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spk06: Good morning and good afternoon, and thank you for joining us today to review BioNTech's first quarter 2022 clinical and operational brokers and financial results. A few housekeeping items before we start. Please view the slides that accompany the webcast and the first quarter 2022 press release. Both were issued this morning and can be found in the investor section of our website. As outlined on slide two, today's presentation will be making several forward-looking statements. These forward-looking statements include but are not limited to our current COVID-19 vaccine revenues as they include figures that are derived from preliminary estimates provided by our partners. Our estimated financial results for 2022, the continued global demand for our COVID-19 vaccine, our target vaccine production capacity for 2022 and beyond, our ability to supply our COVID-19 vaccine, the planned next steps in our pipeline programs, the timing for enrollment, initiation, completion, and reporting of data from our preclinical studies and our clinical trials, the timing of and our ability to obtain and maintain regulatory approval for our product candidates, and other risks described in our findings made with the U.S. Securities and Exchange Commission, including our most recent annual report on Form 20-F. As actual results could differ from those we currently anticipate, You are therefore cautioned not to place undue reliance on any forward-looking statements which speak only as of today, shared today, during this conference call and webcast. Also, please note that Slides 3 and 4 provide detailed and important safety information regarding our COVID-19 vaccine. Finally, you can see the agenda for today's call on Slide 5. It's my pleasure to introduce the members of the biotech management team participating in today's call. I'm joined today by our CEO and co-founder Uwe Sahin, Özlem Tureci, our chief medical officer and co-founder, Jens Holstein, our chief financial officer, and Ryan Richardson, our chief strategy officer. I would like to turn the call over to Uwe Sahin.
spk05: Thank you, Silke. Good morning and good afternoon and a warm welcome to all participants. And thank you for your continued support. Today I am happy to provide you an overview about the key highlights from the first quarter and objectives for the year. Our team will provide further details and then we will open the call for questions. Starting on slide six. Let me remind everyone about a few features of our company. Our vision is to harness the immune system to fight human diseases. Our response to the COVID-19 pandemic provided us with the unique opportunity to help protect well over 1 billion people with our first approved product. It provided us also a historic chance to accelerate our progress towards our long-term vision to bring the next generation of immunotherapy to patients. With a fully integrated spectrum of competencies for biopharmaceutical drug development, covering discovery, translational research, development, GMP manufacturing, and commercial capabilities, we are very positioned for success. We are pursuing a technology agnostic solution focus, multi-platform strategy, and have built an innovation engine that covers various emerging technologies. We are advancing a diversified product pipeline of immunotherapies that aim to address high unmet medical needs in oncology and multiple infectious disease indications. We are building a 21st century immunotherapy powerhouse with a mission anchored to our strong sense of global social responsibility. We seek to make a positive impact on global health and democratize access to cutting-edge medicines. Highlights for the first quarter are summarized on slide seven. Our solid performance continued in the first quarter of 2022, following a strong fourth quarter in 2021. In the first quarter, we reported total revenues of 6.4 billion euros. We signed our first pandemic preparedness contract with the Federal Republic of Germany that runs through 2027. The framework agreement is aimed at pandemic preparedness, including development, manufacturing and supply of mRNA vaccines in emerging situations in Germany. During the first quarter, we also engaged into collaborations that complement our internal innovation engine. The MATINAS collaboration combines our mRNA vaccine development expertise and MATINAS lipid nanocrystal delivery platform technology to advance novel formulations for mRNA vaccines, including a potential formulation for oral vaccines. With Regeneron, we plan to jointly conduct clinical trials, evaluating fixer candidate BNT1-16 in combination with Liptio for the treatment of advanced non-small cell lung cancer. Our impact on human health and economy around the globe continues in 2022. We have invoiced approximately 750 million doses of our COVID-19 vaccines globally in 2022 until the end of the first quarter. In terms of expanding our labor to a broader population, we recently received certain approvals. These include a fourth dose in adults aged 50 and over, as well as in certain types of immunocompromised patients aged 12 years and older. Our pediatric indications now include vaccinations in children aged 5 and over, as well as boosters for those 12 and up in multiple geographies. On the oncology front, our first ribomap program, BNT141, entered a first in human study in solid tumors in January. 141 is an mRNA-encoded IgG antibody targeting Claudine 18.2. In April, we presented a promising preliminary clinical data from 14 available patients in our Phase 1-2 trial of BMP211, our next-generation Claudine 6 targeting CAR T cells in solid tumors at the AACR annual meeting. We documented first antitumor effects even at the lowest CAR T-cell dose in heavily patient population, pointing to an encouraging activity of targeting Clotin-6 and our CARVAC approach. Slide 8. Since the start of the pandemic, we have delivered nearly 3.4 billion doses of Cominati to people located in more than 175 countries and regions, demonstrating our strong global position in the fight against COVID-19. We remain on track to achieve our pledge to deliver a total of more than 2 billion doses to low- and middle-income countries by the end of 2022. To stay ahead of COVID-19, we continue to innovate and optimize our vaccine. This year, we have introduced a ready-to-use formulation that does not require diluent and receives approval for shelf-life extension from 9 to 12 months when stored at minus 90 to minus 60 To further expand the label to pediatric populations, we have filed for the approval of boosters in children five to under 12 years old. The filings were supported by recently reported positive data demonstrating that a third dose increased neutralizing antibodies six-fold in this age group. We are also evaluating a three-dose primary regimen in children six months to under five years old and expect data As part of our approach to pandemic preparedness, we are collaborating with InstaDeep on an early warning system that analyzes globally available sequencing data and predicts high-risk variants of SARS-CoV-2. This warning system allows us to rapidly adapt our vaccine product candidates in a data-guided way. As part of our preemptive approach to variants, we have an ongoing comprehensive development program that we are evaluating several follow-on and next-generation COVID-19 vaccines, including variant-adapted vaccines. We also have initiated a broad research program to study the immune profile after vaccinations, boosters, and breakthrough infections. This research program is informing our vaccine development strategy. To conclude my opening remark, As shown on slide 9, we are building a differentiated pipeline that we believe could usher in a new era of immunotherapy through multiple ways of innovation. Our COVID-19 vaccine program is enabling a transformation of our company that will position us to broaden and accelerate our pipeline toward the market, consistent with our vision to transform medicine. In oncology, we have 16 programs in 20 ongoing clinical trials. including five randomized phase two trials. In infectious diseases, we have one ongoing phase one program and more than 10 preclinical programs, four of which we expect to bring into the clinic this year. Our aim is to bring multiple new products in oncology and infectious disease to market over the next three to five years. We believe that our technology innovation engine has the potential to address a broad set of diseases beyond our current core disease pillar oncology and infectious diseases. There's multiple programs underway in new disease areas that are in the lead candidate selection phase. Advancing our technology into these new areas expands the future for BioNTech and will support our vision in the long term. With that, I will turn the call over to Esther.
spk07: Thank you, Ugo. I'm delighted to speak with everyone today and provide our pipeline update. Our COVID-19 vaccine R&D strategy on slide 11 rests on three pillars, landscape research, product research, and product development. Our landscape research aims to elucidate how the virus evolves within the context of vaccine and infection-induced immunity. We are studying how immunity is being shaped over time by iterations of vaccinations, ongoing boosters, and infections with different variants of concern. The data we are continuously generating will inform our evolving response to the pandemic. A recent research study has added to our understanding and may be crucial in the development of next-generation vaccines. These data have been submitted for peer review in a high-rank journal and published on a preprint server. In the study, we evaluated the sera of individuals who had breakthrough infections with Omicron after either two or three doses of the original vaccine to determine the impact of Omicron infection on immunity. We found that the exposure to Omicron spike by Omicron breakthrough infection of vaccinated individuals strongly enhances not only neutralizing activity against Omicron BA1, but broadly augments immunity, including against Omicron BA2, previous SARS-CoV-2 variants of concern, and even SARS-CoV-1. Omicron breakthrough infections mediated a broad B-cell recall response, primarily through expanded memory B-cells that recognize antigens shared broadly by different variants rather than inducing new B cells against strictly Omicron-specific antigens. Taken together, these results suggest that despite possible imprinting of the immune response by previous vaccination, the preformed B cell memory pool can be refocused and quantitatively remodeled by exposure to spike proteins from different strains. We believe this may allow neutralization of variants that evade a previously established neutralizing antibody response. The observation also may suggest that a vaccine adapted to the Omicron strain spike could similarly reshape the B-cell memory repertoire and therefore may be more beneficial than an extended series of boosters with the existing vaccine directed against the original strain. We believe that the data may also suggest that exposure of ancestral strain vaccine experience individuals to an Omicron spike monoimmune vaccine could provide similar cross-strain immunities. To be prepared for future challenges we may face with further involvement of the virus, we have been engaged since the approval of BNT162b2 in a very robust product research effort to explore various follow-on and novel next-generation vaccines to prevent COVID-19. These are currently in development, and several approaches may move into the clinic this year. We are evaluating mono- and multivalent vaccines, T-cell enhancing approaches, and pan-coronavirus covering vaccine concepts. Our landscape research helps our product development strategy that currently focuses on responding to the need for vaccine adaptation due to the emergence of Omicron and its sub-lineages. Our clinical program evaluating the safety, tolerability, and immunogenicity of various variant-adaptive vaccines in multiple clinical trials is advancing. Emerging data from these trials will be reviewed and discussed with regulators in the coming weeks to determine the appropriate regulatory path forward. for either monovalent or bivalent variant-adapted vaccine product candidates. As a reminder, slide 12 shows our comprehensive clinical response strategy to the Omicron variant. We are investigating different dose schedules of a monovalent Omicron-adapted vaccine, for example, in individuals aged 18 to 55 years and evaluating bivalent approaches as well. We expect data from these studies will be available in the coming weeks. While there is currently no regulatory consensus on the benefit of Omicron-adapted vaccines, we anticipate regulatory developments as clinically meaningful data become available. As we await the data, we remain prepared to adapt our technology and manufacturing processes to ensure that our vaccine provides robust protection against current and emerging variants of concern. Slide 13 highlights our expansive oncology pipeline that is the result of our comprehensive, innovative, multi-modality toolbox and our focused execution for our 2021 and 2022 We have multiple assets in development across different immune therapeutic modalities with the possible potential to tackle tumors using complementary strategies, either by targeting tumor cells directly or by modulating the immune response against the tumor. Many of our product candidates can be combined with our pipeline assets. Our oncology pipeline includes the total of 16 product candidates across four different drug classes and 20 ongoing clinical trials, five of which are randomized phase 2 clinical trials. We expect continued pipeline advancement and expansion as well as further data readout from the ongoing trials in 2022. We believe that this will be a year of focused execution across our five Phase II clinical trials in multiple tumor types as shown on slide 14. First, we have two Phase II trials ongoing that are evaluating fixed-vec or off-the-shelf mRNA vaccine immune therapy platform. BMP111, which is being evaluated in anti-PD-1 refractory relapsed advanced melanoma, encodes four tumor antigens that cover greater than 90% of cutaneous melanoma patients. Our approach may have the potential to improve outcomes when used in combination with anti-PD-1. We have received FDA path track and often drug designations for this program. BNT-113, which encodes HPV-16 oncoprotein B6 and B7, is being evaluated in HPV-16 positive PD-L1-positive head and neck cancers in combination with anti-PD-1. Next, we have, with our partner Genentech, two individualized neoantigen-based vaccine programs, INES programs, evaluating autogen, cerumerin, or BNT1-22 in phase 2 trials, one in frontline melanoma and one in colorectal cancer in the adjuvant settings. If our melanoma trial is successful and accepted by regulators, we would unlock the possible use of INS as a frontline therapy in combination with anti-PD-1 in anti-PD-1 relief advanced cancers. In colorectal cancer, we aim to address the residual cancer cells that remain after treatment with standard therapy, a key driver of relapse. Finally, BNT311 Our bispecific antibody that we are developing with our partner, GenMed, is in an ongoing Phase II study in refractory or recurrent non-small cell lung cancer. This next-generation immune therapy uses conditional 4,1-BP co-stimulation concurrent with PD-L1 blockade with the goal of tumor-targeted enhancement of T-cell and natural killer cell functions. Turning now to slide 15, we recently presented promising efficacy and safety data for BNT211, our next-generation CAR T-cell program at the AACR annual conference. BNT211 combines two of our platforms that we believe have complementary modes of action, clotting six CAR T-cells and a CAR T-cell amplifying RNA vaccine called CARVAX. based on our lipoplex technology used in other cancer vaccine programs. Chloridine 6 CAR T-cells are equipped with a second-generation chimeric antigen receptor of high sensitivity and specificity for the carcinoembryonic tumor-specific antigen Chloridine 6. Chloridine 6 is absent in healthy adult tissue, yet frequently expressed in high medical need cancers. making this tumor antigen an ideal candidate for CAR T-cell therapy. In preclinical studies, we demonstrated that CARVAC drives in vivo expansion of transferred CAR T-cells, increasing their persistence and efficacy. BNT211 aims to overcome CAR T-cell therapy limitations in patients with solid tumors. The ongoing first in human phase 1-2 trial is evaluating the safety and efficacy of Chlorine 6 CAR-T cells as monotherapy and in combination with CARVEC in patients with Chlorine 6 positive relaxed or refractory advanced early tumors. We are testing free dose levels of Chlorine 6 CAR-T cells as monotherapy dose escalation as well as in combination with a fixed dose of the RNA-X. The subsequent dose expansion cohorts will include patients with ovarian, testicular, and endometrial cancers, as well as other rare chlorine-6 positive cancer types, such as sarcoma. Slide 16 provides a summary of the AACR data. The presentation included data from 16 heavily pretreated patients who received chlorine-6 CAR T cells alone at two dose levels, 1 x 10 to the 7th and 1 x 10 to the 8th, or combined with CARBAC after lymphodepletion. Two more indications included eight testicular cancer patients for ovarian cancer patients and one patient each for endometrial cancer, fallopian tube cancer, sarcoma, and gastric cancer. The results demonstrated a tolerable safety profile for both the CAR T-cells as monotherapy and when combined with CARVEC. And eight patients experienced cytokine release syndrome, grade one to two, which was manageable with tocilizumab, with no signs of neurotoxicity seen. So far, two dose-limiting toxicities were observed. Both were manageable and patients fully recovered. One was hemophagocytic lymphohistiocytosis observed in the combination part at dose level 2. The other observed in the monotherapy cohort at dose level 2 was prolonged cytopenia in a testicular cancer patient with a recent relapse on high-dose chemotherapy and autologous stem cell transplantation. a new cohort with reduced lymphodepletion chemotherapy was subsequently opened to avoid prolonged cytopenia in testicular cancer patients with a history of high-dose chemotherapy. The maximum tolerated dose has not yet been reached. The preliminary efficacy data showed encouraging signs of clinical activity with an overall disease control rate of 86%, and an overall response rate of 43%, with partial response observed in patients with testicular and ovarian cancer. Five patients with testicular cancer were treated at 1 to 10 to the 8th CAR T cell dose level and showed encouraging responses with an objective response rate of 80% and a disease control rate of 100%. One patient had a complete response, three had partial responses, and one had stable disease. This sub-analysis includes one additional patient with partial response that received a reduced lymphodepletion regimen. The addition of CARVEX-supported CAR-T engrossment and mediated physiological expansion plus upregulation of survival pathways in patients receiving the combinations. We also observed deepening of responses over time and continuing long-term persistence of CAR-T in some patients with CAR-T persistence lasting beyond 150 days post-infusion. Slide 17 shows the CAR-T engraftment. All 16 patients showed robust CAR-T cell engraftment with peak expansion 10 to 17 days after infusion. reaching cell frequencies above 10 to the 8th total cell count at the 10 to the 8th dose level. We observed that incremental improvement of CAR T-cell expansion either through a higher dose level or by adding the CARVAC vaccine translated into clinical activity and response. Slide 18 provides an overview of the preliminary signs of clinical activity. Fourteen patients were evaluable for efficacy assessment with at least one scan six weeks post-infusion. Six patients showed partial responses, and an additional five patients had stable disease with shrinkage of target lesions, as shown in gray diamonds with green outlines. One patient had no change from baseline, and two patients had no signs of clinical activity, both of which were rapidly progressing prior to adoptive cell transfer. This resulted in an objective response rate of 43% and a disease control rate of 86% across all patients. At 12 weeks, four of the six patients with a partial response showed deepening and durability of responses, with one patient reaching a complete response 18 weeks after infusion. All four testicular cancer patients in the higher dose level had disease control, and three of these patients showed objective responses. In addition, one testicular cancer patient showed a partial response after infusion of the lowest CAR-T dose level in combination with CARB-X. At the very bottom of the slide under the gray bar, we wanted to share one further testicular cancer patient who has shown a partial response after a reduced lymphodepletion regimen. That patient is not included in the 14 available patients we discussed previously. In summary and most encouragingly, all initial partial responses showed deepening at the second assessment, and one partial response patient transitioned to a complete risk. The waterfall plot on the left of slide 19 shows the best response for those four testicular and two ovarian cancer patients who responded focusing on the testicular cancer patients. You see a spider plot on the right depicting the duration of the responses. Besides one patient that only received the lower 10 to the 7th dose level without CARVEC, all other patients showed a clinical benefit. All achieved responses show signs of continuing response durability. This includes the patient whose initial partial response deepened to an ongoing complete response 18 weeks after infusion. Slide 20 shows cancer of two testicular cancer patients with tumor regression. Both patients had multiple prior treatments and relapses before receiving BNT211. Patient one is a 61-year-old male diagnosed in 2008. He had previously received six lines of treatment and showed a complete response after CAR-T treatment at dose level two without CARB-X. The large lung metastasis was completely eliminated over time, and the patient remained tumor-free as of the latest scan with a serum tumor marker alpha-fetoprotein at normal values six months after infusion. Patient 2 is a 56-year-old male testicular cancer patient diagnosed in 2020 who received dose level 1 and was additionally treated with CARBEC. Treatment translated into a robust response, as you can see in those scans, with substantial shrinkage of more than 50 lung metastases. Following the week, 12th scan, the patient had new lesions. As the on-treatment biopsy showed positivity for Claudine 6, the patient was redosed with CAR T-cells on day 197, and we have seen a tumor marker response already. We are very encouraged by the safety and activity data, and another data update from the ongoing Phase I-II trials is expected in the second half of 2022. I'd now like to turn over the call to Jens Holzstein, who will cover our financial results.
spk10: Thank you, Özlem, and a warm welcome to those of you on the phone. I'll start my section by presenting the key highlights for the first quarter of 2022, which you can find on slide 22. The first quarter of 2022 has been an extraordinary one, which also becomes visible by looking at our key financial highlights. Our total revenues reported for the first quarter of 2022 reached 6.4 billion euros, reflecting a record figure for the company since its inception. As a consequence of this top line number, we ended the first quarter with an operating result of 4.8 billion euros and generated earnings per share on a fully diluted basis, of 14 euros and 24 euro cents. In respect of cash, we ended the first quarter of 2022 with 6.2 billion euros of cash and cash equivalents, as well as trade receivables of around 12.7 billion euros. The trade receivables are mainly derived from our collaboration with Pfizer and mainly remained outstanding due to the contractual settlement of the gross profit share under the collaboration. From our outstanding trade receivables as of March 31st, 2022, we had already collected 5.2 billion euros in cash by mid April, 2022, improving our cash and in turn, reducing our trade receivable position subsequent to the end of Q1, 2022. Continuing with slide 23, I want to point out how strong our first quarter in 2022 has been. As mentioned before, we had recognized approximately 6.4 billion euros of COVID-19 vaccine revenues during the first quarter of 2022. This has been the result of an increased order volume initially placed in late 2021 following the then emerging Omicron variant. Let me give you some more details on our revenue stream. As a reminder, on our COVID-19 vaccine collaborations, territories have been allocated between us Pfizer and Fosun Pharma based on marketing and distribution rights. Our COVID-19 vaccine revenues included 4.6 billion euros revenues related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners' territories. These revenues already represent a net figure, meaning that we generate 100% gross margin of those revenues. As we have mentioned in the past and explained in more detail in our financial statements and filings with the SEC, our profit share is to some extent estimated based on preliminary data shared between our collaboration partner Pfizer and us. Our COVID-19 vaccine revenues during the first quarter of 2022 comprised approximately 1.2 billion euro revenues from direct COVID-19 vaccine sales to customers in our territory. which is significantly driven by the orders that we placed in late 2021 following the then-emerging Omicron variant. Also included in our COVID-19 vaccine revenues during the first quarter of 2022 were €0.6 billion from sales to our collaboration partners. Again, we started the year very strong, which we believe gives us a solid foundation for achieving our previously announced guidance for the 2022 financial year. We expect the following quarters to be lower than Q1 given the current situation of the pandemic. I'll be moving to our financial results for the first quarter of 2022 as shown on slide 24. Having explained our revenues on the previous slide, let me move now to the cost of sales that breached approximately 1.3 billion euros in the first quarter of 2022 compared to 0.2 billion euros for the comparative period in 2021. The increase in cost of sales resulted mainly from the recognition of costs related to our COVID-19 vaccine revenues in our own territories that include the share of gross profit that we owe to our collaboration partner Pfizer. This increase in cost of sales is additionally attributed to expenses arising from inventory write-offs and for production capacities derived from contracts with contract manufacturing organizations. Research and development expenses were approximately 0.3 billion euros for the first quarter of 2022, compared to around 0.2 billion euros for the comparative period in 2021. The increase was mainly due to the recognition of costs related to the production of pre-launch Omicron vaccine products as research and development expenses in the period incurred, as well as increase in headcount. The increase was partly offset by lower research and development expenses related to our COVID-19 vaccine program as compared to the prior year period. General and administrative expenses reached 90.8 million euros for the first quarter of 2022 compared to 38.9 million euros for the comparative period in 2021. The increase in G&A was mainly due to the increased expenses for purchase management consulting and legal services as well as an increase in account. Income taxes were accrued in an amount of €1.3 billion tax expenses for the first quarter of 2022 compared to €0.5 billion tax expenses for the comparative period in 2021. The derived effective income tax rate for the first quarter of 2022 was 26.3% and is expected to be around 28% for the full year. For the first quarter of 2022, net profit reached 3.7 billion euros compared to 1.1 billion euros for the comparative period in 2021. Our diluted earnings per share for the first quarter of 2021 amounted to 14 euros and 24 euro cents compared to 4 euros and 39 euro cents for the comparative period in 2021. Moving to slide 24 that shows that we reiterate our outlook for the 2022 financial year. We started very strong with Q1 2022 and reiterate our full year guidance, even though we have to acknowledge the uncertainty derived from the course of the pandemic and the political uncertainties of the recent months. Considering the unchanged order book of approximately 2.4 billion doses for delivery during the 2022 financial year, we are confirming our estimated COVID-19 vaccine revenues of approximately 13 to 17 billion euros for the full year 2022. For 2022, we also reiterate our planned expenses and CAPEX, as well as the estimated annual effective income tax rate, which we have summarized for you on the slide. And with that, I turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our outlook for 2022 and concluding remarks. Thank you.
spk11: Thank you, Jens. Turning to slide 27 and our priorities for the remainder of the year. We continue to focus on supply of our COVID-19 vaccine and the development of our pipeline of next generation vaccines. Earlier this year, we announced a multi-year pandemic preparedness contract with the German government and discussions with other governments are underway. In oncology, we expect our first readout from a randomized phase two trial in addition to data updates from our ongoing phase one, two trial at BNT211, our CAR T-cell program for solid tumors. We continue to prepare for the initiation of multiple registrational trials across our pipeline in the next 12 months, and we'll provide further updates on those plans later in the year. In infectious disease, we plan to initiate first in human clinical trials for four additional mRNA vaccine programs in 2022, in addition to building out our expanding preclinical portfolio. Additionally, we are accelerating the expansion of our platforms into new therapeutic areas such as autoimmune disease, regenerative medicine, and cardiovascular disease, and expect to make lead candidate selections for several programs. To support our focused execution against these goals, we are investing in our foundation, particularly in building out our digital and AI capabilities, as well as our global development team to support further pipeline expansion, which we envision in the coming years. On slide 28, Our COVID-19 vaccine order book for the year stands at approximately 2.4 billion doses, with approximately 750 million doses invoiced by the end of the first quarter. We expect multiple BNT162b2 data updates throughout the rest of the year, including data for a three-dose regimen in children ages six months to five years, which we expect in the coming weeks. We are evaluating a fourth dose in adults ages 16 and older as part of a comprehensive variant adapted vaccine program. In addition, we expect to disclose safety and immunogenicity data for our Omicron adapted and bivalent vaccines in the coming weeks, which will inform our ongoing regulatory discussions. Moving to slide 29 and our expected pipeline milestones for 2022. We expect to initiate seven first in human trials this year, including for our mRNA vaccines for shingles, tuberculosis, HSV2, and malaria. In January, we dosed the first patient for our BNT141 Ribomab program, the first program from this exciting new platform. We anticipate our second Ribomab program, BNT142, which encodes a CD3 Clawden 18.2 bispecific antibody, will enter the clinic in the coming months. BNT116, our fixed vac program for non-small cell lung cancer, which will be evaluated in combination with Liptio as part of our expanded Regeneron collaboration, is also expected to enter the clinic in the second half of the year. We expect data updates from three further programs this year, BNT161, an influenza mRNA vaccine partnered with Pfizer. And in the second half of 2022, we expect to have a data update from BNT122, our INES program, being evaluated in combination with pembrolizumab as a frontline treatment for melanoma. Finally, we expect further data updates this year for our BNT211 CAR T-cell program, which Aslam highlighted. Before concluding, on slide 30, I would like to remind investors that we will have our annual general meeting on June 1st, for which detailed information can be found on our website. And we will host our first virtual Capital Markets Day on Wednesday, June 29th. I would like to thank our shareholders for their continued support and will now open the floor for questions.
spk01: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. Please limit yourselves to one question only. To withdraw your question, press the pound hash key. Once again, star 1 if you would like to ask a question. Your first question today comes from the line of Matthew Harrison from Morgan Stanley. Please go ahead, your line is open.
spk02: Great. Good afternoon. Thanks for taking the question. I guess maybe if you could just give us a little bit more detail on your current thinking around what regulatory discussions you need to have in terms of the boosters and what the regulatory pathway, especially in the U.S., is going to look like here. Is your expectation that you can just run a simple bridging study or might it be more complicated than that? Thanks very much.
spk05: Yeah. So I think I can take the question and maybe Asim can complement. The regulatory path towards authorization of a variant adapted vaccine is not clearly defined yet. We had a number of meetings with regulatory authorities, including FDA and EMA, And they proposed to see the data on monovalent vaccines as well as bivalent vaccines and would like to make the decision based on the data. As you might have heard, the FDA is planning a VRTAC meeting end of June where they indicated that they would provide more clearer guidance about the vaccines, vaccines that are preferred for the next season. A similar statement was made by the EMA. Both authorities seem to prefer an authorization of vaccines in the timeframe of August, September, October. So that the process is ongoing. We are generating data for monovalent and different bivalent vaccines, including lower and higher doses, and we'll have the data available for discussion with the authorities. So I hope that answers the question. The next question.
spk01: Thank you. Your next question comes from the line of Corey Kazimoff from J.P. Morgan. Please go ahead. Your line is open.
spk04: Hi, good morning and good afternoon. I wanted to follow up on this general line of thinking, recognizing that there's data from various COVID programs anticipated over the coming weeks and an uncertain regulatory pathways you just discussed. I'm just curious as to your views on how you see the relative value proposition between an Omicron-specific booster compared with a bivalent one over both the short and the longer term. Thank you.
spk05: Yeah, so what we already know, I refer to public data with regard to antibody titers after Omicron 1 infection, and this data clearly indicates that in pre-vaccinated individuals, and we have generated data for individuals who have received our vaccine with two vaccinations or three vaccinations, and we evaluated what is happening after Omicron exposure. And what we see is that Omicron BA1 exposure resides not only in increased and antibody titles against the Omicron variant, but also against all other variants, including the Delta, Delta, Beta, Alpha, and the original Wild-type variants. So an Omicron exposure in vaccinated individuals really boosts both antibody response. And this was meanwhile, we published that in the meantime, other groups showed the same effects. What is important is that an exposure to an Omicron infection, and we expect this is going to happen also in vaccinated individuals, primarily boosts memory responses. pre-sceptic memory responses, and the naive immune responses will most likely take additional months until naive B cells are generated. We do not see a rational advantage in combining at the moment an Omicron vaccine with another vaccine, but at the end of the day, data count, so that means generating data in different individuals, And we will compare the antibody neutralization titles not only against the prior Omicron variants, but also the newly emerging BA.4 and BA.5 variants, as well as former SARS-CoV-2 variants, regardless whether they might have an impact or not in the future.
spk04: Okay. Thank you.
spk01: Thank you. Your next question comes from the line of Christopher Top from Goldman Sachs. Please go ahead. Your line is open.
spk12: Good morning. Thanks for taking the question. Congratulations on the quarter. Following up again on the same topic, based on the ACIP conversation that happened earlier that sort of started to lay out the framework for this decision, can you give us a sense of what data do you think they're looking for to try to make this decision? You talked a little bit about kind of neutralizing titers against different variants. Is it that simple, or are they going to be looking for kind of other aspects aside from safety, of course? And once these data on Omicron-specific vaccine are in hand, do you anticipate this may have an impact on other regulatory discussions, like in China as well? Thank you.
spk05: Yeah, of course, safety is regarded, will be evaluated and the safety evaluation happens in a few hundreds of subjects who received the booster vaccine. So we don't expect that this is a larger trial will be needed also based on the feedback from the regulatory authorities. I can't say, as already stated, we had a number of conversations with the authorities. And every time they asked for the same data sets, they would like to see monovalent data and bivalent data, but they did not. refer what kind of vaccine, monovalent or bivalent, is preferred by them. I assume that this is a topic for the VRBPAC discussion end of June. I don't think that we are going to be surprised by the request of non-expected data sets in addition to what we are already generating.
spk01: Thank you. I will go to the next question. Your next question comes from Akash Tiwari from Jefferies. Please go ahead. Your line is open.
spk13: Hey, thanks so much. So it seems like you and Moderna have been talking up different approaches for an Omnicron booster. Moderna seems to be talking up bivalent, while you and Pfizer have been talking up more of a modified spike for patients who aren't naive. Can you talk about how antibody titers for both of these approaches may differ, especially at day 28? where Moderna has mentioned there may not be a big difference between wild-type boosters and an Omicron booster, while you've already shown higher antibodies at day 28, at least with your alpha booster. And then given the uncertainty around the regulatory path forward, in a scenario where you would need robust VE data to get onto the market, could there be a scenario where we don't get an Omicron-specific booster in 2022? Thank you.
spk05: Let me just phrase the overall situation in which we are regardless now of the thinking of different companies. We have a situation where with an ongoing Omicron pandemic, so 99.8 or 99.9% of all infections are mediated by Omicron sub-variants. We have a situation that currently multiple Omicron sub-variants exist with different escape profiles. So in Europe, we are seeing sub-variants like Omicron 2.9 or 2.12.1. From Africa and in the East, we are seeing BA.4 and BA.5 variants, which appear to have even higher loss of neutralization titers. And any decision of a seasonal vaccine must be in line with the actual variants which are circulating at the moment. And we and Moderna and other companies started to evaluate Omicron-adapted vaccine, including monovalent as bivalent vaccine. So that means all companies will generate this data. And we have to match this data, which has been generated, with evaluating of neutralization titles against the actual variants. And based on that, we have to come to conclusions. That's the way to go. I can't say what is now going to happen in the next few weeks. whether new variants will emerge, but I am pretty sure that any decisions made by an authority must reflect what is ongoing with regard to the sub-variants that are currently in circulation.
spk01: Thank you. Your next question comes from the line of Dana Graybosh from SVB. Please go ahead. Your line is open.
spk09: Hi. Thank you for the question. I'm going to ask another one on this, but maybe a slightly different direction. You mentioned that the paper that you published showing memory B-cell responses against some conserved epitopes after Omicron infection. I think there was a similar one published, I think, from some scientists at Rockefeller. But you looked pretty soon after that breakthrough infection, I think, 40 to 50 days. And I wonder what gives you confidence that those broader B cells and neutralizing antibodies are going to be as durable as maybe neutralizing antibodies more specific against the variant spikes that have some longer durability as we know from previous vaccinations.
spk05: The durability of antibodies, at least in my opinion, is primarily driven by the initial antibody type. That is what is happening in the body fluid compartments, including plasma and in the mucosal surfaces. Then we have a second reaction ongoing, which is the which is the continued memory B cell maturation process. Directly after infection, we will have the memory B cell response, as we have shown in our paper, is dominated by pre-established memory B cells. But there will be new, naive memory B cells joining into this reaction. But these naive memory B cells will have less mutations and lower affinity antibodies. And this will require several weeks up to three months until the maturation is established. And then a second booster might help to really generate high affinity antibodies against novel epitopes. That is what immunology suggests. And that is what we are going to expect. That means antibody titers will decline. But on the other side, we will generate novel memory B cells, which are better adapted to the new epitopes coming from the Omicron variant.
spk01: That's helpful. Thank you. Thank you. Your next question comes from the line of Zhejiang Xu from Barenburg. Please go ahead. Your line is open.
spk03: Great. Thanks very much. Congrats on the strong quarter. I'd like to ask about the capital allocation. You have 19 billion euros on the balance sheet as of Q1. How do you think about spending that cash, particularly on the backdrop of the the depressed biotech evaluation here, thinking about BDM and MNA opportunity. A quick one on the clotting 18.2 mRNA program. Given your history on that target, how do you see that approach differentiated from antibody approach? Thanks very much.
spk10: Yeah, thanks very much for the question. Let me start and then I'll pass on to Hugo. We have reiterated the guidance as you've seen, so 13 to 17 billion is the figure. After the first quarter, you know, we feel very, very good about it. I mean, the 6.4 billion that we have reported in revenues and the profitability supports that we confirm that guidance. As stated at our year-end call, You know, the main focus of our investments remain to invest in our research and development activities and going forward. But as you remember, we also have announced that we will invest 1.5 billion in the share buyback program that we just had kicked off very recently. And that we also will give our shareholders that have stayed with us for a long time in the past, we give shareholders 500 million euros of a dividend payment in the course of this year. Going forward in terms of M&A activities, et cetera, we have, of course, looked and continuously look into additions in terms of transactions that we can make, collaborations, all kinds of things that we are intending to proceed as we did in the past. But we can give you closer guidance on where and when we will invest and how much. We've got to see how things are evolving. But we feel good about the cash position you've You've heard from me earlier that our cash position increased. We collected another 5.2 billion euros mid-April, so we're in the ballpark of around about 10 billion or above 10 billion at this point in time, so we feel good about our cash position, and that gives us the opportunity to invest money in the years to come. Gur? Ugo, you want to take over the second question?
spk07: Yeah, I can take over the second question, which was about our Claudine-18-2 ReboMAP development. As you have already pointed out, we have experience with clinical activity of an Claudine-18-2 directed antibody And using mRNA to encode the antibody and circumvent the production, the need for producing the antibody as a recombinant protein comes with many opportunities. And we want to leverage these opportunities for using our ReboMAP as a single agent therapy, but also for combining it with other modalities.
spk03: Great. Thank you very much.
spk01: Thank you. We will take one further question, and the last question comes from Ellie Murley from UBS. Please go ahead. Your line is open. Hi.
spk08: This is Sarah on for Ellie. Thanks so much for taking our question. I guess in terms of... BNT211 and sort of moving into later stage development, what are you looking for and what's your expectation that would make you confident in moving forward? And then on a larger scale, I guess, where do you see this fitting in in terms of the other treatment options available and what line of therapy? Thanks.
spk07: With BNT211, our CAR T-cell therapy directed against Claudine 6, we are still in the dose escalation stage. So we have even not reached the highest dose we actually wanted to administer, yet we see already encouraging and promising clinical activity in particular in testicular cancer as well as in ovarian cancer. So what we want to do is to continue to collect the data and decide based on aggregate data how to proceed. CAR T-cell therapy would be something which we would like to position in later lines of treatment. We think that in those indications in which we assess Claudine 6 CAR T-cells, namely advanced metastatic testicular cancer, ovarian cancer, endometrial cancer, rare cancers such as sarcoma, there is considerable medical need. And how exactly we will position will depend on the aggregate data we will produce in dose escalation and dose expansion parts of this initial trials.
spk01: Thank you. I will now hand the call back to Zilke for closing remarks. Thank you for joining us today. We look forward to speaking with you in future.
spk06: Thank you and bye-bye.
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