BioNTech SE (BNTX) Earnings Call Transcript & Summary

Good morning, everyone. Thanks for joining us at the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I'm one of the senior biotech analysts here at the bank. It's my pleasure to introduce our next company BioNTech. Speaking for BioNTech this morning will be Ryan Richardson, Chief Strategy Officer. Good morning, Ryan.

Good morning, Tazeen. Thank you very much for the invitation to join you today virtually. We'll be making some...

You guys have the slide -- yes. So before I let you go into that, I'll -- yes, I'll let you -- everyone know that they can follow your slide deck, if they so choose. And I'll turn it right back over to you.

Great, thank you. So I'll start on Page 3. I'm going to start the presentation with a high-level overview and provide a business outlook, and then I'll dive a little bit deeper into a couple of our programs before making some closing remarks. So to start on Page 4. So BioNTech was founded 12 years ago, in 2008, with a simple vision to develop next-generation therapies, which harness the full potential of the immune system. Our vision fundamentally is to build a global pharmaceutical company and to bring multiple innovative therapies to the market. To achieve that, we've developed a suite of novel technology platforms and are developing a pipeline of immunotherapies across a range of cancers and infectious diseases. We've built and operate an integrated network of in-house GMP manufacturing sites in Germany, and those include both mRNA and cell therapy production facilities. And finally, our business model is built around an industry-leading set of collaborations. And these collaborations help us accelerate our own pipeline of products towards the market and have also brought us supporting capabilities for technologies, which complement our own pipeline. You see some examples of these collaborations on Page 5. In the oncology space, they tended to be cost and profit shares. 50-50 model is a model we've implemented multiple times here, both with Roche, Genentech, with Genmab, similar model with Sanofi and also more recently with Pfizer in the case of our COVID-19 vaccines. But we've also employed a range of different models to expand our presence into different therapeutic areas and/or geographic areas and then these other R&D collaborations. You see on the bottom of the page, we also have the potential to bring additional products forward into our pipeline. On Page 6, we highlight here, our integrated immuno-oncology strategy, which exploits different complementary therapeutic platforms. And I think, this is one of the differentiating factors of BioNTech here, this multi-technology platform approach. What you see here, really, is a strategy that combines an ability to target cancer, often the unique -- oftentimes in unique ways with innovative technologies and you see those on the left-hand side, but it combines that with an ability to modulate the immune response. And so on the targeting cancer side, we have our mRNA cancer vaccines, both FixVac and iNeST, which I'll talk more about a little bit later on, but we also have engineered cell therapies and targeted antibodies. And on the right-hand side, we're developing novel immunotherapies that can help enhance the immune response. An example being our RiboCytokines, engineered cytokines, where we use RNA to encode for a cytokine. And where we see, in the preclinical setting, powerful, implicative effects when we combine with other targeting approaches. We think in some that this broad suite of technologies gives us the opportunity, one, to produce multiple blockbuster candidate opportunities on their own right. But also significant synergy, as we try to address, really difficult-to-treat or resistant cancer types. And you see some of the examples of that synergy on the next page, on Page 7. We've given 3 different examples here. I won't go into too much depth. But what you see here is a range of different cases where this dual approach of targeting and/or immunomodulation has yielded strong results, either in the clinical setting or in preclinical models. So let's take first example. We've demonstrated now with both our FixVac melanoma program, BNT111, but also with iNeST, BNT122, a powerful synergy in combination with checkpoint in the form of objective responses in melanoma patients. In the preclinical setting, we've also shown powerful implicative effects in combining our cancer vaccines with these engineered cytokines, such as RiboCytokine IL-2 or a RiboCytokine IL-7. And then lastly, on the right-hand side of the page, you see an example of combining engineered cell therapies with our cancer vaccines. We published a paper in early January of this year, highlighting an approach that we call CARVac, whereby we use an mRNA vaccine, encoding the same antigen that we target with CAR-T cell approach to actually amplify the CAR-T cell numbers in vivo, significantly. And that was able in the preclinical setting that approach to eradicate large tumors and in preclinical models, as subtherapeutic CAR-T doses. We think that represents a powerful potential new platform that could have merit across a range of different antigens and solid tumors. So moving to our pipeline on Page 8. Here you see our clinical stage pipeline. It consists of 11 product candidates across 12 ongoing trials. 8 of these product candidates are mRNA-based therapies. 3 of these product candidates are antibody-based therapies. All are immunotherapies. And the other point that I would call out here is, is the stage of these. So most of these are Phase I, currently. Several of them are finishing Phase I and we're about to enter Phase II, which, in the case of the cancer therapies, could represent registrational opportunities for the company. I'll talk more about that in a few slides, but I think the programs that I would call out here include BNT111 in advanced melanoma, where we do plan to start registrational trials by the end of this year. And also our iNeST approach, which is our individualized cancer vaccine, where we've already started one randomized Phase II trial. And where we have plans to start additional trials, later this year. And I will provide a little bit more detail on that in a few slides. In total, by the end of 2020, we aim to initiate up to 4 additional late-stage trials. So coming behind this initial group of clinical stage programs, we have a broad array of preclinical programs across different platforms. You see here on Page 9, a number of these preclinical programs, several of which we plan to take into the clinic, already in 2020 or in early 2021. And those include our first programs for RiboMabs, our first RiboCytokine programs and also our first CAR-T approach, the CARVac approach, that I mentioned a few slides ago, where we planned them in the next few months, actually, to start our first trial with a CLDN6-based CAR-T, targeting CLDN6 expressing tumors, such as ovarian cancer and testicular cancer in a basket trial, which we plan to start, as I said, to -- in the next few months. We also have, at the bottom of the page, a number of programs outside of the cancer arena. We have multiple infectious disease collaborations, which we started in 2018, actually, with a Pfizer collaboration, targeting influenza. We had a -- we followed that up with another collaboration with the University of Pennsylvania to develop mRNA vaccines and up to 10 infectious diseases. And we have a collaboration with the Bill & Melinda Gates Foundation as well, which is in the first instance, targeting HIV and tuberculosis. And finally, we have a collaboration, it's a cost and profit share arrangement with Genevant to develop mRNA-based therapies for a range of rare diseases. In the case of these other programs outside of oncology, we expect that our first programs will go into the clinic in 2021. And of course, our first program, actually, already has gone into the clinic, outside of this group, which is the COVID-19 vaccine, which I will spend a little bit more time on, a little bit later on. So in sum, when we look over the next 12 to 18 months on Page 10, you see our expected news flow. I think, we expect it to be a busy period, both in the near term. Through the summer, we expect multiple data readouts, but also over the longer term, over the next 6 to 12 and 18 months. Some of the key readouts that we're focused on here, include, our FixVac BNT111 publication. This will expand on topline data that we released last year in melanoma, both in the monotherapy setting and also in combination with checkpoint blockade in patients for checkpoint experience, but who were progressing at baseline on checkpoint therapy. And as I mentioned, we do plan to start a Phase II registrational trial in the second half of 2020, with BNT111 in melanoma. We also expect to provide data updates in the near term, on our iNeST individualized cancer vaccine program, starting with a data update for our ongoing Phase I/II trial at the AACR conference. Conference dates have been moved around a little bit, but now it's settled in, on June, and we plan to make -- have a virtual presentation of some abstracts in that -- in the June session. In the second half of the year, we expect data updates for our intratumoral immunotherapy program. This is a unique mix of cytokines, which we encode via mRNA. This is a program, partnered with Sanofi. And we also are particularly excited about an update -- the first update on our ongoing Phase I/II trial with our BNT311 program. This is a PD-L1x4-1BB bispecific antibody, which we expect in the second half of the year. And last but not least, our BNT162, our COVID-19 vaccine. As indicated earlier this week, our quarterly -- first quarter update call, we do expect our first-in-human data in the June/July time frame. So now I'll say a few words about our mRNA cancer vaccines, FixVac and iNeST. So turning to Slide 12. So these 2 cancer vaccine platforms, they share our -- an RNA-lipoplex formulation, which was developed in-house at BioNTech, which targets dendritic cells in the spleen and lymphoid compartments. For both of these platforms, we've observed strong immunogenicity in the form of in vivo TLR7-driven adjuvant effects and T cell responses, including both CD4 and CD8 T cell responses, as measured on an ex vivo basis, without amplification. The difference here is that on the left-hand side, the FixVac is our off-the-shelf approach. So this is targeting a mix of shared antigens and is a relatively straightforward, low cost to produce approach that can be tailored to different cancer types, based on antigen representation or expression across a range of tumor types. The iNeST approach is an individualized one. And here, it starts with individual patient samples taken, genomic sequencing analysis and mapping of mutations performed on patient-by-patient position. And then applying a set of algorithms to down-select, which neoantigens to combine it to a vaccine and coupled with on-demand manufacturing, to deliver an individualized immunotherapy for specific patient that targets their own cancer profile. Across both approaches, as I've mentioned, we've seen really strong immune responses. And you see some of those on Page 13. So this is a collection of different trials, actually, different antigens. And you can see the kind of potency that we're achieving here across 4 different examples, 3 of which are FixVac and one of which is iNeST. But the numbers to focus on in this chart are the red percentages on the top right-hand side of each of the charts of the graphs, which represent the percentage of total peripheral T cells that are antigen-specific post vaccination. So in this case, to take the first example, in our -- for BNT111, this is targeting NY-ESO-1, in addition to a range of different antigens. But in this particular patient, we measured NY-ESO-1, and we see here a 10% of total peripheral T cells, targeting NY-ESO-1 after vaccination. Now of course, with each of these experiments, we compare this. We have controls. We look pre vaccination, post vaccination to verify that the antigen-specific response that we're seeing is indeed related to the vaccine. What you can see here that this is -- this represents billions of T cells, antigen-specific T cells, that are functional, that have been generated via the patient's own immune system. So on Page 14, we highlight BNT111 a little bit more. I won't go through all of the data here. Most of this has been reported last year. This is the top line data that has already been reported, where we showed, again, a single agent objective responses in the monotherapy setting in patients who had failed checkpoint therapy or progressed on checkpoint therapy. But also, as I mentioned, we saw a number of responses in a group of 17 patients with metastatic melanoma who had progressed on checkpoint monotherapy, indicating an ability to resensitize patients to checkpoint blockade. This is a vaccine that targets 4 different antigens, which are specific to melanoma and are highly expressed across the melanoma population. And with this approach, we think we can target the vast majority of melanoma patients without the need for a companion diagnosis. And again, this is the topline data with much more detail expected in an upcoming publication in the next few weeks or months. So FixVac pipeline on Page 15, you can see we have 5 different clinical stage FixVac programs, targeting melanoma, HPV-positive head and neck cancer, triple-negative breast cancer, prostate cancer and ovarian cancer. And we've also, since our IPO in October last year, generated a new product candidate. This is a FixVac targeting NSCLC, which is still in the preclinical phase, but which we are currently planning for the start of the first clinical study. Okay. So now shift to iNeST on Page 16. So again, iNeST is our individual approach. We first published clinical data for iNeST in 2017 in Nature, and that was a study you see here for an earlier candidate, which leveraged an intratumoral or intranodal formulation. And that was in 13 patients, 5 of whom were in the metastatic setting, this is metastatic melanoma. So 5 metastatic patients, and 8 patients post-surgical resection, where we followed them now for up to 60 months without any relapses among the 8 patients. And again, in the 5 that were in the metastatic setting, where we could assess tumor lesions, we saw already in the first handful of patients, objective responses, including single agent objective responses. We're now conducting, as I mentioned before, 2 studies are ongoing with the iNeST approach. We're now using an IV formulation. We've called the BNT122. So it's -- we've actually gone from 10 to 20 neoantigens that we're targeting, and we're using the same lipoplex formulation, this dendritic cell formulation, that we're using as well with FixVac in these 2 ongoing trials. So again, one of them is a basket trial, with an upcoming data update at AACR. And the other here is a Phase II randomized trial in first-line advanced melanoma, in combination with Keytruda, which we started last year and where we expect to provide a trial update later this year with first data expected in the second half of 2021. We've also announced earlier this year, our plan to start 2 additional adjuvant Phase II studies in specific indications. We've announced, the first will be NSCLC. And the second will be a yet undisclosed indication, which we plan to make known in the coming weeks. And just to reiterate on Page 17, iNeST, obviously, it's a highly bespoke process that requires manufacturing capability, which is tailored to this drug product, in which we've been investing in for years. Actually, when we first did our -- our first study that I mentioned, in 2017, we had a very manual process back then, and it took almost 90 days on average to manufacture the individual vaccine for each patient. Through automation and through our partnership with Siemens, we've actually reduced the times now to 4 to 6 weeks to manufacture this individualized vaccine. And we do expect that they continue to improve that. The process is only semi-automated at the moment. And there's further room for process improvement, which we think can take us to some 4 weeks on a consistent basis. Of course, we do that in 2 different GMP-certified production facilities in Germany, one of which has been in operation since 2011. Okay. So turning to COVID-19. I'll spend just a few minutes on COVID-19 because I think, this has been covered quite a lot in many recent calls. But for those of you who are less familiar with our program, and I'll start by saying that we made the decision in late January, when we saw the news coming out of China, to move into COVID-19 because we thought that our vaccines and our technology could make a difference here. And we thought we had the ability to move very quickly. And indeed, I think, we were able to do that going from concept to start of clinical trials in about 3 months. So why is mRNA well suited for pandemic vaccines? Well, there's a couple of key reasons. First of all, I'll remind you that mRNA is a naturally occurring genetic molecule with defined -- well-defined biochemical properties. It's of high purity and it's an animal-free product, and we've shown it in the case of the cancer vaccines, but also others have shown that it's highly immunogenic and does not require the need for an additional adjuvant. It's one of the advantages versus some other modalities. We've shown and certainly seen in our own studies, that an mRNA-based vaccine has the ability to stimulate both strong antibody and T cell immune responses at very low doses. And since starting clinical testing with mRNA vaccines in 2013, we have dosed more than 400 patients, in this case, very sick patients, typically, with doses, ranging up to 400 micrograms, which is well beyond what we're testing here in the COVID-19 scenario. And last but not least, the mRNA as a modality. It enables highly scalable production processes and actually relatively low-cost production as well at large batch sizes, which make the ability to manufacture hundreds of millions of doses possible. And in terms of our program on Page 20, you see an overview here. We've titled this program Project Lightspeed. Initially, it includes both vaccines and therapeutics, but I'm going to focus on the vaccine side of things here. So this product, which we call BNT162, is aimed at preventing COVID-19 infection and it exploits a potent lipid-nanoparticle, LNP formulation, which we leverage across multiple vaccine variants actually, that we're currently testing. We've studied this formulation and this technology in a variety of different infectious disease models, including in nonhuman primates, across a range of different indications in disease areas. We plan to manufacture this at our state-of-the-art GMP facilities in Europe. And as we'll come to it in a minute, the first cohorts have already been dosed. For these product candidates in Germany and the United States. Now early on, we decided to enter into partnerships to build a global consortium to advance this program. We thought that, that was the right approach, given that this has become a global pandemic. We're partnered worldwide with Pfizer, which grew out of our existing collaboration around flu vaccine, which we started in 2018 and which will leverage multiple sites from both parties to facilitate rapid development and also scale-up of manufacturing for global supply. That partnership is worldwide ex China. In China, we're partnering with Fosun Pharma. And there, again, we're working very closely with Fosun to initiate clinical studies in China and ultimately, if successful, bringing the vaccine to market. In terms of the study protocol, the study we've started is a Phase I/II trial. It's currently ongoing in Europe and the United States. I mentioned that we have multiple vaccine variants. We actually started with about 20 in the preclinical setting. We did preclinical testing. And we selected 4 for the clinical stage. The Phase I/II trial is focused on the evaluation of safety, efficacy and the determination of the optimal dose. And we actually employ here different types of mRNA. So we're using a uridine-based mRNA, which is what we use in our cancer vaccines, but we're also using a pseudouridine version of RNA and also a self-amplifying RNA, which has the potential to be administered as only 1 dose and also potentially at a much lower dose, which is one of the potential advantages here. So we think that our program with 4 different vaccines in which we expect to have different immunogenicity profiles is differentiated versus some of the other programs that are out there today. One of the other points of differentiation, in addition to the 3 types of mRNA is actually the antigen we're targeting. And so here, we're targeting the folding spike protein, but also an optimized version of receptor binding domain. And to my knowledge, we're the only company, currently in clinical testing, targeting the RBD domain. So in terms of the number of patients for the Phase I portion of the study, we can say that we're targeting 200 healthy subjects, 18 to 55 years old, in Europe. And 360 patients -- up to 360 patients in the United States. The dose range for the study is, of course, the dose escalation study is 1 to 100 micrograms. And as I mentioned, we're going be testing both a Prime/boost approach and also a prime-only vaccine approach in the case of the self-amplifying. So as I mentioned, the next data update for this program, we expect in June, July of this year. Okay. So now just to say a few remarks about antibodies. On Page 23, you see our 3 clinical stage antibodies. The 2 on the left-hand side of the page, BNT311 and 312 are both next-generation checkpoint molecules. These are bispecific antibodies that are partnered 50-50 with Genmab. So we share costs, we share future profit if successful. And both rely on Genmab's dual body bispecific antibody platform and involve a conditional activation of the immunostimulatory checkpoint activity. The antibody on the right-hand side of the page, BNT321 is an antibody targeting, CA19-9, a glycoprotein, associated with a range of different cancers, including some very difficult-to-treat cancers, such as pancreatic. And this is a molecule that we're actually also very excited about. It's -- we brought this in-house last year, in the acquisition of MabVax. And in early Phase I testing, this molecule had actually generated partial responses in first-line pancreatic cancer. Actually 4 of 6 patients had a PR with the remaining 2 achieving stable disease in combination with chemotherapy. So we have -- currently have trials -- Phase I trials ongoing for all 3 of these antibodies. So just to say a few words about BNT311. This is the bispecific PD-L1x4-1BB. On Page 24, you see some of the preclinical data, again, the characteristics here, but this is a bispecific antibody, which combines constitutive checkpoint blockade with this conditional co-stimulatory activity. The real innovation here is, in fact, the conditional 4-1BB agonism. In other words, we don't get 4-1BB agonism, when PD-L1 is not bound. And you see that mode of action, illustrated in the charts at the top of the page, Page 24, showing that PD-L1 is required to get T cell activation, associated with 4-1BB agonism. And in the bottom chart on the page, you see a preclinical model, which compared this molecule to standard PD-L1 and also 4-1BB active molecules, and we show here just superior antitumor activity with this combined approach. So this is one of the reasons that we're quite excited about this molecule. Page 25 highlights the current ongoing Phase I/II study. This is a -- it's quite a large study, 192 patient target enrollment, multiple solid tumor types. You can see that BNT311 is administered in IV formulation, once every 21 days. And the study design includes, both a dose escalation portion in the Phase I and then also a Phase IIa expansion aspect. So the study has been recruiting quite well. And we -- since our IPO, we've moved forward the expected first data update from the first half of 2021 to the second half of this year. And so we expect to provide the first data in humans at that time. So I'll make a few closing remarks now. So we had our Q1 call earlier this week and we updated the market on our cash balance and cash position. And I think the short takeaway is that we've got a strong cash position with cash on the balance sheet at the end of Q1 of $495 million. And in addition to that, we expect $236 million due in Q2. Some of it has already arrived through our Pfizer and Fosun collaborations. We expect net cash used in operating activities and investments into PP&E for 2020 to be on track with originally communicated budget of approximately EUR 300 million for the year. And that's prior to the impact of Neon Therapeutics and the impact of BNT162, the COVID-19 vaccine program. I would note that the majority of the BNT162 costs, the development costs, we expect in 2020 to be funded via the Pfizer and the Fosun cost-sharing equity investment and upfront payment portions of our collaboration. So to summarize, on Page 28. So I think, we've made good progress through Q1 in realizing our vision of moving towards our vision, building a next-generation immunotherapy company. We made progress, both in our oncology pipeline and also in starting our first infectious disease clinical trial in humans. We expect multiple data readouts and late-stage trial starts in the second half of '20 and also in the first half of 2021. And we have since last week, actually, after the closing, of our acquisition of Neon Therapeutics, we have now expanded our operations on a transatlantic basis and established an R&D hub in Cambridge in the United States, which I think is a significant milestone for the company. So in total, we think we have strong momentum moving into the middle half of the year and second half. Thank you very much.

Okay, great. Thanks, Ryan.

Thank you, Tazeen.