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spk10: 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.
spk07: 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.
spk12: 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.
spk09: 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 2021 financial year which you can find on slide 25. The 2021 financial year has been an extraordinary one, which also becomes visible by looking at our key financial highlights. Our total revenues reported for the 2021 financial year reached 19 billion euros and included 18.8 billion euros COVID vaccine revenues, exceeding our guidance of 16 to 17 billion. We ended our 2021 financial year with an operating result of 15.3 billion euros and generated earnings per share on a diluted basis of 39 euros and 63 euro cents. We ended the 2021 financial year with 2.1 billion euros of cash and cash deposits, as well as trade receivables of around 12.4 billion. 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. I will explain the timing effects in more depth in a minute. In summary, we believe that those figures just mentioned reflect a clearly remarkable year for BioNTech. Take a deeper look into our COVID-19 vaccine commercial revenues and touch on the related gross margin on slide 26. During the year ended December 31st, 2021, we recognized 18.8 billion euros of COVID-19 vaccine commercial revenues. As a reminder, under 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 14.8 billion euros, revenues related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners territories, together with a number of sales milestones. These revenues represent already a net figure, which means that we generate 100% gross margin on those revenues. We would like to point out again that our profit share is estimated on preliminary data shared between our collaboration partner Pfizer and us, especially with respect to the month of December for Pfizer's business outside the US, by which hour in Pfizer's reporting cycles differ. The profit share may thus be subject to adjustments pending final data on input parameters like sales volume and values, as well as transfer prices. Any changes in our share of the collaboration partners' gross profit will be recognized prospectively. Our COVID-19 vaccine revenues during the year ended December 31st, 2021, comprised 3 billion euros revenues from direct COVID-19 vaccine sales to customers in our territory, as well as 1 billion euros revenues from sales to our collaboration partners. Together with our collaboration partners, we have delivered approximately 2.6 billion doses COVID-19 vaccine during the year ended December 31st, 2021. We and Pfizer have previously disclosed the objective to deliver about 40% of our vaccines to low and middle income countries while fulfilling the early orders of high income countries. This objective has been achieved. The volume of COVID-19 vaccines delivered worldwide, as well as the allocation of approximately 60% of deliveries to high-income countries, included additional deliveries in December 2021 due to the then-emerging Omicron variant and led to COVID-19 vaccine revenues that clearly exceeded our expectations for the 2021 financial year. Our 2021 COVID-19 vaccine revenues were significantly influenced by the extraordinary circumstances of the ongoing pandemic. For the 2022 financial year, we expect to further increase the share of delivered vaccine doses to low- and middle-income countries, where prices are in line with income levels or at non-for-profit basis. This shift will impact our estimated COVID-19 vaccine revenues for the 2022 financial year. I will give you some more color what this means when we come to our 2022 financial guidance. Overall, we have clearly overachieved our revenue margin expectations for 2020. To remind everyone, the gross margin of our COVID-19 vaccine business during The financial year 2021 is influenced by all three revenue streams listed on the slide. As mentioned before, the revenues related to our share of gross profit from COVID-19 vaccine sales and the collaboration partners territories and our sales milestones have 100% gross margin and have been in 2021 the dominant factor for our gross margin figure. The other two effects on the overall gross margin of the company are the revenues generated in our own territory and the revenues for product sales to our collaboration partners. Those two revenue streams have, of course, a lower gross margin, and the mix has, in consequence, a significant influence on the overall gross margin. The overall mix causes the fluctuations that becomes visible when looking at quarterly gross margin figures. As shown on slide 27, we ended our 2021 financial year with 1.7 billion euros cash and cash equivalents, as well as cash deposits in the amount of 0.4 billion euros. The latter were returned to cash and cash equivalents in January and February 2022. When analyzing our liquidity, we anticipate certain significant balance sheet items that are expected to improve our cash and cash equivalents balance subsequent to the end of the reporting period. Acknowledging that this is only a selection and cash outlays need to be considered as offsetting factors. Our cash and cash equivalent balance subsequent to the end of the reporting period is expected to be significantly improved by our trade receivables. We expect these funds to be used to finance our growth, which we will outline further in our capital allocation framework. As already mentioned, mainly due to the contractual settlement of the gross profit share under our COVID-19 collaboration with Pfizer, trade receivables remained outstanding as of December 31st, 2021. Trade receivables include, for example, the gross profit share for the third quarter of 2021, for which the settlement payment was received subsequent to the end of the reporting period in January 2022. The settlement payment from Pfizer for the fourth quarter of 2021 is expected to be received in April 2022 and is also included in our trade receivables as of December 31st, 2021. In addition, please keep in mind that the settlement for the profit share of December 2021 for the territory outside the United States will only be paid in July of 2022. Of course, there are always certain risk with trade receivables. The settlement timing explains why the cash position is relatively low by year end 2021 versus a relatively high amount of trade receivables. As of December 31, 2021, our trade receivables amounted to approximately 12.4 billion euros, of which the biggest amount is driven by the just mentioned outstanding Pfizer payments. From those outstanding trade receivables, we had already collected 4.7 billion euros in cash by mid-January 2022. I now switch to the comparison between our actuals of the 2021 financial year to the guidance announced in our last earnings call on slide 28. During the year ended December 31st, 2021, we recognized 18.8 billion euros COVID-19 vaccine revenues. As just explained, those included revenues related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners' territories and sales milestones, revenues from direct COVID-19 vaccine sales to customers in our territory, as well as revenues from sales to our collaboration partners. We exceeded our guidance by about 2 billion euros, caused by mainly two factors. Firstly, we were able to increase the volume of COVID-19 vaccine doses delivered to 2.6 billion doses, exceeding our expectation of up to 2.5 billion doses included in our guidance. Secondly, again, exceeding our expectation at this time in terms of price, the proportion of doses sold to high income countries was also higher than anticipated. Both factors were mainly related for the high demand for booster vaccinations, mainly in Europe and the United States in response to the Omicron variant emerging in late 2021. During the year ended 31st, 2021, our R&D expenses reached 950 million euros meeting our guidance. These expenditures included approximately 40% of R&D expenses related to COVID-19 vaccine clinical trials. Moving to the SG&A expenses, during the year ended December 31st, 2021, we recognized 340 million euros SG&A expenses compared to originally anticipated 300 million euros. The expenditures were mainly driven by supporting our rapid and sustainable growth, including accelerating our internal operating activities, as well as investing in inorganic opportunities, adding to the total SG&A spending. Our capital expenditures during the year ended December 31st, 2021 amounted to 180 million euros meeting our guidance. These expenditures included inorganic growth investments, investment in infrastructure and investments in our COVID-19 vaccine production capacities, ensuring our projected production capacities. I'll be moving to our financial results for the fourth quarter of 2021 as shown on slide 29. For the fourth quarter of 2021, we report total revenues of 5.5 billion euros compared to 0.3 billion euros for the comparative period in 2020. Total revenues increased due to the high demand of our COVID-19 vaccine. Now moving to cost of sales. Our cost of sales reached 583.2 million euros for the fourth quarter of 2021, compared to 41 million euros for the comparative period in 2020. The increase was again driven by cost of sales recognized with respect to our COVID-19 vaccine sales and included the share of gross profit that we owe our collaboration partner Pfizer on our own sales in Germany and Turkey. Research and development expenses were 271.5 million euros for the fourth quarter of 2021 compared to 257 million euros for the comparative period in 2020. The increase was mainly due to an increase in research and development expenses from the BNT162 clinical trials. The increase was further driven by an increase in wages benefits and social security expenses resulting from additional headcounts, as well as expenses occurred under our share-based payment arrangements. In the fourth quarter of 2020, inventories had been expensed prior to the launch of our COVID-19 vaccine, and those did not reoccur in the fourth quarter of 2021. General and administrative expenses reached 130.9 million euros for the fourth quarter of 2021. compared to 35.9 million euros for the comparative period in 2020. Similar to R&D, the increase in G&A was mainly due to an increase in wages, benefits and social security expenses resulting from an increase in headcount and expenses incurred under the share-based payment arrangements, increased expenses for purchased management consulting and legal services, as well as higher insurance premiums caused by the increased business volume. There have been expenses incurred caused by new collaborations and acquisitions that drove costs up too. Income taxes were accrued in an amount of 1.5 billion euros tax expenses for the fourth quarter of 2021 compared to 0.2 billion euros tax income for the comparative period in 2020. For the fourth quarter of 2021, net profit reached €3.2 billion compared to €0.5 billion for the comparative period in 2020. Our diluted earnings per share for the fourth quarter of 2021 amounted to €12.18 compared to €1.43 for the comparative period in 2020. Moving to slide 30, I would like to share with you the company's outlook for the 2022 financial year. As of mid-March, we and Pfizer have signed orders of approximately 2.4 billion doses for deliveries during the 2022 financial year. We reiterate our guidance from January 2022 presented at the JPMorgan Healthcare Conference and are providing estimated COVID-19 vaccine revenues of approximately 13 to 17 billion euros for the full year of 2022. This range considers the uncertainty derived from the evolution of the virus. We see three key variables driving the revenues outcome for the 2022 financial year. These are firstly, the number of delivered doses. Secondly, the regional mix in terms of high, middle and low income countries. And thirdly, the effects depending on whether revenues are generated by one of our partners or ourselves, or if we sell products to our partners. We expect to further increase the share of deliveries of COVID-19 vaccine doses to low and middle income countries based on the signed order book. Due to this anticipated shift, we're assuming a lower average price per dose versus 2021, as prices in low and middle income countries are in line with income levels or at a non-for-profit basis. The financial success of 2021 allows us to redeploy in the years to come meaningful investments into our R&D engine, our product pipeline and business operations, preparing us for anticipated strong growth ahead. For the 2022 financial year, we plan to spend 1.4 billion euros to 1.5 billion euros which represents an increase of about 50% compared to 2021. And we intend to accelerate those investments in the years to come. Our clinical trial programs in oncology and infectious diseases, which comprise five ongoing randomized phase two clinical trials in oncology, will be accelerated further while ensuring that we build up our organizational and personal capabilities for continued and sustainable growth. SG&A expenses are estimated to be in the range of 450 to 550 million euros as we plan to continue to invest in our enabling functions to support our operational growth. Capital expenditures for the 2022 financial year are expected to be in the range of 450 million to 550 million euros. We are, for example, planning to extend our R&D and production facilities. and to enhance and continue to invest into our digitalization initiatives. Please note all ranges reflect current base case projections, excluding potential M&A activities and collaborations. Finally, please note that in terms of the 2022 full-year tax impact, our tax burden is expected to improve significantly as we expected the estimated annual effective tax rate for the BioNTech group to decrease from 31.6% to around 28%. On slide 31, I would like to take the opportunity to highlight our capital allocation framework. And there will be some more details presented by my colleague Ryan. Four key areas are at the center of our activities. First and foremost, R&D. We have proven to the world that our science is game changing. On top, we believe that our technologies and science can have an even broader impact on people's health. Therefore, we intend to further accelerate our initiatives to create additional long-term value for our shareholders. Secondly, M&A in business development. To supplement our technologies and digital capabilities, we strive to extend and augment our expertise with synergistic acquisitions and collaborations. Thirdly, We develop our global footprint in Europe, the US, Asia and Africa, and plan to invest in our manufacturing capabilities for key technologies. Finally, after such an extraordinary year, we would like our shareholders to participate in our success. Consequently, we expect to authorize a share repurchase program of ADSs, pursuant to which we may repurchase ADSs in the amount of up to 1.5 billion US dollars, over the next two years. We expect to use all or a portion of the ADSs we repurchase in hold and treasury to certify upcoming settlement obligations under our share-based payment arrangements. In addition, we, the management board and the supervisory board, will propose a special cash dividend of two euros per ordinary share, including those held in form of ADSs. This corresponds to an aggregate of approximately 486 million euros based on the shares outstanding as of March 30th, 2022. The special cash dividend is subject to approval of our upcoming annual general meeting. In this respect, I'm pleased to inform you that our 2022 AGM is scheduled to take place on June the 1st. And with that, I turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our corporate development activities and concluding remarks. Thank you.
spk01: Thank you, Jens. Turning to slide 33, I'd like to highlight five key areas of strategic focus in 2022. We will continue to invest significantly in our COVID-19 vaccine program. We expect multiple data updates throughout the rest of the year, including data from our Omicron-based vaccine for which we are on track to finalize the data package for potential submission to regulators. This year we plan to continue our rapid pipeline expansion with data updates expected for up to three additional oncology and infectious disease programs. We are currently investing to build out our global development organization to support continued pipeline expansion that will include the preparation of potential registrational trials. We also expect to further strengthen and extend our international presence. This will include expansion of our teams and capabilities in the United States, Europe, Africa, and Asia. In addition to further automating our existing production facilities in Germany, we are investing into new manufacturing nodes in the US and Asia to support our future mRNA and cell therapy product portfolio. Finally, we expect to remain active on the corporate development front. Already this year, we have announced a diverse set of new collaborations with Pfizer, Regeneron, MediGene, and Crescendo. we will continue to expand our access to complementary technologies in the field of synthetic biology. And we will continue to invest in our manufacturing infrastructure and digital capabilities. This could include new partnerships, M&A, and in-licensing deals in addition to organic investment. Slide 34 details some selected pipeline milestones expected in the remainder of 2022, which includes eight potential data updates. We expect multiple trial updates for Comirnaty, including data expected for a fourth dose in adults ages 16 to 65 plus, a third dose in children ages five to 12 years, and data for a three-dose regimen in children ages six months to five years, which is expected in April. In addition, we expect preliminary safety and immunogenicity data for our Omicron variant vaccine in April. which includes the Omicron vaccine both as a third dose and a third and fourth dose after primary vaccination with comorbidity. If the data is positive, we intend to submit it to regulatory authorities and subject to a decision from the regulators to support an authorization of our Omicron vaccine worldwide. In addition, we have multiple next generation COVID-19 vaccines in development, including variant combinations, multivalent vaccines. We expect to provide further updates on these programs in the second half of the year. We also expect to provide data updates for several other pipeline programs this year. This includes phase one data from our mRNA influenza vaccine program, which is licensed to Pfizer in the first half of the year. We also expect our first randomized phase two data update for iNest and first-line melanoma in combination with Pembrolizumab versus Pembro alone in the second half of 2022. And we expect further updates from our phase one to a trial of BNT211, our CLAUDIN6 CAR T-cell program against multiple cell and tumors. As in 2021, we expect this year will also be a year of further pipeline expansion. On slide 35, we highlight up to seven planned first in human trials, which we aim to initiate in 2022. This includes four additional mRNA vaccines for infectious diseases, including shingles, tuberculosis, HSV-2, and malaria. In oncology, we expect three additional trial initiations this year. This includes trial starts for two RibonMab programs targeting solid tumors, BNT141 and 142, and the start of a Phase 1-2 trial of our FixVac NSCLC immunotherapy, which we will administer with Liptio in the first-line setting in advanced NSCLC. All these programs have first-in-class potential. Before concluding, I would like to highlight on slide 36 that we will have our annual general meeting on June 1st and our virtual capital markets day on Wednesday, June 29th. We will provide further details in the coming weeks on both events. I would like to thank our shareholders for their continued support. And with this, I'd like to conclude our prepared remarks and open the floor for questions. I will now turn the call over to the operator for Q&A.
spk15: 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. Once again, if you'd like to ask a question, please press star and one on your telephone keypad and please limit yourselves to one question only. Your first question today comes from the line of Corey Kazimoff from JP Morgan. Please go ahead, your line is open.
spk06: Hi, guys. Thank you for taking my question. A question for you on the COVID vaccine front. At what point are you expecting the U.S. market to transition into a private pay environment versus the current government contracts? And what kind of impact do you expect this could have on overall market dynamics? Thank you.
spk01: Yeah, Sean, you want to take that question?
spk02: Yeah. Hi, Corey. Yeah, I think it's difficult to say because The market is so dynamic with variant developments and, of course, Omicron being specific to that. There's lots of things that could happen. The U.S. government may order more or we may go to a different private market dynamic. I think it's simply too early to say. Okay, thank you.
spk15: Thank you. Your next question comes from the line of Tazin Ahmad from Bank of America. Please go ahead. Your line is open.
spk13: Great. Good morning, guys. Thanks for taking my question. As it relates to frequency of the need for booster dosing, can you give us some clarity on how you're thinking about it? Over here in the U.S., it does seem like they are recommending a second booster for certain age groups of the original vaccine, but how much protection do you think that getting a booster from the original is going to confer for Omicron and B2 versus a more specific booster that you're working on right now? Thank you.
spk11: Justine, thank you very much for this question. The recommendation of additional boosters is actually based on the current data. which is being produced by us other groups and also the real world data, which shows that with Omicron emerging, the immune response needs an additional booster. It's very difficult to predict how frequent such boosters would be needed because that really depends also on newly upcoming variants, their potential to evade or partially evade immunity and needs to be simply monitored as long as we are in this still very dynamic situation.
spk15: Okay, thanks. Thank you. Your next question comes from the line of Matthew Harrison from Morgan Stanley. Please go ahead. Your line is open.
spk03: Great. Good morning. Thanks for taking the question. I was wondering if you could just comment on how you think about durability of boosters with Omicron and subvariants. Obviously, Moderna has talked about multivalent boosters is potentially having better durability. I wonder if you see the same thing with your booster and just how you think about monovalent versus multivalent boosters in terms of durability. Thanks.
spk08: Yeah, so it is still, it is at the moment still early to come to a conclusion. However, we believe that this Omicron being now almost 99.5 percent of all variants worldwide there is currently no clear need for a combined combined vaccine it is important to to evaluate also and the exposure of the experience immune system to comic on spike protein they are now published data indicating that the exposure to Omicron spike in pre-vaccinated individuals produce extremely broad antibody responses, neutralizing all different variants. And we believe that it could be even a disadvantage to come up with a vaccine which has different variants because we would dilute the effect of a purely Omicron basis.
spk00: Does that answer your question, Matthew?
spk03: Yes. Yes, it does. Thank you.
spk15: Thank you. Your next question comes from the line of Chris Shivatani from Goldman Sachs. Please go ahead. Your line is open.
spk05: Thank you. It seems we have data coming up for a bunch of different variation options, including the Omicron specific in the next couple of months. Can you clarify what you believe to be the regulatory requirements for the Omicron-specific variant? And what do you think will be the goalposts for determining which of the different regimens you're comparing will be the one that you think will be recommended? And in particular, are we thinking about preventing infection? Are we talking about severe disease? Where are the goalposts? And how should we contextualize the different combination sets and data that are coming up over the next month or so and how the regulators may view this.
spk11: Thank you for this question. So the regulatory pathway which is expected from regulators is simple superiority of neutralization and what we do is to compare against the the emicron omicron adapted vaccine against the current the authorized white type vaccine and its potential to neutralize um omicron and and other variants of of concerns we like to talk about or to name our vaccine Omicron-adapted rather than Omicron-specific, because Omicron-specific somehow creates the impression that we only neutralize against Omicron. But in immunological terms, because an Omicron vaccine spike carries also conserved epitopes. You can imagine that the neutralization may be much broader. And in fact, what we see, it is also much broader, including also other variants. Your second question was about the endpoint. So the objective is to prevent symptomatic disease, and this is also why we compare against wild-type variant and its neutralizing capability, because we know that at the neutralization titus we see there, there is symptomatic disease prevention.
spk15: Thank you. We will take our next question from the line of Akash Tiwari from Jefferies. Please go ahead. Your line is open.
spk16: Hi, this is Leo for Akash. Thank you for taking our question. So previously, last December, you had shown some alpha-specific booster data that had higher neutralizing titer against Omicron than the original Y-type vaccine. Do you think the coming Omicron-adapted booster may outperform the Alpha booster? And maybe I can squeeze maybe another question about flu vaccine. So how should we think about the AE profile of an mRNA flu vaccine? Currently, we have already a vaccine on the market that shows pretty good safety profile. How should we think about the therapeutic window of mRNA vaccine? Is it something related to the size of the encodered protein? always something else. Thank you very much.
spk08: Thank you, Akash. So first of all, we believe that an Omicron-adapted vaccine should be able to induce higher neutralizing antibody responses as compared to the wild-type. We are not comparing and benchmarking against alpha. Omicron has some lineage similarities with Alpha, but the benchmarking partner here is for sure a divide type. With regard to a potential combination with an influenza vaccine, we cannot make any statements at the moment since we don't have data.
spk16: Thank you.
spk15: Thank you. Your next question comes from the line of Dana Graybosh from SVB Learing. Please go ahead. Your line is open. Hi.
spk17: Thank you for the question. I want to ask one about next generation vaccines, Omicron and beyond. And that is, I wonder if you could talk about your hypotheses over whether with an Omicron adapted, we'll need two boosts of an Omicron adapted, to boost that new Omicron spike versus one. And then I also wonder if you're working on any next-generation vaccines beyond variants, so ones that would have an increased breadth and epitope or may work to stimulate mucosal immunity, for example.
spk08: Hi, Dana. Thank you for the question. So let's start with the with the second part of the question, next-generation vaccines. Yes, we are evaluating in the preclinical setting a number of next-generation concepts, including vaccines with improved neutralizing antibody responses, with broader neutralizing antibody responses, or strengthened T cell responses. So these are still in preclinical stage, and we will report on this work definitely within the next three to three to six months. So the first question was about... The first question is also very interesting. Your question refers most likely to the fact that one injection could boost memory responses, whereas two injections and may be also able to prime and boost against new epitopes. And this is exactly what we are evaluating in our clinical trial, and we will be happy to answer that in about six weeks from now.
spk15: Great. Thank you. Thank you. We will now take our last two questions of the day, and the first one of the two comes from the line of, Arlinda Lee from CannaCord. Please go ahead. Your line is open.
spk14: Hi, guys. Thanks for taking my questions. I actually have questions about your oncology pipeline. Can you talk a little bit about what data we're expecting at AACR and then maybe just your broader strategy as you think about potential collaborations and acquisitions as well? Thank you.
spk08: So with regard to AACR, I believe the most important update will be the update about the ongoing BMP211 study. So the study now has recruited more patients to remind you We had seen four objective responses in the, described four objective responses in the December presentation, and there's now longer data, durability data available, plus additional patients who have been treated. So this is an exciting data set. With regard to our further development and collaboration strategy, As Ryan Richards mentioned, our key goals is on the one side accelerating of our pipeline, the SAFE2 clinical trials. To remind you, we will have a readout from our first randomized SAFE2 trial in this year from our INES platform. for comparing the effects of INS plus anti-PD-1 versus PD-1 in patients with first-line melanoma. This trial is important because it could ungate other first-line indications. We expect interim data from multiple ongoing ongoing studies, phase one studies, which could guide us to additional phase two studies this year. And the third aspect, of course, is we will continue to complement our technology portfolio and pipeline by complementary and synergistic technologies and will update on new partnerships in the near future.
spk14: Thank you.
spk15: Thank you. We will now take our last question, and the question comes from the line of Qiqiang Xu from Berenberg. Please go ahead. Your line is open.
spk04: Great. Thanks very much for squeezing me in. I have a question also on the oncology pipeline, if I may, specifically on BNT211, the CAR-T program targeting Clotin-6. I wonder if the data so far has supported Clotin-6 as a safe target for for solid tumor as a CAR T approach? And then also, secondly, does this data so far support the your hypothesis on, on the on the fix that fix our mRNA vaccine can increase the persistence of your CAR T therapy? And then finally, the I want I wonder if the data so far supports further development of other targets in other tumor types. Thank you very much.
spk11: Thank you for your questions. So, the first question was with respect to the adverse event profile, whether it supports further pursuing this strategy. respond that yes, the adverse event profile which we see is a manageable one as expected for a CAR T-cell. We see CRSs, but mild ones, grade 1 and grade 2, which are fully manageable. We do not see neurotoxicity, so that we will continue to explore our CAR-backed approach with this highly tumor-selective target. As you know, Claudine 6 is a carcinoembryonic antigen and selective target. With regard to your second question, whether we see an effect of the vaccine on further boosting the adoptively transferred and circulating CAR T cells, We will report on this in our upcoming AACR presentation, and I don't want to preemptively disclose data, but what I can already say is that we will showcase reports and cases of patients who have been boosted several times with the vaccine, and you will see data which shows how under vaccination the adoptively transferred T cells continue to circulate. The third question was, is the approach as such of interest for other targets, which expressed in other tumors. Also here the answer is yes, and we are actively exploring additional targets and preparing respective CAR T cells. These are currently in preclinical stage, but are evaluated for entering clinical stage as well.
spk04: Great. Thank you very much.
spk15: Welcome. Thank you. I will now hand the call back for closing remarks.
spk10: Thank you for joining today's call. We look forward to speaking with you in future. Thank you and bye-bye.
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