BioNTech SE

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.

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.

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.