BioNTech SE (BNTX) Earnings Call Transcript

Hello, and welcome to all to the UBS Global Healthcare Conference. My name is Navin Jacob, senior analyst, covering large-cap pharma and smid-cap biotech. Our next presentation and fireside chat is with BioNTech, which had a very successful IPO late 2019. I'm very happy to have with me today Chief Strategic Officer, Ryan Richardson. Ryan, thank you for joining us today.

Thank you, Navin.

And so -- exactly. So folks on the line, Ryan is going to walk through a few slides here, just to give some backdrop on BioNTech for folks who are not familiar with the name. And then after that, we're going to have a little fireside chat. Go ahead, Ryan.

Okay. Excellent. So I will be making a few forward-looking statements. And for those of you with the slides in front of you, I'll start on Page 3 and just -- as mentioned, just provide a little bit of overview and sort of give an update in terms of where we are with our pipeline. So BioNTech was founded 12 years ago in Germany as a company focused on developing next-generation immunotherapies for both cancer and infectious diseases. We're a multi-tech platform company. So we're leader in mRNA but also have cell therapy activities and also 3 clinical stage antibodies and even a small molecule, which is poised to go into the clinic. So broad array of technologies but very much focused on immunology, which is the core expertise of the company. From the early days, we've invested into manufacturing. We've got in-house mRNA and also cell therapy manufacturing facilities in Germany at multiple sites. And we've also built our business starting in about 2015 on the back of a number of partnerships with leading companies active in the biopharmaceutical industry. On Page 4, you see some of those partnerships. We've actually got 7 pharma partners plus a couple of university collaborations. And the hallmark of our partnering approach has been to enter into cost and profit share arrangements where we retain the right to commercialize, co-commercialize our product candidates, if approved, alongside our partners. So you see, there are 3 such deals that we've done in oncology. That includes the Roche-Genentech collaboration, which is a 50-50 deal back from 2016. This was focused on our iNeST technology platform. This is a fully individualized immunotherapy, where we develop a just-in-time vaccine for each individual patient based on the molecular signature of their tumor. A Genmab collaboration, which leverages Genmab's bispecific antibody platform, and our target expertise and immuno-oncology knowledge. There, we've got already 2 bispecific antibody candidates in clinical development that's also a 50-50 cost and profit share. And then in the case of Sanofi, we were partnered around an intratumoral mRNA approach. Again, same -- similar model with the cost and profit share. So in addition to that, we've entered into other partnerships using a variety of models. I think Pfizer is a prominent one that you see there on the page. We first entered into a research collaboration. This is our first collaboration in the infectious disease space in 2018 to develop mRNA vaccines against flu. And more recently, we've expanded that collaboration to develop multiple COVID-19 vaccine candidates, which is currently ongoing in clinical trials. I'll speak more about that in a few minutes. But you can see a wide variety of partnerships. Again, Lilly, The Gates Foundation, University of Pennsylvania and our first Asian collaboration with Fosun Pharma, also for COVID-19, entered into earlier this year. So on Page 5, we highlight the hallmark of our IO strategy, which really leverages these different platforms. And I think the important thing here is that we don't think there's a single approach to attack cancer due to the complexity of the disease, the heterogeneity across patients and also across tumor types. And so what we try to do at BioNTech is really bring to bear multiple mechanisms that allow us to target cancer uniquely, which you see on the left-hand side of the page, but also modulate the immune response. And we're developing what we think are very powerful platforms that enable us to do that, including next-generation checkpoint molecules, engineered cytokines in the form of RNA-encoded cytokines where we see really potent synergy with our cancer vaccines in the preclinical setting. And you see some of the examples of this -- these combination approaches on Page 6, which is really, as I said, the cornerstone of our oncology strategy. So 3 examples here on the page. The first on the left-hand side is combining our vaccines with approved checkpoint inhibitors. We've demonstrated clinical data in humans now for both of our vaccine platforms. We've got off-the-shelf vaccine which targets shared antigens. We also have the individualized approach to iNeST that I mentioned earlier. In both cases, we've demonstrated single agent objective responses in the treatment of metastatic disease, refractory metastatic disease. And here's where we see strong combination potential, by combining the checkpoint blockade with vaccines which are potent activators of the immune response and generate oftentimes billions of T cells directed at the antigens of our choosing. In the middle of the page, you see this example I mentioned of the cytokines plus the cancer vaccines. Here, we take an RNA and encode IL-2. We also have a number of these programs actually in the preclinical stage poised to move into development in the next 12 to 18 months, including IL-7 as well and some others where, again, we see really strong amplification of the vaccine effect in terms of inducing T cell responses in preclinical models. And lastly, on the right-hand side, in the CAR-T arena. We published a paper in January this year highlighting our CARVac approach, where we use an mRNA vaccine to actually prime and boost CAR-T cells once infused in patients after initial infusion. And we can do -- what we showed in this paper was an ability to do so in successive fashion and get logarithmic increases in the CAR-T cell numbers. In this case, directed against CLDN-6, which is an antigen that comes out of our own libraries and which is overexpressed in a variety of solid tumors. But we think this an approach in CARVac that could be amplified across -- or could be applied across different CAR-T cell targets and tumor types. On Page 7, we just highlight how we see these different technologies in our toolkit matching against the market need in terms of the cancer segment. And you see here that our primary focus is solid tumors, which is a $90 billion-plus market and obviously growing with high unmet needs still. And we segment this market on the basis of a couple of molecular markers, let's say. So mutation burden or adjuvant stage cancers, where we think, in particular, our iNeST approach is well suited versus low mutation burden cancers which represent a majority of tumors and generally have poor response to checkpoint inhibitors, where we have a number of different approaches that allow us to target shared antigens in differentiated and also powerful ways, examples being FixVac, our CAR-T cell or CARVac approach that I just mentioned and also a number of antibodies, which are also now in the clinic and also extends into cancers with specific resistance mechanisms or immune desert cancers, where we think, again, that a number of our immunomodulatory approaches have a particular promise. Going to Page 8, you see our pipeline. We currently have 11 product candidates in the clinic and 12 ongoing clinical trials. These span both mRNA compounds but also 3 antibodies. So 8 mRNA compounds across different mRNA platforms and 3 clinical stage antibodies. We're really at a sort of transition phase for the company and moving into late-stage development, having now demonstrated clinical activity for our lead candidates, namely our BNT111 program in FixVac melanoma, but also our iNeST program, BNT122, where we've demonstrated first published data in nature in 2017. And just very recently, actually last week, published an abstract showing single-agent activity, again, in a broader range of tumors outside of just melanoma and plan to present more of that data in June at AACR. In addition, we have our first program in the clinic outside of oncology in the form of our COVID-19 vaccine program, it's BNT162, you see on the page, where we're partnered with Pfizer and Fosun. Pfizer worldwide ex China, Fosun in China. We are currently conducting clinical trials in Germany and in the United States and plan to also initiate trials in China. And this is a broad program for COVID-19, where we have 4 different candidates that we plan to study in the first phase and have an upcoming readout, which I'll talk about a little bit more in a slide or 2, but readout expected in June-July time frame in terms of first human data. On Page 9, you see the rest of our preclinical pipeline. You can see that it's quite broad with a number of first-in-human study starts anticipated in 2021 or even later this year, actually. And those, again, span both mRNA, also our cell therapies, CAR-Ts and TCRs, and a small molecule program as well, which we plan to take into the clinic in the second half of the year. And in addition to this preclinical oncology pipeline, we have a number of programs outside of oncology in the infectious disease realm. I mentioned flu vaccine with Pfizer, where we plan to take our first program into the clinic next year. But we've also done other partnerships with University of Pennsylvania and The Gates Foundation in over 10 indications to develop, again, mRNA vaccines across a number of different infectious disease areas. I think this, along with our rare disease partnership with Genevant forms a future growth pillar for the company. And just to summarize upcoming readouts on Page 10. You see that it's -- we expect a busy second half of 2020 and 2021, with multiple data readouts expected, I think. The ones to highlight here are highlighted in green. That includes a publication for our BNT111 program in advanced melanoma. Again, this is where we had -- this is a trial that had -- we reported top line data for last year, both monotherapy objective responses with vaccine alone in heavily pretreated and even CPI progressive patients, but also showed a combination arm where we combined FixVac vaccine. Again, this is a shared antigen vaccine and combined with checkpoint blockade in patients who were progressing at checkpoint monotherapy at baseline, where, again, we showed what we thought are very encouraging response rates. These are objective responses as measured by RECIST criteria, but objective responses in multiple cancer patients who were progressing on checkpoint therapy alone. So we have 5 FixVac programs in the clinic in total. But for this first one, melanoma is our lead candidate, and we expect to publish data very, very soon, actually over the summer, showing much more mechanistic biomarker data highlighting the mechanism of action and then also plan to start a registrational trial by year's end in melanoma. For iNeST, I mentioned that we have -- we just released an abstract for AACR last week. We have a second abstract coming, which is currently embargoed and plan to have a presentation in June to talk about what we think is also very encouraging data, both in terms of safety, but also in terms of immunogenicity and initial signs of clinical activity for our individualized vaccine. This is, again, just-in-time vaccine made for each patient where, for the first time, we'll highlight broad-based immunogenicity and also clinical activity data across a broad range of solid tumors, including some very difficult-to-treat tumors, highly refractory tumors, low PD-L1 expression and what we think is the exciting data that warrants expanding into some additional later stage trials later this year. And then also, I'll highlight that in addition to the BNT, the COVID-19 vaccine data, which we expect, as I said, in June or July. We also expect in the second half of the year first data for our bispecific antibody. This is a PD-L1 4-1BB. This is, again, partnered with Genmab 50-50. We see great potential in this molecule to potentially establish a new standard of care in certain solid tumors. In the preclinical setting, we've seen this molecule outperform first generation checkpoint inhibitors and are excited to present our first data in humans likely in the back end of the year. So to summarize on Page 11, we've seen rapid progress in our pipeline. We actually had an IPO last year in October. We had 7 clinical stage programs. I mentioned now, we have 11. We have a lot of data coming over the near, medium and certainly longer terms as well, with multiple late-stage studies planned to start, actually up to 4 different registrational studies planned by the end of 2020. We've recently expanded our footprint. We're a German-based company in terms of our HQ, but have acquired -- actually closed the transaction acquiring Neon Therapeutics in Cambridge, Massachusetts a couple of weeks ago now, which gives us a hub firmly in one of the biotech hotspots in the United States with operations to support our -- both our clinical trial and other research activities globally. And lastly, I think we've got very strong momentum going into the rest of the year. I'm happy to jump into questions.

Fantastic, Ryan. Thank you so much. So I mean, obviously, very exciting few weeks here, months. It really has only been 4 or 5 weeks since all the vaccine data started reading out and the progress being made by all the various manufacturers and developers, including yourselves. Yesterday, Moderna, of course, came out with their first dataset in human dataset. Wondering what your first take was on the Moderna data as well as the preclinical data that we saw out of University of Oxford. What are some of the read-throughs that one could make with regards to the BioNTech 162 program?

Yes. It's a good question. I mean -- so I think, first of all, I think we find it encouraging. We do believe that a vaccine is likely to be found here, and perhaps multiple vaccines are likely to work based on the totality of the evidence that we see. And in the case of the Moderna program, I think it's doubly encouraging to see an mRNA vaccine using a modified -- pseudouridine-modified mRNA backbone targeting folding spike protein to see that what appear to be some early positive signal. We have a broad program at BioNTech in terms of COVID-19. So we have multiple candidates currently in clinical testing. And one -- we do have a candidate that also is pseudouridine-based mRNA, so similar mRNA construct also targeting folding spike. So I think from that perspective, that's certainly encouraging. We also have a couple of other approaches that we've incorporated into our vaccine program. So I think there are some points that differ in terms of how we're approaching it. I think on one hand, I think our program is quite broad versus some others. So we have multiple mRNA technologies in our toolkit. Those include uridine-based mRNA, the pseudouridine format and then also a self-amplifying format. And those different mRNA technologies have -- we would expect them to have different immunogenic profiles. I think potentially different pros and cons, including, in the case of the uridine mRNA and the self-amplifying, a potential to induce immunity at a lower dose. And that's one of the reasons why we included that in our program. But I'd say -- so that's -- it is encouraging, but I think at the same time, we're also very excited about our multi-variant approach.

And is the approach with the 3 different modalities and 4 candidates, is that based on sort of a risk mitigation strategy or sort of multiple shots on goal? Is that the idea behind it? Or is it -- is the idea that ultimately -- or is the idea that BioNTech ultimately feels that you need to have -- you're going to have different risk parameters for each different groups within the population, and as such, it requires a multi vaccine approach, which is also, by the way, what Merck believes. Or do you ultimately believe that one met vaccine should hopefully address all parts of the population? And really, the strategy that you've employed is just to ensure that you have multiple shots on goal?

Yes. Yes, it's a great question. So I think it's a mix of different rationales. I think on one hand, so when we started the program, and I think it's still largely true today, there's still a lot of biology that we don't know about this virus and about how it manifests and what the relevant clinical thresholds will be. For example, what titer level is needed to really have correlate to a meaningful protection benefit, right? And so because we were starting the program very quickly and didn't know exactly what we're solving for, right, I think that's true across the industry, to an extent. We thought it made sense to leverage the full toolkit that we have at our disposal, right? And we had made investments and have a lot of experience in some of these other technology areas that we thought could -- would add a dimension to our program to give us more flexibility. So I think that's the first rationale, just the simple unknowns associated with the disease. But I think it's also true, your second point, that as we've now progressed and start to see more data from our programs, both preclinical and how we anticipate clinical data soon, I think it's also true that there's certainly a possibility that the different approaches will be -- will have merit, but that actually will be different -- suited to different ends. And so one of our strategies is to get a vaccine to market as quickly as possible. And I would say related strategy is to bring the optimal vaccine profile to the market. And we don't yet know if that's a single product candidate that's met for everyone and that's suited for everyone or if that may actually be multiple candidates. So I think we leave the door open at this point to bringing multiple product candidates forward if we see evidence that -- if there's a strong rationale to do so. And one factor that may provide a strong rationale would be the dose because our assumption is that given what will likely be, let's call it, unprecedented demand for a vaccine globally during a pandemic phase that we're in, that there will be supply constraints. And I think those are certainly likely if an early approval is granted relatively soon or early, let's say, in the back end of 2020, and if the dose required to induce immunity is high, right? And so in that scenario, we think that having a lower dose option could add -- could really be game-changing in terms of the ability, our ability and to the industry's ability to produce the hundreds of millions, if not billions of doses required to serve the global need. So I think the dose is very important here, and I think that's one of the factors that also we have to look at and we're considering -- we're looking at very closely as we evaluate these candidates and how they perform in the clinic.

And so when you think about sort of the goalpost here or sort of the go/no-go decisions that you're going to be making over the next few months, you suggested there's a possibility of going into Phase II with more than one candidate. Does that decision happen in the summer? When do you make the decision of going forward with multiple candidates? Or do you have to see one "fail" or -- before you -- or before moving on with another one? Any kind of clarity would be helpful.

Yes. So we've started the Phase I/II trial currently in the United States and in Europe, and we expect the first data to come in, let's call it, late June or July, first new data. And we expect that data to be -- to obviously be safety data, showing that initially that the vaccine is safe. That would be our hope, our goal. The other intention is to show data that on immunogenicity and to show data that -- on dose, right, for one or more candidates and to also provide more information on the expected path forward. And so we're designing the studies to be seamless in terms of transition to late stage. And our hope is that if the data is positive, that we could be in a position to already go forward -- move forward in the late summer into Phase III. I think that's the -- that would be the goal.

You mentioned trying to understand what's the right level of titer to confer immunity and ensure that you have protection and have memory. What are some of the goalposts that you're looking for that you want to be able to beat? Moderna speaks to being able to achieve the same level of neutralizing antibodies as seen with convalescent plasma and with their high dose above that. Is there a -- in your mind, in the minds of your R&D folks, a marker that's in place, okay, we got to achieve 2x -- I'm just making this up, but just by context, we have to achieve 2x that -- what's seen in convalescent plasma.

No, I don't think that there's a specific threshold. I think that there's not a specific threshold right now. That is the target. I mean, I think it's -- certainly, we're going to look for virus-neutralizing titers and antibody responses. I mean, I think that's important. But we're also going to look at the immunological profile in totality, and we also expect to generate T cell responses as well. And ultimately, I think it's -- there's not yet a consensus among scientists and regulators around what is the relevant threshold to meet. I think there's -- we are -- I think, the industry as a whole is gaining knowledge on this very rapidly, and it's our hope that a consensus will emerge quite quickly. But I wouldn't say there's a specific threshold at this point that we're looking for. I think we'll have to evaluate the data in terms [indiscernible].

And your expectation for sort of best case and base case time lines for approval, whether that's on an emergency use authorization or on a broad scale basis. And what exactly do you use for EUA? What exactly has to be used for EUA versus broad scale approval?