BioNTech SE Q4 FY2022 Earnings Call

Good morning and afternoon. Thank you for joining us today for BioNTech’s fourth quarter and full year 2022 earnings call. As a brief reminder, the slides that accompany this call, and the fourth quarter and full year 2022 press release that was issued this morning can be found in the Investors section of our website. As outlined on slide 2, you can see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings made with the U.S. Securities and Exchange Commission, including our most recent annual report on Form 20-F. Forward-looking statements on the call are subject to substantial risks and uncertainties, speak only as of the call's original date, and we undertake no obligation to update or revise any of the statements. On slides 3 and 4, you can see detailed safety information regarding our COVID-19 vaccine. And on slide 5, you can find the agenda for today's call. Today, I'm joined by the following members of BioNTech's management team. Our CEO and Co-Founder, Ugur Sahin; Özlem Türeci, 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 Ugur Sahin.

Thank you, Michael. Good morning and good afternoon, and a warm welcome to all the call participants. We appreciate your continued support. Today, I will summarize our fourth quarter and full year 2022 highlights and priorities before I pass the call over to my team to provide some further details. Slide 7. We and Pfizer continued our global leadership in the fight against COVID-19 in 2022. We achieved our supply target for the year with approximately 2 billion doses invoiced, which included the successful global launch of our first variant adapted vaccines. In the beginning of 2022, there was no clear regulatory pathway about how to introduce variant adapted vaccines. With our diligent scientific and clinical approach, we were able to navigate this regulatory uncertainty. We have evaluated various variant vaccine candidates, manufactured and have shipped about $550 million by mid-December. We maintained and continued to build on the strong market position we have established for our COVID-19 vaccines franchise to further label expansion in regions around the world. I would like to thank our growing team and our partners for the steadfast commitment, which contributed to these successes. Moving to the next slide. We also continued the rapid advancement and expansion of our clinical pipeline in 2022 and early 2023. We presented clinical data updates for programs from four distinct platforms at major medical congresses. In addition to advancing multiple new COVID-19 programs throughout the year, which led to two new product launches, we initiated nine Phase 1 trials. This included five in immuno-oncology and four in infectious diseases. Slide 9. Turning to the next slide, in 2022, we have started four new collaborations, broadened our pipeline, expanded our team by more than 1,500 new professionals and continued to strengthen our financial position. Slide 10. Our attractive company strategy is technology agnostic and aims to use modular technology platforms to produce novel product candidates. We continued to enhance and connect our platform technology in 2022 and complemented our internal capabilities and pipeline with several new partnerships. One of those which I'm particularly excited about is our partnership with OncoC4, which is based on our next generation checkpoint immunomodulator platform, with the addition of a novel anti-CTLA-4 antibody, which has shown a differentiated safety and activity profile. We believe this antibody is suitable for development as monotherapy, but also can be combined with multiple drug candidates in BioNTech’s pipeline. I will come back to that in a few minutes. Slide 11. The next slide, we kept our strategic priorities for 2023. The first is to build and strengthen our COVID-19 franchise. We believe that the COVID-19 market will continue to be dynamic and we are investing with our partner Pfizer in multiple next generation programs, which have the potential to drive future growth. This includes variant-adapted vaccines, our T-cell strength vaccine and our COVID flu combination vaccine. In immuno-oncology, our goal is to initiate multiple registrational trials in the next 12 to 18 months. Our most advanced programs include our mRNA cancer vaccines, our cell therapy, and several novel antibody programs. We are preparing to advance these programs to registrational study. Third, we aim to expand our portfolio of novel vaccines against infectious diseases with high medical need. To date, we have already initiated programs against HSV-2, malaria, and shingles. And more test starts are planned. Slide 12. Moving now to the next slide. With the new collaboration with OncoC4, we bring an exciting new checkpoint inhibitor molecule into our immuno-oncology portfolio that is going to enter the first registrational trial within the coming weeks. The first anti-CTLA-4 antibody ipilimumab was approved in 2011 by the FDA, followed by tremelimumab a couple of years later. To date, these two anti-CTLA-4 antibodies have been approved in seven cancer indications, either as a monotherapy or in combination therapy. Approved anti-CTLA-4 antibodies have shown lasting remissions in a fraction of responding patients. However, the associated high rate of toxicity especially in combination with anti-PD1 therapy limits the further use of this antibody. ONC-392, the anti-CTLA-4 antibody from OncoC4 was designed to exert and improve therapeutic index to a unique mechanism of action, which enables depletion of intratumoral Treg but preserves Treg function in healthy human tissues by CTLA-4 recycling. We believe this could allow for a longer dosing of this checkpoint inhibitor molecule, which in turn could broaden the spectrum of antitumor efficacy. Our goal is to continue to develop this antibody as a single agent I/O compound and in combination with anti-PD-1. Moreover, we will evaluate its potential in combination with our own immunotherapy candidates. With that, I would like to thank you all for your confidence in our success and your continued support and turn the call over to Özlem, who will give more background on the new assets and our pipeline.

Thank you, Ugur. I'm delighted to speak with everyone today and provide our pipeline update. In 2022, we presented several clinical data updates from our oncology programs from four distinct platforms. A selection is shown on slide 14. At ASCO in June, we presented preliminary data from the ongoing investigator-initiated first-in-human Phase 1 study, evaluating the safety and tolerability of autogene cevumeran, our iNeST program, in combination with one dose of anti-PD-L1 immune checkpoint inhibitor, atezolizumab; and standard of care chemotherapy for adjuvant treatment of patients with resected pancreatic ductal adenocarcinoma. Autogene cevumeran was well tolerated and induced high magnitude de novo neoantigen-specific T cell responses in a fraction of patients. These patients also had significantly lower recurrent free survival as compared to those without vaccine-induced de novo immune response. We are planning a Phase 2 trial in this patient population to open later this year. We had several presentations featuring our BNT211 program this year. At the ESMO Congress in September, we presented updates from our ongoing Phase 1/2 trial, evaluating the safety and preliminary efficacy of BNT211, our CAR-T cell therapy candidate in patients with relapsed or refractory CLDN6-positive solid tumors. The data showed a manageable safety profile and clinical responses. In patients with testicular cancer, the objective response rate was 57% and disease control rate was 85%. This year, we are expecting a data update from the ongoing Phase 1/2 trial, and we are planning to start a Phase 2 trial in second line platinum resistant testicular cancer in 2024. For BNT113, a candidate from our FixVac program, we presented preliminary safety data from the safety run-in phase of the ongoing Phase 2 trial evaluating BNT113 in combination with pembro versus pembro monotherapy as first-line treatment in patients with unresectable recurrent or metastatic HPV16-positive PD-L1 positive head and neck squamous cell carcinoma at ESMO IO in December 2022. Also at ESMO IO, we and our partner Genmab presented safety and preliminary antitumor activity data from patients with advanced metastatic head and neck squamous cell carcinoma treated with chemotherapy, pembrolizumab, and BNT312, a first-in-class bispecific antibody combining CD4 and 4-1BB checkpoint activation. The combination of BNT312 with pembro with or without chemotherapy was well tolerated with no reported DLTs and showed encouraging early activity with two partial responses and two complete responses in all four evaluable patients. We will be sharing more data on several of our oncology pipeline candidates throughout this year. Slide 15 provides an overview of our oncology pipeline, including the collaboration Ugur mentioned earlier, we have a total of 20 oncology product candidates across four different drug classes in 24 ongoing clinical trials, five of which are randomized Phase 2 trials. Our programs address areas of high unmet need and have the potential to tackle tumors using complementary strategies by targeting tumor cells directly or by modulating the immune response against the tumor. Many of our product candidates offer the potential to be combined with other pipeline assets under development. In the course of 2022, we started five first-in-human clinical trials, one on BNT116 together with our partner, Regeneron; a FixVac program in non-small cell lung cancer; two RiboMab programs, namely BNT141 that targets CLDN18.2-positive tumors and the T cell engager, BNT142, including CLDN6-positive tumors. Further, two immune-modulating antibodies, namely BNT13, a HexaBody targeting CD27, and BNT322, two new product candidates from our collaboration with Genmab are being evaluated in solid tumors. Turning now to slide 16 and our new collaboration with OncoC4 and their next-generation anti-CTLA-4 antibody ONC-392. We are very excited to work with our colleagues from OncoC4 on this promising compound. In preclinical models, ONC-392 has shown the most potent antitumor activity while inducing the least autoimmunity. CTLA-4 recycles between the cell surface and the endosomes where it is prevented from lysosomal degradation and recycled back to the cell surface. Interruption of this process is associated with the development of autoimmunity. Approved anti-CTLA-4 antibodies such as ipilimumab disrupt CTLA-4 recycling and induce lysosomal degradation and thereby, immune-related adverse events. In contrast, ONC-392 dissociates from the CTLA-4 molecule in the endosome and allows normal recycling of both the antibody and the CTLA-4 molecule and thus is designed for stronger cancer therapeutic effect and fewer immune-related adverse effects. Turning to slide 17. ONC-392 is being tested in a trial that investigates dose escalation as a single agent and in combination with pembro and in which indications such as I/O naïve and refractory resistant non-small cell lung cancer and melanoma are being treated with the recommended Phase 2 dose. ONC-392 as a single agent was well tolerated in a 0.1 to 10 mg per kg dose range. No dose limiting toxicities were observed and MTD was not reached. The recommended Phase 2 dose is 10 mg per kg every 3 weeks as monotherapy. Patients that received 10 mg per kg were treated up to 12 weeks in this study. ONC-392 in combination with pembro was administered at 3 and 6 mg per kg and was well tolerated with longest dosing at 3 mg per kg for up to 18 cycles and continuing. No DLTs were observed and MTD was not reached in the combination setting. Severe immune-related adverse event rate in the combo dose escalation cohorts was 23%, which is considered lower than what was reported for comparable IO-IO combination. The recommended Phase 2 dose for combination is 6 mg per kg. In summary, ONC-392 dosed as monotherapy or in combination was well tolerated, and the safety profile appears to allow higher dosing for a longer duration of treatment as compared to ipilimumab. Slide 18 shows efficacy data on ONC-392 from various cohorts of the trial as A, monotherapy in patients with ovarian cancer; B, in combination with pembro in various solid tumors; and C, in combination with pembro in relapsed/refractory melanoma patients. The left panel shows 28 evaluable ovarian cancer patients who had failed multiple lines of systemic therapy and received ONC-392 at 10 mg per kg monotherapy. The objective response rate was 21% and the disease control rate was 50% with 1 complete response, 5 partial responses and 8 stable diseases. In the middle, you see data of patients with various solid cancers treated with either 3 or 6 mg per kg ONC-392 in combination with 200 mg per kg pembro. A data cut on ONC-392 showed PRs in 3 of 10 evaluable patients. The right panel shows data from IO or IO-IO experienced refractory resistant patients with advanced melanoma treated with ONC-392 6 mg per kg and pembro, 200 mg every 3 weeks. Out of the 6 first patients enrolled, 5 had a partial response and 1 had stable disease. Based on these promising data, a Phase 2 study evaluating ONC-392 in combination with pembro in platinum resistant ovarian cancer patients has started in 2022. A Phase 3 study evaluating ONC-392 as monotherapy versus docetaxel in patients with metastatic non-small cell lung cancer who have progressed on anti-PD-1, PD-L1 antibody-based therapy is planned to start this year. Slide 19 highlights our infectious disease pipeline. In the past months, we started multiple first-in-human trials with our mRNA vaccine candidates, including next-generation COVID-19, the combination of COVID-19 and influenza mRNA, malaria, HSV-2 and shingles vaccine candidates. In addition, we expect to enter the clinic with a tuberculosis vaccine candidate this year. These programs build on our validated platform of nucleoside-modified mRNA LNPs with optimized backbone design to address diseases with a significant global need. Slide 20. As of December 2022, the original COVID-19 vaccine has been authorized or approved for emergency use or temporary use or granted market authorization in over 100 countries and regions around the world. Through rapid execution, we have broadened the label of our original and Omicron BA.4-5 adapted bivalent vaccine across different age groups. This included full marketing authorization for our original COVID-19 vaccine. The conversion applies to all existing and upcoming indications and formulations of the COMIRNATY product group authorized in the European Union, including original Omicron BA.1 and BA.4-5 adapted bivalent vaccines as booster doses for individuals aged 12 years and older. In addition, we received EC approval for full market authorization for a 3 mg dose of original COVID-19 vaccine as a free dose series for children aged 6 months through 4 years and another EC approval for a fourth dose booster of original COVID-19 vaccine in individuals 12 years of age and older at an interval of at least three months between the administration of our original COVID-19 vaccine and the last prior dose of COVID-19 vaccine. In addition to the approvals of our original COVID-19 vaccine, we received several approvals and authorizations of the original Omicron BA.4-5 adapted bivalent vaccine booster, including an FDA EUA and EC approval for ages 5 to 11 years and an FDA EUA as a third 3 mg dose in the free dose primary series and a single booster dose at least 2 months after completion of primary vaccination with three doses of our original COVID-19 vaccine for children 6 months through 4 years of age. In December 2022, BioNTech and Fosun Pharma received full regulatory approval of our 30-microgram original COVID-19 vaccine as well as of the 30-microgram booster dose of our original Omicron BA.5 adapted bivalent vaccine in individuals 12 years and older in Hong Kong. We continue to monitor protection offered by the original and our original Omicron adapted bivalent vaccines against emerging SARS-CoV-2 variants. Slide 21. In February this year, we and Pfizer announced the start of a Phase 1/2 trial of our mRNA vaccine candidates against shingles, also known as herpes zoster. The mRNA shingles vaccine candidates encode different versions of glycoprotein E on the surface of a varicella zoster virus. The glycoprotein E protein is important for viral replication and the cell-to-cell spread after reactivation of the virus in the nerve cells. The Phase 1/2 multicenter randomized controlled dose selection study will evaluate the safety, tolerability, and immunogenicity of mRNA vaccine candidates against shingles. The study is aiming to enroll up to 900 healthy volunteers aged 50 through 69 years and is being conducted in the United States. Phase 1 will help select for the optimal mRNA vaccine candidate, dose level, dosing schedule, and formulation for advancement to Phase 2. Participants in the study will be followed to determine how long protection may last. While there are currently approved vaccines for shingles, we and Pfizer aim to utilize our mRNA technology to develop a vaccine that demonstrates high efficacy, is better tolerated, and is efficient to be produced globally. I look forward to providing additional program updates in the coming months. I will now pass the presentation to our CFO, Jens Holstein, who will present our financial results.

Thank you, Özlem, and a warm welcome to everyone who dialed in for today's call. I'll start my section with key highlights for the 2022 financial year. During the 2022 financial year, we were able to maintain a strong performance. I would like to underline this by diving into some of the key financial figures for the past year. Our total revenues reported for the 2022 financial year reached €17.3 billion and mainly comprised €17.1 billion in COVID-19 vaccine revenues, whereby we met the upper end of our updated guidance from November 2022. Based on our strong profit during the year ended December 31, 2022, we generated an operating cash flow of €13.6 billion and generated earnings per share on a fully diluted basis of €37.77. With respect to the Company's financial position, we ended the 2022 financial year with €13.9 billion in cash and cash equivalents. Subsequent to the end of the year, we have received €1.8 billion in cash from our collaboration partner, Pfizer, settling our gross profit share for the third quarter of 2022. Let's continue with the next slide that presents the comparison between our actuals of the 2022 financial year to the guidance recently updated in our last earnings call in November 2022. As just mentioned, we recognized €17.1 billion in COVID-19 vaccine revenues in reaching the upper end of our guidance of €16 billion to €17 billion. In total, we invoiced approximately 2 billion doses in 2022. I'll come back to the allocation of the COVID-19 vaccine revenues in more detail in one of the following slides. During the 2022 financial year, our R&D expenses reached €1,537 million, so that we ended the year around the upper end of our guidance for March of 2022. The expenses resulting from the prelaunch production of our Omicron adapted bivalent COVID-19 vaccines contributed to our R&D spend. Our core R&D activities focused on broadening and accelerating our existing pipeline of product candidates in oncology and infectious diseases in line with our expectations. Moving to SG&A expenses. During the 2022 financial year, we recognized €544 million in SG&A expenses and hence, met our guidance for March of 2022. The expenses were mainly driven by supporting our rapid growth, including accelerating our internal operating activities. Our 2022 financial year capital expenditures amounted to €363 million and included investments in infrastructure and production capacities. The spending remained below our expectation, mainly due to certain delays in finishing our various construction projects. During the 2022 financial year, we reached an annual effective income tax rate of 27%, meeting our amended guidance. Certain current tax savings associated with the expenses from the share-based payment programs have been recognized in equity directly. Hence, those cost-effective savings did not have an impact on our annual effective income tax rate under IFRS. Considering this effect, though, the cash effective tax rate is about 24%. Let's now switch to the next page. The 2022 financial year COVID-19 vaccine revenues of €17.1 billion reached the upper end of our guidance, benefiting from stronger-than-expected revenues by our collaboration partners and some favorable U.S. dollar development. Compared to the previous year, we saw a decrease in our COVID-19 vaccine sales, which corresponds with the demand for COVID-19 vaccines. Let me give you some more details on our revenue stream. As a reminder, on 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 €12.7 billion related to our share of gross profit from COVID-19 vaccine sales in the collaboration partner territories. These revenues represent a net figure, meaning that we generate a 100% gross margin on those revenues. As we have mentioned in the past and explained in more detail on our financial statements and filings with the SEC, our profit share is, to some extent, estimated based on preliminary data shared between our collaboration partner Pfizer and us. Our COVID-19 vaccine revenues from direct COVID-19 vaccine sales to customers in our territory reached €3.2 billion during the 2022 financial year. Revenues in our territory were significantly driven by shipments of the Omicron adapted bivalent COVID-19 vaccine cells towards the end of 2022. Also included in our COVID-19 vaccine revenues were €1.2 billion of revenues from sales to our collaboration partners for the 2022 financial year. The sales under the collaboration with Pfizer are influenced from time to time by manufacturing variances such as expenses due to write-offs of inventories and costs related to production capacity derived from contract manufacturing organizations that became redundant. I'll be moving to our financial results for the fourth quarter and the full year of 2022. Having explained our revenues on the previous slide, let me move to the cost of sales that amounted to €0.2 billion in the fourth quarter of 2022 compared to €0.6 billion for the comparative prior year period. This drop was mainly caused by the release of provisions in Q4. For the 2022 financial year, the cost of sales amounted to €3 billion compared to €2.9 billion for the comparative prior year period. The cost of sales included costs of sales from our COVID-19 vaccine sales comprised the share of gross profit that we owe our collaboration partner Pfizer based on our sales. In addition, cost of sales was impacted by expenses arising from inventory write-offs and expenses for production capacities, derived from contracts with contract manufacturing organizations that became redundant. The effects were driven by the introduction of a new COVID-19 vaccine formulation, the switch from the monovalent vaccine to our Omicron adapted bivalent COVID-19 vaccine due to the accelerating internal manufacturing capacities during the year-end of December 31, 2022. Research and development expenses reached €0.5 billion for the fourth quarter of 2022 compared to €0.3 billion for the comparative period in 2021. For the 2022 financial year, research and development expenses amounted to approximately €1.5 billion, as stated before, compared to €0.9 billion for the comparative prior year period. The increase was mainly due to expenses in connection with the development and production of our Omicron adapted bivalent COVID-19 vaccine and from progressing the clinical studies for our pipeline candidates. The increase was further driven by an increase in wages, benefits, and social security expenses resulting from an increase in headcount as well as expenses incurred under our share-based payment arrangements. General and administrative expenses amounted to €0.1 billion for both the fourth quarter of 2022 as well as for the comparative period in 2021. For the 2022 financial year, general and administrative expenses were €0.5 billion compared to €0.3 billion for the comparative prior year period. The increase in G&A was mainly due to the increased expenses for IT consulting and IT services, increased expenses for purchased external services as well as an increase in wages, benefits, and social security expenses, resulting mainly from an increase in headcount. Our business development transactions also contributed to the increase in general and administrative expenses. Income taxes were accrued with an amount of €0.9 billion for the fourth quarter of 2022 compared to €1.5 billion for the comparative period in 2021. For the 2022 financial year, income taxes reached an amount of €3.5 billion compared to €4.8 billion for the comparative prior year period. The derived effective income tax rate for the 2022 financial year was approximately 27% and is in line with our expectations. For the fourth quarter of 2022, net profit reached €2.3 billion compared to €3.2 billion for the comparative period in 2021. For the year ended 31 2022, net profit reached €9.4 billion compared to €10.3 billion for the comparative prior year period. Our diluted earnings per share for the fourth quarter of 2022 amounted to €9.26 compared to €12.18 for the comparative period in 2021. For the 2022 financial year, our diluted earnings per share amounted to €37.77 compared to €39.63 in 2021. Let's now move to the following slide and have a look at the return to our shareholders during the 2022 financial year. We believe that our shareholders should benefit from our strong performance. Following the Annual General Meeting in June 2022, a special cash dividend of €2 per ordinary share was paid out to our shareholders, which led to an aggregate payment of approximately €0.5 billion. In addition, in March 2022, we authorized a share repurchase program of ADSs, allowing us to repurchase ADSs in the amount of up to $1.5 billion during the year 2022 and 2023. On May 2, 2022, the first tranche of our share repurchase program of ADSs with a value of up to $1 billion commenced. And this tranche ended on October 10, 2022. In November 2022, we authorized the second tranche of our share repurchase program of ADSs with a value of up to $0.5 billion, which then started on December 7, 2022. During the period from May 2, 2022 to March 17, 2023, the date when the trading plan for the second tranche of our share repurchase program expired, a total number of 9,166,684 ADSs were repurchased, representing approximately 3.7% of our share capital. The ADSs were repurchased at an average price of $142.04 for a total net consideration of approximately $1.3 billion under the program. The repurchased ADSs were partially used to satisfy settlement obligations under our share-based payment arrangements. Before I provide our 2023 financial guidance, I would like to provide some of the key assumptions and considerations which, amongst others, in our guidance are described on the following page, specifically on the expected full year 2023 COVID-19 vaccine revenues. We expect a transition from an advanced purchase agreement environment to commercial market ordering starting in 2023. In addition, our revenue guidance is based on the assumption that vaccine developers will be asked to adapt the COVID-19 vaccine to newly circulating variants or sublineages of SARS-CoV-2. Our COVID-19 vaccine revenue guidance reflects expected deliveries under existing or committed supply contracts and anticipated sales through traditional commercial orders. Currently, a renegotiation of the existing contract with the European Commission is ongoing with the potential for a rephasing of dose deliveries across multiple years and/or volume reduction. While we expect the need for a new variant-adapted vaccine will increase demand, fewer primary vaccinations and lower population-wide levels of boosters are anticipated. We're also seeing seasonal demand will drive revenue generation significantly towards the second half of the year 2023. Let's now turn to the next slide. I would like to share with you the Company's outlook for the 2023 financial year. Please note, the following numbers reflect current base case projections, include potential effects caused by or driven from additional collaborations or potential M&A transactions to the extent they have been disclosed and are calculated based on constant currency rates. We believe that we and our collaboration partners, Pfizer and Fosun, are well positioned for the future as a leading COVID-19 vaccine provider. For the 2023 financial year, we estimate COVID-19 vaccine revenues of somewhere around €5 billion based on the previously mentioned base assumptions. Thanks to the company's continued strong financial performance, we've never been in a better position to accelerate the advancement of our diversified clinical pipeline and to invest into the further transformation of BioNTech. We aim to accelerate our late-stage programs and expand our platform across our four drug classes. We believe the development, regulatory approval, and commercialization of our clinical pipeline is the basis for our continuing success. The responsible use of our financial resources generated from the sale of our COVID-19 vaccine is paramount to BioNTech as well. Broadening and accelerating our existing pipeline of product candidates in oncology and infectious diseases as well as expanding our capabilities in other disease areas will be our focus. As already shown in the course of last week, we intend to invest in broadening our pipeline going forward. For the 2023 financial year, we plan to spend between €2.4 billion and €2.6 billion in R&D expenses. SG&A expenses are estimated to be in the range of €650 million to €750 million as we plan to continue to invest in making BioNTech the global, fully integrated immunotherapy powerhouse. Capital expenditures for our existing business for the 2023 financial year are expected to be in the range of €500 million to €600 million. We are, for example, planning to further expand and enhance our R&D and manufacturing facilities and to invest in a state-of-the-art IT infrastructure to support our digitalization process, especially in the R&D area. Finally, we expect the estimated annual cash effective income tax rate for the BioNTech Group at around 27%. Please be reminded that the financial guidance does not include the impact from further M&A activities or collaborations that the Company might invest in during the calendar year of 2023. I would like to now take the opportunity to highlight our capital allocation framework. The key areas are at the center of our activities. First and foremost, R&D. We have proven to the world that our science and the translation into novel medicines can really make a difference for people worldwide. We believe that our technologies and science can further improve people's health and how we cope with various diseases. Therefore, we intend to further accelerate our initiatives to create additional long-term value for patients, our shareholders, and society as a whole. This remains the key area of our investments going forward. Secondly, M&A and business development. To supplement our technologies and digital capabilities, we strive to extend and augment our expertise with synergistic acquisitions and collaborations. For example, in January 2023, we announced a strategic partnership with the UK government to provide up to 10,000 patients with personalized mRNA cancer immunotherapies by 2030. Also in January 2023, we announced an agreement to acquire InstaDeep Ltd., a leading global technology company in the field of artificial intelligence and machine learning and a long-time strategic partner. The transaction is subject to customary closing conditions and regulatory approvals. On Monday of last week, we announced that we entered into an exclusive worldwide license and collaboration agreement with U.S.-based OncoC4 to co-develop and commercialize their next-generation anti-CTLA-4 monoclonal antibody candidates. Thirdly, we would like our shareholders to again participate in our success. Consequently, we'll start an additional share repurchase program of ADSs pursuant to which we may repurchase ADSs in the amount of up to $0.5 billion during the year 2023. 2022 has been a truly successful year for BioNTech. 2023 is expected to be a year where contractual agreements with governments are starting to move into a commercial and flu-like setting, first, in the U.S., later in other jurisdictions. We rate this as an opportunity with more and more countries moving towards a standard commercial setting in the years to come. We believe to be well placed given the favorable technology basis that mRNA offers for COVID-19 vaccines and based on the commercial partnership with Pfizer that has been tremendously successful for both partners. We expect to financially benefit from our COVID-19 franchise in the next years and anticipate relevant and ongoing profit and cash flow contributions from our vaccine given the existing relation of revenues and costs for BioNTech.

Thank you, Jens. To wrap up our prepared remarks, I'll provide a brief summary of the strategic outlook for our COVID-19 vaccine franchise and our broader infectious disease vaccine and oncology portfolios before concluding with a few important dates to mark on your calendars. Moving to the next slide. As Jens mentioned, we expect our first commercial market opening in the second half of the year in the United States. We expect this to follow strain selection in the May-June time frame and subsequent booster rollout for the fall season. It will likely take a few years to fully transition from a pandemic to a steady-state market. As this transition occurs, in the midterm, we see growth potential for our COVID-19 vaccine franchise driven by a continued shift to private markets globally. If successful in ongoing trials, our next-generation COVID-19 vaccines and combination vaccine being developed with Pfizer could contribute to this longer-term growth potential. We expect data updates over the course of the year on these pipeline programs. Turning to the next slide. COVID-19 remained a major cause of hospitalizations and death globally in 2022, far outpacing the level caused by seasonal influenza. Last year, in the United States, there were approximately 264,000 deaths and 1.5 million hospitalizations related to COVID-19. In the same period, there were approximately 36,000 deaths and 450,000 hospitalizations due to influenza. Despite the significantly higher burden of disease, COVID-19 vaccine doses administered in the U.S. according to the CDC, lagged those of seasonal flu at approximately 171 million flu doses versus approximately 144 million COVID-19 vaccine doses. To note, these volumes include both bivalent boosters, which rolled out in the fall and boosters administered earlier in the year. While not a perfect analog, we continue to believe that flu volumes represent a benchmark that is relevant for the mid- to long-term COVID-19 annual booster market. While overall volumes are likely to remain lower than flu in 2023, we believe that the disease burden and relatively high vaccine efficacy support increased uptake over time. Turning ahead to the next slide. We continue to advance our infectious disease vaccine portfolio outside of COVID-19, including two additional Pfizer-partnered vaccine programs and our growing pipeline of wholly-owned vaccines. Our focus here is on prophylactic vaccines against diseases of high global incidents and medical need. The diseases we are targeting with our technology platforms include those where no marketed vaccine exists as in the case of HSV-2 or where there is room to improve on currently marketed products as in the case of malaria. We anticipate multiple additional trial starts in the next 12 months. As you can see from the right-hand side of the slide, we also anticipate multiple data updates from these newer infectious disease vaccine programs over the course of the year. Turning to the next slide and our 2023 strategic outlook in oncology. As Ugur stated earlier in the call, we plan to initiate multiple registrational trials in the next 12 to 18 months. In parallel, we plan to accelerate the build-out of our oncology commercial capabilities in 2023 and 2024 with the goal of commercial readiness in the United States, EU, and other selected regions, to support first oncology launches from 2026 onwards. We anticipate further M&A and/or product candidate in-licensing will further complement our organic pipeline with synergistic programs. Finally, we expect several pipeline updates from our oncology pipeline in 2023, including from our individualized cancer vaccine program in first-line melanoma, BNT122, our CLDN6 CAR-T program, BNT211, and from several of our next-generation checkpoint programs, including BNT311 and BNT312. The next slide summarizes our pipeline news flow expected this year. Many of these points have been covered, so I won't go through them in detail again here. What is clear is that our pipeline of 26 clinical-stage programs will lead to many readouts this year across a range of our technology platforms and also now across multiple therapeutic areas. We expect this broadening will continue as we look to accelerate selected programs towards registrational trials and ultimately to the market. Before concluding and opening up the floor for questions, I would like to highlight on the next slide that we will hold our Annual General Meeting on May 25th and our next Innovation Series event on November 7th. We will provide further details in the coming weeks on both events. With that, I would like to thank our shareholders for their continued support. Now, I'll conclude our remarks and open the floor for questions.

One point of clarification. Maybe this is best for Ryan to answer. On issuing your €5 billion in revenues to expect from the COVID franchise, can you walk us through what the drivers were that you used? It does seem to be a slightly lower number than perhaps the Street has been expecting. And can you tell us what of those drivers could still be variable that could still be potentially a reason to have to adjust, let's say, later in the year? And then secondly, you talk about M&A. I'm just wondering what are the types of candidates that BioNTech would think to be most beneficial because you are in several clinical trials planned and already started, what would be the most complementary to what you're trying to do? Thanks.

Yes. Thank you, Tazeen. I'm going to turn it over to Jens, actually for the first part of the question, and I'll come back to the second.

Thank you for the question, Tazeen. I want to refer back to one of the slides I mentioned earlier. We are seeing a transition from our traditional model of selling to governments towards a more commercial approach. This shift presents new opportunities for us. We view 2023 as a transitional year since we expect some government-based doses to enter the market, which we anticipate will lead to further growth in the future. Additionally, with new variants anticipated, there will be a need for more vaccines that utilize our mRNA technology. In the second half of this year, we expect to initiate our commercial strategy in the U.S., which we hope to expand to other regions afterward. It's challenging to predict the pace of this transition, but we expect to see developments in Europe, particularly in Germany and other countries. We are moving from multi-dose vials to single-dose vials, which will also affect pricing. We remain optimistic about the ongoing development of our COVID-19 vaccine franchise. Furthermore, when comparing our cost structure to that of other market players, we are in a strong position due to the gross profit share we have with Pfizer. Overall, we are very positive about the future of our COVID-19 vaccine franchise. Ryan, would you like to add anything?

Yes, I want to emphasize that one of the key factors behind our revenue guidance of approximately €5 billion is the European Union contract, which is our largest contract and is currently undergoing renegotiation. This highlights the importance of demand on the ground, and we will continue to provide updates as they arise. The expected changes to that contract have already been included in our financial projections. Regarding your question on M&A, we are primarily focused on acquiring synergistic assets that would enhance our proprietary BioNTech pipeline. An example of this is the new anti-CTLA-4 molecule that we announced and discussed today; it shows a differentiated profile and potential for combination therapy as well as opportunities to expand treatment options through an immune-oncology mechanism. Additionally, it could complement our pipeline in the future. This example involves assets that are transitioning from Phase 2 to Phase 3, so we are targeting mid- to late-stage assets, and we have several in the deal pipeline, some of which are at more advanced stages.

Is there a dollar number, Ryan, that would be an upper limit of how much BioNTech is looking to spend right now?

So, our sweet spot, I think, as a normal course would be a sub 1 billion. And I think we certainly like the proposition of this deal, this OncoC4 deal where we paid 200 million upfront and then there are some success-based milestones and royalties, but where we share some development costs, but we take control of the asset and can really direct the development. I think that's really what we're looking to do. There could be some variation depending on the asset in question. But I think we really like that sort of approach. We will look at larger deals, but I think the sweet spot for us is the sort of product-centric, product-focused in-licensing and/or M&A.

Yes. I have a couple of questions regarding your oncology pipeline. First, I'm really interested in how you plan to expand the development of ONC-392, now that you have it. Should we expect any head-to-head studies with ipi/nivo to demonstrate a broader therapeutic window and potentially better efficacy? Secondly, now that you have a large portfolio, I’m curious about the criteria you’re using for go/no-go decisions. In this presentation, you highlighted certain focus programs in oncology, and I wonder why those specific programs were chosen and what criteria they met to reach the focus program designation. What does that imply for the programs that are not considered focus programs?

Yes, I can address that. Hi Daina, thank you for your questions. First, regarding ONC-392, we believe the key differentiator is its larger therapeutic window and its capability to induce higher and prolonged exposure to the anti-CTLA-4 mechanism, especially through expected depletion of Tregs in the tumor microenvironment. This contrasts with currently approved anti-CTLA-4 products, which maintain lymphatic Treg function. We do not plan to conduct head-to-head studies with those approved products. Instead, we will explore two types of applications. The first focuses on the single compound activity of ONC-392, as seen, for example, in ovarian cancer, and we will also report on its activity in non-small cell lung cancer patients, which will enable us to explore indications not yet authorized for ipilimumab or other anti-CTLA-4 antibodies. The second application involves using this as a combination partner. We believe anti-CTLA-4 is well tolerated and serves as an excellent partner for our cancer vaccine pipeline. We have previously shown synergy between our personalized vaccines and anti-PD-1. We also anticipate that certain types of vaccines will exhibit synergy with the anti-CTLA-4 mechanism. As for your third question about how we define focus, we aim to meet two key goals regarding personalized cancer immunotherapy: first, to enhance the overall response rate and activity in the same indication, and second, to provide clinical benefits to patients throughout their disease journey, from the very beginning to later stages. This drives our selection of compounds. As Ryan mentioned, one important aspect is whether the compound will close existing gaps in our portfolio, and the other is whether it will enhance the impact of our compounds’ synergistic effects.

I have a couple of questions related to PCV. First, I wanted to clarify the timing. You previously mentioned that we could expect data in the first half of 2023 for the information presented on the slide marked 2023. Has there been any change in that timeline? Second, regarding the outcome of the study, could you provide some general expectations for it and what you would consider a positive result? I ask this in the context that for some mid-stage trials, a p-value greater than 0.05 might still be seen as a reason to proceed. Can you elaborate on that? Thank you.

Thanks, Matt. I will address the first part, and then Ugur can discuss the interpretation of the data. Regarding the readout, you are correct that we have expanded the readout timing expectation to the entire year of 2023. It's reasonable to expect that it could be released in the second half.

Yes. The second point pertains to how we interpret the results. The clinical trial aims to assess the potential effectiveness of a personalized cancer vaccine when used alongside PD-1 in advanced metastatic cases. We will evaluate the performance of the compound specifically for melanoma, which has evolved from a single immunotherapy indication to multiple combination trials, with several combination treatments now approved. This suggests that a favorable outcome could be viewed in light of the existing medical needs in this area and the challenges we face when proceeding in the first-line melanoma setting. Additionally, a successful trial in the first-line metastatic context could open doors for further indications in conjunction with checkpoint blockade treatments.

Hi. This is Ivy on behalf of Akash. We have a couple of questions, if that's okay. Let's start with the first one. Regarding your COVID guidance, Pfizer is currently projecting full vaccine-like penetration of the COVID vaccine in the latter half of this decade, estimating about 100 million to 160 million global doses annually moving forward. We're observing that the market seems to reflect much lower demand for vaccines at the current valuation. What are your thoughts on Pfizer's assumptions? It appears there is a discrepancy between your 2023 guidance and Pfizer’s, which indicates approximately 5 billion versus 6.5 billion as implied by Pfizer's estimates. Additionally, with the increased operational expenditure you projected from around 2 billion in 2022 to over 3 billion in 2023, can we reasonably assume that COVID vaccines may not generate cash this year? Thank you.

I will begin and I'm sure Jens will add his insights. Regarding the comparison to Pfizer's guidance, I believe there was a market aspect to your question. Aligned with Pfizer's disclosures, we feel that 2023 could be a low point for the COVID market as it shifts over the next couple of years to a more stable, commercially driven environment. You might have heard that in our comments today. This transition won't be complete this year since many countries are still bound by government contracts that stem from the pandemic. We do anticipate some commercial markets will open this year, but this transition will take time. We expect this transition might lead to greater volumes and potentially higher prices, though this will also require time. We've identified some midterm drivers that could enhance growth potential, like increased uptake of COVID-19 vaccines and possibly follow-on vaccines. Our next-generation vaccines currently in Phase 1 and combination vaccines could also play a significant role in this. As for the guidance comparison to Pfizer, you mentioned the rough estimate of around $12 billion from Pfizer, and perhaps Jens can clarify that you can't simply split that estimate in half when comparing our guidance to Pfizer's.

It was quite challenging to understand you due to the connection issues. However, what I gathered is that our revenue guidance comes from three main areas, particularly from our profit share with Pfizer. This profit share implies that there are costs of goods sold that affect the final revenue figure when calculating gross profit. If we consider our full-year COGS figure at 82.7% gross profit, you need to factor in a specific percentage for COGS. For the €12 billion you mentioned, assuming an 80% gross margin makes sense. Additionally, we generate revenue by selling products to Pfizer, which contributes minimally to our profits. We also have revenues from Germany and Turkey with a profit share from Pfizer. Taking all of this into account, Pfizer's guidance of $5 billion to $13.5 billion for 2023 aligns well with what we've observed in 2021 and 2020.

Yes. Regarding your question about profitability, we expect to remain profitable this year. While we're not providing specific guidance for the future, our expectation is that, as Jens mentioned, our partnership with Pfizer allows us to keep fixed costs low, making the product highly cash generative for us.

Got it. That's very helpful. I have one quick follow-up. When can we expect to see bivalent data? Will you assist when the data becomes available? Thank you.

Yes. We are not providing guidance on bivalent data at this time. We shared safety and immunogenicity data last year. Currently, our focus for the vaccine is on strain selection for the upcoming fall season, and we are in discussions with regulators about this. We anticipate that the new data will rely on safety and immunogenicity findings. There will be additional discussions in the coming months, but we expect the new data to be available in May or June.

I just have a couple. The first one is on BNT211. What solid tumor data do you anticipate having this year? Is it going to be something outside of the testicular and ovarian and sort of what comes to mind? And then secondly, just to go back on BNT122, the PFS should have potentially read out second half next year. So, as you're thinking about releasing data in the second half of this year, is it that you're waiting for the survival data, or sort of what are the gate marks that you're waiting for you to release that data? Thank you.

Thank you for your question. BNT211, we have a clinical trial ongoing, which recruits patients who have CLDN6-positive cancers, specifically testicular cancer. And as you have already pointed out, we have already reported some of that data. We will have a larger cohort of testicular cancer patients. And this will be one part of the data we will report this year. On top of that, the clinical trial is continuing to enroll patients with ovarian cancer, with endometrial cancer, and other rare CLDN6-positive cancer types like gastric and some small cell lung cancer, for example, so that also these indications will be reported.

BNT122, maybe I can take the question. So we are indeed collecting objective response data, PFS data and documenting OS data and potentially read out in the second half of 2023 will be most likely limited to PFS and ORR data.

This is Steven on for Chris. Thank you for taking our questions. Two for me. So currently, in select territories, BioNTech and Pfizer have a 50-50 gross profit share. Can you speak to what the economics of that might look like for a COVID-flu combo vaccine, if that's approved in the future? And then with the renegotiations with the European Commission, where there's potentially lower volume and potential rephasing, could you elaborate on what that might mean for price, could we see a higher price going forward with that contract?

Yes. Maybe let me start with this, and then Ryan can chime in. So for the combination of COVID-flu, we can't give you any details. This is confidential in the discussions with our partner Pfizer. And then in terms of the EC, of course, I mean, these are also ongoing discussions, as you know. We wanted to make sure and be transparent that these outcomes could be the case that the existing 450 million doses contract that we have with the EC could be split over several years or that potentially a certain volume could go down overall. But on the details in terms of pricing, you've got to bear with us. Yes, we can't give any details here. We're in the middle of negotiations, so we can't give any more details than what I just said.

Yes. I would like to add that, for the COVID vaccine, we have a 50-50 gross profit share with Pfizer. We only incur SG&A expenses or sales and marketing expenses in the BioNTech commercial territories, primarily in Germany. Most of the sales and marketing expenses are with Pfizer and outside of our collaboration, so our effective economics on the product exceed 50%. The situation with flu is different. We licensed the flu mono program to Pfizer before COVID-19, so it operates under a licensing agreement, and we don’t cover any development costs for the flu mono program. It's a different structure. We are eligible for milestones and royalties on flu mono. Until we can provide more information on the combo economics, assume it falls somewhere between those two, and we believe it will be economically significant for us from a profit and loss perspective, but that’s all we can share for now.

Forgive me if this seems a bit redundant, but I just want to follow up on an earlier question or two. I just want to confirm that the comment that an anticipated update to the European contract has been factored into your numbers means that any apparent disconnect between the guidance you're providing and that that Pfizer gave earlier this year is not solely driven by a disconnect on assumptions around gross profitability of the COVID vaccine business, but is also driven by just different overall revenue or assumed doses delivered? Thank you.

So Jess, I'll start, and Jen should join in here. We work closely with Pfizer on various levels to estimate market potential and vaccine uptake, among other things. Several factors affect the communication between our two companies. It’s not just about expectations regarding the EU contract. We also have different fiscal years, which Jens can elaborate on and which may also play a role. Additionally, it’s important to distinguish between contracted doses, which may relate to your reference regarding Pfizer’s disclosure, and the expected revenue from those contracted doses compared to our current guidance. Our guidance reflects our best estimates for expected revenue for the year, which does take into account potential changes to the EU contract. Jens, do you have anything to add?

Yes. You mentioned this earlier. We can't comment on how Pfizer is communicating their guidance from a few weeks ago. As of now, we still don't have clarity on what the contract with the European Union will entail, including volumes, timelines, pricing, or any related details. Each company needs to provide their own guidance. If you compare the figures, as I mentioned before, we are actually quite close. A mathematical comparison shows that Pfizer and we are well aligned regarding the COVID business and the numbers we have both presented.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.