BioNTech SE (BNTX) Earnings Call Transcript & Summary

It's Navin Jacob. I'm a senior analyst covering SMID-cap biotech and large-cap pharma here at UBS. I'm happy to have with us BioNTech, our next presentation and Q&A session fireside chat. I will be hosting with Ryan Richardson from BioNTech, who is the Chief Strategy Officer. Ryan, welcome. Hope you're well.

Thanks, Navin. Good to be with you.

Fantastic. So folks, we're going to have a little fireside chat presentation here with Ryan. And if you have questions, please don't be shy, please e-mail them in -- or rather, not e-mail them in. Just post them on this web chat here at the bottom of your screen. They will be anonymous, and I'm happy to read them out to Ryan and -- but let me start with some myself, Ryan. So obviously, you and 1 or 2 other folks out there, you being BioNTech, have done an amazing job helping address this pandemic once-in-a-century event. I guess, broadly speaking, even taking a step back away from COVID, because everybody always thinks about BioNTech as it relates to COVID, but you obviously have so much more than just a COVID vaccine. But if we just talk about the platform itself of mRNA, what is it about mRNA that might be -- that may allow it to, in a better way, induce an immune response than other traditional modalities?

Yes. It's a great question. I think fundamentally, what mRNA allows us to do is be very precise and targeted in the type of immune response that we can elicit. And you see, you got an example of that with the COVID vaccine where we encode a specific antigen or simply a sequence that's encapsulated with a lipid nanoparticle. There's no extraneous virus that we use to infect cells that would itself elicit an immune response. So we reduced the background noise, so to speak, of the immune response. So that's one point. I think the other point is that because we're just simply inserting the sequence, we -- that allows us to be very precise, but also to insert multiple sequences, which is what we do actually in the cancer field. So one of the reasons that we chose RNA as a vaccine platform for cancer was that cancer is heterogeneous and, oftentimes, only going after one target is not sufficient. And so for example, for our personalized cancer vaccine, we target 20 different neoantigens that are specific to each individual patient. And we can do that very readily with RNA, not only from a therapeutic perspective, but also from an industrial perspective because it's very simple to produce. And all of those neoantigens that go into a single vaccine, for example, can be produced with the same chemical synthesis process without the need for complicated cell lines, et cetera. So really end-to-end, it's a new modality that we think has profound disruptive potential across the whole field of immunology.

Fantastic. And then as a follow-up, just sticking into the infectious disease side of things. Are there some viruses that are more susceptible to mRNA-based vaccines than others? There's been some suggestion that, I mean, you guys were perfectly set up to take advantage of the situation and help the world as it relates to SARS-CoV-2 because coronavirus is maybe particularly susceptible to an mRNA type of vaccine. I guess, said differently, are there other viruses that may be more challenging, some that are easier to attack? For example, is HPV a virus that could be seen as a target that could be good or as good as targeting as coronavirus is?

Yes. I think you framed it well. I think when we started out with COVID, what wasn't known was, was this a virus that could be targeted with a vaccination approach, right? And now we know that it is. I think the question of where mRNA is applicable, I think, is a slightly different one. I think that what we've shown is that RNA can actually outperform some of the other vaccine technologies. In this particular case, we believe that it also -- those same benefits could translate into other disease areas. But you're right, you have to test that on a case-by-case basis. When we look at the infectious disease field, we see opportunity in indications where there's a low bar, maybe there's an existing vaccine but the standard of care is -- has low efficacy, where we think there could be room for improvement with RNA. But there's also many indications where there's no approved vaccine but we think RNA has a chance to actually establish a new standard of care. So we've got a broad preclinical pipeline of RNA candidates in the infectious disease space. Our goal is to try to accelerate development of that pipeline and bring additional vaccines to market to treat a range of infectious diseases.

Got it. And then oftentimes, we're asked about the size of the "booster market" because you and Moderna and a couple of others have, for the most part, addressed, especially here in the U.S., this pandemic phase, and certainly there's lots of parts of the world that still need to be vaccinated. But there is at least a light at the end of the tunnel for the pandemic phase. But after that, folks are trying to understand what the commercial value of that "booster market" will be. So first of all, just at a high level, how do you guys think about what vaccination rates might be for the first set of vaccinations post the pandemic phase?

Yes. So we've assumed from the beginning that there was going to be a substantial proportion of people who don't get vaccinated, even though that runs counter to the public health goals that we all -- I think we all share. That's going to -- those rates are going to differ by country and region and may differ -- range dramatically. I think what is clear already though is that there's demand for a booster -- for a booster shot. And the demand, we think, is going to be significant. I think the first indication that we have of that demand and what it might look like could be informed by the first couple of signed deals that we've just announced in the last couple of weeks. We've announced booster doses, and this is additional supply of vaccine on top of the original pandemic supply, for Canada, for Israel and now more recently for the European Union. And actually, the European Union was a large order. So on top of the 600 million committed doses we had for the first wave of pandemic in the booster stage, we now have committed to supplying 900 million doses with an option to supply 900 million more -- or for the EU, to purchase 900 million more over the next 2 years. So starting in December 2021 into December 2023. So I think that gives you some indication for the demand that's already out there. Of course, we think that the order book for booster doses is going to continue to develop. We're still in the early stages there. We plan to maintain our capacity of at least 3 billion doses of supply capacity for 2022. And I would just add that we also expect that there will be an endemic market for a vaccine that develops post pandemic. And so we're also preparing for that. We're investing in the sort of next iterations of the vaccine that includes new formulations and also exploring additional variant-specific vaccines as well as part of our broader booster strategy. So we do want to stay at the forefront and be prepared because we think that there will be demand for COVID vaccine for years to come.

Got it. And again, one of the biggest questions we often get -- and I realize it's a very hard question to answer at this stage, but it's around pricing in that "booster market" phase. And there's a wide range of pricing that has been thrown out there. On the high end, one could think of why shouldn't -- given the value that COVID vaccines add to the world, given the trillions of dollars of economic losses that's happened because of these shutdowns, if you're preventing that level of trillions of dollars of economic loss, why shouldn't we be able to get -- make a profit on -- in the post-pandemic phase? And so why couldn't you be priced at closer to a Prevnar type of price, which is around $200 per shot? On the low end, people talk about perhaps like a high-dose flu vaccine price, which is roughly $50 per shot. That's a wide range. You're currently priced at a very reasonable $19.50 per shot. How do we think about pricing in that booster segment of the market?

Yes. So I think that I would say 2 points. So number one is, yes, we see some incremental upside in particularly the developed world for the booster stage, given that initially we're priced so low for the pandemic stage. I think the second point though I would mention is that we're also planning to supply large quantities of the vaccine to the developing world. And that could come with a lower -- that will come with a lower price point. So I think just to be transparent about that. I think longer term, I think your analogy or your reference to other innovative vaccines like Prevnar are informative and they highlight just how much space there is between where we're priced now in the pandemic versus what typically an innovative vaccine could command in a "normal" market. I think this -- COVID may never be a normal market, but I think it does highlight that there is significant upside over the longer term, although that may come after the booster phase and years into the future.

We're often talking about, not just us here in the investment community, but you hear about it all the time in the public setting, about the durability of efficacy. Maybe a little bit more technically rather than the sort of layman's discussion around durability of efficacy, how is the agency determining -- by the agency, I mean the FDA, determining the durability of efficacy? How do you guys think about that? Because it's somewhat of an amorphous term in the sense that the efficacy, at least from the initial readout, was 95 percentage, right, and drops to perhaps 90%. But if it drops to 85% at month 12, that's still a very good result. So what is that threshold of when you would consider it's like, okay, we need a booster now to maintain "efficacy?"

Yes. It's a very good question and a hard one to, I think, be precise about at this point in time. I think there's still -- it's still not clear yet what the policy would be from regulators as it relates to recommendations or approvals on the -- for the booster segment. And that -- but I think what's clear to us is that there will likely be a benefit to a third dose. So -- and that's -- we see that or we conclude that based on our assessment of the immune response over time and the apparent reinfection risk that seems to be driven primarily by wild-type virus exposure rather than variants. So our view is that it's likely that there would be benefit to an additional dose. And it could already be that it's in the 6- to 12-month time frame. I think we'll have to leave it to the policymakers and regulators to decide. But in terms of how they're going to decide, to that part of your question, I think we have a growing amount of evidence that highlights the clear correlation between the neutralizing antibody response and protection, right? And so -- and we know what the neutralizing antibody response declines over time. We also believe that T cells play an important role as well. But I think when you look at the picture of how the neutralizing antibody response does evolve over, let's say, within the 6- to 8-month period, where it does drop, as we expected it would, I think what you likely have is a situation where you have a declining protection over time. And so then the question becomes, okay, so what -- how could a third dose augment that decline in protection, to your point? And I think there, again, our view is that it's likely a third dose would be able to increase that protection and it would actually translate into saving lives and would come at a cost in terms of safety that would warrant, right -- warrant its application. Of course, that's going to have to be -- it's going to be the decision of the regulators. But that's our sort of best guess based on what we see. I think what's still open or more open is the potential for booster shots after that third dose. And I think there, too, we think that there could very well be a strong benefit to having repeated vaccination. But it's not clear yet over what time frame and what parts of the population, would it be everyone but in small group. I think that's -- we still need to collect more data on that to be -- to form a view.

Got it. You mentioned variants. You have a variant vaccine designed against South Africa variant specifically. Are you working on any other vaccines against other variants? Or -- and sort of tied to that, as we've all heard about the Brazil variant, the South Africa variant, but are there any other variants? And I can't keep up with all the different variants that are being mentioned every other day, but are there any other variants that are starting to show any concern for you? CureVac, yesterday, whom we also hosted had mentioned that the Peru and India variants may be somewhat concerning. It's not -- that's unclear yet. But just wondering your thoughts on variants beyond South Africa.

So we systematically test new variants on an ongoing basis, and we've done that now pretty methodically. And we tended to publish our findings. What we found so far is that the current vaccine is likely to be protective against the variants that have been identified. You mentioned Indian variant, that one, we do see reduced neutralization in some of our early experiments, which could suggest that there could be a drop in protection, but we still see neutralization. And the same is true for the South African variant. I think the U.K. -- the U.K. variant, we have even more data on, both in vitro and then also in the human population where world evidence suggests that there, we don't an issue. So, so far, we haven't seen a chink in the armor. There could be some, again, some reduced protection against the Indian variant, but more to come on that. We'll actually -- we're planning to release more data on that [indiscernible].

Okay. Great. And then over the last -- and by the way, folks in the audience, please don't be shy. Submit your questions over this web portal and I will read them out. They will be anonymous. I would love to get your interaction here. But I'm happy to keep going. Over the last few weeks, there has been some, let's call it, noise around -- more noise around intellectual property. The U.S., very surprisingly, asked the World Trade Organization for a waiver against COVID vaccine patents. Germany came out against it. So that shuts down the waiver for now. But I mean, if -- just wondering about your thoughts of whether or not there could be pressure to change that ruling and Germany getting on board with the U.S. and some other countries. And therefore, how much risk there could be to mRNA vaccine?

Yes. So I think that the -- there will be continued discussions. I think there's the plan to have a further forum to discuss the topic in early June. And we expect this will continue to be a contentious issue. I think our fundamental view here is that the conversation, while well-intentioned perhaps, is misguided in the sense that it doesn't address the root cause of the problem. I think we all agree that it's vital that we send -- the industry as a whole in the world provides high quantities of vaccine to the developing world. And we're committed to do that. We've just announced actually in the last couple of days with Pfizer our intention to supply up to 2 billion doses in 2021, 2022 to the developing world, starting with up to 1 billion doses this year. Some of those are already in the signed order book and others are being negotiated or in discussions right now. So we're committed to do that. We've increased our supply capacity target 3x since January this year from 1.3 billion to 3 billion doses. And it was always our intention and remains so to deliver a significant portion of that capacity to the developing world. So I think the question about IP really in -- or the link between IP and supply, I think upon further examination, I think, it becomes apparent that that's not what's standing in the way of supply, right? And there are now factories, mRNA factories and teams and know-how in different parts of the world that are just simply being held back from producing this vaccine by intellectual property. And so actually, we think that relaxation of IP could become a hindrance to rapid supply, it could complicate supply chains. And it would take time, as we've learned over the past 12 months, it takes time to actually set up new mRNA production facilities. We've actually managed to construct a transatlantic network where we have 15 nodes that are involved in some aspect of the production process, and we're going to continue to expand that with our own teams in partnership with Pfizer. So committed to the goal. We don't think that's the right solution. And maybe one last point, I think there -- you also asked the question, what is the role of the WTO, right, as it relates to IP? And what would be the enforcement mechanism of such ruling, even if it were to occur? I think there, IP relaxation of the trips related -- IP protections as part of the WTO are enforced or implemented on a country-by-country basis, right? So I think it's not a WTO decision as such. There are -- there is a governing body and there will be further discussions. But we don't see that as a solution to the problem, and we're just focused on trying to increase our supply as fast as we can to address the real challenge.

I just realized I was on mute. Sorry about that. We actually have some questions from the audience, which I'm excited to read, hopefully it fosters some more engagement from the audience. But first, on the contracts signed and announced for 2022 and beyond, is the revenue guaranteed irrespective of whether there is a need for booster shots or not and if the virus fades away? Not sure I quite fully understand that. But I suppose a different way to, I guess, answer that is, is the revenues -- or a different way to question that is, are the revenues booked on delivery or upon contract signing? And is delivery contingent upon -- what is that delivery contingent upon the country's doing?

Right. So generally, it's linked to delivery of vaccine. So we have an order book of signed commitments or governments' commit to purchase and we commit to supply. And the order book as of our last update call was sort of 1.8 billion doses signed. Of course, we had many more discussions underway. And since that time, we've announced the European Union booster commitment, which was signed which was, again, the 900 million doses with 900 million options. So that's in addition to the 1.8 billion doses. What we did on our last quarterly call was we provided an estimate to the market as to what we think the 1.8 billion signed doses would translate into in terms of revenue for BioNTech. And that's -- that was the EUR 12.4 billion figure. Again, that's an estimate based on the signed order book. And that would be booked for the most part at the time of delivery.

Okay. Great. And then another question. How many months in advance will vaccines be manufactured for 2022?

Well, we have a pretty tight supply chain right now. So it's pretty much the vaccines get produced and then they get shipped off because the demand exceeds supply. And we expect that to be the case for the foreseeable future, in the near term, throughout the rest of this year. So I don't see that changing dramatically going into 2022 because we do expect there to be significant demand even in the second half of this year. But generally speaking, I mean the production process itself takes a week or 2 from the time that you actually produce the drug supply and then you get formulation and you have fill-finish. And then there is a release period that can take a couple of weeks. And then it's shipped. So I think that's likely to be the case, like I said, for the near future.

Great. And folks, continue to send me the questions. It's great to have engagements from the audience, but I'll keep going here in the meantime. Ryan, on just finishing up on the discussion on IP. What exactly is the IP that you hold? I realize it's a suite of patents and not one specific patent. But as a therapeutic analyst, we're not used to thinking about IP for mRNA. We're just -- we usually focus on composition of matter for a small molecule or even a monoclonal antibody. So just if you could help us think about how to think about intellectual property for mRNA.

Well, you characterized it correctly. There's levels of IP on the mRNA therapies in our pipeline. So what we have is we have a platform IP, right? So we use different mRNA platforms, depending on the use case. In the case of COVID vaccine, we're using this methyl-pseudouridine format, where we have a co-exclusive license with Moderna for that form of RNA. We took 3 different mRNA platforms into the clinic for COVID, and this was the one that performed the best. And so that was -- that became our product. We do use different formats of mRNA for, for example, the cancer vaccines where we want an even stronger T cell response. We use an unmodified form of mRNA. And we use different formats for other use cases as well. So that's one, just the format itself can be patented. We also can have specific patents or IP related to some of the modification, sequence modifications that we make into the construct itself, right? In some cases, you could have antigen-specific IP. In some cases, you don't, right? So there is that overlapping element. And then the third piece is the LNP, so the formulation step. We use lipid nanoparticles to encapsulate the RNA, protect it from degradation so that we can hit -- we can target the cells in question. And in some cases, we use internally-derived LNPs, where we have our IP portfolio because we develop the LNPs from scratch in-house. Cancer portfolio is a good example of that. In cancer vaccines, we use a lipoplex formulation developed in-house at BioNTech. In some other cases, we use externally sourced LNPs. In the case of COVID vaccine, we've sourced the LNP from Acuitas, right? So that then comes -- most of the IP behind that comes external to the firm, right? So it depends on the case. It is a complex landscape, but we generally have IP protection on multiple lots.

One question from the audience, which kind of ties into what you said, because you have this co-licensing agreement from Moderna on modified mRNA, this kind of leads into this next question from the audience which is, what differentiates the BioNTech mRNA platform approach to infectious disease from the Moderna platform? Obviously, at a very high level, the initial results for COVID vaccine were very similar. How do we see yourself differentiating down the road with other infectious diseases?

Yes. So I think that it's true that there are some similarities. And there are also some differences, right? So one of the differences in the COVID case is that our vaccine is about 1/3 of the dose -- less than 1/3 of the dose, [indiscernible] versus 100. So there are differences. And some of those differences are -- could be described or linked to the construct itself. So we've got different sequence modifications, for example. In some cases, like COVID, we may use a different LNP, right? I think that we also had at BioNTech, like I said before, we have multiple mRNA platforms, so depending on the infectious disease, we may use a different platform in the future. I think we are exploring some of the sort of next-gen RNA platforms as well. So there are differences there, right? And there's also differences in terms of manufacturing processes that could result in differences in product performance. So a lot of that comes down to engineering. We say that in mRNA production, it's a relatively simple chemical synthesis process, production process, which is true, but there's also a lot of steps. And there's also a lot of accumulated know-how and learning that have gone into our vaccine. Our teams have been working with RNA prior to the company being founded. That experience and know-how has been built up over 15-plus years. And that can be applied towards other infectious diseases. So I think there are differences there as well. Maybe last point I'd make is that the opportunity set or the unmet needs in infectious disease are broad. And I think that, that means that different companies may choose different paths in terms of which diseases they choose to focus on. Obviously, we have overlap -- we all have overlap in COVID. But I think going forward, I think you'll see us also advance product candidates in perhaps infectious disease indications where some others may not have been taking priority, right? So I think there could be differences in strategy, too.

Wonderful. And then on manufacturing, you alluded to this, but if you could just kind of remind us the process by which it took you guys in -- it was record time, obviously. But just maybe in more traditional situations, how long it would take to reengineer a plant to be ready for mass production of an mRNA vaccine. And this will kind of also help perhaps give folks some context for the challenges associated with just throwing away IP is not everything that's needed to get mRNA vaccines to the market. But just how should we think about how long it takes for a plant to get up and running for mass production of mRNA vaccine?

Yes. I think it's -- I think a year is probably a decent benchmark. And that includes time to have teams -- our teams go there. And again, not only get the equipment in order and to actually install it, but set up sort of our production processes. So it's a very hands-on effort to do that. It's not just as simple as you receive a blueprint and you just create a factory. We have done it in a shorter period of time in the case of Marburg, which is a site that's about 1 hour from our headquarters. So it was accessible during the pandemic. And it was really a sort of -- the teams there did a tremendous job to get that plant up and running in less than 12 months, substantially less than 12 months. But I think as a general rule, especially when you talk about -- when you think about sites in different countries or travel back and forth, et cetera, probably a year, a year-plus-or-so is the way to think about it.

Got it. And then are there currently any constraints as far as raw materials are concerned? Because it's you and Moderna and others, not just for mRNA, but other vaccines, raw materials are required to produce these vaccines, are you seeing any constraints?

Well, there's been a lot of constraints along the way that we've had to overcome. So I don't want to say there's no constraints going forward. I think to get to the 1.3 -- from 1.3 billion to 3 billion doses for this year, in terms of supply capacity, of course, that required that we identify new supply sources, that we scale up our access to raw materials, and that's an effort that's ongoing. So we're going to continue to do that. I think what's -- where we feel like we have good line of sight and are in a good position now is that we had now 9 months to do that. So it's been a continuous effort working hand and hand with Pfizer. The 2 teams have worked very closely in that regard, and I think between the 2 of us, have been able to dramatically scale up our entire supply chain. And with that, our access to raw materials. So I think we're in a good position. Of course, we still have to adjust as we scale up production. And there could be little -- there could be bottlenecks that come up and we have to address this. But I think we feel good about our position today.

One of the markets that you're going to be entering in, in is China. You have a notable partnership there with Fosun Pharma. Can you discuss what the potential commercial opportunity is there? Obviously, a lot of individuals there. But the Chinese vaccine market is not as familiar to folks here in the U.S. and the U.S. investors. And so just wondering whether pricing will be at a level that can allow for a material impact to your top and bottom line. Any kind of color would be helpful.

Yes. So we do see that as a significant market opportunity over the next couple of years. Currently, there are multiple vaccines, over 5 -- actually, 5 vaccines approved in China, but they're all local vaccines. So most of them are derived from inactivated virus technologies or a adenovirus-based vaccines. We made the early decision to take a global approach. China was an important part of that. And therefore, partnering with Fosun. We also took an early approach to conducting clinical trials locally, which we think is going to give us a chance to get into the market sooner than would have been possible otherwise. So we did conduct a Phase II bridging study just to replicate the results on the safety and immunogenicity side in the Chinese ethnic population replicate the results that we saw from the global Phase III trial. And that's been completed. And we're now in the submission phase, and we expect that we could get approval soon in China. And initially, we would be supplying the vaccine out of Europe. But you mentioned the joint venture, I think the idea with the joint venture is that we would, if certain conditions are met, we would establish a local production for this one product in China. And local production of vaccines, in particular, opens up new opportunities for domestic market access in China in terms of volume. So we do think that there's a significant volume opportunity over the next couple of years. And that's one where -- in particular, on the booster phase. So potentially even vaccination on top of some of the existing Chinese vaccines, where the data so far has indicated that they may not have the same efficacy, we think that, that is a significant opportunity for us, and we want to be prepared to deliver our vaccine in large quantities to that market.

And folks on the line, again, if you have questions, please feel free to enter them to the web chat below. They will be anonymous, and I'm happy to read them out to Ryan. But in the meantime, I'll keep going here. Gross margins on the vaccine, Ryan, how do we think about that sort of at steady state? Is it closer to a small molecule-type margin, a large molecule or not quite as strong as biologics?

Yes. So we haven't given margin guidance as such because there's a lot of variables that go into that, including the mix of developed and developing world in terms of volume. So I think what -- from a product perspective for the developed world, in the pandemic, I think that a 60% to 70% gross margin is probably the right ballpark to think about, but with lower for the developing. And so I think that's on the product level. I think for BioNTech, it's a very different picture because of the way that our collaboration setup is going to be. A big chunk of our revenue stream comes in the form of a gross profit already. So it's already net of cost of goods. And that means that our gross margins as a company will be much higher than that.

Sure, sure. And then I don't think -- there's still a lot of folks who are perhaps not as aware of the different formulations that you're working on that can help with the supply chain and the constraints that you have with the initial formulation. Could you remind us of where you are with some of those other formulations and what those are?

Sure. So first of all, I would just note that we've just recently upgraded our guidance and storage ability for our current formulation. So we've just extended that from 5 days at 2- to 8-degree Celsius to a month, 30 days, which we do think is -- it's a good step forward. It's going to give us more room to maneuver, so to speak, in terms of the supply chain. Next-gen formulations, we've got 2 that we've talked about, 2 in development. RTU formulation, ready-to-use, which is a liquid. Liquid formulation has some changes to the excipient mix. We expect that will have significantly or further extended storage ability at the 2 to 8 degrees temperature and can give us even more flexibility. That's in development right now. We expect that to come -- that could be ready for the market in the second half of the year, probably in Q4. And we're also working in parallel on a lyophilized formulation. And both of these are, of course, with Pfizer. And the lyophilized formulation would have even further enhanced storage ability. And maybe just slightly behind RTU. And we haven't made a decision yet whether we bring both forward or just the RTU, but we are working on both in parallel. And the lyophilized formulation, they have a particular benefit for the developing world, for example. So that's in development, we should also have data towards the end of the year, probably in Q4.

Fantastic. And then you also have -- and Pfizer has also mentioned this now, a flu vaccine that you're working on together. Can you remind us the timing of when that enters the clinic and when we could see some data there?

So we're expecting to enter the clinic in Q3 this year with the flu vaccine. And the trial is going to be conducted by Pfizer. This was the first collaboration that we did in infectious disease, 2018, as you may recall. So those 2 indications have been part of Pfizer today, so COVID and flu. And in terms of data, it's conceivable we'd have data already in 2022.

And then the -- you also are a company that has programs beyond infectious disease and COVID vaccine. Maybe the first 2 that most people are aware of, [ like ] BioNTech is FixVac and iNeST. When could we see some extra readouts for those programs?

So 2021 is a year where we're going to start multiple late-stage studies for FixVac and iNeST. So it's really moving into the randomized Phase II trials. In the case of FixVac, it's -- we're going to initiate a randomized Phase II trial in melanoma in the refractory setting after checkpoint progression. That will be FixVac in combination with checkpoint blockade. And also in HPV16 positive tumors trial, a similar format, refractory tumors in combination with checkpoint. iNeST, we're moving into the adjuvant setting. So we're starting an adjuvant CRC trial this year and are exploring some other opportunities as well, including looking at some other indications also adjuvant. So I think that data-wise, I think it's probably going to be 2022. We have the next update on the cancer vaccines, but I think it's important to remember that we've got many, many other oncology programs, we actually have 14 different oncology product candidates and 15 ongoing trials. And the data that we expect this year is really expected in the second half from a couple of those programs. So we have 2 bispecifics, where we expect data in the second half of the year. These are part of Genmab 50-50 collaborations. We see this as next-generation checkpoint molecules. Here I'm talking about our PD-L1 4-1BB and CD4 4-1BB. And then we also have some other early-stage programs like CARVac that we also could have some data in the second half.

And the CARVac, that leads to next question is, can you kind of give us some background because not everyone is -- that we have a broad audience, not everyone is familiar with that. What exactly it is and how it's different from traditional CAR-T therapy.

Yes, it's different in 2 main respects. So our effort in CAR-T therapy is targeted at solid tumors. And to do that, you have to have the antigens that you can go after. And actually, one of the challenges with CAR-T therapy in solid tumors is a lack of antigen targets. And so here, we have a novel target, CLDN6, which is expressed in a number of different solid tumors, including a subset of lung cancers expressed in ovarian cancer, testicular cancer and others. So that's the first novelty point. The second is that we're planning to combine the CAR-T cell approach. In this case, autologous CAR-T with an mRNA CAR-T cell amplifier. So it's an mRNA vaccine that encodes the same antigen with the CAR-T cells' target. And where we see evidence in the preclinical setting that we can powerfully and very precisely modulate the CAR-T cells in vivo, right, by co-administering a vaccine after initial CAR-T cell infusion. So this is a very novel approach that we think could have platform potential in the field. And we've -- as of our last quarterly call, we had just dosed the first couple of patients with just the autologous CAR-T cells, saw some very early tumor regressions. Very early data still. So I think we have to follow the patients longer. But the idea is that soon, over the course of this year, we're going to start to layer on top the mRNA vaccine amplifier. And the idea is that by amplifying the CAR-T cells in vivo, we could potentially reduce the dose upfront that we have to administer. We've seen evidence of that in the preclinical setting, that we were able to kill tumors at sub-therapeutic doses. But maybe even more importantly, that we might be able to dramatically increase the persistence of the CAR-T cells through repeated vaccination with an mRNA vaccine. And that's indeed what we were able to do in the animal setting. And the key question will be, does this translate into the human field? And if it does, again, we think that this could be an approach that could be used with a number of different CAR-T cell therapies. So we could already have data towards the end of this year, and this is one that we're watching very closely and very excited about.

The company, Ryan, has grown very quickly, has many different approaches and modalities centered on mRNA, but also non-mRNA modalities. Any concern around stretching too far, too fast? How do you stay on top of everything? And how does the management team stay on top of everything without diluting some of your efforts? And sort of tied to that, where are you with staffing for all the different groups and departments that you -- as you continue to grow here?

It's a really important area. Actually, it's a good question. So we're now at just over 2,100 people within BioNTech. So we have grown and we'll continue to hire. I think we're getting access now to some of the best talent, people that want to join BioNTech. And they're excited, I think, by what we've done with COVID and eager to help, help us in the next chapter to bring even more therapies to the market. I think that it starts with focus, Navin. We're very clear about what our focus is. And our focus has always been immunology, right? That's our core expertise. And so while mRNA has many broad applications, our priority is to leverage our immunology expertise, right? And in our technologies, which include RNA, but not exclusively, to develop immunotherapy, right? And we see 2 main therapeutic areas that are our priorities right now for that in terms of scaling up R&D and bringing more products into the clinic and ultimately to the market, and that's oncology and infectious disease. So I think it's actually a very -- it's quite a focused strategy from a therapeutic area perspective. And we do have other areas that we're going -- we are going to work on, incubate, like regenerative medicine, like autoimmune inflammation. Those are longer-term areas. So I think we're very focused right now on these -- on our core areas and really on product development, right? We have great science, great innovation in the company, but we direct that in a very targeted way towards developing new products. That's what we want to do and bring those to market. So you're right, it is a -- we do see a broad opportunity set in front of us. We are going to -- we continue to invest in R&D, scale up R&D and we grow our team and work closely with strategic partners like Pfizer, like Genmab and others, who help us, I think, prosecute more than would have been possible to do simply alone.

Well, with that, we're at the end of our session. I want to sincerely thank Ryan Richardson, Chief Strategy Officer for BioNTech, for joining us today. Very exciting things that you guys have been working on and continue to work on. Thank you so much, Ryan.

Thank you, Navin. Good to speak to you again.