BioNTech SE (BNTX) Earnings Call Transcript & Summary

Good morning, everyone, and welcome to the third day of the JPMorgan Healthcare Conference. My name is Matthew Holt, and I'm a member on the biotech equity research team here at JPMorgan. It's my pleasure to introduce our next presenting company, BioNTech. And presenting today for BioNTech will be CEO and Co-Founder, Ugur Sahin. And please note that following Ugur's presentation, there's a breakout room in the Yorkshire room across the hall. So with that, I'll hand it over to Ugur.

Yes. Good morning. It's a pleasure to have the opportunity to present here. I'm Ugur Sahin. I'm Co-Founder and CEO of BioNTech, and I would like to directly start with our goals. We have -- our goal is to build a 21st Century individualized cancer immunotherapy company. And to this end, we are developing next-generation immunotherapies for cancer and other diseases. So our approach is technology agnostic. We are exploiting novel-targets and novel pathways, and our company is vertically integrated with in-house manufacturing capacity. We have in the meantime, 10 products in the clinical testing. And our plan is to start the first registrational trial in 2020. We are supported by world-leading partners. We have 7 pharmaceutical collaborators in immuno-oncology. We have a 50-50 cost and profit sharing model. Our key focus is the solid cancer space, which comes with an extremely high medical need and is commercially attractive. So cancer is an extremely complex disease, and every patient is different, every cancer is different. And we believe to address that, we need a patient-centric approach. Our vision is to individualize cancer medicine, and we have -- this is based on 4 pillars. This is in-house diagnostics and bioinformatics. We have a multitrack platform approach, including messenger RNAs and engineered cell therapies, antibodies and small molecules. We have off-the-shelf tracks for addressing common targets and common pathways as well as individualized targets to address individual [indiscernible] neo-antigens; and we have built in-house manufacturing and on-demand production capacities. So we are supported in our vision by global leaders in oncology. As already mentioned, we have 50-50 partnerships, allowing us to accelerate the development but also allowing us to get our products and to commercialize our products in partnerships with our partners. So let me give you just a short intro about our therapeutic strategy. Our therapeutic strategy addresses 2 needs for cancer immunotherapy: one side targeting cancer cells by molecules, which specifically recognize cancer cells, and some mRNA vaccines, engineered cell therapies as well as targeted antibodies. On the other side, we are using immunomodulatory compounds, which allow us to amplify T cell responses and antibody responses. This include small molecule immunomodulators, engineered cytokines as well as next-generation immunomodulators. I will come up later on this. So why are we doing this? Because cancer can be segmented into -- in different patient populations. And different patient populations are based either, for example, on clinical parameters, early stage cancer, late-stage cancer, or on molecular mechanisms; for example, the presence of neo-antigens, the lack of neo-antigens or the established molecular escape mechanisms. For example, cancers with beta-2 microglobulin loss do not respond to classical T cell therapies and do not respond to checkpoint blockade. For this, we need antibodies or CAR-T cell therapies. In the messenger RNA field, we have one of the broadest mRNA toolkits. So this includes multiple messenger RNA formats. It includes both formulation spectrum, including in-house developed intravenously applicable liposomal formulations as well as LNP formulations and Polyplex formulations. And this diversity of formulations allow us to bring our products in different routes, either intravenously, intramuscular or intratumoral or tissue-specific manner. So in the next few minutes, I would like to guide you through our pipeline. So starting with our messenger RNA vaccines. We have 2 vaccine approaches. FixVac, which targets shared antigens and iNeST, which is targeting neo-antigens. So we have -- with FixVac we have, in the meantime, 5 clinical studies running including 2 clinical studies started in 2019 in prostate and ovarian cancer. We are planning to expand our pipeline with non-small cell lung cancer product in 2020. And whereas the first product are still in Phase I, we aim to start Phase II and registrational study for our melanoma product, allowing us to transform to late stage. iNeST, we have currently 2 clinical studies running, 1 basket trial in multiple indications as well as a randomized clinical trial, checking the combination of pembrolizumab plus iNeST versus the pembrolizumab alone. Based on the data that we have generated, we decided to start 2 additional studies in adjuvant setting. I will come back to this later on. And of course, we have an intra-tumoral RNA immunotherapy approach together with [Sanofi]. So we are using messenger RNA not only for delivery of vaccines. We've established technologies and approaches, allowing us to encode antibodies -- different format of antibodies, IgG antibodies, bispecific antibodies and as well as cytokines, and we have the goal to bring these approaches in 2020 into the clinic, exploiting the advantages of messenger RNA therapeutics; for example, improved pharmacokinetics. In the non-messenger RNA space, we have now 3 monoclonal antibody products in clinical testing. These are 2 antibody products -- bispecific antibody products together, that codeveloped this Genmab and one targeted antibody product targeting pancreatic cancer antigen, which is fully owned. In 2020, we have the goal to bring additional products into the clinical testing or for like receptor molecule targeting TLS 7 as well as our CAR-T cell therapy target in the solid cancer space. So just a recap of the 2019 highlights. We initiated clinical trials in 2019 for 6 IMPs across various cancer indications, started the first randomized trial for iNeST and dosed more than 400 patients across all programs. So the corporate highlights is that we raised more than $370 million, including Series B as well as the NASDAQ IPO. We signed 2 additional agreements with Bill & Melinda Gates Foundation and Regeneron, and we purchased an iNeST manufacturing site to build the next iNeST manufacturing facility, allowing us to further expand our work. In the management team, we expanded our management with agreeing on Ryan Richardson, who was appointed as Chief Strategy Officer in January 12 and is supporting the global develop -- global growth of the company and strategic expansion into different regions. So in the next few minutes, I would like to give you an overview about our platforms and programs, messenger RNA vaccines, antibodies, CarVac and RiboCytokines and starting with our messenger RNA platforms. As we have 2 approaches, it's FixVac, which is a cocktail of messenger RNAs targeting multiple shared antigens, which can be applied to patients with a defined disease indication; and on the other side, we have iNeST, which is prepared individually, based on analysis of the individual patient's [ temper, ] identification of mutations and individual design and manufacturing of vaccines. So both platforms are using a proprietary RNA-lipoplex formulation for systemic delivery. This is an extremely strong platform for inducing immune responses, which allows -- which has an inherent TLS 7 activity and potent -- induces potent CD8 as well as CD4 T cell responses. Importantly, we have a clinical validation of this platform across different cancer types. So we get extremely strong T cell response in the range of several percent of peripheral T cells without any expansion in melanoma patients against, for example, NY-ESO-1 and MAGE-A3, in head and neck cancer patients against viral onca antigens or in -- for our iNeST approach in triple-negative breast cancer patients and other patient classes. So this is a universal approach, allowing us really to proceed fast and engineer vaccines according to diseases or patients. So just a recap of our interim data for the melanoma trial, which was a dose range expansion trial with different doses up to 100 microgram. We had, in this trial, 74 patients with readouts. And from this, 42 patients were eligible for exploratory analysis of objective responses. So we had 25 of them were CPI experienced metastatic melanoma patients. And in these patients, we're seeing a compound, we showed clear seeing a compound activity with objective responses and complete metabolic response and disease stabilization. And we treated 70 patients, CPI experienced metastatic melanoma patients in combination with anti-PD-1 and vaccine. And here, we have seen that we have a re-sensitization of -- to anti-PD-1 treatment with 6 patients showing a partial response and -- to disease stabilization. So based on these observations, we started a trial with FixVac in prostate cancer, the prostate cancer FixVac back is addressing multiple tumor antigens -- 5 tumor antigens with 2 known tumor antigens and the clinical trial is addressing patients in the early stage as well in the metastatic stage setting. So our FixVac pipeline includes now 5 products in clinical testing. And our goal is in to start the Phase III study for our melanoma FixVac in the second half of 2020 and start another trial -- Phase II trial for HPV in -- also in the second half of 2020. So the iNeST approach is currently in testing in 2 clinical trials. The early learnings from this trial, 1 trial was intra-nodal application of 10 new antigens. Here, we have long-term relapse free disease activity and single compound antitumoral activity with the vaccine approach, which was already published in 2017. We have now updated data, which I'm going to show you. And then we have the ongoing clinical trial with Genentech in multiple tumor indications and the early learnings from this trial is that iNeST can be manufactured for individual patients with clinically relevant turnaround times across a range of tumor indications. The combination as well as the compound alone has a manageable safety profile, and we see strong immunogenicity across a range of tumor types, including tumors with a lower mutational burden. And based on this observation, we had already started Phase II melanoma trial, randomized to evaluate PFS and overall survival. This is the update for the trial that we had published in 2017 in Nature, and we have now longer follow-up for the patients in the last 2 years. This is the green box, the patients did not have any additional progression events. So this is, in our view, remarkable protection from additional relapses, and we believe that iNeST is particularly suited for the early stage cancer, for the adjuvant stage cancers. And based on discussions with our partner, Genentech, we decided to start 2 additional randomized trials in solid cancers in the adjuvant setting in 2 different indications. We will announce the indications in the second half of 2020. So of course, this requires manufacturing capacity. We are heavily investing since years into digitization and automation for our new antigen vaccine manufacturing. We have established paperless documentations in automatic manufacturing. We have 2 manufacturing sites in Mainz and in Idar-Oberstein. We started the construction of our GMP facility, which further advances the manufacturing capacity and will be expected to get licensure in 2022, 2023. And we do that, of course, with partners like Siemens and other construction companies allowing us to proceed with -- to shorten the time and lower the cost for manufacturing. So shortly a few minutes about our antibody program. So we have 2 programs with Genmab in clinical development, both entered clinical testing in 2019. This is one antibody, PDL-1, which targets PDL-1 as well as 4-1BB and one bispecific antibody, which targets CD40 and 4-1BB. And our goal is to bring these 2 dominant molecules in immuno-oncology together to combine for the first antibody checkpoint blockade activity with co-stimulatory antibody. And for the second antibody to combine 2 conditional co-stimulatory activities. So we believe these molecules -- so we are extremely excited about these molecules because they were engineered to have an activity-like checkpoint blockade, so they are fully inhibitory for the PD 1 pathway. But in addition, they bring a conditional 4-1BB agonism. And our excitement relies also in benchmarking this antibody in preclinical tumor models, where we see with these antibodies that we have a superior activity than checkpoint blockade alone. So these approaches are best suited for tumors with high, and we believe also, medium mutational burden, but there are tumors with low mutational burden with immune desert cancers like pancreatic cancers and we need other approaches. And for pancreatic cancer, which has the highest -- one of the highest medical needs in oncology, we acquired a monoclonal antibody, an IgG antibody targeting CA19-9 which is expressed in more than 90% of pancreatic cancers. And this is a very exciting molecule because it's the best-in-class with regard to ADCC and CDC activity as [ nanomolar ] affinity to this target and the target has recently been -- this was a publication in Science in 2019 of our collaboration partners, showing that the target is really an oncogenic driver and prognostic marker of these cancers. So the preliminary data of these antibodies is that 6 patients were treated in combination with chemotherapy, and 4 of them had objective response. We restarted the clinical trial in 2019 with the goal to continue with dose escalation and dose finding, ultimately leading to randomized opening up and getting randomized clinical trials. So our excitement is also based on imaging studies with this antibody, showing that this antibody enriches in a highly significant manner in metastatic lesions of pancreatic cancer. This not only allows radio imaging and radiotherapy, but we believe this is really essential -- an essential aspect for therapeutic targeting of metastatic pancreatic cancer. So the last few minutes to our now extension of our program to T cell therapies. So CAR-T cell therapies are extremely successful in B cell malignancies, but the big promise, of course, is the solid cancer space. And there are more than 30 clinical studies in the solid cancer space and the challenge here is that the CAR-T cells do not further expand after infusion. The second challenge is targets, which are really tumor-selectively accessed, and we believe that we can address both challenges with a target CLDN6, which is not present in healthy tissues, but in malignant tumors, and we developed an approach to amplify CAR-T cells in vivo with an RNA vaccine. This is shown here. It has been published a few days ago in Science. And the exciting aspect of this vaccine is that you can fuse lower amount of T cells and expand the T cells with the vaccine more than 100 fold by sequential vaccinations. If you stop vaccination, the CAR-T cells go down. If you wait a few weeks and then restart vaccination, CAR-T cells go up. And we believe that with this approach, we can bring together the best of 2 worlds, the safety of vaccines, plus the potency of CAR-T cells. And we are extremely excited to start the clinical trial in this -- in the upcoming few months. A few strategies to address refractory tumors. So T cell therapies -- so I personally believe that T cell therapies have a bright future, and we are investing heavily into research and expansion of our facilities in T cell field, so we will start our first CAR-T cell program this year. We have a second CAR-T in the pipeline. We are quickly developing other CAR-T cell therapies and plan to announce in this year, engineered T cell receptors, and we are expanding our manufacturing capacity. Last, not least, our RiboCytokine program, which we believe could help in immune desert cancers as well as advanced tumors. The concept is that we encode cytokines. We are on [ A]. And by this, we have the opportunity to prolong the half-life of cytokine, reduce toxicity, and we have, of course, opportunity to engineer the cytokines to, for example, avoid TREX stimulation, or too much toxicity. So we have 2 programs, an optimized IL-2 and modified IL-7 and IL-2 molecules, which we expect to enter clinical testing in 2020. And why we are excited about this program is because for vaccines, including PD-1 blockade, the challenge is still that large tumors do not respond well. So you can see that in plain models, the vaccine works in a small tumor, but if the tumor is too large than the tumor just outpaces the immune response. In combination with the RiboCytokines, we can dramatically increase the speed of expansion. And now we have, in combination with PD-1 blockade. Vaccine plus RiboCytokines, we get now control of large tumors in the preclinical setting. And that excites us that we might be able to bring vaccines also to advance tumors, and this is something that is going to be tested in clinical testing. So I mentioned the multiple synergy across different platforms. This is not only vaccines, plus cytokines but also engineered cell therapies, mRNA vaccines and of course the combination with checkpoint blockade. So what is the outlook for 2020? We have really a busy, busy news flow and with readouts in 2020 and starting in number of clinical trials, including our Phase III trial, and our goal is to continue to build 21st century immunotherapy company. So the highlights will be 5 trial updates. We will initiate the Phase III registrational trial. We will initiate 2 additional iNeST trials in the adjuvant stage cancers. We will initiate our first CAR-T cell trial. We will initiate an HPV neck cancer trial -- randomized clinical trial. And of course, we want to continue to be a global clinical development organization, and we are looking to build a team -- or a development team on the East Coast. Thank you for your attention.

The [indiscernible] break out. Yes. All right. Should we get going then? Do you want to introduce yourself?

Yes. I'm Ugur Sahin, I'm Co-Founder and CEO of the company.

Yes. I'm Sean Marett, I'm Chief Business and Commercial Officer of the company.

And I'm Ryan Richardson, Chief Strategy Officer.

I'll start out asking the first question, and then I'll hand it over to [ agency. ] But in regards to all you know about your iNeST programs, including the updates you provided today, I'm curious if you could just like help frame your thoughts on where you see iNeST most appropriately suited for, like whether it's in the adjuvant or the metastatic setting? And then also, given your very initial combination commentary with pembroizumab. Just how do you see these programs as monotherapies or being used in combination?

Okay. Maybe I answer the question. So first of all, first of all, the immunological common sense tell us from the very beginning that iNeST is well suited for the adjuvant setting. And we have now good evidence for that. And iNeST, either in combination with checkpoint blockade, or iNeST as a single compound, could be eligible for patients after surgery, post resection, and this is something which we are going to test in 2 randomized clinical trials, patients after surgery, receiving the vaccine, it alone or in combination with checkpoint blockade. That's fine. We don't know if the vaccine adds value if combined with checkpoint blockade in -- as compared to checkpoint blockade alone. And to address this, we started in 2019, randomized clinical trial where we tightly evaluated in melanoma. That means pembrolizumab, which is the set standard of care for metastatic melanoma compared to pembrolizumab Plus iNeST to evaluate whether the addition of the vaccine has an influence on objective response rate on PFS and ultimately on OS. So this study could ungate -- if it's positive, it could ungate other studies in the advanced setting, but we would like to wait until we have this data. This data will be available, end of 2021.

[indiscernible] expectations for the data -- I mean not necessarily the data, but what types of data you plan to show...

In 2021?

[indiscernible]

At the end of 2020, it's too early to have PFS readouts. And we do this trial really in a [ branded ] fashion, yes. And to maintain the potential if the data really looks good to expand the trial towards registrational approaches. Therefore, we will provide as minimum as possible information. So the information might include the numbers of patients who have been recruited, the turnaround times in certain statistics, but no efficacy or comparison data. So this was the randomized trial, and Ryan just said, could you also say something to the basket trial. The basket trial, we will have a first report in -- at ACR, showing why we came to the conclusion that the approach is safe and is able to deliver vaccines and the conclusion of immunogenicity. We will provide also activity data -- clinical activity data, which will not allow to draw conclusions with regard to the additional benefit to the clinical activity of iNeST.

And I guess before that data update, should we be expecting to see data across multiple tumor types...

Yes. Yes.

And if [indiscernible] provide on more tumor types.

Yes. So I just would like to remind you the trial -- the trial the Phase Ia/b trial is a dose escalation trial. It's in multiple indications, including some patients in first line, some patients in second line. And it is because of that heterogeneity, there is no chance to provide information about clinical efficacy, and this was not the intention. And -- but yes, we will provide data for multiple clinical indications and enabling us to, for example, evaluate whether tumors with a lower mutational load are as immunogenic as tumors with higher mutational load.

And then also with iNeST. You mentioned during your talk that your -- the turnaround times are on the scale of being clinically relevant. Can you expand on that comment more? What's clinically relevant? When have you disclosed in the past about your turnaround times and where you think you can head with these?

Yes. So we -- you might remember that we started with a turnaround time of 3 months. We are now consistently below 6 weeks, yes? And we have the objective to further reduce that. So this is an interactive approach and our manufacturing process is just iterating from round to round with improvements in turnaround time. Our goal is to come to less than 4 weeks, which would be the goal for randomized clinical trials. So that means the melanoma trial is driven with the goal to stay in the range of 20 days.

Yes. Does any one have a question they want to ask?

So you approach [indiscernible] composites on the T cell. But very frequently, we can see that [indiscernible] in patients towards that in patients, particularly, relates [indiscernible] tumors. So can you give any idea of how you can outcomes those things with your product.

Yes. It's an excellent question. So first of all, we are developing antibodies. So we have a pancreatic cancer antibody, which is MHC-independent. We have CARVac, which is a type of encoding our CAR-T cell approach, which is targeting coding 6, which is expressed in multiple tumors. And we are developing Ribomaps, which includes a number of antibodies targeting tumor targets. And by this, we have an approach, which at least in the immunological [indiscernible] to overcome these limitations of MHC loss.

How high-tech is your streaming approach for clinical trial participants, and where are most of your trials?

So the question was, how high-tech is your -- the screening approach?

To make sure you have the right participants [indiscernible].

Yes. Yes, I think the clinical development is always something which is related to the study design. And for the study design, we, of course, discussed intensely the eligibility criteria, whether the patient would fit. We are defining the biomarker criteria. We define, for example, for iNeST, we define the targets on an individual basis, we have created a large database. So for all patients that we have generated, we have now the data available. We are using machine learning approaches to exploit the [neutonome] data and the IL-6 data to really come with an unbiased and parameters, which indicate which clinical parameters or molecular parameters are associated with response. So this is really -- I would say this is cutting edge, yes, and the conclusions coming from this database and machine learning approaches will help us to further refine the protocol.

And where are the trials, most of them, going to be?

Regionally. Yes, maybe I'll speak to that. So I think as Ugur mentioned at the end of the presentation, one of our strategic goals is to expand our clinical development presence in the United States. Historically, a lot our exploratory early stage trials were done in Europe. And increasingly with our partners, a lot of our trials now that are going into the later stage are more global in nature. And as we go forward, we're going to seek to pursue more global trials as well.

So related to your programs, what's the capacity utilization you have right in terms of how many programs you can be running right now as a company without needing to really do some of the scaling of your operations to your staff in that sort of capacity?

I think that's one of the reasons why we have our partnerships, which allow us to leverage the clinical operations of the likes of Genentechs and Genmab to continue to accelerate our programs. So that provides us with really a strong footprint, particularly to your question earlier about the U.S. and Europe and where do we do our trials? Genentech, of course, and that was one of the reasons why we partnered with them, has the most exquisite network of investigator centers here in the United States, which is highly complementary and allows us to do the trials in a very cost-effective way.

You mentioned you really tend to do [indiscernible] approach in your product. So then why do you select [indiscernible]

So the question was...

Why that [ 20 ] or...

Why 20?

Yes. It's a good question. So it is -- you can assure that this was a question 6 months, 12 months ongoing, yes? So you know it later on. But 20 makes a lot of sense because of a number of reasons. We want poly specificity. We believe cancer immunotherapy should be poly specific. We have -- not every select antigen is immunogenic. Not every antigen is expressed around all metastatic regions. Therefore, it does make sense to have a sufficiently high number of new antigens. On the other side, we would not like to include as many as possible because this dilutes also the vaccine response because every antigen has to compete with the other antigens. And therefore, we believe 20 is a number which is rational but...

I understand, but why not use 10?

We have used 10 and they are comparing now also the -- this with 20. And in -- with 10, the adjuvant setting, the adjuvant setting, you have just one metastatic region. So for the adjuvant setting, 10 could be okay. But if you have 20 different metastatic regions. Then there is a lot of distribution. So -- but I think that we can continue with this discussion for hours.

Yes. To a [ 7 ] [indiscernible] develop [indiscernible] You always stated IO2, IL-7 program.

Was it in [indiscernible] support?

No. No. This is an in-house program, which is fully owned. And with regard to the future, I can't make predictions.

But I think it's fair to say that with any potential future partnership that we might see, the rationale would be the same as it has always been for us, which is if a partner provides acceleration of our programs to market over what we can do ourselves, then we will consider partnering.

For BNT111, can you help frame for us the data you've already shipped like shown relative to other data in the space? And what should we expect for data updates in 2020 for this program?

So I think the data -- the trial objectives are reached and the data that we have shown is almost complete. We have another cohort in the adjuvant setting, which we are going to publish in 2020.

And then just more broadly for your FixVac programs that use different targets and different indications. How do you dignify or read through huge wins within the programs?

Can you elaborate what you mean?

When you say, can you predict if you see good stuff in melanoma, can you also say, "oh, I'd like that [indiscernible]."

Yes, I think the -- so there's no guarantee for that. But what makes us confident is, first of all, that the induction of T cell response that we see is not restricted to melanoma. I have shown you a slide and that our pipeline or our vaccines induced from T cell responses in melanoma and head and neck cancer and in different solid cancers, so that's the immune response. Every tumor comes with its own immune suppressive mechanisms, yes? And it might be that for different type of tumors, you need different type of combinations. But what makes us confident is the broad success of checkpoint blockade in different tumor entities, so there is no tumor -- so there is, at least for the immunotherapy responsive tumors, we would expect that we increase the success rate of CPIs in these tumors.

And then specifically in the prostate indication, how would you characterize like the [indiscernible] or ability of those types of tumors to be reactive to T cells versus, let's say, melanoma or other indications?

I don't see any reason why prostate cancer is different from other cancers. So the challenge for prostate cancer is, it does not have -- or it has a relatively lower amount of neo-antigens. And the second is that the prostate cancer antigens have a relatively weak immune response. So we have our liposomal vaccine platform and the hypothesis -- our hypothesis is that we could induce strong T cell responses against these antigens, which are expressed in 100% of metastatic prostates. So we belief that if this approach is immunogenic, and we will see that in 2020, then it should also translate to a clinical activity in prostate cancer.

And then, I guess, real quickly for BNT116 in lung cancer. Can you -- I understand if you can't say much, but it would be helpful if you could either share the types of antigens you're targeting, or how you're -- like what percentage of the current [indiscernible] CLC population would be eligible for treatment with this program?

Yes. I can't give you details, but what I can say to you that our overall goal for FixVac approach is to cover more than 90% of patients with a disease indication, and we would like not to make an exception. And with regard to the targets, we would like to keep them confidential until we announce the clinical candidate.

So I have a question of your FixVac product. So you usually [indiscernible] antigens in one FixVac product. So will that equal patient with any one of them expressing their tumors or the patients [indiscernible] like a fine antigen expressed with the tumors?

So we will -- like we did that for the [lipoplex] trial. The patients will be recruited if they express at least one of this FixVac...

On your bispecific platform and programs, are you thinking this as being replaced for PD-1 -- PD-L1s or you're thinking about them more, being able to expand the opportunity within the space in terms of different tumor types or whatnot.

For us, it's very clear, a replacement of PD-1.

And just in terms of the initial clinical trials, can you just remind us of the study design and how quickly it does escalate within these trials?

Which trials?

I would say your [indiscernible]...

In Genmab.

Yes, we are in the dose escalation, and I'm not allowed to share any information about that. But we go the classical pathway of identifying a safe dose, which is not limited by dose limiting toxicity.

Okay. And then as I guess, maybe just moving to the next modality CAR-T therapy, for your CLDN6 CAR-T program, why specifically try or decide to pursue CAR-T as opposed to the other modalities you have in your pipeline in this target?

Yes. I referred to that at the end of my presentation. We believe that T cell therapies have a bright future, giving us a number of additional angles. For example, the coding 6 is expressed in ovarian cancer, and these patients have tumor masses up to several kilograms of tumors. And for this, we really need powerful -- extremely powerful T cell therapies.

So [indiscernible] very late state of cancer patient, for example, or technically you can go ahead and exchange the [indiscernible] state. Is that the view?

Yes, our -- so our goal is to be a personalized, you can say, immunotherapy company. So that means personalization means that there are patients with advanced tumors. And our question is, what can we offer these patients? And this is also the reason why make CAR-T cell therapies.

Then some very bigger picture question. At this stage of the BioNTech's [indiscernible] stage. How do you think about or how much of your time is allocated to developing the current pipeline versus more program or like [indiscernible] platform. Like how do you think about those 2 different?

Yes. So I'll start. So I think that the primary focus of the company right now is advancing our late-stage or about to be late-stage product candidates into the late-stage and towards the market. So we talked about BNT111 in melanoma. We also talked about iNeST, which where we just started a randomized Phase II trial in 2019. If we think about 2020, it's an important crossroads for the company because we're really transitioning with those platforms into the late stage. So we have one trial that's already started in a Phase II. And as Ugur outlined today, we'd expect within around 12 months to have 4 or 5 trials up and running in the later stage. In addition, we have the earlier stage compounds moving in, into first-in-human trials as well, so we have another wave of compounds. But the primary focus of the company is advancing those later-stage compounds.

I have a follow-up on that. I mean, forgive the metaphors but you've planted this huge green garden, you water it, you have all these ideas, you did it privately, a little bit under the radar until recently and it's great. You encouraged all these programs, which makes sense. They connect with each other. Now how the hell do you manage all of this, who's the air traffic control? There's so much that you're doing, your pipeline is a mess. So how does the management resolve this?

Yes. I think it comes down to prioritization, management allocation of resources and I think what helps us is that most of our pipeline, the vast majority of our focus is in an area where we have deep domain expertise in oncology. And so you're absolutely right. It is a -- portfolio management is a key strategic focus of the company.

You have [ disappointing, ] you're also going [indiscernible]. So how do you keep it in the management that are -- how big is the management team?

So we have 5 members on the management Board. Right? But we have a very strong layer at the Vice President and Senior Vice President level as well, so -- with deep industry experience. But you're absolutely right, and that's -- we're aware of this challenge now as we move into later stage. And I think we're in the, on one hand, luxurious position where we have many different products that we can fund. And we have to make those funding decisions based on the best available data that we have. And because we have multiple platforms, we're not wedded to having to make a single technology work everywhere, and so we can make decisions on the basis of data.

Yes. And again, we, of course, use CROs and we have global agreements, of course, with 2 very large CROs who do a lot of the heavy lifting for us. But again, please don't forget the partnerships. We have 7 partnerships, 7, and they're there for a reason to do some of this heavy lifting.

Maybe just one financial for me. On the balance sheet, what's your current cash position and cash equivalent?

Yes. So we finished the year, 2019, and these are unaudited numbers that I'm going to share, with EUR 520 million on the balance sheet. And we'd expect to have cash out of about EUR 300 million this year. So that would give us cash runway through Q3 2021.

2021?

Yes.

Great. So I think we're pretty much out of time. So I guess, maybe one more question.

With respect to the mRNA, [indiscernible] of your platform, how do differ from [indiscernible] and do you have freedom to operate? Forgive me if you already discussed this.

Yes, we have freedom to operate. And the differentiation is based on continued, iterative optimization of our products. For example, our vaccine platform, the RNA LPX, is an intravenous vaccination platform, which we published 2016 in Nature, which is unmodified or TLS-7 and TL-8 activating messenger RNA. So this type of vaccine is a proprietary product class, which we use. We have also the IP for [indiscernible] modified mRNA, like [indiscernible] has -- co-owns some IP. We licensed technologies for LNP. We are collaborating with all companies in the field and have a license agreement for LNP delivery. So we have freedom to operate as well as both IP portfolio.

Yes. So, do you use pseudouradine and utilize its own...

Yes. Yes. We have a license from...

What about pseudouradine? What about the nucleic acid actual that you won.

Yes. So we use different mRNA formats for different applications and pseudouradine is 1 of the 4 different mRNAs in our toolbox that we do use. Yes.

Great. Thank you so much.

Thank you.