BioNTech SE

Good morning and good afternoon. Thank you for joining us today to review BioNTech's second quarter 22 clinical and operational progress and financial results. A few housekeeping items before we start. I invite you to view the slides that accompany the webcast of the second quarter 2022 press release, both of which were issued this morning and can be found in the investor section of our website. As outlined on slide two during today's presentation, we will be making several forward-looking statements. These forward-looking statements include but are not limited to our current COVID-19 vaccine revenues, as these 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, reporting of data from 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 filings made with the U.S. Securities and Exchange Commission, including our most recent quarterly report filed today. 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, 4, and 5 provide detailed and important data information regarding our COVID-19 vaccine. Finally, you can find the agenda for today's call on slide 6. It's my pleasure to welcome the members of BioNTech's management team participating in today's call. I'm joined today by our CEO and co-founder, Uwe Schein, 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 Schein.

Thank you, Silke. Good morning and good afternoon, and hearty welcome to all call participants. We appreciate your continued support. Today is my pleasure to provide an overview of the key highlights from the second quarter and our objectives for the remainder of the year. Our team will provide further details before we open the call for questions. We have made significant progress in the second quarter as we continue to advance toward our vision of building our global immunotherapy powerhouse. With our deep expertise in immunology, and fully integrated spectrum of translation research, development, manufacturing, and commercialization competencies, we are all well positioned for success. We are leveraging a multi-platform strategy built on our innovation engine comprised of various cutting-edge technologies. This approach enables us to advance our differentiated pipeline of novel immunotherapies for multiple waves of innovation. We have earned a position of market leadership with our COVID-19 vaccine. Our goal is to continue to deepen that leadership. We believe that SARS-CoV-2 will be with us for the foreseeable future. It is therefore necessary to evolve our products to address the ever-changing challenges posed by the virus. In oncology, we have 18 programs in 23 ongoing clinical trials. including five randomized phase two trials. We intend to advance several of these programs into pivotal studies in the coming years. In infectious diseases, we have one ongoing phase one program and more than 10 preclinical programs addressing diseases which represent significant health challenges globally. We expect to bring four of these programs into the clinic this or beginning of next 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 cancer and infectious disease. We envision application of our mRNA technology in the treatment of inflammatory, cardiovascular, and neurodegenerative diseases and in regenerative medicine. We have several active exploratory programs in these areas that are in the product candidate selection stage. We aim to continuously impact the health of people around the world and thereby create long-term value for our shareholders. I will now provide an overview of our accomplishments from the second quarter, starting with the corporate and pipeline updates on slide eight. Following a better than anticipated first quarter, the second quarter of 2022 was in line with our financial expectations. We reported total revenues of 3.2 billion euros, contributing to total revenues of 9.6 billion euros in the first half of the year. broke ground and began construction of our first biotainer mRNA manufacturing facility on the African continent in Kigali, Rwanda. The site will manufacture a range of mRNA-based vaccines to address the needs of the African Union member states. This potentially includes our COVID-19 vaccine, as well as investigational malaria and tuberculosis vaccine candidates that we expect to advance into the clinic the coming months. We have signed a new equal share cost and profit collaboration agreement with GenMAP for the joint development of an antibody targeting CD27. This expands our existing strategic collaboration for developing next-generation immune checkpoint modulators. There are several positive developments in our Oncology pipeline. Positive data from an investigator-initiated phase 1 study of BNT122, our INS product candidate partnered with Genentech, were reported at the 2022 ASCO meeting with encouraging signs of immunogenicity and disease control in patients with resected pancreatic cancer. We recently initiated two more clinical trials. This includes a phase one trial of BNT-142, our second product built on the Ribomac platform. We also dose the first patient in the first human phase one trial of our fixed product candidate, BNT-116, in patients with advanced non-small cell lung cancer. Finally, BNT-211, our next generation CAR T-cell therapy, receives an AMA priority medicine or prime designation for third or later line treatment of testicular cancer. As a result, BNT211 will benefit from early and more frequent interactions with the EMA for the next development phase. The prime designation came on the use of exciting preliminary clinical data from 14 available patients presented at the AACR meeting. We reported details of the data in our earnings called last quarter. On slide nine, we highlight several significant achievements in our COVID-19 vaccine program that further strengthen our market leadership position. We continue to expand our label and have received multiple regulatory approvals for COVID-19 vaccine in the second quarter. We received emergency use authorization for vaccination of children six months to four years of age. The label now includes a three-dose series in this age group. We also received emergency use authorization for a third booster in children aged 5 to 11 years old. Recently, our COVID-19 vaccine received full approval in the United States for adolescents 12 years and older, and they have submitted for full approval in this age group in several other geographies. With these regulatory approvals, our COVID-19 vaccine has achieved one of the broadest labels among available vaccines. On the distribution front, at the beginning of July, we have delivered more than 3.6 billion doses to 180 countries and regions since launch in December 2020. The strong global distribution makes us the market leading provider of COVID-19 vaccines. We recently signed a new agreement with the U.S. government to supply an additional 105 million COVID vaccine doses as an option for the U.S. to purchase up to an additional 195 million doses. Our 2022 order book now includes approximately 2.5 billion doses. Global health equity is a priority for us, which we are pursuing with a multi-point strategy. This includes our pledge to provide 2 billion doses for low- and middle-income countries by the end of 2022. We are on the track to achieve this goal. As part of our long-term COVID-19 strategy, we aim to develop vaccines that generate a more robust, broad, and long-lasting immune response and enable fast response to the dynamics of emerging new variants. In our clinical programs, our Omicron BA.1 adapted monovalent and bivalent vaccine candidates demonstrated high immune responses and tolerable safety profile. As part of our relentless development work aimed at addressing COVID-19 variants, we now have regulatory submission for Omicron BA.1 and BA.4.5 adapted bivalent vaccines ongoing worldwide. Our strategy includes multiple next generation COVID-19 vaccine approaches. This effort is progressing with the initiation of a phase two trial of BNT162B5, the first of several vaccine candidates designed to optimize and prolong the immune response. BNT162B5 is a bivalent vaccine candidate based on enhanced versions of SARS-CoV-2 encasperal strain and Omicron BA.2 variant spike proteins engineered for broader immunity. Slide 10 underscores the critical need to reduce vaccine adaptation timelines to match the speed at which the virus mutates. We have all experienced the rise and fall of multiple COVID-19 variants over the last two and a half years. Since the emergence of the Omicron lineage, every two to three months, we have seen a new sub lineage. Because SARS-CoV-2 is rapidly changing, it is imperative to establish vaccine development protocols and regulatory pathways that keep up with the pace of virus mutants. With the current development path, It generally has taken us eight months to develop a new variant-adapted vaccine and progress it for clinical trials. Discussions with regulators are ongoing to define the most appropriate pathways to leverage current experience and ensure that variant-adapted vaccines can be made available in the future to address newly emerging variants or sublineages in a timely manner. We believe that based on the plethora of generated data, there's a potential to reduce the existing vaccine adaptation timelines to as little as three months, flat 11. Regulatory bodies around the globe agree that current vaccines require adaptation to the new Omicron strain sub-lineages. Based on the scientific evidence, including our BA.1 adaptive vaccine clinical data and BA.4.5 preclinical data, presented at the FDA Advisory Committee meeting in June. The FDA published guidance recommending the introduction of bivalent booster vaccines incorporating the spike protein from the Omicron BA.4.5 sub lineage for the vaccination compliance this fall. In Europe, we have finalized BA.1 adapted bivalent vaccine submission to EMA, including a comprehensive clinical data package. In addition, we are preparing a rolling submission of preclinical and CMC data for an Omicron BA.4.5 adapted bivalent vaccine to EMA, which we expect to begin submitting this month. In parallel, submission of our Omicron adapted bivalent vaccine data packages is advancing with regulators worldwide. We are preparing for a clinical trial of our Omicron BA.4.5 adapted bivalent vaccine which is expected to commence in August. In anticipation of a launch of the Omicron-adapted bivalent vaccines as early as October 2022, we have started to manufacture both BA.1 and BA.45 variant-adapted vaccines. This proactive approach enables us for multiple launch scenarios based on the different regulatory recommendations. We plan to supply both vaccines for the booster campaign this fall. I am proud of our team and the cooperation of our partners. I am grateful for the hard work that has been continuously delivered to provide vaccines to people around the globe to address this evolving COVID-19 threat. With that, I will turn the call over to Özlem.

Thank you, Ugur. I am delighted to provide our pipeline update to date. First slide 13, as Ugo mentioned, we shared our most recent data from the clinical trial evaluating safety and immunogenicity of Omicron BA.1 adapted vaccine candidates with the regulators, including the FDA Vaccine Advisory Committee. This slide shows one of our representative datasets. Testing of adapted vaccine candidates as a booster dose in vaccinated individuals. One month after administration, the fourth dose of the monovalent Omicron BA.1 adapted candidate in triple vaccinated individuals increased neutralizing geometric mean titers against Omicron BA.1 13.5 and 19.6 fold above pre-booster dose levels. Booster vaccination with the Omicron BA.1 adapted bivalent vaccine candidates at the 30 and 60 microgram doses resulted in a 9.1 and 10.9 fold increase in neutralizing geometric mean titers against Omicron BA.1. This means both monovalent and bivalent Omicron BA.1 adapted vaccine candidates met superiority for the ratio of geometric mean titers and non-inferiority for zero responses compared to the current vaccine. The monovalent Omicron adapted vaccine candidate showed super superiority for the ratio of geometric mean titers. The safety and reactogenicity profile of the Omicron BA.1 adapted vaccine candidates were overall similar to BNT162b2 with similar local reactions and systemic events. Overall, these data provide the proof of concept for Omicron-adapted vaccine candidates achieving immunogenicity and safety goals and meeting the regulatory requirements for a successful trial. We also tested neutralization activity of the sera generated in this trial against the Omicron BA4-5 sublineage. These were lower compared to the neutralization activity against Omicron BA1 for both monovalent and bivalent BA1-adapted vaccine candidates. This is not surprising, given the mutational differences between the spike proteins of these two sublineages. On slide 14, the sequences show how Omicron BA.4.5 is distinct from the BA.2 and BA.1 strains. BA.4.5 sublineage is carrying its own unique mutations, including changes in the receptor binding domain, the RBD, and the N-terminal domain, the NTD. The new mutations in the RBD may change its ability to latch onto host cells and evade immunity resulting from exposure to earlier strains. Of note, BA.4.5 are distinct from BA.1 in their N-terminal domain and, in fact, are more closely related to the wild-type ancestral strain in that regard. Our clinical development program has extended to include BA.4.5 adapted vaccine candidates in addition to BA.1 now. As previously mentioned, for the BA.4.5 candidates, we expect a clinical trial will be initiated in August this year. We, however, already have cross-neutralization data in most models. As shown on slide 15, Omicron BA.4.5 adapted monovalent and bivalent boosters in mice substantially increased neutralization responses to all Omicron subvariants, as well as the wild-type strain, compared to Omicron BA.1-adapted boosters. Both the monovalent Omicron BA.4.5-adapted vaccine, as well as the bivalent Omicron BA.4.5-adapted vaccine, show strong neutralization of the Omicron sublineages, including the most distinct sublineage, BA.1. Based on our previous experience, we consider across neutralization data from such mouse models to be predictive for what will be observed in humans. Our extensive clinical experience with variant-adapted vaccines and the broad database may enable preclinical immunogenicity data and CMC package to be sufficient for future emergency use approvals and authorizations subject to regulatory approval. This may enable a first regulatory pathway for timely response to emerging variants. Now to slide 16, our long-term scientific strategy includes exploring multiple next-generation COVID-19 vaccine approaches to achieve a broad and longer-lasting immune response and high levels of protection against SARS-CoV-2 as it evolves. We are designing and testing several different constructs that engage multiple effector arms of the immune system, including antibodies and T-cells. In July, we and our partner Pfizer dosed the first patient in the Phase II study evaluating the safety, tolerability, and immunogenicity of BNT162b5, our first next-generation vaccine candidates to enter the clinic. BNT162B5 is a bivalent vaccine candidate which includes enhanced SARS-CoV-2 spike antigen of the ancestral strain and the Omicron BA.2 sub lineage engineered for increased immunogenicity. BNT162B5 is modified to elicit antibodies that we believe will offer superior protection against infection regardless of the circulating variant. This is accomplished through the introduction of modifications designed to expose more neutralization-sensitive epitopes to the immune system. We have also initiated preclinical work on other next-generation vaccine modalities, including multi-antigen T-cell-enhancing vaccines and potential PANSAS-CoV-2 vaccines. We believe that T-cell immunity to COVID-19 is important when striving for more durable and broad protection and protection against severe disease cause. We anticipate advancing candidates for both T-cell enhancing and pan-SARS-CoV-2 approaches into the clinic in the second half of 2022. We believe that taking this multi-pronged approach will enable us to achieve our ultimate goal of delivering a pen SARS-CoV-2 vaccine with higher and more durable protection and superior breadth, helping us to better manage future variants of concern. Slide 17 highlights our expansive oncology pipeline. that is grounded in our multi-modality toolbox and our focused execution over the last years. We have reviewed our oncology pipeline intensively at our innovation day in June. However, we had developments since then. We now have a total of 18 clinical product candidates leveraging immune therapeutic modalities that are either targeting tumor cells directly or that are modulating the immune response against the tumor. Our programs have combination potential both within our pipeline and with other approved therapies. Our product candidates are currently being evaluated in 23 ongoing clinical trials, five of which are randomized phase two trials. We initiated phase one trials for BNT116, a new program of our FICSEC platform, and for BNT142, a second program from our RiboMet platform. We also have a new preclinical program through our collaboration with our partner, GenMet, BNT313, a CD27 antibody for solid tumors. Moving to slide 18, FIXVAC leverages our proprietary uridine mRNA backbone for full actualization of the intrinsic adjuvanticity of RNA It encodes cancer-specific shared antigens for intravenous administration using the proprietary RNA LPX formulation. It is optimized for induction of strong antigen-specific immune responses. Our FICSEC product candidate, BNT1-16, contains six of such tumor-associated antigens covering up to 100 of patients in all major histological subtypes of non-small cell lung cancer. In July 2020, the first participant was dosed in a first in human clinical trial evaluating the safety, tolerability, and preliminary efficacy of BNT1-16 alone and in combination in patients with advanced or metastasized non-small cell lung cancer. The trial will comprise several cohorts to establish a safe dose for BNT1 16 monotherapy, as well as for VNT1-16 in combination with Simiplimab, which is Regeneron's Liptayo in patients who have progressed on prior PD-1 inhibitor treatment and are not eligible for chemotherapy. And in combination with Docetaxel in patients who have received prior platinum-based chemotherapy. On slide 19 now, another first in human trials started recently for our second Ribomab product candidate, BNT142. Our Ribomab product candidates encode cancer cell targeting antibodies and are based on nucleoside optimized RNA designed to minimize immunogenicity and to maximize protein expression. Product candidates are formulated using liver-targeting LNPs for intravenous delivery and aim to address the limitations of recombinant antibodies, including complex manufacturing processes. The REBOMAR product candidate, BNT142, is a nucleoside-modified RNA that encodes a bispecific T-cell-engaging antibody. This antibody targets CD3. a T-cell receptor component, and Claudine 6, an oncofetal cell surface antigen found in solid tumors such as testicular and ovarian cancers. The Phase I-II dose escalation trial evaluates the safety and pharmacokinetics of BNT142 in patients with Claudine 6 positive advanced solid tumors. On slide 20, At the ESCO meeting in June, positive data from an investigator-sponsored Phase I study of autogen-savumarone individualized cancer vaccine partnered with Genentech was reported. This study was conducted by our colleagues at Memorial Sloan Kettering Cancer Center in adjuvant treatment of patients with localized pancreatic adenocarcinoma. After standard of care surgery and resection of the tumor, R0, R1 resected patients were treated with one dose of atezolizumab. Patients then received eight doses of our individualized vaccine, followed by standard of care adjuvant chemotherapy with modified Folfirinox. After 12 weeks of chemotherapy, patients received one additional booster vaccination with our individualized vaccine. The five-year survival rates after resection alone are as low as 10% in pancreatic cancer, so that the need for further improving adjuvant treatment of early stage pancreatic cancer is urgent. We believe our new antigen vaccines are well suited for the treatment of this low mutation burden tumor, especially in the adjuvant setting. The main findings in the valuable patient set were Firstly, half of the patients developed high magnitude immune responses against at least one of the targets in their individualized set of neoantigen candidates they were vaccinated with. As in this study, an assay with a high threshold was used to interrogate the immune response of all patients on an individual target basis. Lower magnitude vaccine-induced immune responses against further neoantigen targets cannot be excluded. So even though pancreatic cancer is considered a low mutation tumor type with an unfavorable cold tumor microenvironment, engineering of an individualized vaccine was shown to be feasible that was capable of mobilizing an adaptive T cell response. Second, patients with high magnitude vaccine-induced neoantigen-specific immune responses in this study shown by two immune response assays had a higher median recurrence free survival compared to non-immune responders, suggesting that the vaccine is conferring clinical benefit. While early, This data is encouraging and has motivated us to plan for a randomized phase 2 trial. Turning to slide 21, I provide an overview of our strategic collaboration with our esteemed partners from GenMed, in which we are developing multiple next-generation immune checkpoint immune modulators designed to prime and activate anti-tumor T-cell and natural killer cell functions. BNT3-11 is our bispecific antibody, which conditionally co-stimulates 4,1-BB while blocking the PD-1, PD-L1 axis. This candidate is being evaluated in two ongoing trials, including a Phase II trial in refractory or recurrent non-small cell lung cancer and a Phase I-II trial in advanced solid tumors. BNT3-12, our second bispecific antibody, being evaluated in advanced solid tumors, stimulates the immune system through a combination of dual conditional activation of CD40 on professional antigen-presenting cells and 4,1-Bb on antigen-specific T cells. We have expanded our collaboration with GenMAP through a new agreement in which we will develop BNT313, a monospecific hexabody targeting CD27 on naive and activated T cells. We are planning to initiate a phase 1, 2 clinical trial in solid tumors. The first patient is expected to be dosed in the second half of this year. With that, I conclude the pipeline update and will now turn over the call to Jens Holzstein, our CFO, who will provide the financial update.