3.1 million new cases and just over 54,000 deaths at the beginning of October. Absent the emergence of a new variant able to evade vaccine-generated immunity, a gradual transition from acute pandemic to endemic SARS-CoV-2 is expected to occur in vaccinated regions in 2022. Managing a pandemic response is incredibly difficult. However, emerging from a pandemic is just as challenging. As we continue to move away from the overarching state of crisis, we are approaching a state where the virus and emerging variants are still a very real danger but cease to be predominant health -- public health threat. But what will the endemic COVID-19 state look like afterwards? And how can the technologies that have enabled potent pandemic vaccine to safeguard the long-term protection of people? A gradual change in the urgency and vaccine demand is expected to lead to the need for more differentiated vaccines targeting endemic COVID-19, which differ dramatically from the first-generation pandemic vaccines, in that they provide flexible and long-term protection against current and new variants in one vaccine via multivalent vaccines, broad protection against several different infectious diseases in one vaccine via combination vaccines, improved convenience of administration via single-use formats and efficient, scalable and cost-effective vaccine manufacturing and delivery as well as stability. At CureVac, we remain fully committed to providing a safe and efficacious vaccine. This goal has not changed at all. However, we recognize and acknowledge that the requirements to effectively address the virus and potential future variants will require differentiated solutions going forward. Current regulatory review timelines for COVID -- for CVnCoV suggest that due to the complexity of the data we have, we, at CureVac expect a decision on approval for CVnCoV would be expected only to come in later 2022. In this context, we have made the strategic decision to withdraw our first-generation vaccine candidate, CVnCoV from the current regulatory review from the European Medicines Agency, who is doing a fantastic job until now with a lot of efforts, to fully focus now on a suite of improved second-generation vaccine candidates we are developing in collaboration -- in close collaboration with GSK. While we acknowledge that we cannot be part of the first wave of pandemic vaccines anymore with CVnCoV, together with our partner, GSK, we fully intend to be at the forefront of delivering improved second-generation vaccines. Let me now go into further detail of this decision in the next slide. On Slide 4, I would like to further walk you through the factors that have informed our decision to terminate CVnCoV development program. In light of the anticipated vaccine demand in 2022, we have drawn a number of conclusions, which have led us to the strategic decision to withdraw CVnCoV from regulatory review process. We acknowledge that CVnCoV will not be able to still have an impact on the current pandemic. Going into 2022 with CVnCoV as a first-generation pandemic vaccine, we will likely not be able to meet the anticipated demand for more differentiated vaccines in an endemic COVID-19 world. And this is why we will now focus our efforts and resources on the second generation vaccine to be fast. The context of the pandemic evolving into endemic COVID-19 and the corresponding change in vaccine demand structure and urgency, meaning in diminished medical need for first-generation vaccines in the second half of 2022, was a major factor in our decision process. This includes a decreased demand for all organizations such as COVAX. Due to the expectation to have reached vaccination coverage objectives by mid-2022, they have indicated to us that there is limited interest in distributing CVnCoV in the second half of the next year. Most importantly, our decision awaited the expected development status of the broad second-generation program that we currently develop together with our strategic partner, GSK. Towards mid-2022, we expect first candidates from the second-generation program to have progressed to an advanced stage of clinical development. The first representative of such program, CV2CoV recently demonstrated the strong potential of our improved second-generation mRNA technology. In preclinical studies, CV2CoV was able to show a better and more balanced activation of immune responses compared to first-generation CVnCoV, demonstrating faster onset of immune response, higher antibody titers and stronger memory B and T cell activation. CV2CoV also showed higher neutralizing capacity across relevant variants, including the Delta variant. Together now with GSK, we will put our undivided focus and resources on the clinical development and manufacturing activities for the second-generation vaccine program to accelerate market readiness of second-generation solutions for an endemic vaccine demand and beyond. CureVac is a pioneering company that has been establishing mRNA as a potential medical modality for more than 20 years, and it has much to contribute to the continuing effort against COVID-19 and other infectious diseases, nevertheless of the outcome of CVnCoV. I would like now to hand over to Pierre, who will briefly address the financial implications of our decision.

Thank you, Franz, and good morning, good afternoon to everyone on the call. I'm now on Slide 5 to give you a first overview of the financial considerations in view of today's announcement. Before we go into further details, please let me underline that while we would like to answer all of your questions today, many aspects are currently being worked on simultaneously. It is, therefore, not possible to provide exact figures at this stage as continuing exchanges with third parties such as partners and suppliers, will be further refined in the coming weeks and months, and we hope to provide more clarity within this time frame. Over the last 1.5 years, we have protected our significant investments in clinical development of CVnCoV and mitigated associated financial risks through payments received from collaborations, grants and upfront payments. As a direct consequence of the potential approval shift to CVnCoV well into 2022, the existing Advanced Purchase Agreement with the European Commission, which was based on employing CVnCoV to address the acute pandemic need, will cease. This is in line with the diminished medical need, enhanced commercial demand for pandemic first-generation vaccines in 2022 that Franz has just highlighted. In the development of CVnCoV, it was very important for us as a company to limit the risk and financial exposure. We are thankful to several governments and authorities to have shared the risk with us. Two major elements have financially protected the company. The Advanced Purchase Agreement with the European Commission, we secured an upfront payment of EUR 450 million. This was -- this represented a significant part of the financial buffer aimed to minimize the risk around our efforts in accelerating vaccine research and buildup of production capacity. Additionally and importantly, we have spent more than EUR 450 million developing CVnCoV pursuant to the terms of the agreement and expect not to make any repayment back to the EU. This upfront payment was strengthened by an overall EUR 252 million grant by the German Federal Ministry of Education and Research. Due to the withdrawal of CVnCoV from regulatory review, we will not be able to claim more than EUR 196 million. So far, we have claimed approximately EUR 140 million. So a total of approximately EUR 650 million provide an important basis to manage the development and financial risk around CVnCoV. We have been able to balance the amounts received with our financial obligations. These financial commitments include our European manufacturing network to expand our mRNA manufacturing and formulation capacity. So in September of this year, we responded to the change in demand for first-generation vaccine as a result of the first wave of large-scale vaccination and associated demand projections for CVnCoV by terminating collaboration with 2 network partners to adjust our peak production capacity. We continue to monitor and match demand and capacity, specifically with the shift towards a large second-generation program, including multiple vaccine candidates. We also made some significant early investments into inventory, large quantities of raw materials to manufacture CVnCoV. In order to reduce raw material write-offs and manage commitments with our raw material suppliers, we are now primarily assessing the possibility of using our material for the production of second-generation vaccine candidates, while also evaluating resale opportunities to support any shortage at other vaccine manufacturers. Lastly, we have made property, plant and equipment investments for the buildup of production lines and the production facilities of our European manufacturing network. These investments will now be used for manufacturing of our second-generation vaccine candidates. Some production lines will be applied in our large-scale in-house GMP IV plant, which is expected to come online at the end of 2022, early 2023. Some production lines will be transferred to GSK for clinical material supply. We will ensure that we maximize the use of production lines and alternatively favor a resell of some material and equipment. While we expect there will be write-offs following the decision to withdraw CVnCoV, we will maximize our efforts to leverage existing commitments related to CVnCoV for our second-generation COVID-19 candidates. With this, let me hand back the call to Franz.

Thank you, Pierre. I'm now on Slide 6 to give you an overview of our current status and plans for manufacturing capacities in view of our decisions. As Pierre has already highlighted last month, we responded to the change in demand for -- short-term demand for pandemic first-generation vaccines and streamlined our manufacturing capacities to ensure that we can rapidly and flexibly deliver a potential second-generation vaccines in line with the endemic COVID-19 vaccine demand going into 2022. For this purpose, we have already started to switch the manufacturing setup at GMP III, our own manufacturing unit, and the European manufacturing network facilities through the production of clinical material of second-generation constructs. This includes the implementation of process for flexible adoption of the new variant-specific constructs as well as processes for the production of modified mRNA constructs, which will be explored as part of our second-generation development program. For CV2CoV, the first representative of our broad second-generation program, we have already produced clinical material -- clinical trial material in our in-house plants, GMP I and II, and we aim to kick off the second-generation clinical development program with CV2CoV to start with within the next month. As Pierre said, to expand our internal manufacturing capacities and to focus resources to be more independent with our overall production process, we further expect our internal commercial scale manufacturing plant, GMP IV, to be built up soon. Together with GSK, we strive to shape the manufacturing process and organization to efficiently deliver in future public health needs. I now hand over to Klaus, our Chief Development Officer.

Thank you, Franz, and hello, everyone. I will now be on Slide 7, and I would like to start giving you an overview of our collaboration with GSK, in which we jointly developed a suite of potentially improved second-generation vaccine candidates for COVID-19, but also for a broad range of other infectious diseases. We have recently strengthened our collaboration through an extension to the agreement, in which both companies commit to a large number of dedicated experts and additional resources to further accelerate the development program. Please let me remind you that our second-generation vaccines are based on an improved messenger RNA setup, which differs from the setup of the CVnCoV and which was generated on the basis of our learnings over the past year, targeted optimization, focused on improved messenger RNA translation for increased and extended protein expression as well as improved and faster immune responses at low doses. We believe these characteristics will be key to develop vaccine candidates, focusing on specific features decide to address the demand for differentiated vaccines in an endemic COVID-19 world. These include, among others, addressing current and emerging variants in one multivalent vaccine, broadening protection against several different diseases in one combination vaccine and improving convenience of administration via single-use vaccination formats. To select and advance the best candidates, we also plan to work together on a technology extension into modified messenger RNA in parallel to the development of unmodified messenger RNA constructs. We expect the withdrawal of the CVnCoV to enable us to fully focus on accelerating the second-generation program based on the learnings and infrastructures built up during the development of CVnCoV. With CV2CoV, we have already preclinically advanced the first representative of the second-generation COVID-19 program, which is expected to initiate the clinical development program within the next couple of months. Let me briefly go into the recently published preclinical data of CV2CoV, demonstrating the strong potential of our second-generation messenger RNA setup. I will now move on to Slide 8. These data represent selection of what was published of a data set in a non-human primates together with Harvard Medical School. The manuscript is currently available from the bioRxiv preprint server and has been submitted through a high-ranking peer review journal. The data, as I said, is based on animals immunized with CV2CoV or CVnCoV according to the vaccination schedule applied in humans, which includes 2 vaccinations with a 12-microgram dose, 4 weeks apart. The difference between the time-dependent induction of utilizing antibodies show in this graph between the first and the second-generation is striking. Antibody titers of CV2CoV are not only about 10x higher at peak level after 6 weeks but also show faster onset of utilizing antibodies already 2 weeks after first injection -- first vaccination. I will now move on to Slide 9. Higher antibody titers for CV2CoV compared to CVnCoV were also observed in response to a last set of highly relevant COVID-19 variants, including the Delta variant. The impact of variants on neutralizing antibody titers is illustrated in these 2 graphs next to the wild type. A general reduction of antibody titers in response to the variants compared to the wild type is clearly visible. However, CV2CoV antibody titers range consistently higher than the CVnCoV antibody titers. In summary, the data demonstrate how an improved setup and targeted optimization of the second-generation messenger RNA approach can substantially improve immunogenicity against multiple variants in nonhuman primates. With this, it is my pleasure to hand over to Rino Rappuoli, Head of Vaccines R&D at GSK.

Well, thank you, Klaus. Well, at GSK, actually, we welcome very much the decision of CureVac to focus the effort in the collaboration with us, and into the development of a second-generation platform that we're going to use as non-modified and modified RNA technology. So I think the fact that we are focusing on a common goal is going to speed up our ability to deliver in the short term. As you know, at GSK, we value a lot the RNA. I think it's an -- we have seen is a very exciting technology. And we see that as a major opportunity for the future of the vaccine field. And at GSK, we are investing in RNA a lot. And we are focusing our collaboration with CureVac and we are building a possibility to basically, to master the technology end-to-end, including [ fund ] reserves to manufacturing. Internally, we have a really big number of people dedicated to RNA, GSK experts. And they basically master well the RNA technology. And with the announcement today, those -- our people are going to work together hand to hand with the people from CureVac. And basically, this collaboration will make a much stronger team. We initially will focus on the COVID-19 vaccine. I mean now we are starting to see that vaccines are basically relaxing the COVID, but somehow, we do believe that vaccines would be needed in the future. There are still many people around the world that have not been vaccinated and the virus keeps evolving. So surprises are more than one time and will probably continue to surprise us in the future. So we need to be there with new vaccines and with this technology, I think we can do it. As you've seen from Klaus, basically, we are very confident in the second-generation vaccine platform that CureVac has built together. They've engineered the 5 prime and 3 prime end of the RNA and basically the expression in vitro and the ability to immunize to induce antibodies in vivo and T cell is much improved compared to the previous one. Klaus has just shown the data in preclinical model that have been published recently about the second-generation vaccine. And clearly, the antibodies are induced by the second-generation vaccines are much higher, significantly higher than the previous -- the one from the first generation. In one of the studies were as high as tenfold higher than the other ones. So we are excited about the second-generation module. We're going to use it, as I said, as a non-modified and modified basis and we have obviously applied to COVID-19 vaccines, but the same platform, we're going to apply to many other diseases and vaccines that we have in our pipeline. And so we see this as a basically the basis for a future pipeline in the field of RNA. And working together with CureVac, basically, we believe we are going to grow much faster, now that their priorities, our priorities are fully aligned. So with that, I would like to conclude saying, I'm really looking forward advancing our second-generation COVID-19 assets. We would like to see in the clinic in the next few months and from there to build our pipeline for the future. So with that, let me give you -- hand back the call to Franz.

Thank you, Rino. Let me quickly summarize the key messages from today's presentation. Changes in vaccine demand and urgency are starting to shift the requirements for a new generation of differentiated vaccines towards the endemic COVID-19 world and beyond. In the ongoing transition from acute pandemic to endemic, withdrawing CVnCoV as a first-generation vaccine from the regulatory review is a direct consequence of these expected changes in public health needs and timing. We will, therefore, have the freedom to focus our priorities and resources on delivering advanced second-generation vaccine for COVID-19 and beyond, together with our partner, GSK, to address global post-pandemic medical needs. The first representative of the second-generation vaccine program, CV2CoV has shown promising preclinical data and is expected to kick off the overall second-generation clinical development with several candidates within the next month. The expected technology improvements will contribute to our entire mRNA platform beyond COVID-19 and even beyond infectious disease. We are convinced the partnership with GSK, in people, in combination with CureVac's deep and diverse roots in mRNA technology, put us in an excellent position to play a prominent role in tackling future public health challenges. With this, we conclude our presentation and would like to open the webcast for your questions. Thank you.

[Operator Instructions] And our first question comes from the line of Jonathan Miller of Evercore ISI.

And I guess we're looking forward to seeing more advancement of the second gen programs here. Let's just dive right into the clinical expectations. Is it fair to say that immunogenicity is possible -- immunogenicity data possible first quarter next year or relatively soon, given when you're anticipating getting into the clinic with this? And beyond that, do you think efficacy trials are going to be more challenging to run as the pandemic wanes? And on the same lines, do you anticipate being eligible for accelerated approvals on the basis of a correlative protection? And if so, when might that transition from needing to do efficacy trials to being able to get accelerated approval to happen?

May I transfer this question to you, Klaus and Rino?

Yes. No, absolutely. Klaus Edvardsen here. Your first question is whether we would expect to see immunogenicity data on the initial part of the clinical program in first quarter of next year. That is absolutely our ambition. And as we indicated, we are ready to start the Phase I part of that program for the first part of the CV2CoV expansion within the next couple of months. So that is a reasonable time frame to expect that we would start to have an idea on how to position this program. The other part of your question is that it's very clear now that the trial concept moving forward, in a world where a significant part of the population is either vaccinated or naturally infected, is that a trial design that will have a naive baseline, so to speak, is likely not going to be feasible in many territories any longer. And the other element that it would likely also not be an acceptable approach from an ethical standard that you do the traditional design vaccinated group and compare that to a nonvaccinated group and then wait and see the differences in infection rate between the 2 groups. So yes, absolutely. I think from a development and registration purpose, it is likely very slow, that you would have to compare your effort to potentially already licensed vaccines and with correlate of immunogenicity.

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

Can you guys provide some more timelines around clinical development for both unmodified and modified constructs? The language around 4Q or within the next couple of months...

Do you want to comment Rino? Or should we go to Klaus? Up to you?

No. Go ahead, Klaus, and then I'll follow up after you.

No, no, I'm happy to address that also. Right now, the way that we have structured the program is that the CV2CoV construct is an improved background compared to the first construct, as Rino alluded to. The spike protein that's going to be expressed in the second construct is not different from what it was in the first construct, but the whole stability of the messenger RNA by changes in the 5 prime and 3 prime non-coding regions of the construct, have been improved. And what we can directly see here is that the antigen expression level that we can obtain with that construct is significantly higher than with the first construct and that element very likely drive the nonprimate increase in immunogenicity. We have fully accepted that if you look at the outcome of our trial result to trial results from other messenger RNAs that are now licensed, that at face value, it looks like one of the significant differences between the approaches has been utilizing modified from others and be using non-modified. And we obviously take the scientific learning out of that and therefore, have decided also together with GSK to implement modified in our continued endeavor in creating a COVID-19 vaccine. But with regard to timelines we ready, as we said, to move very, very fast with the second-generation construct as is and we'll follow-ups with the modified construct and then have a direct comparison of what would be the right thing to take fully into development.