BioNTech SE (BNTX) Earnings Call Transcript & Summary

Great. Good morning, everyone, from the Virtual JPMorgan Healthcare Conference. My name is Cory Kasimov. I'm the senior large-cap biotech analyst, and it's my pleasure to introduce our next company, BioNTech, and CEO and Co-Founder, Ugur Sahin. Please note that following this presentation, we will have a Q&A session right here in this Zoom room where you're also able to submit questions via the little blue ask-a-question button in your conference portal. So with that, Ugur, thank you so much for being here today. Very interested in this discussion. So let me turn things over to you to get started.

Thank you, Cory. Can you hear me?

Yes.

Yes. Good morning, everyone. I'm Ugur Sahin. I am the CEO of BioNTech. I'm delighted to be here to tell you about the exciting progress that we made last year and what are our plans for this year. Before I get started, I will mention that I will be making forward-looking statements, and please refer to our filings for more information. And in the filing is also our -- the label of our newly launched vaccine community. So let's start with Slide #4. So BioNTech, in a short description, is a next-generation immunotherapy company. Our goal is to harness the full potential of our immune system, and the immune system is really powerful for it. It can protect us against diseases like COVID-19, but it is also implicated in about 80% of all human chronic diseases. And we believe that by harnessing the full potential of the immune system, we might be able really to have this -- to be able to address medical need in multiple, multiple disease areas. So on the next slide, I would just summarize how important 2020 was. 2020 was truly transformational year for BioNTech. So we have successfully developed our COVID-19 mRNA vaccine and got authorizations and approval in many countries in less than 10 months. So we are transforming into a fully integrated biopharma company and have already product launches in more than 45 countries. Parallel to this development, we broadened our clinical-stage pipeline of 11 immuno-oncology product candidates. And we established in 2020 also research and development hub in the U.S. as well as extended our presence in Asia by collaborations. Our company before the COVID-19 era where we're able to produce clinical material, messenger RNA for clinical studies, we are now a company, which is able to produce messenger RNA vaccines at a global commercial scale. And this is, of course, everything together, is a transformative event. On the next slide, I would like to show you why this is so important not only with regard to our COVID-19 vaccine and the commercialization of this but also how this will impact our other business. The first thing to do is, of course, we want to execute our competencies to further develop our COVID-19 vaccine and commercialize that. The COVID-19 vaccine gives us the opportunity to invest the cash flows generated by the vaccine distribution into our further development. And we will use that in 2 ways: One is to advance our broad pipeline of already existing 20 product candidates in infectious disease as well as in cancer. The second is we would like to expand our competencies and immunotherapies in multiple third-party areas. We believe that the transformational event of developing of COVID-19 vaccines will give us the chance, together with the basic competencies that we have built over the last 20 years, the opportunity to build a global multi-product immunotherapy powerhouse. On Slide 7, I would just shortly summarize the profile of our COMIRNATY COVID-19 vaccine. It is the first vaccine authorized in the U.S. and in Europe. We have authorization for emergency use, temporary use, conditional approval in more than 45 countries. And we managed that in a time frame of a few weeks. We have already almost 33 million doses vaccine shipped, but we have produced much more in the meantime. Our vaccine is characterized as being potential best-in-class efficacy. We have 90% vaccine efficacy evaluated in more than 40,000 participants. Most importantly, we have a high vaccine efficacy even in the older group with 94% of more efficacy in participants in older than 65 years. The safety profile is very benign. This is a low frequency of grade 3 adverse events. All of these adverse events known as typical vaccine-related side effects. What we have also observed and what is very encouraging is the rapid onset of efficacy as early as 12 days after the first dose of the vaccine. The maximum benefit is observed after 7 days after revaccination. That means 28 days after starting -- after receiving the vaccine. What is important, particularly with regard to the emergence of new variants, is that we have an extremely broad immune response profile. So we have this neutralizing antibodies, we have CD40 cell responses, and we have best-in-class CD8 T-cell responses. And all of this different type of immune responses collaborate to provide an important, important -- and control and prevent disease. So on the next slide, we have summarized our manufacturing activities. So 2021 will be the most important year to deliver as much as possible vaccines. So our initial plan was to manufacture up to 1.3 billion doses. So we increased by different means our vaccine production capacity for up to 2 billion doses. And this is done currently by 7 manufacturing sites in the Pfizer and BioNTech alliance in the United States as well as in Europe and in Germany. We have approached additional CMO sites, which will help us to deliver the site number of vaccines, which means that we can reach up to 1 billion people with our vaccine. What is important is that we have already orders for more than 1 billion doses. So that we believe that this -- the capability to produce up to 2 billion doses is really important to ensure that our vaccine could be globally delivered in a sufficient manner. On the next slide, we would -- I would like just to shortly summarize what are our key objective with regard to COMIRNATY. So first of all, one important aspect is to increase supply capacity. I already told that we will increase our capacity to 2 billion doses. What is important is that we had a label change in the United States and in Europe and the various other regions from a 5-dose vial to a 6-dose vial, which increases the number of vaccine doses 20% overnight by -- without changing the vial doses. We are applying continuous improvements in our vaccine manufacturing process and have a high success rate. And we are -- we have implemented collaborations with a number of raw material suppliers as well as CMOs supporting us in the production process. The next thing to come is to broaden our global distribution by continuous regulatory authorizations in new countries. We plan to submit the BLA in U.S. and in other regions. And we will, of course, continue to discuss with government for additional supply orders. With regard to the vaccine use, we would like to expand our label by including pediatric indications, pregnant women and additional subpopulations characterized, for example, by immunosuppression. We would also like to continue to optimize our formulation, and this will include several independent aspects. This is ongoing stability testing to update our current formulation and to provide longer stability times. We are working on improved thermostable formulation, which will most likely be available in the second half of 2021. And we are also evaluating other formulations, which do not contain PEG. So on the next slide, on Slide 10, summarizes what we believe is important to continue to successfully fight COVID-19. So there is a extremely high likelihood that COVID-19 will become an endemic disease. And this provides a huge medical need not only for this year and for the next years but also for the coming decade. So one is, of course, the need for a safe and effective vaccine. And we -- our vaccine has already shown a compelling efficacy and a very benign safety in all tested age groups, and we will continue to evaluate how we could continue to further improve the safety profile of the vaccine. The second challenge, of course, is we knew that this virus mutates and there are new strains coming up. We will monitor these strains, and we will evaluate whether our vaccine is still active also against these new strains. And we have the ability to create a reengineered vaccine and make this available within 6 weeks. So this is one of the key advantage of messenger RNA technology. And the third thing, of course, it is well known that the immune response against COVID-19 as any other immune response against any other virus is waning over time. So we consider that the vaccinations will be necessary at certain time points. We do not know, but we are prepared. Again, messenger RNA technology is well suited for revaccination purposes. We know that from our oncology trials where we have revaccinated some of the cancer patients more than 25x, so revaccination works very well for messenger RNA vaccines. On the next slide, on Slide 11, I would like to share with you what we believe why COVID-19 is not only the only target, which is interesting, but whole infectious disease field provides a high unmet medical need. So there is an increasing number of highly unaddressed indications -- infectious disease indications. These are large indications like HIV or tuberculosis. But what is also clear is that the number of approved vaccines, for example, in the United States by the FDA in the last 3 years, only 7 vaccines have been approved. So there is room for further improvement and for acceleration. We know that several type of infectious diseases do not have vaccine approvals, so there are no vaccines available. And we know that for several other indications, for example, for the seasonal flu, the efficacy of the vaccine, particularly in the older population, is low. So what we have already started and what we are doing is we are working on influenza, HIV and TB vaccines; influenza, together with our partners, Pfizer. And we have 6 undisclosed infectious disease program, which will go enter into clinical testing. Some of them will enter into clinical testing in 2021, and some of them will enter into clinical testing in 2022. So the infectious disease field is, of course, an important ongoing field. But we see, of course, for the messenger RNA technology a much broader application space. So what is the application space? So we have already a number of applications and clinical trials ongoing in oncology. So we have mRNA vaccines, cancer vaccines targeting neoantigens and mRNA vaccines targeting shared tumor antigens. We have recently described an mRNA vaccine to amplify and promote the activity of CAR-T cells, and we have now recently described an mRNA vaccine approach to modulate autoimmunity. In future, we will provide more data and extend our activities for developing mRNA vaccines for autoimmune diseases, rare diseases as well as mRNA treatment modalities to -- for other therapeutic areas, for example, areas associated with inflammatory type of diseases. On the next slide, Slide 13, I would just reiterate that our approach for oncology is much broader than messenger RNA technologies. So we are here following the concept of developing different treatment modalities, which have the opportunity to synergize because on the one side, we have approaches allowing us to target cancer, for example, by vaccines, by cell therapies, by antibodies. On the other side, we have approaches allowing to modulate immunity and improve immune and support antigen-specific T cells and antibody responses by immunomodulators, bi-specific antibodies, engineered cytokines as well as small molecule immunomodulators. We believe that this such a broad approach gives us really the opportunity to overcome limitations of resistance, primarily and secondary resistance, in advanced cancer. On the next 2 slides, I would like to just shortly summarize our vaccine approaches in -- for treatment of cancer. We have in principle 2 technology approaches. So this is the FixVac approach, where we leverage shared antigens to break immune tolerance by using a nanoparticulate vaccine, which induces type I interferon. And the platform has the ability that we can combine multiple antigens in one vaccine and thereby increase the likelihood or the coverage of cancer patients as a given indication to more than 90%. We have now shown and published data, most recent in September in Nature, showing that this approach is really allows extremely strong T-cell responses indications and even in patient populations, who have [ said ] prior checkpoint blockade and allow us to [ resynthesize ] treatment of advanced cancer patients with checkpoint blockade in combination with vaccines. So we have here 2 clinical trials, which are going to Phase II clinical trials, which are going to start in advance, PD-1 experienced melanoma patients and in first-line metastatic head and neck cancer is different type of target antigens. We have clinical trials running in prostate cancer to evaluate the single compound activity as well as the clinical activity with anti-PD-1 treatment. And we are currently consolidating a non-small cell lung cancer FixVac vaccine, which could allow us to address this space of huge unmet medical need. On the next slide, on Slide 15, there is the complement to our vaccine approach, iNeST. So here, the targets are individual mutations. So that means this is a fully individualized vaccine approach. The vaccine is consist of a -- is customized to each individual patient and targets up to 20 neoantigens per patients, which have been identified by next-generation sequencing. So we've generated now -- we are generating data in 3 type of disease settings. So we have, on the one side, the late-line metastatic disease, where we generated data in patients with 5, 6, 7 prior type of treatments. We have seen single-agent activity in melanoma and gastric cancer. And we have seen efficacy signals in combination with anti-PD-L1 treatment. We have generated data in adjuvant setting, where we have observed that patients with post -- after surgery melanoma after receiving iNeST remain tumor free for a long period of time with a statistical significant increase of progression-free survival as compared to prior vaccination. And we have, in the first-line metastatic setting, a clinical trial together with our partner, Genentech, in the first-line setting where we combine our vaccine approach with pembrolizumab and the control arm is pembrolizumab alone. And here, again, the question is can we increase the objective response rate and can we increase the PFS by this approach. We believe that this fully individualizez approach is particularly interesting in an early stage of setting either the first line or in the adjuvant setting, and we will certainly invest into clinical trials here. We have already started a clinical trial in the adjuvant setting in colorectal cancer patients after surgery. So this were our vaccine -- cancer vaccine approaches. On Slide 16, I would just shortly update you about our collaborative program with Genmab. BNT311 is a molecule. It's a bi-specific molecule, which binds to anti-PD-L1 and blocks in a constitutive manner PD-L1 activity and has on the other arm a 4-1BB binding agonistic activity, and agonistic activity is a conditional activity. So that means antibody agonistic activity is only seen if the other arm, PDL-1 arm, is bound. And thereby, we enable a broader therapeutic window of 4-1BB, which is one of the most strongest and co-stimulative molecule in our immune system. We have seen -- we have -- we went to a dose-escalation study, a basket study with multiple indications. And what we have observed is a encouraging activity of the bi-specific antibody in CPI refractory solid tumors. Particularly, what is interesting, we have observed objective responses in patients with non-small cell lung cancer who fail prior entire PD-1 blockade. And this is ongoing. We are collecting data and increasing this cohort. So we have currently 7 expansion cohorts, patients who are currently recruited in non-small cell lung cancer, in urothelial cancer, in endometrial cancer, triple-negative breast cancer, in head and neck cancer and cervical cancer. And we will update about this expansion cohorts in 2021. On the next slide, Slide 17, I would like to just give you a helicopter view on the different type of innovations, which could really change the way how certain treatments are used and change the activity and efficacy of [ type of ] treatments. So on the left, you see our CARVac approach. CARVac stands for CAR-T cell amplifying vaccine approach. And the idea here is very simple. That means we are stimulating -- we are using a messenger RNA vaccine to stimulate CAR-T cells after delivery -- after infusions to the patients. And we believe that this approach is extremely important to enable treatment of solid tumors, epithelial tumors with CAR-T cells because CAR-T cells so far don't work or only work for solid type of neoplasm. The second approach is our NEOSTIM T-cell therapy and approach, which was developed by our colleagues in Cambridge. The idea here is to develop antigen-specific and neoantigen-specific T cells using peripheral blood from cancer patients. And if this approach is successful, we would overcome the limitation of T-cell therapies based on using tumor-infiltrating lymphocytes because we know in most hospitals, there's no access to tumor-infiltrating lymphocytes. But peripheral blood lymphocytes are available everywhere. And therefore, if this approach is successful, it could open up a new avenue for T-cell therapies. The third approach is RiboCytokines. In RiboCytokines, and we have here programs, for example, of a sequence modified IL-2 or optimized IL-7 molecule. We believe that the use of messenger RNA, which is optimized for some in the pharmacokinetic profile give us the opportunity to have full and long cytokine therapy and targeted cytokine therapy, thereby allowing to stimulate T cells and engage cells in the body of the patient after delivery of RiboCytokines. And instead of daily infusion of these cytokines, we can go for weekly or even 3-weekly applications. So this is a clinical trial, which is going to start or 2 clinical trials going to start in 2021. And the last category -- the new category I would like to discuss are RiboMabs. RiboMabs are RNA-encoded antibodies. Again, the idea is not simply to use messenger RNA instead of an antibody. But we are asking the question, what are limitations for normal antibody treatment for using the traditional protein-based antibodies? And how can we overcome these limitations using RNA-encoded antibody? And for example, one of these limitations are bi-specific antibodies, particularly, the single gene antibodies are eliminated very fast from the blood. And again, here with the RiboMabs approach, we can address that by optimizing the pharmacokinetic profile of the messenger RNA. So all of this products are owned by BioNTech -- fully owned by BioNTech. And all of the studies will start in 2021. Here on this Slide #18, I would just show you the concept what we aim with our CARVac approach. So what is well known is that patients with solid tumor, epithelial tumors, if they receive CAR-T cells, the CAR-T cells disappear from the blood within a few weeks. So the engulfment is suboptimal and the activity of this -- the clinical activity of this type of treatments are below measurable clinical activity. The concept that we are addressing here is after delivery of the CAR-T cells, we use the messenger RNA vaccine which displace the antigen, which is recognized by the CAR-T cells on the surface of antigen-presenting cells. We have here intravenous liposomal vaccine, which delivers the RNA to the cells in a spleen, for example. And in the spleen, these CAR-T cells are stimulated and they are not only stimulated by seeing the antigen, they are stimulated because they see also the co-stimulatory molecules in the lymphatic tissues. And we have observed in preclinical models that we can increase the number of CAR-T cells by [ hepatic ] stimulation up to 10,000 folds after infusion of the CAR-T cells. And what is important is we can keep the CAR-T cells in an optimal therapeutic window because if we vaccinate, the numbers of T cells go up. If we stop vaccination, the numbers of T cells drop again. And if we revaccinate, we can increase that. So that means our approach is here to bring 2 treatment modalities together: on the one side, CAR-T cells treatment, which is powerful; on the other side, vaccination, which gives you really a wonderful tool for controlling safety and efficacy profile of a product. On the next data slide, I would like to introduce you our newest generation of immunotherapy. It's a messenger RNA vaccine for autoimmune diseases. And here, we use pseudouridine modified mRNA with a non-immunostimulatory formulation. And by this, we can stimulate certain T cells which are known as regulatory T cells, which can dampen immune response. And we have shown in preclinical models in an impressive way that by this approach, we can prevent the onset of experimental autoimmune encephalitis, which is a model for multiple sclerosis. And even after onset of the disease, we can treat and improve the disease outcome by starting vaccination. So we believe that this, what we have shown now for multiple sclerosis model, could be eligible also for different type of autoimmune diseases. And again, here, we have the tools for personalization and for using a FixVac like approach, and thereby being -- we believe that this could be applicable for a plethora of different autoimmune diseases. So I would like to end up with just the key pipeline milestones, which we expect for 2021. Of course, there will be multiple community updates. We will update about the clinical trials with our bi-specific antibodies, the 4-1BB anti-PD-L1 and CD40 4-1BB antibody, BNT311 and 312. We will update you about our CARVac trial, targeting Claudin 6 and multiple solid tumors, and we will update you about our TLR7 molecule. Our goal is to bring up to 3 programs into randomized Phase II. This is our FixVac approach in melanoma and the FixVac approach in head and neck cancer. And we have -- we'll, of course, continue with our randomized trials for our iNeST approach in melanoma, colorectal cancer and most likely also other indications. Six of our preclinical programs will move into Phase I or are expected to move in Phase I. These are 2 RiboMab programs, 1 -- 2 RiboCytokines programs addressing either IL-2 or IL-7. The Claudin 6 CARVac will start this year. We will have the first patient in a few weeks, and we will have our first adoptive T-cell therapy with NEOSTIM in -- again, in melanoma. So what is the outlook? We have in 2021 the opportunity to deliver our COVID-19 vaccine to up to 1 billion people globally. We will advance 3 oncology programs into randomized Phase II. We'll initiate our first potentially registrational trials in oncology, extend our messenger RNA approach into other disease areas, expand our global footprint in the U.S. as well as in Asia as well in Germany and in Europe. And in the long term, our vision is really to pioneer the field of individualized cancer medicine, particularly using personalized vaccine. We would like to build a global business and commercialize our own product. And our vision is and remains to become the 21st-century immunotherapy powerhouse and enable -- that we are able to provide solutions for indications for disease areas with high medical need. Thank you for your attention. I'm happy to take questions.

Okay. Great. Unfortunately, we're down to about 2 minutes left in the session, so we don't have time for many. I do want to make sure I ask you one that we've gotten a lot on it. And we have actually a ton of questions overall we'll get back to people on. But clearly, there's a lot of talk and concern about the emergence of these new variants of the SARS-CoV-2 virus. So how confident are you that your vaccine will protect against them? And how concerning is it that the virus could mutate to a point where the vaccine could be ineffective? And do you think about future multivalent vaccines?

So first of all, we have evaluated 2 of these mutations, which are present in the U.K. variant, and both seem not to be affecting our vaccine efficacy. And we will provide data in the coming 7 days for the U.K. variant and in the coming 10 days for the South African variant. I'm more or less comfortable that our vaccine, because it has antibody responses, CD4 T-cell responses and CD8 T-cell responses, will be not directly affected by this type of mutation. We are still -- still understand that 99% of the virus sequence is unaffected. And at a certain time point, if we get variants which require adaptation of the vaccine, we can do it. I have already shown how this could be possible.

Okay. And then one more before we end. How do you think about duration of immunity at this point? Is it simply a question of waiting to see and follow your early volunteers as they approach their 1-year anniversary of your shots? Or are you able to do any predictive modeling beyond that right now?

I think that the most scientific and medically sound approach is really continue to observe vaccinated people and collect data about disease protection over time and combine that also with the antibody titers and T-cell titers and come up with a reasonable approach for revaccination.

Okay. Unfortunately, that's all the time we have today. I'll try to get back to all the people who submitted questions. But thank you so much, Ugur, and thanks for everything you're doing on this front, and we look forward to following progress and we'll talk to you soon.

Thank you.