BioNTech SE (BNTX) Earnings Call Transcript & Summary

Hello, everyone. Welcome to our post-lunch fireside chat with BioNTech. I'm really thrilled that Ugur Sahin is giving us a half an hour of this time, and we could take hours, I'm sure, with everything going on with COVID infectious disease and oncology at BioNTech.

So with that, I think I will jump right in. I will say, please do send me any questions. There's a place to enter it below this video, and I will try to fit them in as well in this half an hour. So maybe starting broad, Ugur. The last year has been really transformational for mRNA vaccines. And I wonder how the year now has changed BioNTech in terms of your focus and journey and what will BioNTech be in 5 years from now?

This is a great question, Daina. Yes, indeed, last year was transformational and we cited that we unexpectedly got our first product to the market. And this is, of course, a transformational event. It validates our -- one of our key technologies. It brings -- it transforms us into a commercial company. It transformed us into a company which is producing under GMP for the market. We are building at speed our commercialization team, our quality assurance team, everything what is required. So we actually became a market commercialization company. And it provides us, of course, with the opportunity to invest into our technologies into our product development. And this, for sure, will have an impact not only on our infectious disease pipeline, but also on our cancer immunotherapy pipeline, allowing us to accelerate programs to broaden programs and even to consider to acquire additional technologies and product candidates.

That's great. And speaking of oncology. You have one of the most diverse immunotherapy portfolios even before you transformed to a late-stage commercial company. Do you have a grand plan? And how and when do you think it will all come together?

Yes. Our plan we communicated that from the very beginning, we won't really become immunotherapy powerhouse. So we strongly believe in the power of our immune system. And the way -- how we see ourselves is on the one side to understand disease, yes, and the disease mechanisms. And on the other side to understand how to interfere with the hundreds of functions of the immune system to either prevent disease or to treat disease. And this sounds simple, but at the end of the day, the immune system is as complex as our own nervous system, and we believe that we combine -- we use technology to engineer immune responses, which are beneficial for the half of the individuals. And we continue to do that. We built a number of different tools as on the messenger RNA is a pharmaceutical platform, which allows us to be -- to develop versatile tools. And then we ask the question, of course, what can we do on the level of antigen-specific recognition because diseases are mediated or prevented by antigen-specific immune responses, so it is about the right target antigens and about inducing specific T cells, CD8 T cells, CD4 T cells, antibodies or inhibiting disease-inducing cells. And then we have the immune regulatory network understanding to end power, yes, or to dampen immune responses. And this is something that we believe that the current pharmaceutical market just uses 10% of the power of the immune system, and we want to go beyond that.

That's great. I wonder -- one last sort of broader question before we get into COVID. How are you managing the scale-up in terms of your scope of projects, your focus, the senior leadership bandwidth and can you -- how fast can we expect new infectious disease programs? And can we expect the oncology to keep progressing at the same speed that we had anticipated prior to COVID?

Yes. This is, of course, a challenge. So we have to deal with different levels of complexity. And one aspect is, of course, of course, it is extremely important to make the right decisions at the very beginning in the preclinical development. That means we really only bring products into clinical testing if we strongly believe that they could succeed to become products which can be registered and approved. And we always ask the question: Can we come up with mechanisms that are not yet exploited in that manner? Because we want to have something novel. So we don't want to reinvent things which are already in place, but come up with complementary [ syllogistic ] mechanisms. And this is what you can see from our pipeline. It's either new targets or new mechanisms or new ways in dealing with complexity. So this is -- this is the first filter. And the second filter, of course, is the filter of failing early. So our way, how we design our clinical trials is early on, understand whether the mechanism that we anticipated really work in the human setting, yes; do a deep Phase I/II clinical trial where we understand the immune mechanisms. And if we are encouraged by clinical activity, then continue. If we are not encouraged by the clinical activity, go back, yes, and evaluate, if we can improve that, but not to undo progress. And the way of dealing with that avoids us that we -- avoids that we fail late, which is the greatest risk in the pharmaceutical industry. So avoiding this large clinical price with [ fleet ] out of thousands of patients and then seeing that the trial does not work. So we need to come up with a new biotech conform model where we can show is relatively small, small trials powered for significant hazard ratios and get products in place which produce a significant benefit, not only marginal benefits. That is our overall strategy.

That's good. I mean I think you had the opportunity to show that kill fast of COVID bringing 4 vaccines parallel into the clinic and killing 3 and taking 1 forward, really a great example. And I think moving on to COVID, probably the biggest question on everyone's mind is how much they should worry about the SARS-CoV-2 variance of concern. Now I wonder if you can help us understand what we know today and what we don't know about the protection from BNT162, B2, your COVID vaccine, against the variance, especially the B1351 variant.

Yes. Yes. So we -- with regard to the variance, we have to consider 2 types of investigations. We have on the one side, this neutralization assets or so neutralization assays, which are somehow potential indicators of efficacy indicators that we should be concerned or less concerned. And on the other side, we have the clinical data which is, at the end of the day, what counts. That means the real work data against protection against variants. And we do not have own data published so far. They are data around, which I can't comment, for example, for the B117 U.K. variant. And we are expecting data from our Phase III clinical trial updates in the coming weeks, for example, for the South African variant and also for the U.K. and Brazil variant. So the data will come in from this trial. Until we are there, we do this type of bioneutralization asset. And so far, every variant that we have tested showed more or less equal neutralization. The only variant which showed some reduction of neutralization titer is the South African variant, which showed a threefold reduction in the neutralization titer, but still high neutralization titers. So we have to expect that we will have some trade-off of the vaccine activity. And -- but on the other side, we have to deal with another that can we not yet confirm hypothesis. It's the T cell response. So my hypothesis is that, particularly the CD8 T cell response is an important layer of protection against variants. We have to see that. So vaccines which do not induce CD8 T cell responses might have a more dramatic drop in their protection, disease protection activity as compared to vaccines which have, in addition to the neutralizing activity, a CD8 T cell responses. But this is a hypothesis to be evaluated. But it makes sense from the mechanism because the CD8 T cells, if the virus achieves to come into the cell because the neutralizing antibody titer is low, then the second layer, which can protect and kill the cells, are CD8 T cells. CD4 T cells play a minor role in direct killing of impacted cells; they are more the coordinator. But we have to see better this hypothesis too. In the next 6 to 12 months, there will be a number of published papers which will deal with that.

Of the in vitro assays, one thing that concerns me is you're taking a snapshot in time, and a lot of these are taking Sierra that's relatively soon after a vaccine or -- natural infection. And I think of convalescent plasma, people have looked 6 months out and seeing that they saw affinity maturation. And that Sierra taking 6 months out was better against antibodies in that Sierra was better against the variance than ones taken 1 month out. And I wonder with an mRNA vaccine versus natural infection, do you expect the same kind of affinity maturation and that the antibody effectiveness will improve over time?

Yes, the proportional antibody effectiveness will improve over time. So we have 2 mechanisms, which are going in parallel. We have overall reduction of the titers, yes? So this starts. So the -- usually, the peak of the titer is 14 days after the boost. And then thereafter, there starts a decline of the overall titer. But on the same day, there is, of course, an evolution ongoing in the vaccinated individual as well in the infected individual where high affinity, high affinity B cells survive longer, yes? And this results in affinity maturation. And there is -- we see affinity maturation for our vaccine. And I expect that affinity maturation will happen to any kind of vaccine. Because this is just the way how B cells try to survive. If the antigen is becoming limited, the B cells, which have the highest affinity, survive.

Several groups, including Regeneron, whom you were working with on some of your publications in Rockefeller, predicted some of the immune, if you allow me, escape mutants that we're seeing in some of the variance of concern. And we saw that as early as last summer. I assume you're very aware of this work and probably did your own. Have you been anticipating these mutants? And already creating new vaccines against some of these over time? And I wonder if you could tell us what is the antigen in BNT162b3 that entered the clinic last September, your fifth COVID vaccine, or when you will tell us that.

Yes. So let's start. So of course, of course, we anticipate that the virus will change. That is what viruses do. At the end of the day, a virus is a evolving genetic piece of information. And since antibody is neutralizing, antibodies provide the selection pressure, the virus tries to circumvent that. And this will continue to happen. And I could imagine that there will be variants which are even more difficult to neutralize as compared to the South African variant. This will happen, yes? And the way how to deal with that is to come up with an adaptive vaccine, which is paid into the value. And the second way to deal with that is just to increase the titer of the neutralization titer because we know from flu that increasing the overall titer increases the path of protection, and this will also happen to SARS-CoV-2 variance. That means if someone has a very high titer, it will be -- will have a broader neutralization of variance. I don't have any doubt that this will happen. The question, of course, is not about whether you show that, that you can change a vaccine, this is a technical issue. It is more about the timing issue. So that means if we change to the South African variant, yes? Then we might end up with a little bit weaker immune response against the wiretap, then you can, of course, see, say, you can deal with that with prime-boost protocols or by mixed vaccines and so on. But regardless what you do, you pay a price for that for changing too early, yes? So that means what we need to do is really to remain calm and see how the vaccines, how the new variants evolve, get real data in and make informed decisions. That is the most important aspect. And I really mean that this is not only BioNTech Pfizer problem, it is an overall challenge of the whole vaccine community to come up with ideally harmonized, harmonized decision-making processes allowing us to come with a changed vaccine if it's needed.

A question from an investor asked, when should we expect the results from BNT162b2 with various children cohorts of patients?

This should come -- so we have done -- we have evaluated in our Phase III clinical trial already children at the age of 12 to 15 years. So the data are already there. We expect data -- expect data from our pediatric plan. It's not yet fully approved because we are still in discussion, discussion with FDA and EMA. We expect that in summer, we should have the data for different age groups, children age groups.

That's great. Moving on, spending 10-minute on oncology. A couple of things on iNeST. When we saw that you withdrew your adjuvant iNeST study. For the investors, this is your personalized neoantigen vaccine. And you withdrew the adjuvant lung cancer study. This came on top of some recent news that Genentech has a second partnership with a different neoantigen vaccine company in addition to their partnership with BioNTech. So overall, given the results from last summer and some of these shifts, where does the iNeST program stand?