BioNTech SE (BNTX) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the BioNTech's COVID-19 vaccine program update call. [Operator Instructions] I must advise you that this call is being recorded today on Thursday, the 23rd of April 2020. I would now like to hand the call over to the Vice President, Investor Relations and Business Strategy, Sylke Maas. Please go ahead.

Thank you for joining us today for BioNTech's COVID-19 vaccine program update call. Before we start, I encourage you to view the slides for the webcast as well as the press release issued yesterday, April 22, both of which are accessible on our website in the Investors section. As shown on Slide 2, during today's presentation, we will be making several forward-looking statements. These forward-looking statements include, but are not limited to, BioNTech's efforts to combat COVID-19; the planned next steps in BioNTech's Project Lightspeed; the timing to initiate clinical trials for BNT162 in Germany; collaborations between BioNTech and Pfizer, BioNTech and Fosun Pharma to develop a potential COVID-19 vaccine; the expected timing of clinical trials for BNT162 in the United States and China; and the ability of BioNTech to supply the quantities of BNT162 to support clinical development. Actual results could differ from those we currently anticipate. You are, therefore, cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this conference call and webcast. Speaking and available for questions today will be Ugur Sahin, Chief Executive Officer; and Ryan Richardson, Chief Strategy Officer. I will now hand the call over to Ryan Richardson.

Thank you, Sylke. It's a pleasure to welcome you all to today's call. We're excited to discuss the progress we have made in our COVID-19 vaccine program, highlighted by the clinical trial approval for the BNT162 program in Germany yesterday. I'm going to provide a quick overview of the program and then turn over the call to Ugur Sahin to go into a deeper dive, and we'll then open the call up for questions. So turning to Slide 3 of the slide deck. For those of you who may not be familiar with BioNTech, we're building a global next-generation immunotherapy company. We have a broad suite of novel therapeutic platforms to exploit the full potential of the immune system and are developing a pipeline of potentially first-in-class immunotherapies for the treatment of cancer and an expanding number of programs targeting a range of infectious diseases. Many of these programs are supported by world-class partnerships. We've invested significant sums in our manufacturing capabilities in the mRNA and cell therapy arena, and those represent -- those investments represent a key pillar of our longer-term strategy and also are relevant to our COVID-19 strategy. So today, we'd like to provide an update on the vaccine development program for COVID-19. This is a program that we initiated in late January as part of a Project Lightspeed in response to the global coronavirus pandemic. This program builds on our own experience in the cancer vaccine field and our efforts over the past 2 years in the infectious disease space as well. So turning to Slide 4. At a high level, we initiated this program because we felt a duty to fully utilize our technology and immunotherapy expertise to help address this pandemic. Ugur is going to go into some details on the program and the development. But I think in short, some of the key highlights include that this program makes use of a number of different vaccine variants and also exploits a highly potent lipid nanoparticulate formulation, which we leverage across those different variants. We also make use of our GMP manufacturing infrastructure for this program as well as our global clinical development capabilities and also those of our partners. So on the partnering side here, we've assembled a broad consortium of partners, including Pfizer and Fosun to develop this vaccine globally. We're partnered with Pfizer for worldwide development of a vaccine outside of China and partnered with Fosun for the Chinese territory. We already had a successful collaboration with Pfizer dating back to 2018 in the infectious disease realm, and we were able to leverage that relationship to immediately begin work on the COVID-19 -- in the COVID-19 space. We plan to utilize multiple sites from both Pfizer and BioNTech to develop the vaccine. Fosun represents our first strategic collaboration in Asia. And here we're jointly developing BNT162 in China. And we intend to conduct clinical trials in China, leveraging this mRNA technology and also Fosun's extensive clinical development, regulatory and commercial capabilities in the country. And under the terms of the agreement, both companies will collaborate to conduct the trials in China. So with that, I'll now turn over to Ugur Sahin, our Chief Executive Officer, for a more detailed program update.

Thank you, Ryan, and thank you all for joining today's call. I'm incredibly pleased to be with you today. We have achieved a major goal ahead of our previous expectations. I believe the speed from the start of the program to trial initiation is not only a strong validation of our technologies, but also our commitment to provide a sustainable solution for the current COVID-19 challenge. Moving to Slide 5. We are proud to note that the Paul-Ehrlich-Institut, which is the German authority for pharmaceutical products approved our Phase I/II trial for BNT162 for the prevention of COVID-19 infection. It is one of the first regulatory approvals worldwide for vaccine candidate testing. While this trial will be conducted in Germany, it is important to note that we are pursuing a global strategy. Additional trials are expected to start in the U.S., in Europe as well in China. In the U.S., we plan to conduct these trials with our partner, Pfizer. We may expect a regulatory approval in the U.S. shortly and will initiate trials [indiscernible] after. In Europe, we plan to discuss with EMA our broader European strategy. And finally, in China, we will work with Fosun Pharma, as previously mentioned. We have created 4 vaccine candidates, developed with 3 different messenger RNA technologies and are targeting 2 antigens. Two of the candidates use our nucleoside-modified mRNA. One includes our uridine-contained messenger RNA, and the last one utilizes our self-amplifying messenger RNA. The larger spike sequence of the SARS-CoV-2 virus is included in 2 of the vaccine candidates, and the smaller optimized receptor binding domain, which is known as RBD, is included in the 2 other candidates. Just for explanation, the RBD base candidate contains the piece of the spike that is the most important for illustrating neutralizing antibodies, which can inactivate the virus. I'm also pleased to report that the clinical trial material from our GMP-certified mRNA manufacturing facilities was used to manufacture all 4 candidates. So moving to the next slide. I would like to give you a background about our motivation and summarize the overall program. So first of all, vaccines represent the only long-term solution to the COVID-19 pandemic. We, as other experts, believe that the SARS-CoV-2 virus will stay with us for the next years until we have a situation where most -- more than 90% of people have immunity, either by infection or induced by a vaccine. Our goal is the rapid development, clinical testing and regulatory approval of well-tolerated and safe vaccines to prevent COVID-19. We are using our established messenger RNA technologies. This messenger RNA technologies were validated for their immunogenicity and safety in oncology indications, and are now used, in adapted fashion, for infectious disease vaccines. Our goal is the induction of long-term memory immune responses which protect vaccinated individuals from SARS-CoV-2 infections and inhibit or prevent COVID-19 illness. Our 4 vaccine candidates use different technologies. Three of the vaccine candidates will be used as prime-boost vaccine. One candidate, which is the self-amplifying messenger RNA is expected to work also as a single-shot prime-only vaccine. As Ryan already explained, we have collaboration with Pfizer worldwide outside of China, and Fosun for development of the vaccine in China. Let me give you a short summary about mechanisms of action of mRNA vaccines. mRNA vaccines are based on the delivery of messenger-RNA-coded genetic information. And this information serves as a blueprint to make proteins in the vaccinated individual. The mRNA is taken up into cells and the antigen -- the vaccine antigen is produced by the translationary machinery of the cell. The mRNA synthesis is associated with the parallel stimulation of the immune system of the vaccinated individual. And this combination, the protein, the antigen production by the cells plus the mRNA-based stimulation results in the induction of the immune response. We and many others believe that messenger RNA pharmaceuticals are particularly suited as pandemic vaccines. I'm now on Slide 8. So messenger RNA is a synthetic variant of a naturally occurring genetic molecule. After delivery, messenger RNA is completely degraded into products which are repurposed in the human body. It is a biochemically well-defined biopharmaceutical, it can be produced with a high purity and is free of animal materials, which makes it easier to scale up and test. As already mentioned, messenger RNA has an inherent immune-activating quality. So that means there is no need for an additional adjuvant. We know from many, many studies that messenger RNA stimulates both antibody responses as well as T cell responses. And what is particularly important, messenger RNA has a high-potency that it means that these immune responses can be generated at very low doses. We have tested -- clinically tested our messenger RNA vaccines, mainly in oncology patients. We have so far created activity and safety data on more than 400 dosed patients in the cancer setting. And we have, in the meantime, also built a manufacturing facility allowing us, in combination with expansion processes, to scale the production to manufacture up to hundreds of millions of vaccine doses. I'm now on Slide #9. So what needs to be considered to make a good vaccine? First of all, what is the target antigen? SARS-CoV-2 is a new member of the SARS family. And fortunately, it is well-known that the SARS family members have a special protein, the spike protein, which is involved in the uptake of the virus in the cell. The receptor is ACE2, a molecule which is expressed in many human cells, including the lung, which resides in the lung disease. So one goal of vaccine development is to target this molecule and inhibit the interaction of this molecule with this receptor by inducing and by making antibodies. And the structure of the SARS-CoV-2 spike protein has been recently sourced and it has high structural homology to the first variant of the SARS virus, which was described more than 16 years ago. And for this variant, it is well-known that the binding to the receptor is mediated by the receptor binding domain, which is again a smaller domain, which provides about 90% of the binding surface to the receptor. It is well-known that antibodies against the receptor binding domain can inhibit the uptake of the virus. But it has also an advantage to target not only the receptor binding domain, but the full antigen, which provides a better opportunity to generate more T cells against multiple different epitopes. Therefore, we decided to evaluate both antigens, the full antigens in a prefusion-stabilized version as well as the receptor binding domain as immunogens. The next question is the platform. So BioNTech has developed several platforms. We have, in total, 4 different platforms. And we are using, for development of COVID-19 vaccine, 3 of our platforms. This is the uridine messenger RNA based on uridine nucleosides. Uridine-containing messenger RNA stimulates TLR7 and TLR8, has a strong adjuvant effect and is active at low doses, is able to induce strong antibody responses and induces CD8 T cells as well as CD4 T cells. We have a second version of the messenger RNA, the nucleoside-modified messenger RNA. In this nucleoside-modified mRNA, the TLR-stimulating uridine is replaced by pseudouridine and thereby, the messenger RNA is not anymore able to activate TLR7 and TLR8 and has a less adjuvant activity. The nucleoside-modified mRNA has the advantage that it is expressed at a higher level and it is expressed to longer and thereby induces extremely strong antibody responses. And it has been proven that this particular format of messenger RNA induces CD4 T cell responses, particularly follicular helper T cells. The last platform which we are going to apply in for this vaccine is the self-amplifying RNA format. The self-amplifying messenger RNA is able, after entering the cell by the presence of a replicate to amplify itself in the cell so that within 2 days, several thousand copies of the messenger RNAs are produced in the cell. By this amplification, we have 2 effects. First of all, one effect is that we -- by delivering less mRNA, getting more antigen produced. So that means with this messenger RNA as compared to, for example, uridine mRNA, we have observed, in preclinical setting, that a 60-fold lower dose is required to induce the same strength of immune response. The second advantage of this platform is the prolonged activity of the RNA. We have seen, in preclinical models, activity of the messenger RNA and the protein translation up to 14 days. And by this, we believe that a single injection, a prime-only injection, could be sufficient to induce a potent antibody as well as T cell response with this messenger RNA format. On Slide #11, I would like to just shortly summarize the path from development until approval of the clinical trial 2 days ago in Germany. So we established the research and development concept in 2 weeks and initiated our research and development activities end of January. We have met the German authority and we have also had meetings with the Chinese authorities and later on also with the FDA several times to discuss our development concept and discuss the rational for development of multiple vaccine candidates. We developed assays for analyzing immune responses and to identify the quality of immune response. We tested more than 20 messenger RNA vaccine candidates and selected 4 candidates, which went into GLP toxicology studies, which were used to analyze vaccine activity. We observed, for all vaccine candidates, a strong antibody response, including antibodies detected by ELISA as well as neutralizing antibodies, and we observed T cell responses. We manufactured the candidates in GMP-grade and formulated them. We applied for clinical trial testing in Germany on April 9. And we submitted requested document on April 18 and got the approval on April 21 from the German authorities, including the Ethics Commission. Further regulatory applications are currently in preparation for trails in the U.S. as well as in China. On Slide 12, it -- you can see the product for the first candidate, which will go into clinical testing. It is a messenger RNA encoding a nucleoside-modified RBD subunit of SARS-CoV-2. We have seen very strong immune responses with this candidate and will use the candidate in a dose range of 1-microgram to 100-microgram. You can also see here an electron microscopy image which was kindly provided by Tom Madden from Acuitas in Vancouver, which is the partner for us in formulation development. So on Slide 13, I would like to summarize the first phase of our clinical trial. So the clinical trial will be, of course, a clinical trial which will go from Phase I/II and to Phase III registrational trials. But what we have discussed with the German authority is the Phase I/II design, and depending on the results, we will continue with a fifth free design. It is one trial with the objective of testing 4 vaccine candidates. We have an approval -- every vaccine candidate so that the trial is approved for all vaccine candidates, but each vaccine candidate will have to be released by the authorities by providing the full data sets. So the next one which will come is a uridine messenger RNA candidate, and then we will have a self-amplifying RNA vaccine candidate coming later on. We will test prime-boost vaccination for nucleoside-modified mRNA as well as uridine mRNA and prime-only for the self-amplifying mRNA. We will test several vaccine doses in about 200 healthy subjects focusing on the age of 18 to 55 years. Subjects with higher risk for severe infections will not be included in the first part, but included into the second part. The objective of the study, of course, is first of all safety and tolerability. Immunogenicity, we will measure virus neutralization titers and pseudovirus neutralization data, and we will determine the optimal dose or optimal doses for further studies. Now finally, moving to Slide 14. In summary, we have demonstrated a rapid progress from the start of the program to study approval of our first-in-human trial. We have established an international collaboration consortium to address this severe pandemic, including both Pfizer and Fosun. We expect that additional trials are started in the U.S., in Europe and in China. Our program includes 4 vaccine candidates, each coming with differentiated features, not only to identify 1 vaccine candidate which works, but really provide a differentiation, allowing us even to proceed with 2 vaccine candidates if this would be useful for different target populations. The Phase I/II dose escalation trial is designed to determine the optimal dose for further studies and to evaluate safety in the first 200 subjects. Finally, we will -- we have proven that our manufacturing competence can be used for manufacturing different mRNA formats which can be used in a single trial. So thanks, again, for joining today's call. Before I turn the call over to the operator, I would like to take the opportunity to thank our employees for their tireless efforts that have allowed us to make such significant progress during these difficult times. Operator, can you open up the call for question and answer, please?

Your first question comes from the line of Cory Kasimov, JPMorgan.

I guess, the first one I have for you is, can you just talk a little bit more about your strategy of advancing 4 different candidates? I mean do you intend to pick just one to move forward with into larger studies? And what would this be based on? And do you think you could get that type of information from Phase I trials? And I have a follow-up.

So maybe, Ryan, if okay, I would like to take this question.

Yes.

Yes. So we have 4 vaccine candidates, and they have different differentiation factors. So the Phase I/II trial will show us which of the vaccine candidates induces, in the human setting, sufficient antibody responses. We will look into T cell responses, and we will identify each candidate with those. Decision-making, if we continue to take just 1 candidate or 2 candidates, will be based on the overall observation. So we are, in principle, open to continue with several candidates, since we have to understand that we have a population which is not homogeneously responding to a vaccine. It is well-known, for example, that elderly patients -- elderly people have a much lower antibody response and require higher dose. It is quite possible that for the elderly population, a self-amplifying mRNA could be more effective than a nucleoside-modified mRNA. The second aspect for decision-making is the dose. So we have to evaluate which vaccine can be used at the lowest dose to induce a potent antibody as well as T cell response. So that will be another decision factor. The third decision factor will be the tolerability. And based on this observation, we might either decide to just continue with one candidate or decide to move ahead with 2 or even 3 candidates.

Okay. That makes sense. And then how quickly do you think you can scale up here and to what number of doses? Also, is this complicated by the fact that you're advancing 4 candidates into development?

No, in principle, the manufacturing technology that they are using is pretty similar to all candidates. So that means expanding our manufacturing capacity does not mean that we are increasing the capacity and building devices and tools for 3 different vaccines. It is the same technology which is used, and therefore, this is the elegance of the approach that we can build on established processes applicable for all 3 platforms.

Okay. And then if I could just squeeze one more. I just wanted to ask you for your thoughts on potential time lines here, both in the short-term to get some initial data, but more importantly, like what's a realistic time line in your view to when you could have a vaccine on the market? You see lot of numbers and thoughts thrown around kind of in the media and stuff like that. But what do you think is a realistic time line here?

Yes. I think it is really not appropriate to talk about time lines now. So we have, first of all, to see whether the vaccine is safe and observe the efficacy of the vaccine. So that's the first. We of course know how fast we can move ahead, but we don't know what will be the requirements for an approval. And therefore, discussing about time lines is a discussion based on at least 1 or 2 unknowns at the moment. And therefore, it would be only speculation.

Your next question comes from the line of Navin Jacob from UBS.

This is Alanna Murday on for Navin Jacob. Just one question. There was a study in the Journal of Virology that showed that antibodies that bound to the receptor binding domain actually induce a conformational change that led to enhanced proteolysis and viral entry. Are there specific studies you've done to demonstrate that this type of response is not induced by the receptor binding domain of your vaccine?

Yes. So the literature is not consistent. So there are a number of publications showing the receptor -- that antibodies against the receptor binding domains are fully protected. And the last one published about 2 weeks ago showing really that a vaccine against the SARS-CoV-2 RBD domain induces antibodies which do not mediate an enhanced uptake and ADE effect of the virus. I think the problem with publication is there are too many publications and the field is not consistent. The vast majority of the publications clearly show that vaccines regardless against the RBD domain or the spike protein are protected. I believe that the most important aspect for vaccine development is proper development of a vaccine -- of a Th1 vaccine which induces strong antibody responses, specifically to the spike protein or sub domain. And we have to go into clinical trials to really understand and carefully monitor the vaccinated subjects over time to exclude any risk mediated by a potential ADE.

Your next question comes from the line of Daina Graybosch from SVB.

Two questions more around costs. I wonder -- you guys have already been scaling up manufacturing significantly. And I wonder if you could speak to how additional manufacturing scale-up you're going to do at risk? And how you're splitting up cost of that scale-up and work between you and Pfizer? And then I have a follow-up after that.

Yes. Thanks, Daina. I can maybe address that briefly. So I think it's -- I think overall, the structure with Pfizer that you should think about is a 50-50 collaboration in the territories where we're collaborating, which is worldwide, ex China. As part of that, development expenses will be covered by Pfizer. Our portion of the development expenses under that framework will be covered by Pfizer in the first instance. The capital expenditures for each company will be made independently. And I think it's too early for us to try to give you a number in terms of the overall expense. But I think we do plan to provide a further update in the future once we have more information on the full extent of that scale-up. In part, it will depend on the dose. But it is true that already now we're planning to make at-risk investments to facilitate as rapid of a scale-up as possible. And I think there could well be additional potential sources of capital that could come available, including some nondiluted sources.

That's great. And the second question is more of a science one. I wonder if you guys can speak to -- I mean you're taking 3 different RNA technologies in. And we're very early in the overall development of RNA vaccines. I wonder if you could speak to the validation for each of these in human. And specifically, you've talked about your cancer setting, does -- which of these technologies is used in the cancer setting? And then the ones that aren't used, is there any human validation we can look to, to be confident?

Yes. Yes. Excellent question. So first of all, in the cancer setting, we have generated experience with the uridine mRNA platform and pseudo -- the nucleotide-modified messenger RNA platform. We have so far no clinical data with self-amplifying RNA. This is mainly based on studies and multiple studies in different animal models, including nonhuman primates.

Your next question comes from the line of Arlinda Lee.

I was hoping that you could talk more about your choice of epitope that you -- I think on your last call, you alluded to some eliciting different kinds of responses. And I was hoping that you could elucidate on what work you've done on that.

Yes. Yes. So we are continuing our work on the type of immune responses generated by our vaccine candidates. So we will have a more complete data package, including disease models available in the time frame of June. And this would be the time where we would, in detail, provide information, how our vaccines work and how they impact disease, and provide also information from mechanistic studies.

Okay. And then on the preclinical side, have you -- can you go through, maybe for your 4 vaccine candidates, what those epitopes might be and how you chose those particular ones?

Yes. Yes. So we tested 20 candidates and every candidate was evaluated with different epitopes. And we have selected the -- for the nucleotide-modified mRNA, we will have the RBD domain as well as the full-length spike protein. As candidate for the self-amplifying mRNA, we decided to take a full-length spike protein as an antigen. And we for the uridine mRNA, we have a RBD variant which are going to be tested. And this is based on really evaluation of each of the platforms for the different candidates.

Great. And then can you maybe discuss maybe the idea of immune enhancement or back firing? And how this -- you might have done studies on -- preclinically to show or if there would be any evidence or something like that?

Yes. Yes. I believe the problem with potential disease enhancement is that there are no accepted model -- disease model. So we know that even the regulators and the authorities struggle to make suggestions, what should be done to exclude that because there are no validated models available. What is perplexing is that for -- the models that described disease enhancement were used by other groups showing that there is no disease enhancement. So the literature is not consistent. And this might be really depending on the experimental conditions, how this type of disease enhancement was investigated. And therefore, relying on just preclinical models could lead us to wrong conclusion. We have to be very careful, and the only way to answer that is careful clinical development and observation of subjects and a lot of mechanistical studies that are associated to understand the immune response and how the immune response translates into inactivation of the virus. And that's exactly what we are going to do.

Your next question comes from the line of Tazeen Ahmad, Bank of America.

Maybe just on your use of resources given that the COVID pandemic happened suddenly. I'm sure it wasn't in your original plan for spending a decent amount of your resources on developing a vaccine for this. So in line with that, by dedicating resources now with all of the programs that you're moving into the clinic, did you have to make any decisions to perhaps slow down development of anything else that you might have planned as far as your vaccines go? And then I have a question on financing.

Yes. Maybe I can take that one, Tazeen. So I think in principle, when you look at the Fosun and the Pfizer deals together, those 2 partnerships brought us about -- approximately $250 million in upfront and near-term funding for this program, which we started now less than 3 months ago. And in addition to that, on both fronts, we have the majority, let's say, of our development expenses in terms of clinical trial costs picked up by partners as well, at least in the near term. So I think that the direct cash impact of the program, I think, is not -- actually has not had a big impact on our overall pipeline decisions in the near term. With that said, as I mentioned on an earlier question, we are still in planning to address the broader question around the CapEx needs for scale up and those requirements. I think that's one that we will -- we're still working on. But I think the short answer to your question is, no, there hasn't been a direct financial impact. Now there has been an impact to our pipeline from COVID-19 in terms of trial progress. On our last update call, we did allude to the fact that we had moved some of the time lines for some of our -- in particular, our first in-human study starts that were planned for this year, we have pushed into next year. But those changes were driven primarily by the COVID-19 impact operationally, the impact to sites rather than portfolio decisions.

Okay. And maybe to follow-up with you, as we think about, hopefully, one of these candidates being successful and being able to become available to patients. This is a question, I think, investors have across the board, which is how are you going to balance the cost of developing a product like this for what is clearly an important humanitarian need with balancing what the potential for value to the company financially would be if a molecule like this were to become commercial? A number of companies have already said that they think that the commercial opportunities for the products that they are developing would be minimal. How are you thinking about your particular programs and what that would mean for potential revenue generation?

Yes. On the commercial side, I can start and Ugur, please jump in. I think -- yes, I think we would share the view that it's too early to comment on the commercial opportunity here, and we -- in fact, we did start the program before we had a view on the commercial opportunity. We felt like we had a duty to do so. And I think it's still the case that the commercial opportunity is still -- I think it's too early to comment on still. I don't know, Ugur, if you want to add to that?

Yes. I think this is really something that can't be addressed at the moment. I personally believe that if you would like to use the word commercial opportunity that -- you can't say that this couldn't be financially attractive. But it does not make sense to discuss that in a situation where something is needed and you would do it anyway regardless whether this is a commercial opportunity or not.

Yes. And I think maybe just lastly, just the last part of the question, Tazeen. In terms of how we weighed the balance, what we tried to do was, through our partnerships, set up a framework where we could mitigate the potential cash impact to the company. Right? And I think you've seen us do that with these 2 deals, while still being very much in -- let's say, a driver of the program with -- along with our partners, we've been able to offset the potential near-term cost impact. And of course, we're going to look to continue to build out the consortium in terms of additional partners or collaborators that could help us along the way to bring these vaccines to market.

And your final question today comes from the line of Akash Tewari from Wolfe Research.

This is Andrew Newton on for Akash Tewari, and I have 2 questions. First, in your clinical trial protocol, the seroconversion is defined as a minimum of a fourfold increase of functional antibody titer compared to baseline which is a lot more than 40 times [indiscernible]. What did you see biologically at these levels that helped you determine this is a minimally effective titer? And then secondly, when we think about using an RBD versus full-length S protein antigen, could there theoretically be more risk of neutralization escape when using an RBD or should we assume that an engineered RBD would still show multiple epitopes that your body would naturally develop antibodies against? I know this has been a concern with antibody cocktails in the past.

Yes. So it's -- so let's start with the last question. So the RBD domain is well-known that it induces -- it has multiple binding domains. And it's large enough and comprises more than 90% of the overall binding surface for the receptor. So -- and we have, of course, looked into the mutational profile, particularly in the RBD domain and in the spike protein. And even though the virus mutates, here there are only singular amino acid changes, which we detect in the genome and as a result of result of the different virus variants. So we don't expect that this singular amino acid changes would have the chance to provide an escape by an RBD domain. That will -- so I would like to say that will not happen -- that is not a real risk. And I would also like to state that there is, as far as I know, not a single study really comparing the use of both and systematically analyzing what happens. And we have done these studies. And based on the data, we have decided to go with both antigens into clinical testing, which means that we did not find a clear evidence that one domain is better than the other. So that's the reason, just as a reduction of the risk to evaluate both into -- regard both. With regard to the threshold levels, at the moment, we can't say which is an active threshold level. So we have just to consider that there are, at the moment, not yet both the available standard, which can be used for measuring antibodies and for determination, for example, it's -- how vaccine 1 can be benchmarked with vaccine 2. We expect that these reagents and standardization tools will be available in late summer. And thereby, with availability of these tools, we can start to discuss about real thresholds, which can translate into protection.

That was your final question.

Okay. We are closing the call now. Many thanks for your interest, and we are looking forward to providing you further updates during our Q1 corporate update call on May 12. Thank you so much. Stay safe.

Thank you.

Thank you. Thank you. Thank you.

Ladies and gentlemen, that does conclude your call for today. Thank you all for participating, and you may now disconnect.