Earnings Call: Q4 2020

Mar 30, 2021

Good morning and good afternoon. Thank you for joining us today to review BioNTech's 4th Quarter and Full Year 20 20 operational progress and financial results. Before we start, we encourage you to view the slides for this webcast as well as the operational and financial results press release issued this morning, both of which are accessible on our website in the Investor section. 18. As shown on Slide 2, during today's presentation, we will be making several forward looking statements. 18. These forward looking statements include, but are not limited to, our current estimate COVID vaccine revenues based on current contracted supply orders, expenses, expenditures and tax rate for 2021. Our target vaccine production capacity for 2021 our COVID-nineteen vaccine revenues, which are subject to numerous estimates as more fully described in our annual report in Form 20 F, the ability of BioNTech to supply our COVID-nineteen vaccine, the plan's next steps in BioNTech's pipeline program the timing for enrollment, initiation, completion and reporting of data from 1 hour clinical trials, other risks described in our filings made with the U. S. Securities and Exchange Commission, including our most recent annual report Form 20 F. Actual results could differ from those we currently anticipate. 18. You are therefore cautioned not to place undue reliance on any forward looking statements, which speak only as of today, share today during this conference call and webcast. Also, please note that Slide 3 provides details important safety information regarding our recently launched COVID-nineteen vaccine. On the call from BioNTech Management today will be Uwe Zahein, our Chief Executive Officer and Co Founder Eslam Tureci, our Chief Medical Officer and Co Founder Jean Marat, our Chief Business and Commercial Officer Zviq Pudding, our Chief Financial and Operating Officer and Brian Richardson, our Chief Strategy Officer. I'll now hand the call over to Uwe Zarin, BioNTech's CEO. Good morning and good afternoon, and thank you to everyone joining the 18. I'm delighted to be here to discuss the progress that we made in 2020, and I would like to introduce important milestones we have planned in 2021 and beyond. Slide 5. 1 year ago, 2017. The whole world was witnessing the rapid spike of the SARS CoV-two virus. At BioNTech, we made an early decision in January last year to tackle the virus head on. We utilized the powerful mRNA vaccine platform and our deep immune engineering competences we have been developing for over a decade. This early decision and the enormous amount of work and energy that followed it resulted in a highly effective vaccine in less than a year. Now, 1 year later, we are already seeing the first signs of the positive impact 2019. Our work against COVID-nineteen is not finished. In today's presentation, I will summarize what we are currently doing and what will come next. Turning to Slide 6. 2020 has literally transformed BioNTech. Our COVID-nineteen vaccine has now been authorized for use in more than 65 countries with more than 200,000,000 doses having been supplied as of March 23. During the Q4 of 2020, we will recognize our 1st commercial product sales. This is a major milestone given the considerable investment in research and development, which we have made over the past 13 years. We are now a fully integrated biopharmaceutical company. We have built a sales force in Germany and we have built global commercial scale manufacturing capacity. We expect to be able to produce up to 1,000,000,000 doses of our vaccine in 2020 1 in BioNTech's own manufacturing network. Our Marvell facility has made remarkable progress since we acquired it 18 and will be ramping up production in the Q2. Despite COVID-nineteen being the spotlight last year, We made progress in advancing our oncology pipeline. We now have 13 oncology product candidates and 14 ongoing trials 18. Of course, 4 different drug classes. Many of these products demonstrate promising activity in Phase 1 clinical trials, And we plan to initiate multiple Phase 2 trials this year. We recently started certain human trials for our CARBAC product BNT 2/11 and for our ribosychocrine product BNT151. Further, we are advancing our 1st wave of 18 product opportunities towards the market. We expect up to 3 product candidates, including our mRNA cancer vaccines and our lead bispecific antibody, We'll be entering to randomized Phase 2 trials by the end of this year. Ultimately, the core of our success is our employees. We have built a global footprint with establishment of our U. S. Research and development hub, and we have increased our workforce to over 1900 employees worldwide. I want to again thank our employees for their tremendous efforts during a challenging and exciting year. Moving to Slide 7. I want to highlight some key takeaways for us as we reflect on 2020. 1st, it became clear that our mRNA pharmaceuticals have a great potential to address major health challenges. 18. The 1st generation of our mRNA vaccine technology has already proven to be powerful. We are working on rapid iterations to further improve this new class of 18 products. Our mRNA approach is not based on a simple technology. Our way of developing our technologies is not based on the idea of a 18. Rather, our goal from the very beginning was to build a novel industrial approach for precision pharmaceuticals that can address medical need in multiple disease areas. We did more than a decade long research to develop a broad 18.2% toolbox of mRNA technology platforms. Each of these technology platforms is tailored and optimized for potency and immunological 18.2% to enable the development of best in class product candidates for various disease areas. 18. 2nd, we believe that mRNA will revolutionize the field of immunology, and BioNTech is well placed to continue to lead the revolution, 18, given our broad technology based, vast IP portfolio and the deep know how in the field. 6. We intend to increase further our investment in the space given the tremendous opportunity we see. In addition, we learned from our COVID-nineteen experience that product development can be faster. We intend to apply the capabilities and learnings we develop 18.7% during the project life speed to rapidly advance our pipeline products towards the market. And 2019. Finally, we learned that our collaboration model works. Our focus on innovation and our strategic partnership with powerful collaborators like Pfizer has helped us not only develop a product in record time, but establish an early market leading position. We intend to continue to leverage our strategic partnerships by building our own capabilities in long term. As depicted on Slide 8, we see a great opportunity ahead. We will accelerate the development of our innovative pipeline and eighteen and expand the number of product candidates and indications we pursue. Our goal is to launch several additional products in oncology and infectious disease field over the next 5 years. And long term, our long term goal remains to build a 21st center global immunotherapy powerhouse developing products for multiple disease areas. Later in our prepared remarks, Ryan will provide some more details into the 6 steps we are taking to realize this vision. Moving to Slide 9. 18. MRNA vaccines are now established as a powerful new drug class. On the back of this validation, we intend to rapidly industrialize our mRNA technology. We believe mRNA vaccines are poised in the near term to displace or complement traditional modalities in a range of infectious diseases and in the field of immuno oncology. The proceeds from our COVID-nineteen vaccines will allow us to accelerate our pipeline development 18 in this core area. Longer term, we see applications for the technology in the field of autoimmune diseases, allergy inflammatory diseases and even regenerative medicine. We have established early research program at BioNTech in this research areas and we plan to significantly ramp up the effort in the coming years. Finally, it is important to point out 2019. Our ability to industrialize our technology is linked to the deep expertise and know how we have built over the course of more than a decade. This is also underpinned by our broad IP portfolio covering our platforms, product candidates and often the targets and formulations we use. Now moving to Slide 11. The strong clinical results observed for our vaccine, our global Phase III trial where a clear highlight in the Q4. The study results demonstrated that our vaccine can prevent symptomatic COVID-nineteen is a well tolerated safety profile. BNT162b2 demonstrated 95% efficacy in a prior with approximately 44,000 participants, including 94% efficacy in participants older than 65 years. The safety profile was favorable with a low frequency of Phase 3 adverse events and mostly typical vaccine related side effects. Key characteristics of our vaccines are both immunogenicity profile that is polyepitopic and multi effector. 18. The vaccine induces high targets of neutralizing antibodies, PH1 type CD4 T cell responses and robust CD8 T cell responses. We believe all of these factors contribute to the protection conferred by our vaccine. 18. Turning to Slide 12. We recently announced 1st real world evidence data supporting the clinical profile of our vaccine. This exciting news comes from an observation analysis conducted by the Israel Ministry of Health between January 17 March 6, 2021. During this time, our COVID-nineteen vaccine was the only vaccine available in the country. Specifically, the data from Israel shows that 2 weeks after the second dose vaccine effectiveness was at least 97% in preventing symptomatic disease, severe and critical disease, hospitalization and death. The analysis also showed a vaccine effectiveness of 94% against asymptomatic SARS CoV-two infections. At the time of the Israeli study, the U. K. Variant B117 was the dominant strain in the country, indicating 2019. The likely effectiveness of our vaccines against COVID-nineteen caused by this variant. In this context, it is important to point out that in vitro data also supports our COVID-nineteen vaccine's efficacy against several variants. We have published data in the new journal from in vitro studies of our vaccine neutralization activity against 3 different variants. In this study, Cera neutralized all the virus was tested and showed no significant reduction in activity against B117 and P1 spike virus. The neutralization of the South African variant B1-351 spike virus was lower, but it was still robust. In addition to this in vitro testing, we are continuing to monitor real world efficacy against several emerging variants. As outlined on Slide 13. We anticipate that COVID-nineteen may become an endemic disease over the next few years. We already see evidence that immune responses in vaccinated In addition, there is a growing body of evidence showing that new variants with antibody escape mutations are driving new infections in many regions. As a result, we believe that there is likely a future need for additional vaccine boosters and potentially also variant specific vaccines. Due to the ability to be rapidly designed, customized and rapidly produced at scale, we believe that mRNA vaccines are We're suited to play an important role in addressing the next stage of the disease. Expanding broad access to BNT1 and BNT2 remains a key focus for us, as shown on Slide 14. We highlight here 6 key levers to expand BNT1 and the C2B2 reach. The first is supply. We have increased our supply target for 2021 to 2,500,000,000 doses. This will require further process improvements and further expansion of our supplier and CGM owned network, but we believe we are on track to achieve this. Continuing to broaden our vaccines label is also a key priority. We have extended our 18 clinical programs to additional vulnerable populations such as pregnant women. In February, 1st participants were dosed in global Phase 2 trial 6 in healthy pregnant women. The study will recruit 4,000 healthy pregnant women 18 years of age or older during the 20 1334 weeks of gestation. Another important pillar is our pediatric task. We plan to submit the safety and efficacy data in 2,000 children, 12 to 15 years of age from the Phase III trial to the regulatory authorities in the Q2. Another study in healthy children 6 months to 11 years of age has started. We are also planning further studies in the individuals with compromised immune system. Another key lever is geographic expansion. Our vaccine has now been approved for emergency or temporary use We're granted conditional marketing authorization in more than 65 countries, and we are moving in additional regions. In Japan, a Phase 1 clinical trial started in October to evaluate our vaccines activity in adults of 20 to 85 years of age. In February, Japan Health Minister approved BNT162b2 under the 18. Last November, a Phase 2 clinical trial of our vaccine started in China to evaluate BNT1 is to be 2.5 individuals of up to 85 years of age. We now have initiated the regulatory submission process in Mainland China and hope to be able to provide an update soon. We are working to broaden, access, enable more than centralized approach to vaccine provision. While BNT162 is available in the U. S. Under emergency use authorization, we are preparing BLA filing in the 2nd quarter for full regulatory approval. Further regulatory submissions and other reasons are also expected. Stability and formulation eighteen. Testing and optimization work remains another key focus. Over the past few weeks, the U. S. FDA and EMI approved the update that undiluted frozen virus of our vaccine may be transported and stored at minus 25 degrees Celsius to minus 15 6 degrees Celsius for a period of 2 weeks. We expect additional stability profile updates over the next few months. We are also developing ready to use and lyophilized formulation with improved thermostability profiles. We are fast tracking development of the ready to use formulation and do not currently expect additional clinical studies to be required for this formulation. Percent. For the LIFO life formulation, we announced today that we will start a trial to evaluate the safety, tolerability and immunogenicity of this formulation. We expect data from this trial in Q3 or Q4 2021. Antibody responses vein over time. To address the veiling of immune responses, 6. We are evaluating the safety and immunogenicity of our 3rd dose of our vaccine. The aim of this trial is to understand the effect As mentioned, today there is no evidence that an adaptation of our current vaccine against key identified emerging variants is necessary. Despite this, we have developed a comprehensive strategy to address these variants should the need arise in the future. In March 2021, the FDA approved an additional amendment to the study protocol of the global Phase III trial to include 2. For our 3rd dose of BNT162, our 3rd dose is modified version of the vaccine carrying the spike protein sequence, the so An additional group of BNT1 and C2b2 naive participants will be enrolled and receive 2 doses of the South African variant vaccine version to discuss protection against the emerging variants of concern against this reference rate. The part of this trial 18, with the variant expected to start by end of March. I will now turn the call over to eighteen. Thank you, Wugor. Slide 15 shows the flexible manufacturing process of our COVID-nineteen vaccine. We can go from DNA Although 50,000 steps are required from manufacturing the mRNA to the bulk drug substance, The overall manufacturing from DMA template to full and finish can be done in less than 2 weeks. Following production, quality control and release can take another 4 to 5 weeks, and then we are ready to deliver the vaccine. One of the advantages of our mRNA technology is that it allows for rapid adoption of the vaccines to variants. Unlike traditional vaccine production, we can adapt our manufacturing to encode a new variant if needed simply by providing a DNA template that includes all the sequence of the new variant. This can be done within a couple of weeks and without the need for new scale up of the overall 18 and pending regulatory approval. Another advantage I would like to point out, ability to respond to market demands. Moving on to Slide 16, we have firm orders 1 point 4,000,000,000 doses to date. Recently, we announced that the United States have exercised its option for an additional 100,000,000 eighteen doses, bringing the total to 300,000,000 doses. We also announced that the 18. EU will be supplied with an additional 200,000,000 doses with an option for an additional 100,000,000 further doses. This brings the total number of doses to be delivered to the EU member states by the end of 2021 to $500,000,000 with the potential to increase further up to $600,000,000 doses. Discussions for additional commitments worldwide are ongoing. BioNTech comprises initial goal was up to 1,300,000,000 doses in 2021, but we've been able to increase our target capacity to up to 2 point 25 billion doses for the year. The increase was driven by a number of factors, including the increase from 5 to 6 doses profile, additional suppliers and CMOs, continued success in process optimization and initiation of production at our Marburg facility. On March 26, we announced that the EMA approved the manufacturing of the COVID-nineteen vaccine drug product at the facility Marburg. The approvals made BioNTech's Margaret manufacturing site, one of the largest mRNA vaccine manufacturing sites worldwide. With an annual production capacity of up to 1,000,000,000 doses of our COVID-nineteen 2019 once fully operational. Due to optimized operational efficiencies, which were initiated last year, We were able to increase the expected annual manufacturing capacity by 250,000,000 doses. The first batches of vaccine manufacture 250,000,000 doses of BNT162b2 in the first half of twenty twenty one. Lastly, we have taken our first step in executing our commercial strategy for our COVID-nineteen vaccine in Germany and Turkey. Pfizer is responsible for the rest of the world outside of China. This is the first time that BioNTech has commercialized the product 2 quarter. Thank you, Sean, and hello, everyone. As usual and in the interest of time, I'm going to provide updates on selected programs. For further details on the stages of our other oncology programs, please refer to our annual report, which 2018 filed with the U. S. Securities and Exchange Commission today. As to be expected, we have continued to see some ongoing impact from the COVID-nineteen pandemic on our clinical operations. Specifically, there has been a slowdown in the enrollment in and some of our ongoing studies. Despite these constraints, we expect to present several data sets and initiate multiple new trials this year. Slide 18 outlines our immune oncology strategy. 3. Our strategy is based on several first in class therapeutic approaches to target cancer and to modulate the immune 4. The programs address a broad range of cancers in different disease stages. Our 6 technology platforms have all reached 20.5% clinical stage by now with 13 clinical stage product candidates. We see multiple blockbuster 18.5% of our 2018. Starting with BNT-one hundred and eleven, our fixed back product candidate for the treatment of advanced melanoma. We expect to start a randomized Phase 2 trial in the U. S. And EU in the first half of twenty twenty one. 18. The trial will evaluate BNT-one hundred and eleven in combination with Regeneron's Libtayo versus both BNT-one hundred and eleven and 22ndtayo monotherapy in patients with advanced melanoma progressing during or after prior TRP with a PD-one inhibitor. In February, we received permission from FDA to move forward with the trial. The next fixed vac product candidate is BMG-one hundred and thirteen, our mRNA vaccine encoding E6 and G7 protein of human papillomavirus 16. We expect to start a Phase II trial evaluating BNT-one hundred and thirteen 18. In combination with pembrolizumab versus pembrolizumab monotherapy as a first line treatment in patients with unresectable recurrent half of twenty twenty one in the U. S. And EU. BNP-one hundred and thirteen has not been combined with anti PD-one hundred and twenty four. And the Phase II trial will start with a run-in portion designed to demonstrate the safety of 13 combination of BNT-one hundred and thirteen and pembrolizumab. These data are required to address the partial clinical hold on the 18 randomized part of the Phase II trials. Moving to our individualized neoantigen 6 Immune Therapy or INS platform, which is partnered with RocheGenentech. Our INS product candidate BNP-one hundred and twenty two has been given the international non proprietary name autogene sevomeran. 2017. The Phase 2 trial in first line melanoma and the Phase 1 Basket trial in solid tumors remain ongoing. Data updates are not 16 for these trials this year. We along with Genentech have made the strategic decision to discontinue the previously planned Phase 2 trial in patients with high risk, restricted early stage non small cell lung cancer, given challenging accrual timelines in the context of the SARS CoV-two pandemic and the evolving landscape of treatment options. We and our partner Genentech are evaluating other 18 options for treating early disease cancer patients with IMS. 1 of these early disease development options in the eighteen. We expect to dose the first patient in the first half of the year in a randomized Phase 2 trial evaluating BNT122 in circulating tumor DNA positive, surgically resected Stage 2 high risk or Stage 3 colorectal cancer. We strongly believe that Inez could be best positioned in the earlier stage or adjuvant setting and minimal residual disease settings. Moving to our next generation checkpoint immunomodulators program, which is partnered with Genmab. We expect to present a data update in the second half of twenty twenty one for the first in human Phase III trial of 202311, also called GEN1046. BNT311 conditionally targets checkpoint immunotherapies. We remain very encouraged by the results presented at last year's TPSI conference and seen to date and believe the product has significant potential across multiple oncology indications. We look forward to moving this program forward with Genrel. For BMT-three twelve, which conditionally target CD40 and 4.1BB. We plan to present data from the ongoing Phase III trial in the second half 12 of 2021. In addition, an abstract highlighting preclinical data for BMT-three twelve conditional CD4 and 4 1BB activity to induce dendritic cell maturation and enhancement of T cell activation and effect function. Slide 20 provides an overview of programs across 4 different technologies that have the potential 3 to advance innovation beyond current boundaries. We are pleased to announce that from our CAR key technology, our first CARBAC product candidate has entered clinical testing. We dosed the first patient in a first in human trial in February for BNT-two eleven. I'll discuss this program in detail shortly. In the first half of twenty twenty one, we also expect to dose our first patient with BNT-two twenty one, the first product from our Neostem 18 key cell therapy program, which features adoptive transfer of individualized neoantigen specific autologous T This Phase 1 dose escalation trial will evaluate the safety, immunogenicity and efficacy of BNT21 in patients with checkpoint inhibitor refractory or unresponsive metastatic melanoma. 1. I'm also pleased to report that the first patient was dosed in the Phase 1 trial in solid tumors in February for BNT151, our first ribocylkilline to enter clinical testing. I'll also discuss this program in greater detail shortly. For BNT-one hundred and fifty two and BNT-one hundred and fifty three in combination, our second ribocytokine program. The Phase 1 trial in multiple solid tumors is expected to start in the first half of twenty twenty one. Eighteen. As our ribo cytokines, also our ribo map BNT-141 and 18 expressed in the liver and deployed into the vascular compartment to reach therapeutically active duration. Phase 1 trials with our first ribo mab in multiple solid tumors are expected to start in the second half of twenty twenty one. The FDA recently allowed our BNT-one hundred and forty one IND. Starting with Slide 21. More details to BNT-two eleven, the first clinical stage product candidate from our engineered 18 T cell program, which is expected to overcome CAR T cell therapy barriers that restrict the efficacy and the widespread use 18.5% of CAR T cell therapies, particularly in patients with solid tumors. BMT-two eleven consists of 2 components. 1 is the novel chimeric antigen receptor functionalized with an antibody derived Chordin VI binding domain with exclusive specificity and high sensitivity for CLARITY6. CLARITY6 is an ideal 18.5% candidate for CAR T cell therapy due to its absence in healthy adult tissue, while high medical need cancer frequently show expression of its tumor antigen. The 2nd generation CAR scaffold quarter. It also includes a co stimulatory domain for 1BB, which we believe mediates prolonged survival and the repetitive killing ability of engineered CAR T cells. In preclinical studies, BMT-two eleven demonstrated strong recognition and sizes of 13 6 positive target cells. As shown in Slide 22, the second component of BNT-two 2/11 is a CAR T cell amplifying RNA vaccine named CARBECK. We use our proprietary RNA plex technology known from 6x studies to encode full length Claudine 6, namely the CAR T target. Following intravenous administration of RNA lipoplexis, the mRNA is specifically delivered to antigen presenting cells residing in secondary lymphoid organs. This mediates eighteen. The expression of Claudine 6 on the surface of those specialized cells. Thus, Claudine 6 is recognized by a doctorly transferred CAR T cells in the lymphoid compartment that provides an ideal context for strong stimulation of these engineered T cells. Repetitive administration of CARBAC allows for controlled in vivo expansion to keep the frequency of CAR T cells 21 therapeutic levels. The expansion also results in increased persistence and superior functionality of CAR T cells, which acquire a memory phenotype in preclinical models. We are optimistic that our CARBEC approach. It allows to overcome key challenges related to CAR T cell therapy, which includes severe toxicities, restricted eighteen. Weibo This is an excellent example for the potential of our therapeutic modalities for synergistic combination. Slide 23 shows the trial design for BNT-two eleven. The Phase 1 trial will recruit patients with thawdeen6 positive relapsed or refractory advanced cell tumors. Part 1 of the trial is the dose escalation of Clodine 6 CAR T cells as monotherapy, 25. Part 2 of the trials displays the combination of Clodine VI CAR T cells with Clodine VI CARBAC. Once 18. The maximum tolerated dose or recommended Phase 2 dose is determined dose expansion cohorts will follow in ovarian, 18.2. Initial Phase 1 data from this trial is expected in the second half of this year. The clinical material for this trial is manufactured at our GMP certified IMFS facility in Ida Oberstein, Germany, which has 16.7% of cell and gene therapy manufacturing capabilities. Our ribo cytokines on Slide 24 are another example for a novel class of RNA based therapeutics from our immune oncology pipeline designed to address the limitations of current 18 therapeutic approaches. Major challenges associated with the therapeutic use of cytokines relate to their short serum half life and low Encoding cytokines by mRNA and producing them in the patient addresses these shortcomings. The right side of the slide describes our first ribocylakine candidate, BNT-one hundred and fifty one, which has entered clinical testing. BNT151 is a nucleoside modified mRNA that encodes an optimized Intel Eukin-two fusion protein. Launch. The drug design is optimized to improve pharmacokinetic properties with an increased tolerability and activity of IL-two. Importantly, BNT-one hundred and fifty one has been designed to stimulate 25. The ongoing Phase 1 trial in solid tumors with no available standard therapy features monotherapy and combination therapy dose escalation. 2019. BNP-one hundred and fifty one will be combined with anti PD-one or other standard of care in cancer types such as 9 I just featured. HAVEC, ribocidal kinds and ribomap are mRNA based approaches. They quite obviously differ one from another from the version of our mRNA technology used for creating the first COVID-nineteen vaccine, again demonstrating the high diversification of our mRNA platform and the many years of know how development 18. I will now hand the call over to Dirk to provide an update on our financials. Thank you, Aslem. I will summarize our financial results for the Q4 and the full year 2020 as shown on Slide 27. I'll start with the total revenues, which were estimated to be €345,400,000 for the Q4 of 2020 compared to €28,000,000 for the Q4 of 2019. For the full year of 2020, total revenues were estimated to be €482,300,000 compared to €108,600,000 for the full year of 2019. Total revenues increased due to the eighteen. Submission of revenues under our new collaboration agreement signed with Pfizer and Fosun Pharma as part of our vaccine program against COVID-nineteen. 18. Newly generated COVID-nineteen vaccine commercial revenues significantly drove our total revenues. As a reminder, Under the Pfizer collaboration, territories have been allocated between the companies based on marketing and distribution rights. A breakdown of our commercial revenues is shown on Slide 28. 20. Our 2020 commercial revenues comprise an estimated amount of €188,500,000 share of gross profit from COVID-nineteen vaccine sales in the Pfizer territory. Please note this is a net figure. Additionally, as it will be detailed in our annual report filed with the SEC, this figure is only estimated based on preliminary data shared 23 Pfizer and us and may be subject to adjustments as we receive final data on input parameters like sales and transfer prices. Changes in our share of the collaboration partners' gross profit will be recognized prospectively. Our COVID-nineteen vaccine commercial revenues also include $61,400,000 sales to our collaboration partner of product manufactured by us and €20,600,000 of direct COVID-nineteen vaccine sales to customers in our territory, Germany. Now returning to Slide 27 and moving to cost of sales, which were estimated to be €41,000,000 for the Q4 of 2020 compared to €4,400,000 for the Q4 of 2019. For the full year of 2020, cost of sales were estimated to be at €59,300,000 compared to €17,400,000 for the prior year. The increase was driven by estimated €35,600,000 cost of sales, 2019, which were recognized for the first time with respect to our COVID-nineteen vaccine sales and include Pfizer's share of gross profit earned by us. Note that cost of sales do not include costs related to the production of prelaunch products since those were expensed as R and D expenses in the period incurred. R and D expenses were €257,000,000 for the Q4 of 2020 compared to €65,400,000 for the comparable period in 2019. For the full year of 2020, R and D expenses were €645,000,000 compared to €226,500,000 full year 2019. The increase was primarily due to an increase in R and D expenses related to our BNT162 program. R and D expenses include our share of expenses under the terms of the Pfizer collaboration agreement. As a reminder, 18. Development costs are equally shared between the 2 companies. Higher expenses for purchase of laboratory supplies as well as an increase in headcount leading 2019. Higher wages, benefits and social security expenses contributed to the increase. And in addition, from the date of acquisition, our U. S.-based Subsidiary BioNTech U. S. Inc. Also contributed to our R and D expenses. G and A expenses were €36,100,000 for the 4th 20 compared to €11,100,000 for the comparable period in 2019. For the full year of 2020, 18. G and A expenses were €94,000,000 compared to €45,500,000 for the prior year period. The increase was mainly due to higher expenses for professional services, an increase in headcount leading to higher wages, benefits and social security expenses and higher insurance premiums. In addition, from the date of acquisition, our U. S.-based subsidiary BioNTech U. S. Inc. Also contributed to our G and A expenses. Following the authorization of approval of our COVID-nineteen vaccine for emergency or temporary use or having been granted conditional marketing authorization, the recognition of deferred tax assets was reevaluated. As of December 31, 2020, net deferred tax assets with respect to the accumulated tax losses and temporary differences of the German tax group were recognized with €161,000,000 income tax 2. For the Q4 of 2020, we showed a net profit of €366,900,000 This compared to a €58,200,000 net loss for the Q4 of 2019. For the full year of 2020, We were also profitable showing a net profit of €15,200,000 compared to €179,200,000 net loss in the prior year period. We ended 2020 with cash and cash equivalents of €1,200,000,000 as a result of successful financing transactions in 2020, which strengthened our position for the execution of our strategy, Which will be accelerated by 2021 growth. Now moving to Slide 29 that outlines our 2021 financial outlook. Based on the current contracted supply orders of approximately 1,400,000,000 doses, We are providing estimated COVID-nineteen vaccine revenues to BioNTech of approximately €9,800,000,000 This estimate reflects 22. Expected revenues from direct COVID-nineteen vaccine sales to customers in our territories, expected revenues from sales to our collaboration partners, expected sales milestone payments from our collaboration partners and expected revenues related to our share of gross profit from COVID-nineteen vaccine sales in the collaboration partner territories. We expect additional revenues related to further supply contracts for deliveries in 2021. I would like to point out again We have raised our manufacturing capacity target from 2,000,000,000 to 2,500,000,000 doses for the full year 2020 to be able to address increased demand. In terms of guidance for the full year 2021, we expect R and D expenses to incur in the range of €750,000,000 to €850,000,000 for the full year 2021, reflecting our aspirations to broaden and accelerate our pipeline development, which we plan to ramp up, especially in the second half of twenty twenty one. SG and A expenses are estimated to rise up to €200,000,000 Capital expenditures For the year 2021 are expected to be in the range of €175,000,000 to €225,000,000 18. I would like to emphasize that all these figures reflect our current base case projections. Finally, please note that in terms of full year 2021 tax impact, we expect a German tax group corporate tax rate of approximately 31%. We have approximately €450,000,000 accumulated tax loss carry forwards with respect to the German Thank you, sir. Turning to Slide 32 to our 2021 strategic priorities. While we work to broaden access to our vaccine, our goal is to build and maintain a leadership position into 2022 and 1. With proceeds from the COVID-nineteen vaccine, we plan to accelerate pipeline development in our core therapeutic areas of immuno oncology and infectious disease. We currently have 9 active preclinical programs in the infectious disease field and intend to advance additional mRNA vaccines against other infectious 18. We will provide more details on some of these programs over the course of the year. We remain as committed as ever to our goal of ushering in a new era of immuno therapy for cancer patients. In 2021 and beyond, we intend to accelerate and broaden our immuno oncology pipeline, where we see a significant opportunity for BioNTech to lead in the emerging fields of individualized cancer medicine and cell therapy among others. Finally, we plan to ramp up investments in our platforms and early product development in select emerging therapeutic areas, such as autoimmune disease, 18.5%. While these areas will not be a major component of our capital allocation near term, we believe they could become major opportunities for BioNTech in the Slide 33 highlights some of the key pipeline milestones we expect in 2021. These include trial updates for our FixVac and IMS programs in 2021. Finally, we're on track to initiate up to 6 first in human Phase I trials across a range of novel IO 12. With the start of Phase 1 trials for BMT-two eleven and BMT-one hundred and fifty one in the Q1, 2 of the 6 milestones 20.6% year have already been reached. Importantly, all of the product candidates entering the clinic in 2021 are wholly owned by We are also pleased to announce our 1st Capital Markets Day, which will be held in the second half of the year. We will confirm the date in the coming weeks. Turning to Slide 35. We believe we are better positioned than ever to bring innovative immunotherapy to 18. We see a tremendous opportunity ahead to build long term value for patients, our shareholders and society. To broaden our global reach, we will continue to expand in key strategic locations in the U. S. And Europe and have near term plans to establish a presence in Asia. To support our expanding pipeline, we intend to further invest in our clinical, commercial and manufacturing infrastructure and we'll also make further investments to build out our digital infrastructure and capabilities. Finally, we will double down on what got us here, true innovation. Alongside planned increases in internal R and D investment, we will continue to actively source complementary external innovation that fits with our long term strategy 18 to harness the full power of the immune system to address serious disease. And with that, I will conclude our presentation. We 18. Thank our shareholders and partners for their ongoing collaboration and support. And we'll now open up the floor for questions. 18. Your first question today is from the line of Tazeen Ahmad from Bank of America. Please go ahead. Hi, good morning. Thanks for taking my questions. As it relates maybe to the COVID vaccine, can you give us a little bit more color, 2018. Ugur, about your thoughts about the need for boosters, maybe a couple of parts to that. Do you have any sense of the frequency with which If needed, people would need boosters. Secondly, you talked about doing work on the different variants. So on a go forward basis, would the booster shots be inclusive of all variants that would be presence at the time. And the last part of the question is, do you see value still for switching from the 2 dose vaccine to a one dose in the future. Thank you. Okay. Thanks for the questions. Actually, these Topics are related. So first of all, what is important is that the booster dose And the variant question are somehow related because some variants, For example, the South African variant come with a reduced neutralization titers. 2020. And we, of course, know that antibody titers will drop over time. And we see a first drop now after 6 months. So we definitely will need 1st booster dose in yes, maybe after 6 months, after 9 months. And then the question will be, of course, after So the boost, how long after the boost the immune response will continue to stay stable whether the 6 months, 9 months or 12 months. So we strongly believe that booster doses will be required. And the second reason to ensure that it is we are now seeing with mRNA vaccines and with the data coming from Iskair that vaccine indeed, indeed enables prevention of infection, which is one of the key parameters 18. Reducing also the emergence of variants because every infected person is somehow Creating the chance for new mutations. And if we want to get a full control of this pandemic, we need to ensure to have high antibody titers to ensure prevention of infection. With regard to the 18. 3rd topic. So we will see, of course, with the upcoming data that our booster doses are required every 12 months, every 18 months. So this is data coming in. With regard to single versus a double dose vaccine. It is very clear that Also, our vaccine is able to provide protection against disease It was a single dose, but this is limited, yes. And we see we clearly see that a second dose is required to have a full immunity. We will have a situation end of this year That in many regions, we will have already a pre existing immunity in the vast majority of the population. And then we are not anymore dealing with the question 6. Whether we need a 2 shot vaccine or single shot vaccine because everyone who is receiving Receiving a vaccine additional vaccine will be regarded as a booster dose vaccine. And we already know From published data and from our own data, if someone had received prior dose or had COVID disease before, then a single dose is sufficient. So we are now talking About starting we need to start to talk in 2020 beyond about the vaccination, 6. And there is no any more difference between single dose and 2 dose vaccines here. 2020. The next question is from the line of Cory Kasimov from JPMorgan. Please go ahead. Hey, good morning guys. Thank you for taking my question. Ugar, I wanted to follow-up with you and the comments you just made with around boosters. Are you saying that the participants in your Phase 3 trial who were vaccinated back in late summer, early fall Are now in need of booster shots that they're no longer adequately protected from COVID. I guess just to follow-up on that. How clear is the regulatory process for boosters and variant vaccines for that matter in terms of the burden of proof on your end to enable authorization twenty. Yes. So to the first part of the question, no, I did not say that The participants are not any more protected. And just saying that we are seeing we are starting to see a drop of the antibody response. And there are now clear publications showing a correlation between the neutralizing antibody titers and protection over time. So we will see a decline of antibody titers, and we have to identify the right timing for a booster dose, yes? And the right timing of a booster dose comes, of course, with the objective one would like to accomplish. And if the accomplish is really to ensure prevention of infections, the booster dose has to come earlier. 6. And I believe that we need to go for to accomplish in the population strategy to avoid infections, not only to avoid diseases. And therefore, a booster dose would be needed earlier than later. So that's the first part of the question. Can you repeat the second your second question, please? 18. Yes. Just how clear the regulatory process is for boosters and variant vaccines in terms of the burden of proof to enable authorization? Yes. So we have already started a clinical trial with boosting participants who had received 2 doses of our vaccine, yes? And this will at the end of the day, it is More or less an automatic approach based on understanding of titers protection and the level of improvement That can be accomplished by a booster dose. Okay, great. Thank you very much. Appreciate it. Thank you. The next question is from the line of Arlinda Lee from Canaccord Unity. Please go ahead. 18. Hi, guys. Thank you for taking my questions. I wanted to maybe clarify something. You alluded to single and double doses for the booster studies that are planned and underway. Can you please explain how the study is designed, what you hope to see and when might we see data flow from that? Aslam, would you like to take the question or should I take the question? Yes. Can you please repeat the audio of the JT? It was about booster doses? Right. You were talking about the single and double dose for the booster studies that would address the variants that are planned and underway. Can you please explain how that study is designed? What you hope to see and when we might see data flow? 18. So the studies assess a couple of questions. One question is that we assess a 3rd dose, meaning after prime booster, the second booster dose of our vaccine in its current form and will assess how immunogenicity after this dose is boosted and whether it also protects from circulating variance. So not only test neutralization of the vaccine strain, but also further variance. What these studies will also test is boosting of BNtu 162b2 boosted participants with new strain of Interests are of concern. And here, we will use the South African strain eighteen. Participants who are naive for vaccines and will be tested 18, which represents a variant strain, meaning in this case, the South African strain. These studies have partly already started as amendments of our ongoing, for example, Phase III trial where those Subjects and participants who have been already vaccinated with Comirnaty are now, for example, getting the 3rd boost with the same vaccine or with a new strain. And partly we are we have submitted them. They have not started yet. Okay. Thank you. Thank you. The next question is from the line of Daniel Wendorff from Commerzbank. Please go ahead. 3. Yes, good afternoon and thanks for taking my questions. I have a question on the on your development efforts of different formulations. Can you maybe elaborate a bit on where we stand there? And is it technically Possible and also to bring a Cominati vaccine to the market, which is stable at normal refrigerator temperatures 20. For a longer time, is it something we work on? So any more color here would be much appreciated. Thank you. 18. I can take the question, if okay. Yes, we are continuously working on new formulations, but also on extending the use of our current formulation. So we have recently announced 2. The existing formulation is can be start for a longer time at minus 20 degree. 18. We will update this data also with regard to stability of our formulation at 2 to 8 degrees. So we had announced that this is an ongoing study with the existing formulation to relax the conditions for the existing formulation. We are developing ready to use formulation and lyophilized formulation, which will come into the market in the second half of twenty twenty one. And this new formulations will allow much longer stability at such temperature at 2 to 8 degrees. Thank you. You're welcome. Thank you. The next question is from the line of Dana Garisboth from I'm going to ask another one on the boost in variant. Specifically, you have suggested that you need to maintain a threshold tighter of antibodies. And I wonder what evidence you have that informs what that target threshold is? What's the impact of B cell affinity maturation on the required threshold and where did T cells fit in and could they come save us and not require multiple boosts? 16. Yes. So great questions, Dana, as always. So 2020. What is emerging is really a correlation between prevention of disease and prevention of infection by different type of vaccines and neutralizing antibody titers. 2020. So it is now more and more studies are publishing, which provides a clear correlation between vaccine effectiveness, vaccine efficacy and neutralizing antibody titers. And we do not yet have a concrete number, but this will clearly come in the next 6 to 9 months. And prevention of infection is clearly dependent on authorizing antibody titers. Severe disease, prevention of severe disease and even Maybe also prevention of disease is also driven, of course, by T cell responses, yes? But T cell responses Coming in only if the virus has reached already the target cells and start nineteen application. So we are confident that particularly CD8 T cell responses will provide long term 16. Protection against severe disease, including the variants, yes? But they will not be able to prevent effectively infection. In combination with neutralizing antibodies, of course, there will be There will most likely be a situation where lower titers neutralizing titers can be in part compensated By stronger T cell responses and vice versa, but this is signs to come or data which will be which will emerge in the next 6 to 12 months. Thank you. The next question is from the line of Navin Jacob from UBS. Please go ahead. Hi, yes. Thanks. I know you said one, but hopefully these two questions are very quick. I just wanted to clarify the lyophilized version of 162 that you're working on. You mentioned that you're starting the study. I just wanted to understand, I'm sorry I missed it, but What exactly is required to get that approved? Is it just immunogenicity data or do you have to run a full outcomes based study or is it just PK data? And then, of the 450,000,000 doses contracted in other regions, How much of that is China? Any color there would be appreciated. I can take the first question maybe and the second question is Ryan or Sean. Is that okay? 2018. Yes, I can take a second. That's fine. Yes. So the first question is, So there are different guidelines or guidances at the moment how to approve a process to ensure that 2. As requested by the FDA is to show for a variant strain That a vaccine addressing a variant strain can be manufactured in the same way, at least in the same way, then provide eighteen. Safety data for this new variant vaccine and provide immunogenicity data and Show comparability of titers accomplished against this variant strain. And then on the data package on the full data package and on the comparability data, this could result in A blueprint, approved blueprint process so that if a variant vaccine is needed, it could be introduced 2016? Without the need for an additional clinical trial. So that's the general date to address that. There are differences as suggested by regulators in U. K. And by EMA. But at the end of the day, for each of the parties, some sort of 2020 study data will be required. Yes. And Navin, on the China question, so the answer is very little has been included in the 1,400,000,000 currently signed figure. We've included the doses that have been committed to Hong Kong in Macau where we have an EUA approval, which is just under 10,000,000 doses. We've also committed to Fosun, our partner for Mainland China to supply up to 100,000,000 doses or at least 100,000,000 doses in 2021 if approval occurs and we're in the approval process as we speak, but 18. Those doses have not been included in the 1,400,000,000 number. Thank you. And the last question today is from the line of Akash Tewari from Wolfe Research. Please go ahead. Thanks so much. So Pfizer has publicly made, I would argue, some unusual comments on its desire to go after mRNA themselves 18. Moving forward, can you comment on your current COVID partnership? How long it lasts? If there are any outs? And would either company be able to develop a vaccine candidate for SARS CoV-two at solo at some point? And then maybe on your PL-onefour-1BB bispecific, 20. Genmab mentioned one of the reasons they selected the 100 mg dose is they wanted to have optimal trimer formation And that kind of translates to about 60% to 70% occupancy for the PD L1 receptor. How important is that formation of a trimer? And why not target a higher PD L1 occupancy from an efficacy perspective. Thank you. Okay. Thanks Akash for the question. So 2020. The first question is, 1st of all, we have an excellent collaboration with Pfizer where the teams are really closely 18. Collaborating and we at the management level, for example, with Albert Bourla, we have daily conversations about Ongoing collaboration, but also about future collaboration opportunities. And with regard to the 16. Existing COVID-nineteen project, it is a partnership. We have a fifty-fifty partnership, and there is no room for any of The partners, yes, to do something alone. Everything has to be decided, We started in a partnership manner and by understanding, of course, that COVID-nineteen will stay with us Most likely for at least a decade, this is a long term partnership. With regard to other potential collaborations. I would put us that they like to work with us, but they don't need to do it. 20. And this is actually a comment I made in the same way. It is a fantastic partnership, And we would like to continue to do additional projects with Pfizer, 6. But we don't have to do it. And I think it's an excellent situation where you just Enter into a partnership if you see the benefits. We see a lot of benefits in doing additional projects together, 2018, but we will come up with updates about this in the next weeks. Yes. And Ugo, I'd just like to add to that. Of course, I'd just like to remind everyone that we've been developing IP around mRNA for over a decade. And of course that's important for any collaborator when they're thinking about Entering into the space themselves. And of course, the other thing we do 18. Important for the conditional activation of the for 1 BBR. And with 100 microgram, we have the sweet spot of PD L1 or PD-one blockade plus primer formation In a sufficiently long time. So we exploit here the optimal 16. And this is also in line with the objective responses that we have observed with this compound, Which seem to be associated with the stores window. Thanks 18. Thank you. I'll now hand back to the speakers. Yes. Thank you again for joining the call today. We look forward to speaking to you in the future. Thank you and bye bye. 18. Thanks, Evelyn. Thank you. Thank you.