Biontech SE (BNTX) 2022 Q3 法說會逐字稿

Welcome to the BioNTech Third Quarter 2022 Update Call. I would like to hand the call over to the Vice President of Investor Relations and Strategy, Sylke Maas. Please go ahead, Sylke.

Thank you all for joining us today as we review our third quarter operational highlights and provide you with some financial update. BioNTech is in exciting phase of its corporate development, and we are delighted to share our progress with you. A few housekeeping items before we start. I invite you to view the slides that accompany the webcast and the third quarter 2022 press release, both of which were issued this morning and can be found in the Investors section of our website.

Taking the first look at Slide 2, I would like to remind you that during today's presentation, we will make several forward-looking statements. These forward-looking statements include, but are not limited to our COVID-19 vaccine revenues as we include figures that are derived from preliminary estimates provided by our partners, our estimated financial results for 2022, the continued global demand for our COVID-19 vaccine, expected COVID-19 vaccine production, supply and deliveries for 2022 and beyond.

The planned next steps in our pipeline programs; the timing for enrollment initiation, completion and reporting of data from our clinical trials; the timing of and, our ability to obtain and maintain regulatory approval for our product candidates; and other risks described in our filings made with the U.S. Securities and Exchange Commission, including our most recent quarterly report filed today.

Actual results could differ from those we currently anticipate. You are, therefore, cautioned not to place undue reliance on any forward-looking statements, which speak only as of today, shared today during the conference call and webcast. Also please note that Slides 3 and 4 provide detailed and important safety information regarding our COVID-19 vaccine.

Finally, today's agenda can be found on Slide 5. It is my pleasure to welcome the BioNTech management team, who will guide you through our third quarter update. I'm joined by Ugur Sahin, CEO; and Co-founder of BioNTech; Ozlem Tureci, our Chief Medical Officer and Co-Founder; Jens Holstein, our Chief Financial Officer; and Ryan Richardson, our Chief Strategy Officer. With that, I would like to turn the call over to Ugur.

Thank you, Sylke. A warm welcome to all participants of today's conference call. I'm pleased to update you on BioNTech's operational progress during the third quarter of 2022.

Before I start, let me value the fundamentals of our success. With our deep expertise in immuno-oncology, our scientific rigor, our fully integrated spectrum of translational research and manufacturing competencies, we succeeded, together with our partner, Pfizer, in developing and supplying various adapted vaccines globally. We did so at an unprecedented speed.

Since BioNTech's inception, we have pursued our vision to establish a fully integrated global immunotherapy powerhouse aspiring to translate science into survival. We follow a technology-agnostic, solution-focused multi-platform strategy. Our innovation engine leverages various emerging technologies and therapeutic approaches. Our aim is to address high unmet medical needs in oncology, infectious diseases and beyond.

We are advancing a diversified pipeline of immunotherapies and are chasing an unprecedented opportunity to accelerate our progress towards our long-term vision to bring the next generation of immunotherapies to patients.

Moving to our third quarter highlights. We reported total revenues of EUR 3.5 billion, contributing to total revenues of EUR 13 billion for the first 9 months of the year. The strong performance can be attributed to the continued successful execution in our COVID-19 vaccine franchise, and reflects shipments of the Omicron-adapted vaccine booster, which started early in September. We are updating our 2022 financial guidance by raising our vaccine revenues estimated to EUR 16 billion to EUR 17 billion.

We have expanded our team to more than 4,000 employees around the world. We are expanding our global M&A manufacturing network to ensure access to our innovative medicines worldwide. We recently signed a letter of intent with Australia's State of Victoria for strategic partnerships to establishing an mRNA research and innovation center and have to translate encouraging academic research into the clinic. We will establish one of our modular BioNTainer manufacturing facilities in Melbourne to enable end-to-end clinical scale manufacturing of mRNA product candidates.

In oncology, we are executing across our broad pipeline. We have advanced a total of 19 candidates in 24 ongoing clinical tariffs, including 5 Phase II trials. In the third quarter, 3 new programs enter Phase 1. At this year's ESMO Conference in September, we presented another positive clinical update for BNT211 for the treatment of solid tumors. Ozlem will share more detail on the data update momentarily.

Slide 7 highlights our quarter 3 progress of our COVID-19 franchise. This quarter, we and our partner, Pfizer, continued to build on our global COVID-19 vaccine leadership with first-to-market Omicron BA.4/BA.5 adapted vaccine launches across multiple countries and regions worldwide.

As of mid of October 2022, we have invoiced approximately 300 million doses of our BA.1 or BA.4/BA.5-adapted bivalent vaccine with multiple regulatory developments around our original COMIRNATY vaccine. The vaccine is undergoing conversion to full market approval in several regions around the globe. It has received full marketing authorization in the EU for all existing and upcoming indications and formulations.

Additionally, we received EC approval for 3-dose primary series in children aged 6 months to 5 years in the EU and for a third booster dose for children aged 5 to 11 years. The third booster dose was recently approved by the EC for individuals aged 12 and older. With this regulatory approvals, our COVID-19 vaccine is one of the broadest labels among available vaccines.

Our Omicron BA.4/5 bivalent vaccine boosters now have approvals for use in more than 45 countries and regions worldwide. We recently reported initial positive data at the 30-day post boost time point in the Phase II clinical trial of our Omicron BA.4/5 adapted bivalent vaccine in individuals 12 years and older.

Additionally, we initiated a Phase I/11 trial of the Omicron BA.4/5 bivalent vaccine in children aged 6 months to 11 years. At the end of October, as part of our ongoing collaboration, we and our partner, Pfizer, initiated a Phase I clinical trial evaluating our Omicron BA.4/5 adapted bivalent vaccine in combination with an mRNA influenza vaccine.

The mRNA influenza vaccine candidate is also partnered with Pfizer and has now advanced to Phase III clinical testing after positive data from the Phase II trial were reported in second quarter of this year.

Slide 8 highlights our COVID-19 vaccine execution on a global scale. Our mRNA platform and established processes allows for development, testing and manufacturing of variant-adapted vaccine at an unprecedented speed, supporting a rapid regulatory path.

With the occurrence of Omicron end of 2021, we and Pfizer started evaluating monovalent and bivalent vaccines directed against Omicron sublineages and other strains of SARS-CoV-2. Data from these studies were presented to regulatory agencies in June and July 2022, which supported regulators' definition of the most appropriate regulatory pathway.

It took us approximately 2 months to go from the first regulatory recommendation for BA.4/5 adapted vaccine for our first shipment of the respective vaccine. The ability to execute with such a speed was enabled by 3 factors: our continued surveillance and analysis of variance of concern, our extensive and proactive COVID-19 clinical program and the rapid manufacturing adaptation. We are well positioned to supply countries and regions around the globe.

I thank our team and collaborators for their tireless efforts to make this accomplishment possible again in such a short period of time.

Slide 9. The need for an Omicron BA.4/5-adapted booster supported by current research, including our own data, as shown on Slide 9. In the Northern Hemisphere, we tend to see case numbers steadily rising. Epidemiologically speaking, BA.4/5 and their related sublineages continue to be the dominant strains. Omicron BA.4/5 adapted bivalent vaccines may also consider robust protection against potential future emerging Omicron sublineages or new variants of concern that are closer to the wilt-type strain.

The enhance neutralization breadth may be driven by expansion of memory B cells against epitopes shared broadly among variants as well as in part induction of de novo immune responses against new epitopes. Moreover, expansion and preservation of T cell responses may protect against severe disease.

Slide 10. Looking at the evolution of COVID-19 pandemic and current real-world evidence, we anticipate a long-term need for annual or seasonal variant adapted boosters. If the virus is in a state of continuous evolution, the possibility of a new wave of infections driven by novel immune evasive trends remain. We are vigilantly monitoring the landscape and are prepared to adapt our vaccines as needed.

The risk of severe COVID-19 disease remains high in the vulnerable population. The full extent of the prevalence of COVID-19 patients who go on to experience longer term health consequences is also not yet fully understood.

Clinical data has demonstrated that boosters extend the protection offered by COVID-19 vaccine, which research has shown natural immunity acquired by SARS-CoV-2 infection is variable across individuals and the protection it offers wanes over time. The booster restores an enhanced infection-acquired immune protection and further reduces the risk of reinfection.

Slide 11 shows our framework to support a sustainable vaccine business in the future. First, we have demonstrated the safety, tolerability and efficacy of our mRNA COVID-19 vaccines. Second, we have shown our ability to rapidly adapt our products and processes to address emerging variance of concern.

Third, our expertise at navigating the evolving regulatory landscape on a global scale has positioned us as a first mover and enabled us to receive one of the broadest labels among currently available COVID-19 vaccines. This applies to both the original COMIRNATY vaccine and our Omicron BA.4/5 adapted vaccines.

Fourth, with continued innovation, we are improving the already strong product profile of our COVID-19 vaccine, targeting continued protection from current and future virus threats.

These 4 pillars are built on our validated mRNA platform, of proven science, discovery, development, manufacturing and commercialization, and position us for success as we continue to expand and advance our pipeline and build our 21st century immunotherapy powerhouse.

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 Ozlem.

Thank you, Ugur. I'm delighted to provide you with our COVID-19 vaccine and pipeline update to date. On Slide 13, we have our multi-pronged innovation strategy to respond to the evolving pandemic and improve upon our vaccines with next-generation approaches that generate broader and more durable immunity. We have successfully delivered our first variant-adapted vaccines to address Omicron BA.1 and BA.4/5 variants.

We believe that our vaccine has potential to be combined with a seasonal flu vaccine. Across many parts of the world, people are currently receiving the only COVID-19 vaccine booster at the same time as their flu shot. Health agencies, including the U.S. CDC now recommend coadministration of COVID-19 booster with the annual influenza vaccine. A combination product has the potential to provide seasonal protection from both viruses with a single shot. We are working together with our partner, Pfizer, to develop an influenza combination vaccine, which leverages our mRNA technology.

In the midterm, we are also developing next-generation engineered vaccine candidates to expand the breadth of the immune response and provide more durable protection. This includes our T cell-enhancing vaccine candidate and engineered spike vaccine approaches. Our approach is supported by insights from continuous surveillance of variants and our robust clinical program.

On Slide 14, our innovation strategy has already yielded success with our Omicron BA.4/BA.5 adapted by bivalent vaccine, approved for use in more than 45 countries and regions around the world through the rapid execution that Ugur highlighted. We are continuing to broaden the label of our Omicron BA.4/5 adapted bivalent vaccines across different age groups.

This includes FDA emergency use authorization for individuals aged 5 and older in the U.S. In the EU, we received EC marketing authorization for individuals aged 12 and older. Submission for ages 5 to 11 years in the EU has been completed, and we are awaiting CHMP recommendation.

As a next step, we plan to submit data to regulatory agencies from our ongoing trial in age 6 months to 4 years in the first quarter of 2023 to extend accept to our Omicron-adapted bivalent vaccine to young children. Our regulatory activities are supported by our ongoing clinical program evaluating the BA.4/5 adapted boosters in various age groups.

Slide 15 highlights the positive data in the ages 18 and older cohort reported from the ongoing Phase II/III trial of our BA.4/5 adapted booster in individuals 12 years and up. The study was initiated in August and enrolled approximately 900 healthy volunteers aged 12 and order, all of whom had already received at least 3 doses of an approved COVID-19 vaccine.

The adults who received either 30 or 60 micrograms of BA.4/5 adapted bivalent booster over original vaccine as a comparator. Adolescents aged 12 to 17 received a 30-microgram dose of Omicron-adapted vaccine over original vaccine. The data at the 30-day time point is in from the sentinel cohort, which included 40 people in each age group, 18 to 55 years of age and older than 55 years, each having received the 30-microgram dose of a bivalent COVID-19 vaccine. The comparator group included 40 individuals over 55 years of age who received the original vaccine. The data showed that the safety and tolerability profile of the bivalent booster remains favorable and similar to the original vaccine.

On Slide 16, you can see the titers of neutralizing antibodies broken down by age goup and by prevaccination status. While 18 to 55 year old had a 9.5-fold increase over baseline, for the group as a whole, the increase was notably higher, namely 16-fold for those who are baseline negative. In the individuals who were older than 55 years, the group, as a whole, experienced a 13.2-fold increase in neutralization titers, whereas for individuals who were negative at the baseline experienced 28.3-fold increase. These responses were higher than those observed in the comparator group receiving the original vaccine who saw only a 2.9-fold increase over baseline.

There was not much difference between the groups who were negative or positive at baseline in the comparator. The reference strain neutralization titers were at least as high as that observed in those who received the original vaccine. Overall, adult saw a substantial increase in response with the bivalent vaccine compared to the original vaccine and the improvements were most pronounced in those over age 55 and those who were baseline negative prior to vaccination.

Given that Omicron BA.4/BA.5 and their sublineages continue to be the dominant circulating strains, these data provide strong evidence of protection that boosting with the bivalent vaccine can provide to adult, particularly the elderly.

Slide 17. The second pillar of our innovation strategy includes our collaboration with Pfizer to develop a COVID-19 influenza combination vaccine built on BioNTech's validated mRNA technology. The Phase I clinical trial has been initiated to evaluate the safety, tolerability and immunogenicity of mRNA quadrivalent influenza vaccine candidate in combination with our Omicron BA.4/BA.5 adapted bivalent vaccine.

We are building on the experience made in the BNT161 program partnered with Pfizer developing an influenza mRNA monovalent vaccine, for which a Phase III trial was initiated by Pfizer in September.

In the combination trial, the quadrivalent influenza vaccine candidate contained a 2 type A strains and 2 Type B strains that have been selected for the current season traditional to vaccine. 180 people aged 18 to 64 will be enrolled across 6 trial arms to test various combinations of the influenza vaccine candidate and the Omicron adapted vaccine at 30 and 60 microgram doses for influenza vaccine candidates individually and the standard license influenza vaccine as the comparator arm.

Slide 18 details our 2 development tracks to create next-generation vaccine. One track includes our engineered spike protein vaccine candidates designed to exhibit broad neutralizing antibody protection against the vast array of variants, including those, which have not yet evolved. The other track of vaccine candidates designed to enhance the T response against SARS-CoV-2.

Our first-testing candidate for this program, the BNT162b4 targets multiple, highly conserved, non-spike proteins that have been selected based on their potential to engage with T cell arm of the immune system. This approach has the potential to increase immune resilience, enhance and broaden T cell response and provide memory T cell resistance and durability of B cell response. A clinical trial starts in combination with our Omicron BA.4/BA.5 adapted bivalent vaccine is expected in the coming weeks.

Slide 19 highlights our infectious disease pipeline. In addition to the previously mentioned COVID-19 vaccine trial initiations from the third quarter, we expect the start of multiple first-in-human trials of our mRNA candidates over the coming months. This includes our shingles and HSB2 vaccine candidates, which are expected to enter the clinic in the final part of this year.

Our malaria vaccine candidate trial, either in the fourth quarter of 2022 or early '23, and our tuberculosis vaccine candidates expected to dose the first patient in early 2023. These programs are built on our validated platform of nucleoside-modified mRNA LNPs with optimized backbone design to address diseases with a significant global need.

Moving to our oncology program update. Slide 20 provides an overview of our oncology pipeline that is grounded in our multi-modality toolbox and advanced through focused execution. We now have a total of 19 oncology product candidates across 4 different drug classes in 24 ongoing clinical trials, 5 of which are randomized Phase II trials.

Our programs address areas of high unmet need and have a potential to tackle tumors using complementary strategies by targeting tumor cells directly or by modulating the immune response against the tumor. Many of our products can be a potential to be combined with other pipeline assets.

In the third quarter of 2022, preclinical programs advanced to Phase I clinical testing. This includes our FixVac candidate BNT116 for second-line treatment of non-small cell lung cancer and our bispecific RiboMabs product candidate BNT142 for solid tumors. In collaboration with Genmab, we recently initiated a Phase I study evaluating BNT313, our anti-CD27 Hexabody product candidate in solid tumors.

At the ESMO Immuno-Oncology Congress in December 2022, we expect to have two presentations. One is about preliminary safety data from the safety run in part of a study that precedes randomization in the ongoing Phase II trial of our FixVac program, BNT113. This trial is evaluating BNT113 in combination with pembrolizumab in patients with first-line HPV16-positive, PD-L1-positive head and neck squares carcinoma.

The other is preliminary efficacy and safety data from another Genmab collaboration, the Phase I trial of BNT312, a CD40 4-1BB dual body in advance solid tumors. Finally, we have BNT211, our next-generation CAR-T therapy product candidate designed to overcome first generation CAR-T cell therapy gene mutation in patients with solid tumors. We recently presented follow-on data for BNT211 at the ESMO Annual Conference. The Phase I dose escalation data continued to show encouraging clinical activity and safety.

Turning to Slide 21. BNT211 is a chimeric antigen receptor directing T cells against the novel target Claudin-6, that is tested alone and in combination with the Car T cell amplifying mRNA vaccine called CARVac encoding Claudin-6. CARVac is based on our uridine mRNA-lipoplex technology used in other cancer vaccine candidate programs.

Claudin-6 CAR-T cells is fixed with a second-generation chimeric antigen receptor of high sensitivity and specificity for the carcinoembryonic tumor-specific antigen Claudin-6. Claudin-6 is absent in healthy adult tissue, yet frequently expressed in high medical need cancer, making the tumor antigen an ideal candidate for CAR-T cell therapy.

The ongoing first-in-human Phase I/II trial is evaluating the safety and efficacy of Claudin-6 CAR-T cells as monotherapy and in combination with CARVac in patients with Claudin-6 positive relapsed/refractory advanced solid tumors. Our dose escalation study is testing pre-dose levels of Claudin-6 CAR-T cells, as monotherapy as well as in combination with the fixed dose of RNA vaccine. The expansion cohorts include patients with ovarian, testicular and endometrial cancers and rare Claudin-6 positive cancer types.

Slide 22 provides a summary of the ESMO presentation that included data from 21 heavily pretreated patients who received Claudin-6 CAT T cells at 2 dose levels, 1x10 to the 7 and 1x10 to the 8, alone or in combination with CARVac. Patients received lymphodepletion for treatment with BNT211 with the exception of two testicular cancer patients. The CAR-T cells as monotherapy and combined with CARVac were well tolerated.

Adverse events included manageable cytokine release syndrome and one transient grade 1 ICANS dose-limiting toxicities were observed in two patients, both were manageable, and the patients fully recovered. One was prolonged cytopenia in the dose level 2 monotherapy group in a patient with testicular cancer after lymphodepletion. The second was hemophagocytic lymphohistiocytosis in the dose level 2 combination group prior to administration of CARVac. The maximum tolerated dose has not yet been reached.

We observed dose-dependent expansion of CAR-T cells in all patients. As of August 16, overall response rate was 33% and disease control rate was 67%. This includes one complete response, 6 partial responses and 7 patients with stable disease. We are particularly encouraged by the observed activity in patients with testicular cancer, receiving the 1x10 to the 8 CAR-T dose levels after lymphodepletion. Of 7 evaluable testicular cancer patients included in the analysis, one had a confirmed complete response, three had partial responses, and two had stable disease, resulting in a disease control rate of 85% and an overall response rate of 57%.

Slide 23, shows engraftment and expansion of infused CAR-T cells in all patients with persistence from more than 100 and in some cases, 200 days, including in the patient with a complete response shown in blue. In cases of CAR-T cell redosing, which has expanded successfully as shown here in the 10 to 7th dose levels.

Slide 24 highlights testicular cancer patients, where we saw encouraging signs of activity with impressive tumor shrinkage, as you can see in these CT scans. For 11 patients with testicular cancer who received lymphodepletion regimen, the response rate reached 45% and even 57% when looking only at the 1x10 to the 8 CAR-T cells. The disease control rate was 85% at 1x10 to the 8 CAR-T dose level. One patient at the 1x10 to the 8 CAR-T dose level was assessed by the investigator as having a complete response at 12 weeks. This complete response continued and was confirmed at the 18-week and 52-week time point. We are very encouraged by the safety and clinical activity data from this promising program.

Turning now to Slide 25, and our next-generation immuno-modulators partnered with Genmab. These programs, which aim to prime and activate antitumor T cell and natural killer cell function are continuing to advance. Extracts to cover this conference were just announced earlier today. We will present a poster highlighting preclinical results supporting BNT311, our bispecific antibody designed to elicit conditional 4-1BB co-stimulation concurrent with PD-L1 blockade.

Additionally, an extract of preclinical data demonstrating the mechanism of action of BNT313 has been accepted for poster presentation. BNT313 is an anti-CD27 antibody that carries a Hex summarization enhancing domain to support antibody (inaudible) that drives the B27 clustering on the T-cell surface necessary for activation. BNT313 is designed to induce CD27 agonist activity without binding to Fc gamma receptor-bearing cells and thus circumvent T-cell depletion.

A Phase I clinical trial of BNT313 was initiated (inaudible). As previously mentioned, for our BNT312 program, an abstract has been accepted for presentation at the ESMO Immuno-Oncology Congress in December. Overall, the progress of these programs is very encouraging for us.

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, Ozlem, and a warm welcome to those of you on the phone. I would like to begin by presenting the key financial highlights for the third quarter of 2022, which you can find on Slide 27. Our total reported revenues for the third quarter reached EUR 3.5 billion. Together with a strong first half year, we are in line with our prior year revenues for the year-to-date figures. I will elaborate on this shortly.

Given this top line number, we delivered operating income of EUR 2.4 billion, and generated earnings per share on a fully diluted basis of EUR 6.98. With respect to the company's liquidity position, we ended the third quarter of 2022 with EUR 13.4 billion of cash and cash equivalents as well as trade receivables of around EUR 7.3 billion. The trade receivables are primarily derived from our collaboration with Pfizer and remained outstanding due to the contractual settlement of the gross profit share under the collaboration.

As of October 15, we collected EUR 3.2 billion in cash from our outstanding trade receivables at September 30, improving our cash position and, in turn, reducing our trade receivable position subsequent to the end of Q3.

Continuing with Slide 28. We recognized EUR 3.4 billion of COVID-19 vaccine revenues during the third quarter and EUR 12.9 billion during the first 9 months. Revenues for the first 9 months are in line with our expectations. We believe the development of the pandemic has been and remains dynamic, causing a rephasing of orders and, with this, fluctuations in quarterly revenues. Let me give you some more details on our revenue streams.

Under our COVID-19 vaccine collaborations, territories have been allocated between us, Pfizer and Fosun Pharma based on marketing and distribution rights. Our COVID-19 vaccine revenues included EUR 2.5 billion for the third quarter and EUR 9.1 billion for the first 9 months that are related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners' respective territories.

These revenues represent a net figure, which means we generate 100% gross margin of those revenues. As we have mentioned in the past, and explained in more detail in 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.

The gross profit share is also impacted by write-offs, so for example, for vaccine doses produced by our collaboration partner, Pfizer. Those write-offs reduced the gross profit share between the 2 companies, and therefore, reduced BioNTech's revenue figure, but not those of our partner, Pfizer.

Our Cohort 19 vaccine revenues from direct COVID-19 vaccine sales to customers in our territory were EUR 0.6 billion for the third quarter and EUR 2.3 billion for the first 9 months. Those revenues were significantly driven by the orders that were placed in late 2021 following the then emergent Omicron variant, and the Omicron adapted vaccine launches started beginning of September 2022. Also included in our COVID-19 vaccine revenues were EUR 0.3 billion for the third quarter and EUR 1.5 billion for the first 9 months of revenues from sales to our collaboration partners.

Now I'd like to move on to our detailed financial results for the third quarter and first 9 months of 2022, as shown on Slide 29. As I discussed revenues on the previous slide, let me move to cost of sales that reached approximately EUR 0.8 billion in the third quarter of 2022 compared to EUR 1.2 billion for the comparative prior year period.

For the first 9 months of 2022, the cost of sales reached approximately EUR 2.8 billion compared to EUR 2.3 billion for the comparative prior year period. The change in cost of sales resulted mainly from the recognition costs related to our COVID-19 vaccine revenues in our own territories, including the share of gross profit that we owe to Pfizer.

In addition, cost of sales were impacted by expenses arising from inventory write-offs and expenses for production capacities derived from contracts with contract manufacturing organizations. Research and development expenses reached EUR 341.8 million for the third quarter of 2022 compared to EUR 260.4 million for the comparative prior year in 2021.

For the first 9 months of 2022, research and development expenses amounted to EUR 1 billion compared to EUR 0.7 billion for the comparative prior year period. The increase was mainly due to the increased head count and higher expenses in the context of the share-based payments.

General and administrative expenses reached EUR 141 million for the third quarter of 2022 compared to EUR 68.2 million for the comparative period in 2021. For the first 9 months of 2022, general and administrative expenses reached EUR 361.8 million compared to EUR 154.9 million for the comparative prior year period. The increase in G&A was mainly driven by the planned increase in headcount and increased expenses for purchased external services.

Income taxes were accrued with an amount of EUR 0.7 billion for the third quarter of 2022 compared to EUR 1.5 billion for the comparative period in 2021. For the first 9 months of 2022, income taxes were accrued with an amount of EUR 2.6 billion compared to EUR 3.2 billion for the comparative prior year period. The derived effective income tax rate for the first 9 months of 2022 was 26.8%.

In the third quarter of 2022, net profit reached EUR 1.8 billion compared to EUR 3.2 billion for the comparative period in 2021. In the first 9 months of 2022, net profit reached EUR 7.2 billion compared to EUR 7.1 billion for the comparative prior year period. Our diluted earnings per share for the third quarter of 2022 amounted to EUR 6.9 compared to EUR 12.35 for the competitive period in 2021. For the first 9 months of 2022, our diluted earnings per share was EUR 27.7 compared to EUR 27.46 in 2021.

Now let's move to Slide 30 for the outlook for the 2022 financial year. We are updating our 2022 financial guidance, raising our COVID-19 vaccine revenue estimate for the full year to the upper end of the original range, EUR 16 billion to EUR 17 billion from EUR 13 billion to EUR 17 billion previously. The narrowed guidance reflects delivery of the Omicron-adapted bivalent vaccine boosters, which started early in September and is expected to continue throughout the fourth quarter of 2022, as well as higher prices and a positive foreign currency effect.

We reiterate our planned expenses and CapEx, which we have summarized for you on the slide. We also updated the estimated annual effective income tax rate from previously 28% to approximately 27%, which is a further improvement to previous year.

I will be moving to the completion of the first tranche of our share repurchase program, as shown on Slide 31. The share repurchase program approved by the Management Board and the Supervisory Board permits the repurchase of ADSs for a value of up to $1.5 billion over 2 years. Our intention is to use some or all of the repurchase ADSs to meet pending obligations from share-based payment arrangements. The first tranche of the repurchase program had a value of up to USD 1 billion and began on May 2, 2022, and ended October 10, 2022.

As shown on the slide, a total of 6,945,513 ADSs were repurchased at an average price of USD 143.98, representing 2.8% of the shares issued as of April 30, 2022. In addition, we had paid out a dividend of approximately EUR 0.5 billion to shareholders in 2022. In November, the second tranche of the repurchase program with a value of up to $0.5 billion has been approved, commencing on December 7 this year. More information and an overview of the buybacks can be found on our IR website.

With that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our outlook for 2022 and concluding remarks.

Thank you, Jens. Turning to Slide 33. Our COVID-19 vaccine continued to play a major role in addressing the pandemic, with the launch of variant-adaptive B4/B5 vaccine. We and our partners have received approval in over 45 countries and territories since our first approval in August this year, and have rapidly deployed approximately 300 million doses of our variant-adaptive vaccines as of mid-October.

We have updated our full year 2022 order book and now expect to invoice up to 2.1 billion doses this year, reflecting some rephasing of deliveries to early 2023 due to supply availabilities and projected uptake of our variant-adapted vaccines. By year-end, we expect to fulfill both our existing contract with the United States government for 105 million doses, and our contract with the European Union for 650 million doses.

As we turn to 2023, we anticipate that the COVID-19 vaccine market will start to shift toward a hybrid public private market, with some geographies, namely the United States, likely shifting to a commercial contracting model in 2023. In the United States, we and our partner, Pfizer, expect the list price for a single dose vial of adult vaccine to be in the range of $110 to $130 per dose, reflecting both the cost effectiveness and public health value of our vaccine.

In the future, we expect seasonal demand to be weighted to the second half of the year, consistent with other seasonal respiratory infectious disease vaccines. As shown on Slide 34, we continue to make progress against our 2022 clinical milestones. As we enter the final months of the year, we expect a number of additional updates, some of which are shown here and on the following 2 slides.

In infectious diseases, we expect continued expansion of our COVID-19 vaccine pipeline with multiple next-generation vaccine constructs entering the clinic before year-end. We also expect data updates from our ongoing clinical trials evaluating our variant-adaptive vaccine. Outside of COVID-19, we plan for multiple mRNA vaccines to enter the clinic this year and early next year. By the end of 2023, we expect to have up to 5 new clinical trial starts in infectious diseases.

Turning to Slide 35. In oncology, alongside the first patient dosed in the Phase I trial evaluating BNT313, our anti-CD27 HexaBody partnered with Genmab, which we announced today. By year-end, we also expect to have the first patient dose for a second Phase I trial evaluating BNT116 in first line NSCLC. We also will present a clinical data update at the ESMO IO Annual Meeting in December for BNT312.

Our CD40 4-1BB dual body partnered with Genmab. As we look ahead to 2023, we expect a busy year for our oncology pipeline, with as many as 10 clinical trial updates across a diverse range of programs.

Concluding on Slide 36, we expect 2023 to be a momentous year for BioNTech. We will continue to invest for the long term in our next-generation COVID-19 vaccine pipeline as we continue to deliver our variant-adapted vaccine around the world. We will continue to expand and accelerate our innovative oncology and infectious disease pipelines in anticipation of multiple late-stage data readouts and clinical trial starts that we expect will fuel future growth. And with increasing balance sheet strength, which we expect into next year, we will continue to reinvest in the company to build world-class capabilities and accelerate our growth.

We will also continue to look for additive bolt-on BD and M&A opportunities that fit with our strategy. We remain as optimistic as ever in our ability to continue to create long-term value for patients, our shareholders and society. I would like to take the opportunity to thank our shareholders for their continued support, and we'll now open the floor for questions.

(Operator Instructions) We will now go to our first question. One moment, please. And your first question comes from the line of Tazeen Ahmad from Bank of America.

Can I just get some color from how long do you think that the current BA.4/5 bivalent shot is going to be in use? Should we expect it to have any coverage of the newer variants, like, for example, the BQ.1 or BQ1.1? And if it doesn't, how should we think about some of the shipments that you mentioned in your prepared remarks that have been shifted into 2023. With those be delayed until later next year to the parties that have ordered and have the right to delay shipment for a newer version of the vaccine?

I would like to respond to your first question, Tazeen. With regard to how long the BA.4/5 Omicron-adapted vaccines would allow us to respond to the pandemic. That will really depend on how the virus further evolves. Some of currently emerging variants of concern are closely related with BA.4/BA.5 are from the BA.2 lineage. And there is some probability that there will be cross neutralization and cross protection against these variants. We will continue to test this by cross neutralization assays, which are ongoing and can then say more. But it really depends on how the virus further evolves.

Ryan, do you want to take the second question, or should I give an answer?

Yes. Absolutely. I can start over. So on the question of shifting of doses, Tazeen. A significant portion of those doses that were shifted for delivery next year were actually donation doses to a variety of countries around the world. So really, we see that dynamic as not specifically related to the variant vaccine in question. And generally speaking, these contracts are flexible. So while we see some of those doses shifted to 2023, we still have -- expect a significant proportion of contracted doses next year and beyond. And that could be -- those contracts can be served by, again, either the current vaccine or future vaccines, if a future variant vaccine is needed.

We will now go to our next question. One moment please. And your next question comes from the line of Matthew Harrison from Morgan Stanley.

This is Steve on for Matthew. My question is, as you think about the PCV data next year, what kind of PFS difference would you like to see to think about moving it ahead?

So just to clarify the question. You referenced the PCV. So you're talking about the INS program?

In melanoma, yes.

In melanoma. And your question, just to clarify, your question is what PFS improvement are we looking for?

Yes.

Ugur, do you want to address that?

Yes. I think this is too early to give -- to define a threshold. We are working with that ratios. We have to understand whether any type of improvement is in line with the further progress in the field that was made in the frontline melanoma. We have to align this understanding also with the progress that we have made in the manufacturing of our INS platform.

So we in the meantime, improved the algorithm and reduced the turnaround time for the vaccine and came up with process improvements. And this would also require discussions with the authorities to make the final decision that we will progress and can just use the study to expand the clinical trial for a potential accelerated approval or do a confirmatory trial.

And your next question comes from the line of Chris Shibutani from Goldman Sachs.

Recent media reports suggest the potential for distribution of your COVID vaccine in China with the initial target population being expats. As we're trying to better understand the potential scope of this opportunity, thinking in terms of units and pricing, can you, #1, give us any updates on development when perhaps your vaccine might be approved in China? #2, would this be an approval that might enable broader distribution to Chinese nationals? And then on the price front, help us at all with anything that we can understand about the potential pricing in that market?

Yes. Thanks for the question, Chris. I think it's a little too early actually to get some specifics there. We have seen some positive reengagement as has been reported, and we can confirm that we have been taking part in some discussions, which are very positive. However, it's still too early to say, or to try to predict to what extent an approval for the expat population could be granted, when it might be granted, what that would mean commercially? So at this stage, we're continuing to monitor the situation very carefully and hope to provide updates in the near future.

And your next question comes from Jessica Fye from JPMorgan.

On the COVID-19 vaccine market, Moderna has talked about how they expect the COVID-booster market to be in the range of 500 million to 600 million doses per year, not unlike flu, but potentially a bit below that in 2023, and working up to that 500 million to 600 million thereafter. Do you share that view that cover vaccine volumes could trail that 500 million, 600 million range next year, but then increase in '24 and beyond to something closer to the flu range?

Yes. Maybe I'll start -- this is Jens. I will start with answering the question and then Ryan might chime in or Ugur. I think we all know that the pandemic has evolved well this year. And how it will evolve in the future is really very difficult to predict at this point in time. But we all know that COVID is a deadly disease. It's much more deadly than flu. We see much higher death rate, dead cases than we know from flu. And elderly people and high-risk patients will be, for sure, the population that needs vaccinations.

But of course, everyone else, too, who feels he or she needs to be protected against severe diseases. So that's maybe the base first. Going forward, I mean, it all depends on if and how often additional variants will pop up and how severe those variants will be going forward. At some point, it is -- there is a high likelihood, of course, that there could be a flu-like business model coming up.

It remains based on what I said before on the fact that COVID is a deadly disease, a large multibillion-dollar market going forward. And specifically, in such an endemic scenario that the private market opens up, we know that pricing will be very different to the current pricing that we had. So there is upside at that end.

And in addition, maybe last comment from my end. I think BioNTech and Pfizer together have shown and have proven that we are well placed in the market. We have I think a very good market position, and we have been able, over the time, to defend that market position very well. So we are very confident that, going forward, this remains a very sizable, very good market for us. And Ryan, you maybe want to add something?

No, I think you covered most of it. I would just second the notion that in 2023 -- it's not -- we're not going to yet be into a true endemic market because it will be a hybrid market with significant contracted volumes. And also we expect emergence of a private market on top. I think the volume numbers that you've said are plausible. We have still seen evidence of higher uptick in the booster segment than, for example, we see with flu. And so that's one data point there. And obviously, here, we do expect a very different price point versus the flu market. So I think those factors combine to create the multibillion long-term market opportunity that we expect that you've just outlined.

We'll now go to our next question. And your question comes from Daina Graybosch from SVB Leerink.

I want to ask about some academic applications that were posted as preprints from the (inaudible) recently, and they were on their own looking at the immunogenicity of the bivalent boosters versus another booster for wild-type monovalent. And their data showed pretty modest increases in antibody titers with the bivalent booster, much more modest than what you today have shown in the greater-than-55 population.

I wonder if you can talk about how you interpret their data. And if their data, let's say, is correct, in that you get a very modest difference with the bivalent, let's say, for younger people under 55. What does that tell you about the bivalent booster? Weather boosters will be needed and what kind of booster we may need in the future?

Daina, thank you for the question. So first of all, to the preprint, of course, we studies the preprint and we see that the study is missing to differentiate between individuals who had prior infection and without prior infection. And we have seen in our data set that this is really important to come to conclusions since individuals without prior infections have a much higher increase with regard to the overall for neutralizing titers and as compared to those who have been -- who had prior infections.

And so our data, we have published a 7-day data and 1-month data, and the data are very consistent within the groups, with homogeneous findings. We are confident that the report that we made also with the larger number of subjects, even not very large, with a larger number of subjects will be -- will turn out to be the real findings.

So just to repeat the key finding is that, so far, in the elderly population, we have a fourfold higher increase in neutralization titers as compared to the wilt-type vaccine. And we are talking here about the immediate antibody response. What we have also to consider is that every vaccination as a variant-adapted vaccine has a second effect. The second effect is the induction with a clear delay of immune responses and forming of de novo B-cell responses that come up later in the timeframe of 3-plus months.

So we believe that in -- as in the flu case, we will need to have a booster market with variant-adapted vaccines to retrain the immune system to the new variant sequences. And this can't be addressed by sticking to the existing wilt-type vaccine. Just to also repeat findings that were generated with the wilt-type vaccine, even the booster with the wilt-type vaccine reduces the severe disease rate and reduces the mortality.

So that means, regardless whether we are immunizing, boosting with wilt-type or with variant-adapted vaccines, we have a reduction of severe disease rate. And with the variant-adapted vaccines, we have now an evidence that the neutralization titers appeared to be significantly higher with the wilt-type vaccine.

We will now go to our next question. And your next question comes from the line of Akash Tewari from Jefferies.

This is (inaudible) for Akash. We have one on COVID vaccine sales. So how many of the total 300 million EU contracted doses remain to be delivered in 2023? Also, you mentioned some of your shipments have been pushed to next year. So in total, how many confirmed orders are there for next year? (inaudible) 2023 total vaccine sales of around 10 billion. Do you feel you will be able to hit the number with your existing orders signed for 2023?

Well, so yes, thank you for the question. I think, look, I'll start, and then I think Jens Holstein will chime in. So I think you first asked about next year and the EU contract. And I think what we announced in our prepared remarks was that we plan to deliver the planned doses for the EU this year that we plan for 2022, and also complete the U.S. -- existing U.S. contract that was announced earlier this year.

We were not disclosing an order book number for next year. What we can tell you is that, of course, our signed -- overall signed orders have continued to grow throughout this year overall, regardless of the delivery time period, but we're not guiding at the moment to a future order book because we think it's premature to do so, and frankly, not relevant or not as relevant now given that the demand picture continues to be dynamic, that we continue to expect the emergence of a private market in some geographies next year as we mentioned.

So it's really more of a hybrid market next year. But overall, we feel very good about overall demand and how we're tracking to be able to serve that. Jens, maybe you want to add to it?

Yes. Okay, sorry, Ryan. I myself had a little bit of problem to understand you because of the line. The connection was not that good. But as you pointed out correctly, we deliver according to the plan for 2022 for the EU. We're not expecting any shift here. We had, as you know, contractual agreements signed for '23 with the EU, 450 million doses and an option of 450 million doses.

But as Ryan correctly said, I think maybe for the EU, that might be at a later point in time. But overall, I think we got to move away from this thinking on the order book because what we have seen is there're certain shifts. It all depends on market demand, on the evolvement of variants that are coming up. And specifically, as Ryan correctly said, there will be markets that move into a private setting going forward, assuming that this is seen as an endemic market going forward.

And that will take probably a few years. And then I think the danger really is to draw the wrong conclusions from some number on an order book, and therefore, we are moving away from giving some guidance on this.

We'll now go to our next question. And the next question comes from Yaron Werber from Cowen.

This is Brendan, on for Yaron. Congrats on another strong quarter. Just a quick one from us. When we think about maybe the emergence of future variants and look at kind of the time line from the first Omicron wave in December and then BA.4/5, maybe around April or so, then rollout by September of your BA.4/5 booster, do you think this is more or less the reasonable time line we could expect for future variants in terms of your interactions with FDA and materials and data, you need to get them really to get future boosters authorized? Or are there important considerations we should really be keeping in mind as the landscape inevitably shifts over the coming months and years?

Ugur, do you want to take that?

Yes, I can take that. I think the future vaccine adaptation and booster process will depend on two aspects. One, the regulatory landscape, and the second one is how fast we can respond to new variants. Starting with the second part is, as you know, the BA.4/5 variant emerged only recently. And the FDA -- after the FDA decisions, we were able to come up with an adaptive vaccine and enable delivery within about 2 months.

So that means our processes, internal processes for vaccine adaptations are now even faster than what we had indicated beginning 2022, and we are going to further optimize the vaccine adaptation process to be able to respond quickly to new variants.

And the second thing, what is important is, and we have now the case with the FDA and with the EMA. We got an authorization of the vaccines based on pre-existing clinical data on multiple variants. And just to remind everyone, we have done multiple clinical trials with different variants and the safety profile that we have identified was always consistent for all variant-adapted vaccines.

And the second aspect is that we found that preclinical data and clinical data in subjects with flu infections are very predictive on what we are seeing in the clinical setting. And authorization now of this variant-adapted BA.4/5 vaccine followed this logic and enabled rapid authorization and availability of a BA.4/5 adapted vaccine.

And we believe that this will become also in future, the model -- the working model. That means once new variants emerge that require a boosting, we will be able to respond quickly, and there will be a regulatory process to allow that such variant-adapted vaccines can get -- can be delivered within a few months after the emergence of the variant.

We will now go to our next question. And the question comes from Ellie Merle from UBS.

Just a financial one, given you booked the gross profits from the Pfizer collaboration, can you comment, I guess, on your latest thoughts on how you're thinking about the profit margin and the Pfizer collaboration, COVID business longer term, and how you see that changing? And also how this could change if there, say, were to be a combination COVID flu vaccine, for instance?

Yes. Thanks, Ellie, for the question. Not an easy question to answer, I have to say. Well, in terms of the gross margin, I think you have seen pretty stable gross margin development throughout the year. I mean, in the quarters, you have some ups and downs once in a while given that we had some write-offs and we have elaborated on this in the documentations that we have published.

Going forward, I mean, with the higher pricing, of course, it depends then what the costs are, what the COGS will be that we have to deduct. It's a bit too early to really give you clear guidance on this, what that means for our gross margin for '23 and the years beyond. And specifically then, when flu comes in, which will take a while, we will see that at a later point in time.

So there will be some mixture that we will see going forward, and therefore, you've got to bear with us a little bit until we're able to really give you some more clarity on the impact.

And your next question comes from the line of Simon Baker from Redburn.

A question on pricing, if I may. You very helpfully gave us the list price range for the U.S. of around $110 to $130 per single dose. I appreciate it's not the same thing, but I just wonder how we should think about contrasting that number with the $64 per dose that CMS talked about in April. Obviously, your's covers a far broader remit than the CMS was talking about, but just how we can think about how those numbers triangulate together?

And on a similar point, could you give us any early indications for pricing outside the U.S. for 2023?

Yes. Thank you, Simon. I mean as you know, we're expecting this market to be a heavily-tiered priced market like for any other vaccines. And so the price that we've quoted there is a U.S. list price. We would expect, of course, that sometimes there can be differences depending on the segment that you're in. That's pretty much all we can tell you at this point.

In terms of the dynamic, we do think that this market will have some important differences to some of the other vaccine markets like flu in the sense that it's -- we expect that this will not be -- this will be a branded market for the foreseeable future. And there's also a very different market structure here than you have in some of the other vaccine markets where you have many, many players.

And so I think we're -- we do feel like we're in a good position here by virtue of having a very strong product, with a very strong product profile, both on safety and efficacy and have continued to build up our safety database and have a strong brand.

So I think we feel good about our -- about the price that we put out there, but that's pretty much what we can say at this point. In some geographies, there could be differences, and there's likely to still be a link to volumes on some level, as you would expect in a heavily contracted market like this where you have purchases in bulk.

And maybe to add to what Ryan just said. I mean what Pfizer said to the topic, that pricing has been set given -- or in relation to what sort of benefit we see that we bring with the product. Of course, as Ryan said, it's also a question of volume. So I mean, we have signed huge contracts with various governments. The contract size with other parties in the U.S. market to use that example is, of course, a totally different one, and that will have an implication.

Overall, I mean, how the pricing will develop over time is to be expected to go up, of course, because more and more countries, if it becomes endemic of course, that's the base assumption for this, will then have similar sort of developments and what the pricing that means in Japan or in Europe -- when the European contract runs out, that has to be seen. It's a bit early to really be -- to be able to give you more precise indications here. But that's the sort of broad direction that we see.

We will take one more question. And the question comes from the line of Zhiqiang Shu from Berenberg.

Great. I want to ask broadly on the mRNA cancer vaccine. Obviously, there is some skepticism around the cancer vaccine space. So maybe, Ugur, can you discuss a bit of your confidence on this modality in the cancer vaccine space? And maybe some updated thoughts on where whether this modality will play the most significant role?

And a quick follow-up on BNT211, the CAR-T. Can you also discuss the potential registration path for this program given you have seen quite encouraging data from early trials?

Thank you, Zhiqiang. So let's start with the cancer vaccine question, and Ozlem will take the question related to the (inaudible). So of course, there are -- the discussion about cancer vaccine is the same. Why do you believe that cancer vaccines will work in the background of so many failures in the past.

So my answer is always the same. We believe that cancer vaccines must be positioned in a way that they can do the job, and we believe that the best market and the best indication and clinical setting to address cancer vaccine is post surgery, where tumors are in a micrometastatic manner left. So this is minimal residual disease or ctDNA-positive patients after surgery.

And we know that in this setting, there is a huge medical need. To give you just examples, in colorectal cancer, about 30% of patients after surgery have a relapse in the time of 2 to 3 years after surgery. In triple-negative breast cancer, this is also in the range of 30% to 40% in the first 4 years after surgery. In pancreatic cancer, it's even about 70% of patients relapsing after surgery. And the same is -- similar data described for stomach cancer, GI cancers and so on.

That's where we want to position our personalized cancer vaccines, allowing us to induce neoantigen-specific immune responses, T cell. We know now from clinical data, early clinical data in pancreatic cancer, in melanoma patients and also from publications of either academic groups that this could be an ideal setting to induce strong T cell responses that could have to control and eliminate residual tumor cells. And Ozlem, would you like to take the second question?

Yes. This was about our CAR-T cell program, BNT211, (inaudible) and the regulatory path, which we would foresee there. Let me remind you that in this program, we are still actually in the dose finding part of our Phase I/II trial, which means that we have only tested the first 2 dose levels or 3 dose levels of our CAR-T cells and are also still in the process of exploring whether adding to this new CAR-T cell product vaccine makes a difference or not and how the treatment regimen should be.

Having said that, we are also very excited as you about the data, which we already see at this early stage, namely a manageable safety plus exciting clinical activity, in particular, in the patients with testicular cancer. Therefore, we are also -- have also started about thinking about the best regulatory path here. We have not made any positions and cannot speak about that at this time point, but will, for sure, do next year.

I will now hand the call back for closing remarks.

Thank you for joining today's call. We look forward to talking to you soon. Stay safe. thank you and bye-bye.

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