BioNTech SE

Good morning and good afternoon and thank you for joining us today to review BioNTech's fourth quarter and fiscal year 2021 operational progress and financial results. A few housekeeping items before we start. I invite you to view the slides that accompany the webcast and the fourth quarter and full year 2021 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 figures 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 clinical trials, the timing of our ability to obtain and maintain regulatory approval for our our broader candidates, and other risks described in our findings made with the US Security and Exchange Commission, including our most recent annual report on Form 20F. 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 note, that slide three and four provide detailed and important safety information regarding our COVID-19 vaccine. Finally, you can find our agenda for today's call on slide five. It's my pleasure to introduce the members of BioNTech's management team participating in today's call. I'm joined today by our CEO and co-founders, 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 the call participants. We appreciate your continued support. Today, I'm delighted to point out a few key fourth quarter and full year 2021 highlights and priorities before I pass the call over to my team to go through some further details. We will then open the call for questions. Slide six. Since our company was founded in 2008, we have followed our vision to harness the immune system to fight human diseases. The COVID-19 pandemic has provided us with a unique opportunity, not only to help protect well over 1 billion people with our first product, but also accelerate our long-term vision to bring the next generation of immunotherapy to patients. BioNTech integrates the full spectrum of competencies for biopharmaceutical drug development, covering discovery, translational research, development, GMP manufacturing, and commercial capabilities. We are pursuing a multi-platform strategy powered by a technology agnostic innovation engine, coupled with strong leadership and competencies in powerful emerging technologies. And we are rapidly expanding and advancing a diversified product pipeline of immunotherapies that address multiple high medical need oncology and infectious disease indications. We are building a 21st century immunotherapy powerhouse with a mission anchored by a strong sense of our global social responsibility. We seek to make a positive impact on global health and democratize access to cutting edge medicines. Moving to slide seven. 2021 was a year of historic impact that BioNTech has made on human health and the economy around the globe. We ended the year with a strong fourth quarter, demonstrating our commercial execution and clinical pipeline advancement. Together with our partner Pfizer, we have delivered approximately 2.6 billion doses of our COVID-19 vaccines to more than 165 countries as over the end of last year. The global deployment of our vaccine has likely saved millions of lives and is helping people all over the world find their way back to a more normal way of living. By the end of 2021, as part of our commitment to equitable access to COVID-19 vaccines globally, we provided more than 1 billion doses or approximately 40% of our COVID-19 vaccine supply globally to low and middle income countries. We are committed to provide more than 2 billion doses to low and middle income countries by the end of 2022. It has also been an active year for our oncology pipeline. During 2021 and 2022 and to date, we expanded and advanced our clinical pipeline extensively with multiple novel oncology platforms entering the clinic. We have five ongoing randomized phase two trials across a range of solid tumor indications. This includes our fixed-back INS by specific antibody programs. We advanced four new platforms into first in human studies, comprising of our mRNA-encoded ribocytokines and ribomaps, our next-generation CAR T-cell therapy, and our neoSTEM ex vivo T-cell therapy. We brought in multiple assets, and forge collaborations to complement our existing technologies and capabilities. This includes the cell therapy facility we acquired from Kite, as well as the MediGene asset acquisition and discovery collaboration that further expanded our TCR pipeline. Given the scope of transformation efforts, we have grown our global organization to more than 3,000 employees and expanded our footprint to include new offices in the US, Europe, and Asia. Taken together, our advancement and expansion has built the foundation for our 21st century immunotherapy powerhouse. We are well capitalized to continue rapid pipeline advancement and global expansion in pursuit of our mission. The COVID-19 vaccine supplies in 2021 both reported full year revenues of approximately 19 billion Euro and diluted earnings per share of 39.63 Euro. It is historically unique moment to advance the next frontier of immunology to transform medicine and we are well positioned to seize this once in a generation opportunity. Slide eight. Slide 8 illustrates the building blocks of our technology and innovation strategy. Our strategy aims to drive therapeutic innovation by developing and linking a toolkit of versatile modular technology platforms for precision medicine. Our first-in-class therapeutic technology platform include mRNA vaccines, gene and personalized T-cell therapies, targeted antibody therapeutics, and next generation immunomodulators. We have strengthened our capabilities through synergistic acquisitions and collaborations, and we will continue to do so. The MediGene collaboration provides us the opportunity to expand the spectrum of personalized T-cell therapies against various targets, One example is the PremTCR, which we believe has the potential to be best in class for a range of solid tumors. Similarly, with the acquisition of Phagomate, we have entered the field of lysine-based precision antibacterials, a powerful new drug class that could overcome the challenges posed by multidrug-resistant bacteria. And with Crescendo Biologics, we gain access to technology and know-how that strengthens our capabilities in the field of engineered cell therapies and multi-targeted antibodies. This modular and multi-platform approach has enabled us to generate a robust pipeline of clinical stage candidates. Currently, we have more than 16 clinical stage product candidates spanning 10 different modalities in 20 clinical trials. Moving to slide nine. Our strategic priorities for 2022 can be summarized in four areas. First, we will continue to address the evolving challenge of COVID-19 around the world. We are developing next generation COVID-19 vaccines and further continuing to focus on label and geographic expansion. In parallel, we have several innovation initiatives underway for pandemic preparedness. Second, in the oncology space in 2022, we will continue to accelerate our programs towards seeking marketing approval. We have started preparation for registration studies for our mid-stage programs. 2022 is expected to bring our first readout from a randomized phase two trial in oncology. In addition, we plan to provide proof of concept data for our CAR T-cell therapy in solid tumors. Third, we believe that infectious diseases are a long-term growth pillar for BioNTech. Our objective is to develop mRNA vaccines against infectious diseases that have a major impact on global population health. We plan to initiate clinical trials for four infectious disease programs in 2022. herpes simplex virus 2, mycobacterium tuberculosis, malaria, which are all fully owned by BioNTech, and shingles, which is partnered with Pfizer. In addition, our preclinical infectious disease portfolio includes more than 10 other mRNA vaccine programs and precision antibacterials. Fourth, we are expanding the reach of our platforms into new therapeutic areas, such as autoimmune disease, regenerative medicine, and cardiovascular disease. We continue to drive our future growth and transformation by reinvesting in the foundation of our company. We are further strengthening our digital and AI capabilities and technologies, as well as expanding our development team, manufacturing infrastructure, and our global footprint. We believe delivering on our 2022 strategic priorities will position the company for long-term success. Slide 10, global social responsibility is at the core of who we are as a company. It is best demonstrated through our commitment to democratizing access to innovative products. As part of our 2021 pledge, we and our partner Pfizer plan to supply more than 2 billion doses of COVID-19 vaccine to low- and middle-income countries by the end of 2022. We are increasing the reach of our innovations worldwide, taking geographical needs and sustainability into account. One example of this is the way we are handling infectious diseases with high medical needs on the African continent. We have launched mRNA vaccine discovery programs for prevention and treatment of HIV, malaria, and tuberculosis, the latter two of which will enter the clinics this year. Recently, we announced the launch of our BioNTenas initiative to provide modular mRNA manufacturing facilities. Our BioNTenas are designed to enable local production of our mRNA vaccines on a flexible scale according to the needs of each partner country. We believe that local production of vaccines that meet international standards is the most sustainable way to achieve vaccine equity. Another example from new avenues for access to our vaccines is that we are introducing drone vaccine delivery program in Ghana. We are also committed to responsible governance, environmental and climate protection, as well as respecting human rights. We set climate protection targets, fulfilling the requirements of the science-based targets initiatives. We target an absolute reduction of 42% in our scope 1 and 2 greenhouse gas emissions by 2030 against base year of 2021. We strive to adhere to ethical business practices, including good corporate governance, social and societal responsibility, and sustainability. We have signed the United Nations Global Compact. We are committed to continuously strengthening our employee recruiting and development. Our team is very diversified with employees from more than 60 countries. With that, I conclude my remarks and hand over to SM Theology, our chief medical officer, who will give you the latest update on COVID-19 vaccine and our oncology programs.

Thank you, Ugur. I'm delighted to speak with everyone today. Our achievements to date have positioned BioNTech well for continued success in 2022. This is also supported by a solid financial foundation backed by a strong order book for 2022, which already includes 2.4 billion signed doses. We continue to broaden the label of our COVID-19 vaccine, gaining approval in the US and EU for a two-dose primary regimen for children aged five to under 12 years. As for adults with the emergence of the Omicron variant, a third vaccine dose may also be needed in the pediatric age group to prolong protection. And we are evaluating a booster dose in the five to 12 year olds as well. In children six months to under five years of age, we are evaluating a primary regimen of three doses. Data on the third dose are expected in April 2022 in this age group and we have begun a rolling emergency use application submission with the FDA and with other regulators. The EU product information has been updated to include use of the vaccine during pregnancy and breastfeeding based on the large body of data showing no increase in pregnancy complications or risk to breastfed infants. Regarding booster vaccines, we have received approval in the US and EU for a third dose in individuals 12 years of age and older. This week we have received the approval from the FDA for the expansion of the emergency use authorization to include a second booster dose of our COVID-19 vaccine to individuals aged 50 years and older who have previously received a booster of any authorized COVID-19 vaccine. At the same time, The FDA also authorized the second booster dose to individuals aged 12 years and older with certain kinds of immunocompromised who have received a first booster of any authorized COVID-19 vaccine. Our global manufacturing network continues to grow. We are building state-of-the-art manufacturing facilities in Africa and Asia to ensure sustainable local supply. As Ugo mentioned, the BioNTena initiative is designed to rapidly build modular mRNA vaccine production nodes. We continue to closely monitor the impact of the Omicron variant and other new variants of concern. The development of an Omicron-adapted vaccine is part of our comprehensive development program for variant-adapted vaccines. We are well on track with the development of an Omicron-adapted vaccine, which we started in early December 2021. We have designed the Omicron-adapted vaccine, scaled up production, and started manufacturing. We are conducting clinical trials with this vaccine in support of a potential regulatory submission and expect to have the first data from these trials in April 2022. Our vaccine development strategy continues to be based on scientific data. It is based on our extensive research in the development of SARS-CoV-2 directed immunity and how it is further shaped by vaccination, booster vaccination, and natural infection. As part of our preventive we are collaborating with InstaDeep on further development of an early warning system for new variants of concern. The approach is based on a new computational method that analyzes globally available sequencing data and predicts high risk variants of SARS-CoV-2. The early warning system is capable of evaluating new variants in just minutes and performing near real time risk assessment of variant lineages. It is also fully scalable as new variant data becomes available. The need for a pandemic vaccine continues, as you can see on slide 13. Large portions of the world's population are still not fully vaccinated or not vaccinated at all. At the same time, COVID-19 continues to spread worldwide, and infection rates are increasing with the emergence of highly transmissible variants. The Omicron variant, which emerged late last November, is the most evolutionarily distant reported COVID variant and one that partially escapes the immune system. Omicron is highly transmissible and has outcompeted the Delta variant. Countries at higher risk of COVID-19 spread are those with low vaccination rates, with inadequate population protection, often accompanied with high natural immunity rates, which went faster than vaccine-induced immunity over time. Reinfections with emerging sublineages of Omicron and newer variants of concern are possible even in persons with prior infections, as evidenced by the current Omicron wave. On slide 14, whilst the primary two-dose regimen of BNT162b2 alone provides insufficient protection against symptomatic Omicron-caused infections, it continues to protect against severe disease and hospitalization. There is a plethora of global real-world data supporting the importance of a booster dose in improving protection against Omicron. A third dose provides higher vaccine effectiveness against Omicron, 70 to 80% against overall infections, 50 to 85% against symptomatic infections, and 75 to 90% against hospitalizations. For certain populations, a fourth dose of BNT162B2 may be beneficial as long as an Omicron-adapted vaccine is not available. We have submitted an application to the U.S. FDA for emergency use authorization of a fourth dose of BNT162B2 for adults aged 65 and older who have received any prior authorized or approved COVID-19 vaccine. We observed that at 12 days post-fourth dose, rates of confirmed infections were two times lower and rates of severe illness were four times lower among individuals who received a fourth dose of BNT162b2 four months or more after the third dose compared to individuals who received a third dose only. However, vaccine effectiveness of BNT162 B2 boosters against Omicron start waning after the first few months. We believe that Omicron-adapted vaccines are required to prolong duration of protection, reduce transmission of disease, improve breadth of response, and protection against emerging variants of concern. As you can see on slide 15, Omicron comprises almost 100% of sequenced genomes in most parts of the world. While new variants can arise from any lineage, they are more likely to arise from the variant with high infection rate especially if such a variant is the main reservoir for ongoing replication. We see evidence of this with further sublineages of Omicron that evolved in recent months, such as BA.1, BA.2, and BA.3. Real-world data has confirmed that vaccine-induced immunity provides a higher degree of protection than natural immunity, and that as natural immunity wanes, vaccination can extend the level of protection against reinfection. Vaccination remains an important critical strategy to protect against current and new emerging variants of concern. We anticipate that as SARS-CoV-2 further evolves, either seasonal or annual variant-adapted boosters will be required to sustain protection against COVID-19. On slide 16, already last year, we preemptively launched a program to test and develop variant adapted vaccines as part of our comprehensive pandemic preparedness strategy. With the emergence of Omicron, this program has been expanded to include the development of Omicron-adapted vaccines. We are investigating the safety and immunogenicity of different treatment regimens of a monovalent Omicron booster in vaccine-experienced individuals aged 18 to 55 years. Treatment regimens include a third dose after the primary two doses of a BNT162B2 vaccine series, or a fourth dose after three doses of BNT162B2, or a third plus a fourth dose of an Omicron-based vaccine after the primary series with BNT162B2. In vaccine-naive individuals aged 18 to 55 years, the Omicron-matched monovalent vaccine will be administered as the primary vaccine and booster. Data from these studies will be available in April. We are also studying Omicron-based bivalent and combined vaccines at the standard dose of 30 microgram and at a higher dose in older people over 55 years of age. Our goal is to understand the protection these vaccines provide against Omicron as well as the cross-protection they provide against previous variants of concern. Currently, there is no regulatory consensus on the need for Omicron-based vaccines. However, we anticipate regulatory developments as clinically meaningful data become available. We remain prepared to adapt our technology, manufacturing, and regulatory processes to ensure that our vaccine provides robust protection against current and emerging variants of concern. Slide 18 highlights our strong clinical execution in 2021 and 2022 for our oncology pipeline and the key milestones achieved. In 2021, we presented multiple clinical data updates from our oncology programs at medical conferences. I would like to highlight our data updates from the ongoing phase 1-2 trial of our first CAR-T product candidate, BNT211. I will discuss these data in more detail in a few minutes. We also made significant progress in advancing and expanding our clinical programs with four randomized trials. phase two trial starts, and five phase one trial starts. In the fourth quarter, we dosed the first patient in a randomized phase two clinical trial of our bispecific antibody BNT311 in PD-L1-positive refractory relapsed non-small cell lung cancer patients, a patient population with significant need for new treatment options. Additionally, the first product candidate of our ReboMark platform, BNT141 entered clinical testing with the first patient dosed in January of this year. Our RepoMAP product candidates encode antibodies directed against cancer cell surface markers and have the potential to address limitations of recombinant antibodies. Complemented by the progress we made earlier in 2021, including our phase two trial starts for FixVac in melanoma and HPV-16 positive head-neck cancer and INEST in adjuvant colorectal cancer. And first in human trials for our self-healing platforms, our ribocytokine and riboma platforms, we believe we are entering an important new era of growth for our oncology pipeline, which is poised to continue to advance and expand in 2022. Moving to our bispecific antibody BNT311 on slide 19. Through blockade of PD-L1 on tumor cells and antigen-presenting cells and conditional 4,1-BB stimulation on T-cells and natural killer cells, BNT311 primes and activates anti-tumor immune effector functions. BNT311 is partnered with our colleagues from GenMEP. At CITC 2021, we presented data from the ongoing phase 1-2 trial. These data, along with a semi-mechanistic pharmacokinetic pharmacodynamic predictive model and translational work, established 100 milligrams of BNT311 every three weeks as the dose for expansion cohorts. We observed encouraging signs of clinical activity and a manageable safety profile in patients with advanced solid tumors during the dose escalation and dose expansion phase of this trial. BNT311 elicited pharmacodynamic effects consistent with its proposed mechanism of action. Patients with tumor reduction had mainly PD-L1 positive tumors. The tumor reduction was observed in seven of 11 patients with PD-L1 positive tumors, including patients with checkpoint inhibitor experience non-small cell lung cancer. These findings support that patient selection and or anti-PD-1 combination therapy may lead to further improved clinical efficacy. The randomized trials shown on slide 20 were started in December 2021. It will enroll 130 patients with PD-L1 positive refractory relapsed non-small cell lung cancer that have failed checkpoint inhibitor treatment. After an initial safety run-in for the combination with pembrolizumab, The trial has three treatment arms, one evaluating BNT311 as monotherapy and two arms with different treatment schedules evaluating BNT311 in combination with pembrolizumab. The primary endpoint of the trial is overall response rate, while the secondary endpoints include progression-free survival and duration of response. The study outcome will be compared against standard off-care chemotherapy treatment with dosatexel. We believe BNT311 has the potential to provide a new treatment option for a high medical need patient population. Worldwide, about 1.8 million people die of lung cancer every year, with non-small cell lung cancer being the most common type, accounting for 85% of lung cancers, while with existing approved therapies, the five-year survival rate is only 4% in advanced disease. Despite the success of checkpoint inhibitors in the treatment of non-small cell lung cancer, the majority of patients eventually fails to respond to checkpoint inhibitor therapy due to evolution of therapy resistance. Non-small cell lung cancer patients that have progressed after treatment with a checkpoint inhibitor have a particularly poor prognosis with a progression-free survival of about six months and overall survival of less than a year. Clearly, there is a gap for new treatment strategies to overcome resistance and improve efficacy. On slide 21 now, we are continuing to evaluate BND311 in 10 dose expansion cohorts in our ongoing phase 1-2 trial, each enrolling up to 40 subjects. Those cohorts include non-small cell lung cancer, orophilia cancer, endometrial cancer, triple negative breast cancer, head and neck squamous cell carcinoma, and cervical cancer. BNT3-12 The second antibody we are developing together with our colleagues from GenMAP is a bispecific antibody targeting CD40 and 4,1BB. The phase 1,2 trial of this antibody includes a monotherapy expansion cohort and melanoma post-checkpoint inhibitor treatment and combination therapy expansion cohorts in melanoma, non-small cell lung cancer, head, neck, squamous cell carcinoma, and pancreatic adenocarcinoma. The combination therapy expansion cohorts are currently recruiting. We expect expansion cohort data from both phase one, two trials for BNT311 and BNT312 in early 2023. These data will inform the clinical development path forward for these programs, including potential later stage trials. If approved, we foresee potential combination therapy with the existing standard of care and with our FIXVEC and INUS products in development as well. Moving to BNT211 on slide 22, which combines two of our platforms with complementary modes of action, Claudine 6-CAR-T cells and a CAR-T cell-amplifying RNA lipoplex vaccine, in short, CARBEC. Claudine 6-CAR-T cells are equipped with a second-generation chimeric antigen receptor of high sensitivity and specificity for the carcinoembryonic tumor-specific antigen Claudine 6. Claudine 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 is expected to overcome CAR T-cell therapy limitations in patients with solid tumors. The first in-human phase 1-2 trial evaluates the safety and efficacy of Claudine 6 CAR T-cells as monotherapy and in combination with CARVEC in patients with Claudine 6 positive relapsed or refractory advanced solid tumors. We are testing three dose levels of Claudine 6 CAR T's as monotherapy dose escalation, as well as combined with a fixed dose of the RNA vaccine. The subsequent dose expansion cohorts represent ovarian, testicular, and endometrial cancers, as well as other rare Claudine 6 positive cancer types, such as sarcoma. We had several data presentations from the trial, which started only about a year ago. The most recent data presentation shown on slide 23 from our BNT211 trial was at the ESMO I.O. conference in December last year, reporting data from 15 patients. Claudine 6 CAR T-cells as monotherapy and combined with CARVEC were well tolerated at the dose levels evaluated with only one case of dose-limiting toxicity observed. Cases of cytokine release syndrome were grade one or two and manageable. Neurotoxicity was not observed. The analysis of CAR-T cell frequency in the peripheral blood of the patients revealed robust CAR-T cell engraftment in nine of 10 available patients. We have observed initial disease control. Four of these nine patients experienced partial responses. Three patients with partial response were testicular cancer patients who were pretreated with recent relapse and progressive disease after high-dose chemotherapy and autologous stem cell transplantation. We are very excited that we will be sharing more data, including safety and efficacy data from a longer follow-up period, an updated cortisol engraftment analysis, and selected clinical case reports at the upcoming AACR conference on April 10th. I'd now like to turn over the call to Jens Holstein, who will cover our financial results, 2022 guidance, and our capital allocation framework.