BioNTech SE

NASDAQ:BNTX

Earnings Call Transcript 2022-Q2

[Operator]

Welcome to the BioNTech Second 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.

[Sylke Maas, Vice President, Investor Relations and Strategy]

Good morning and good afternoon. Thank you for joining us today to review BioNTech’s second quarter ‘22 clinical and operational progress and financial results. A few housekeeping items before we start. I invite you to view the slides that accompany the webcast in the second quarter 2022 press release, both of which were issued this morning and can be found in the Investors section of our website.

As outlined on Slide 2, during today’s presentation, we will be making several forward-looking statements. These forward-looking statements include, but are not limited to, our current COVID-19 vaccine revenues, as these include figures that are derived from the preliminary estimates provided by our partners, our estimated financial results for 2022; the continued global demand for our COVID-19 vaccine; our target vaccine production capacity for 2022 and beyond; our ability to supply our COVID-19 vaccine; the planned next steps in our pipeline programs; the timing for enrollment initiation, completion, reporting of data from our clinical trials; the timing of 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 this conference call and webcast. Also, please note that Slides 3, 4 and 5 provide detailed and important safety information regarding our COVID-19 vaccine. Finally, you can find the agenda for today’s call on Slide 6. It’s my pleasure to welcome the members of BioNTech’s management team participating in today’s call.

I am joined today by our CEO and Co-Founder, Ugur Sahin; Ozlem Tureci, our Chief Medical Officer and Co-Founder; Jens Holstein, our Chief Financial Officer; and Ryan Richardson, our Chief Strategy Officer.

I would like to turn the call over to Ugur Sahin.

[Ugur Sahin, Chief Executive Officer and Co-Founder]

Thank you, Sylke. Good morning and good afternoon and hearty welcome to all call participants. We appreciate your continued support. Today, it’s my pleasure to provide an overview of the key highlights from the second quarter and our objectives for the remainder of the year. Our team will provide further details before we open the call for questions.

We have made significant progress in the second quarter as we continue to advance toward our vision of building our global immunotherapy powerhouse. With our deep expertise in immunology and fully integrated spectrum of translational research, development, manufacturing and commercialization competencies, we are all well-positioned for success. We are leveraging a multi-platform strategy built on our innovation engine comprised of various cutting-edge technologies. This approach enables us to advance our differentiated pipeline of novel immunotherapies for multiple waves of innovation.

We have earned a position of market leadership with our COVID-19 vaccine. Our goal is to continue to deepen that leadership. We believe that SARS-CoV-2 will be with us for the foreseeable future. It is therefore necessary to evolve our products to address the ever-changing challenges posed by the virus. In oncology, we have 18 programs in 23 ongoing clinical trials, including 5 randomized Phase 2 trials. We intend to advance several of these programs into pivotal studies in the coming years. In infectious diseases, we have 1 ongoing Phase 1 program and more than 10 preclinical programs addressing diseases which represent significant health challenges globally. We expect to bring 4 of these programs into the clinics this or beginning of next year.

Our aim is to bring multiple new products in oncology and infectious disease to market over the next 3 to 5 years. We believe that our technology innovation engine has the potential to address a broad set of diseases beyond cancer and infectious disease. We envision application of our mRNA technology in the treatment of inflammatory, cardiovascular and neurodegenerative diseases and in regenerative medicine. We have several active exploratory programs in these areas that are in the product candidate selection stage. We aim to continuously impact the health of people around the world and thereby create long-term value for our shareholders.

I will now provide an overview of our accomplishments from the second quarter, starting with the corporate and pipeline updates on Slide 8. Following a better-than-anticipated first quarter, the second quarter of 2022 was in line with our financial expectations. We reported total revenues of €3.2 billion contributing to total revenues of €9.6 billion in the first half of the year. In June, we broke ground and began construction of our first BioNTainer mRNA manufacturing facility on the African continent in Kigali, Wanda. The site will manufacture a range of mRNA-based vaccines to address the needs of the African Union member states. This potentially includes our COVID-19 vaccine as well as investigational malaria and tuberculosis vaccine candidates that we expect to advance into the clinic in the coming months.

We have signed a new equal share of cost and profit collaboration agreement with Genmab for the joint development of an antibody targeting CD27. This expands our existing strategic collaboration for developing next-generation immune checkpoint modulators. There are several positive developments in our oncology pipeline. Positive data from an investigator-initiated Phase 1 study of BNT122, our IMS product candidate partnered with Genentech, were reported at the 2022 ASCO Meeting with encouraging signs of immunogenicity and disease control in patients with resected pancreatic cancers. We have recently initiated 2 more clinical trials. This includes a Phase 1 trial of BNT142, our second product built on the RiboMab platform. We have also dosed the first patient in our first human Phase 1 trial of our FixVac product candidate, BNT116 in patients with advanced non-small cell lung cancer.

Finally, BNT211, our next-generation CAR-T cell therapy received an EMA Priority Medicines or PRIME designation for third or later line treatment of testicular cancer. As a result, BNT211 will benefit from earlier and more frequent interactions with the EMA for the next development phase. The prime designation came on the heels of exciting preliminary clinical data from 14 evaluable patients presented at the AACR meeting. We have reported details of the data in our earnings call last quarter.

On Slide 9, we highlight several significant achievements in our COVID-19 vaccine program that further strengthened our market leadership position. We continue to expand our label and have received multiple regulatory approvals for our COVID-19 vaccine in the second quarter. We have received emergency use authorization for vaccination of children 6 months to 4 years of age. The label now includes a three-dose series in this age group. We also received emergency use authorization for our third booster in children aged 5 to 11 years old.

Recently, our COVID-19 vaccine received full approval in the United States for adolescence 12 years and older and we have have submitted for full approval in this age group in several other geographies. With these regulatory approvals, our COVID-19 vaccine has achieved one of the broadest labels among available vaccines.

On the distribution front, at the beginning of July, we have delivered more than 3.6 billion doses to 180 countries and regions since launched in December 2020. The strong global distribution makes us the market leading provider of COVID-19 vaccines. We have recently signed a new agreement with the U.S. government to supply an additional 105 million COVID vaccine doses with an option for the U.S. to purchase up to an additional 195 million doses.

Our 2022 order book now includes approximately 2.5 billion doses. Google health equity is a priority for us, which we are pursuing with a multi-pronged strategy. This includes our pledge to provide 2 billion doses for low and middle-income countries by the end of 2022. We are on the track to achieve this goal. As part of our long-term COVID-19 strategy, we aim to develop vaccines that generate a more robust, bold and long-lasting immune response and enable task response to the dynamics of emerging new variants.

In our clinical programs, our Omicron BA.1-adapted monovalent and bivalent vaccine candidates demonstrated high immune responses and tolerable safety profile. As part of our relentless development work, aimed at addressing COVID-19 variants, we now have regulatory submission for Omicron BA.1 BA.4/5-adapted bivalent vaccines ongoing worldwide. Our strategy includes multiple next-generation COVID-19 strategy includes multiple next-generation COVID-19 vaccine approaches. This effort is progressing with the initiation of a Phase 2 trial of BNT162b5, the first of several vaccine candidates designed to optimize and prolong the immune response. BNT162b5 is a bivalent vaccine candidate based on enhanced versions of SARS-CoV-2 ancestral strain and Omicron BA.2 variant spike proteins engineered for broader immunity.

Slide 10 underscores the critical need to reduce vaccine adaptation timelines to match the speed at which the virus mutates. We have all experienced the rise and fall of multiple COVID-19 variants over the last 2.5 years. Since the emergence of the Omicron lineage, every 2 to 3 months, we have seen a new sub-lineage. Because SARS-CoV-2 is rapidly changing, it is imperative to establish vaccine development protocols and regulatory pathways that keep up with the pace of virus mutants. With the current development path, it generally has taken us 8 months to develop a new variant adapted vaccine and progress its full clinical price. Discussions with regulators are ongoing to define the most appropriate path base to leverage current experience and ensure that variant adapted vaccines can be made available in the future to address newly emerging variants or sub-lineages in a timely manner. We believe that based on the plateau of generated data, there is a potential to reduce the existing vaccine adaptation panels to as little as 3 months.

Slide 11. Regulatory bodies around the globe agree that current vaccines require adaptation to the new Omicron strain sub-lineages. Based on the scientific evidence, including our BA.1 adaptive vaccine clinical data and BA.4/5 preclinical data presented at the FDA Advisory Committee meeting in June, the FDA published guidance recommending the introduction of bivalent booster vaccines incorporating the spike protein from the Omicron BA.4/5 sub-lineage with the vaccine compounds this fall.

In Europe, we have finalized BA.1-adapted bivalent vaccine submission to EMA, including a comprehensive clinical data package. In addition, we are preparing a rolling submission of preclinical and CMC data for an Omicron BA.4/5-adapted bivalent vaccine to EMA, which we expect to begin submitting this month. In parallel, submission of our Omicron-adapted bivalent vaccine data packages is advancing with regulators worldwide. We are preparing for a clinical trial of our Omicron BA.4/5-adapted bivalent vaccine, which is expected to commence in August.

In anticipation of a launch of the Omicron-adapted bivalent vaccines as early as October 2022, we have started to manufacture both BA.1 and BA.4/5 variant adapted vaccines. This proactive approach enables us for multiple launch scenarios based on the different regulatory recommendations. We plan to supply both vaccines for the booster campaign this fall. I am proud of our team and the cooperation of our partners. I am grateful for the hard work that has been continuously delivered to provide vaccines to people around the globe to address this evolving COVID-19 threat.

With that, I will turn the call over to Ozlem.

[Ozlem Tureci, Chief Medical Officer and Co-Founder]

Thank you, Ugur. I am delighted to provide our pipeline update to-date. First, Slide 13. As Ugur mentioned, we shared our most recent data from the clinical trial evaluating safety and immunogenicity of Omicron BA.1-adapted vaccine candidates with the regulators, including the FDA Vaccine Advisory Committee. This slide shows one of our representative datasets. Testing of adapted vaccine candidates as booster dose in vaccinated individuals, 1 month after administration fourth dose of the monovalent Omicron BA.1-adapted candidate in triple-vaccinated individuals increased neutralizing geometric mean titers against Omicron BA.1 13.5 and 19.6-fold above pre-booster dose levels.

Booster vaccination with Omicron BA.1-adapted bivalent vaccine candidates at the 30 and 60 microgram doses resulted in a 9.1 and 10.9-fold increase in neutralizing geometric mean titers against Omicron BA.1. This means both monovalent and bivalent Omicron BA.1-adapted vaccine candidates met superiority for the ratio of geometric mean titers and non-inferiority for zero responses compared to the current vaccine. The monovalent Omicron-adapted vaccine candidate showed super superiority for the ratio of geometric mean titers. The safety and reactogenicity profile offer Omicron BA.1-adapted vaccine candidates were overall similar to BNT162b2 with similar local reactions and systemic events.

Overall, these data provide the proof-of-concept for Omicron-adapted vaccine candidates, achieving immunogenicity and safety goals and meeting the regulatory requirements for a successful trial. We also tested neutralization activity of the sera generated in this trial against the Omicron BA.4/5 sub-lineage. These were lower compared to the neutralization activity against Omicron BA.1 for both monovalent and bivalent BA.1-adapted vaccine candidates. This is not surprising giving the mutational differences between the spike proteins of these two sub-lineages.

On Slide 14, the sequences show how Omicron BA.4/5 is distinct from the BA.2 and BA.1 strains. BA.4/5 sub-lineage is carrying its own unique mutations, including changes in the receptor binding domain, the RBD; and N-terminal, the NTD. The new mutations in the RBD may change its ability to latch on to host test and evade immunity resulting from exposure to earlier strength. Of note, BA.4/5 are distinct from BA.1 in their N-terminal domain and in fact are more closely related to the wild type ancestral strain in that regard. Our clinical development program has extended to include BA.4/5-adapted vaccine candidates in addition to BA.1 now. As previously mentioned, for the BA.4/5 candidates, we expect a clinical trial will be initiated in August this year. We however already have cross neutralization data in mouse models.

As shown on Slide 15, Omicron BA.4/5-adapted monovalent and bivalent boosters in mice substantially increased neutralization responses for all Omicron subvariants as well as the wild-type strain compared to Omicron BA.1-adapted boosters. Both the monovalent Omicron BA.4/5-adapted vaccine as well as the bivalent Omicron BA.4/5-adapted vaccine show strong utilization of the Omicron sub-lineages, including the most distinct sub-lineage BA.1. Based on our previous experience, we consider a cross neutralization data from such mouse models to be predictive for what will be observed in humans. Our extensive clinical experience with variant-adapted vaccines and the broad database may enable preclinical immunogenicity data and CMC package to be sufficient for future emergency use approvals and authorization subject to regulatory approval. This may enable a fast regulatory pathway for timely response to emerging variants.

Now to Slide 16. Our long-term scientific strategy includes exploring multiple next-generation COVID-19 vaccine approaches to achieve a broad and longer lasting immune response and high levels of protection against SARS-CoV-2 as it evolves. We are designing and testing several different constructs that engage multiple effector arms of the immune system, including antibodies and T-cells. In July, we and our partner Pfizer dosed the first patient in the Phase 2 study evaluating the safety, tolerability and immunogenicity of BNT162b5, our first next-generation vaccine candidate, to enter the clinic.

BNT162b5 is a bivalent vaccine candidate, which includes enhanced SARS-CoV-2 spike antigens of the ancestral strain and the Omicron BA.2 sub-lineage engineered for increased immunogenicity. BNT162b5 is modified to listed antibodies that we believe will offer superior protection against infection regardless of the circulating variant. This is accomplished through the introduction of modifications designed to expose more neutralization-sensitive epitopes to the immune system. We have also initiated preclinical work on other next-generation vaccine modalities including multi-antigen T-cell-enhancing vaccines and potential pan SARS-CoV-2 vaccines. We believe that T-cell immunity to COVID-19 is important when striving for more durable and broad protection and protection against severe disease calls. We anticipate advancing candidates for both T-cell enhancing and pan SARS-CoV-2 approaches into the clinic in the second half of 2022. We believe that taking this multi-product approach will enable us to achieve our ultimate goal of delivering a pan SARS-CoV-2 vaccine with higher and more durable protection and superior bets, helping us to better manage future variants of concern.

Slide 17 highlights our expenses oncology pipeline that is grounded in our multi-modality toolbox and our focused execution over the last years. We have reviewed our oncology pipeline pensively at our Innovation Day in June. However, we had developments since then. We now have a total of 18 clinical product candidates leveraging immune therapeutic modalities that are either targeting tumor sets directly or that are modulating the immune response against the tumor. Our programs have combination potential both within our pipeline and with other approved therapies. Our product candidates are currently being evaluated in 23 ongoing clinical trials side of which are randomized Phase 2 trials. We initiated Phase 1 trials for BNT16, the new program of our FixVac platform; and for BNT142, a second program from our RiboMab platform. We also have a new preclinical program through our collaboration with our partner Genmab, BNT313, the CD27 antibody for solid tumors.

Moving to Slide 18. FixVac leverages our proprietary UroGen mRNA backbone for full extralization of intrinsic adjuvanticity of RNA. It encodes cancer-specific shared antigens for intravenous administration using the proprietary RNA LPX formulation. This is optimized for induction of strong antigen-specific immune responses. Our FixVac product candidate, BNT116, contains six of such tumor-associated antigens, covering up to 100 of patients in all major histological subtypes of non-small cell lung cancer. In July 2020, the first participant was dosed in the first-in-human clinical trial evaluating the safety, tolerability and preliminary efficacy of BNT116 alone and in combination in patients with advanced or metastasized non-small cell lung cancer. The trial will comprise several cohorts to establish a safe dose for BNT116 monotherapy as well as for BNT116 in combination with cemiplimab, which is Regeneron’s [indiscernible] in patients who have progressed on prior PD-1 inhibitor treatment and are not – or are not eligible for chemotherapy. And in combination with docetaxel in patients who have received prior platinum-based chemotherapy.

On Slide 19 now, another first in human trials target recently for our second RiboMabs product candidate, BNT142. Our RiboMab product candidates encode cancer cell targeting antibodies and are based on nucleoside optimized RNA designed to minimize immunogenicity and to maximize protein expression. Product candidates are formulated using liver-targeting LNPs for intravenous delivery and aim to address the limitations of recombinant antibodies, including complex manufacturing processes. The RiboMab product candidate, BNT142 is a nucleoside-modified RNA that encodes the bispecific T-cell engaging antibody. This antibody targets CD3, the T cell receptor component and Claudin-6, an oncofetal cell surface antigen, found in solid tumors such as testicular and ovarian cancer. The Phase 1/2 dose escalation trial evaluates the safety and pharmacokinetics of BNT142 in patients with Claudin-6 positive advanced solid tumors.

On Slide 20, at the ASCO meeting in June, positive data from an investigator standard Phase 1 study of autogene cevumeran individualized cancer vaccine partnered with Genentech was reported. The study was conducted by our colleagues at Memorial-Sloan Kettering Cancer Center in adjuvant treatment of patients with localized pancreatic adenocarcinoma. After standard-of-care surgery and resection of the tumor R0R1 resected patients were treated with one dose of atezolizumab, patients then received eight doses of our individualized vaccine followed by standard-of-care adjuvant chemotherapy with modified Folfirinox.

After 12 weeks of chemotherapy, patients received one additional booster vaccination with our individualized vaccine. The 5-year survival rates after resection alone are as low as 10% in pancreatic cancer so that the need for surge improving adjuvant treatment of early-stage pancreatic cancer is urgent. We believe our neoantigen vaccines are well suited for the treatment of this low mutation burden tumor, especially in the adjuvant setting. The main findings in the value of the patients that were, firstly, half of the patients develop high-magnitude immune responses against at least one of the targets in their individualized set of neoantigen candidates, they were vaccinated first.

As in this study, an assay with a high threshold was used to interrogate the immune response of all patients on an individual target basis lower magnitude vaccine-induced immune responses against further neoantigen targets cannot be excluded. So even though pancreatic cancer is considered a low mutation tumor type with an unfavorable tumor macroenvironment, engineering of an individualized vaccine was shown to be feasible that was capable of mobilizing an adaptive T-cell response. Second, patients with high magnitude vaccine-induced neoantigen-specific immune responses in this study shown by two immune response assays had a higher median recurrence-free survival compared to non-immune responders, suggesting that the vaccine is confirming clinical benefit. While early, this data is encouraging and has motivated us to plan for a randomized Phase 2 trial.

Turning to Slide 21. I’ll provide an overview of our strategic collaboration with our esteemed partners from Genmab in which we are developing multiple next-generation immune checkpoint immune modulators, designed to prime activate anti-tumor T-cell and natural killer cell function. BNT311 is our bispecific antibody, which conditionally co-stimulate 41BB while blocking the PD-1, PD-L1 access. This candidate is being evaluated in two ongoing trials including a Phase 2 trial in refractory or recurrent non-small cell lung cancer and the Phase 1/2 trial in advanced solid tumors. BNT312, our second bispecific antibody being evaluated in advanced solid tumors stimulates the immune system for a combination of dual conditional activation of CD40 on professional antigen presenting cells and 4-1BB on antigen-specific T-cells. We have expanded our collaboration with Genmab through a new agreement in which we will develop BNT313, a monospecific HexaBody targeting CD27 on naive and activated T-cells. We are planning to initiate a Phase 1/2 clinical trial in solid tumors. The first patient is expected to be dosed in the second half of this year.

With that, I conclude the pipeline update, and we will now turn over the call to Jens Holstein, our CFO, who will provide the financial update.

[Jens Holstein, Chief Financial Officer]

Thank you, Ozlem, and a warm welcome to those of you on the phone. I’ll start my section by presenting the key highlights for the second quarter of 2022, which you can find on Slide 23.

Our total revenues reported for the second quarter of 2022 reached €3.2 billion. Together with the strong first quarter, we outperformed our prior year development as I will show you when taking a look at the year-to-date figures. As a consequence to this top line number, we ended the second quarter with an operating result of €2.2 billion and generated earnings per share on a fully diluted basis of €6.45, with respect to the company’s financial – earnings per share on a fully diluted basis of €6.45.

With respect to the company’s financial position, we ended the second quarter of 2022 with €9.3 billion of cash and cash equivalents as well as trade receivables of around €10.4 billion. The trade receivables are mainly derived from our collaboration with Pfizer and mainly remained outstanding due to the contractual settlement of the gross profit share under the collaboration. From our outstanding trade receivables as of June 30, we had already collected €5.6 billion in cash as of July 15, improving our cash and in turn, reducing our trade receivable position subsequent to the end of Q2. By end of July 15, 2022, our cash and cash equivalents were €14.9 billion.

Continuing with Slide 24, we recognized approximately €3.2 billion of COVID-19 vaccine revenues during the second quarter and €9.5 billion during the first 6 months of 2022. The half year numbers are fully in line with our expectations and are based on invoice doses in the amount of approximately €1.2 billion. We believe the development of the pandemic has been and remains dynamic, causing a rephasing of orders and with this leading to fluctuations in quarterly revenues.

Let me give you some more details on our revenue streams. 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 €2 billion for the second quarter and €6.6 billion for the first 6 months of 2022 that are related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners territories. These revenues represent a net figure, meaning that we generate 100% gross profit on 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. Our COVID-19 vaccine revenues from direct COVID-19 vaccine sales to customers in our territory were €0.6 billion for the second quarter and €1.7 billion for the first 6 months of 2022. Those revenues were significantly driven by the orders that were placed in late 2021 following the emergent Omicron variant. Also included in our COVID-19 vaccine revenues were €0.6 billion for the second quarter and €1.2 billion for the first 6 months of 2022 of revenues from sales to our collaboration partners.

I’ll be moving to our financial results for the first quarter of 2022, as shown on Slide 25. Having explained our revenues on the previous slide, let me move to cost of sales reached approximately €0.8 billion in the second quarter of 2022 compared to €0.9 billion for the comparative prior year period. For the first 6 months of 2022, the cost of sales reached approximately €2.1 billion compared to €1.1 billion for the comparative prior year period. The change in cost of sales resulted mainly from the recognition of costs related to our COVID-19 vaccine revenues in our own territories. This includes the share of gross profit that we owe to our collaboration partner, 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 €399.6 million for the second quarter of 2022 compared to €201.1 million for the comparative period in 2021.

For the first 6 months of 2022, research and development expenses amounted to €685.4 million compared to €417.3 million for the comparative prior year period. The increase was mainly due to the recognizing costs related to the manufacturing of pre-launch Omicron vaccine candidates as research and development expenses in the period incurred as well as an increase in head count. General and administrative expenses reached €130 million for the second quarter of 2022 compared to €47.8 million for the comparative period in 2021.

For the first 6 months of 2022, general and administrative expenses reached €220.8 million compared to €86.7 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 €0.6 billion for the second quarter of 2022 compared to €1.2 billion for the comparative period in 2021. For the first 6 months of 2022, income taxes were accrued with an amount of €2 billion compared to €1.7 billion for the comparative prior year period. The derived effective income tax rate for the first 6 months of 2022 was 26.8% and is expected to be around 28% for the full year.

For the second quarter of 2022, net profit reached €1.7 billion compared to €2.8 billion for the comparative period in 2021. For the first 6 months of 2022, net profit reached €5.4 billion compared to €3.9 billion for the comparative prior year period. Our diluted earnings per share for the second quarter of 2022 amounted to €6.45 compared to €10.77 for the comparative period in 2021. For the first 6 months of 2022, our diluted earnings per share was €20.69 compared to €15.14 in 2021.

Before turning to the financial guidance, I would like to take a moment to speak about the natural gas supply situation in Europe, as we feel it is a topic to be addressed. We carefully monitor the impact of the natural gas supply situation on our business continuity. According to our most recent information and analysis, commercial mRNA manufacturing in our facility is not expected to be impacted.

We are currently evaluating the impact of originating from our partners, supply as a service provider. At this time, it is too early to conclude which impact if any, may be driven by our partner suppliers and service providers. In addition, we are closely monitoring potential implications for all of our business. Our R&D and clinical development activities are currently dependent on gas, and we are putting measures in place to mitigate related risks. We are proactively engaging with collaboration partners and governmental authorities to mitigate adverse development from any potential energy shortage in the future.

Now let’s move to Slide 26. We reiterate our outlook for the 2022 financial year. Our very strong start into the 2022 financial year, and the results achieved during Q2 confirm that we are on track to achieve our previous financial guidance for the 2022 financial year. As mentioned, we experienced a rephasing of orders, and therefore, expect an uptick in demand in our key markets in the fourth quarter of 2022 related to the Omicron-adapted bivalent vaccine, subject to regulatory approval.

Overall, we are confirming our estimated COVID-19 vaccine revenue of approximately €13 billion to €17 billion for the full 2022 financial year and also reiterate our planned expenses and CapEx as well as the estimated annual effect of income tax rate, which we have summarized for you on this slide.

And with that, I turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our outlook for 2022 in concluding remarks. Thank you.

[Ryan Richardson, Chief Strategy Officer]

Thank you, Jens. Turning to Slide 28, our COVID-19 vaccine continues to play a major role in addressing the pandemic and the outlook remains strong. As highlighted earlier, we and our partner, Pfizer, have shipped more than 3.6 billion doses of BNT162b2 and to more than 180 countries and territories worldwide. In the first half of the year, we and our partner, Pfizer, believed that we have increased market share in select geographies where we operate and more market share data is reported. In these markets, we estimate that the cumulative share of doses administered increased from approximately 52% in January 2022 to approximately 63% in July. In developed markets over the same time period, we estimate that our share increased from approximately 59% to 68%.

Our 2022 site order book stands at approximately 2.5 billion doses. In the second quarter, the United States government agreed to purchase an additional 105 million doses with an option for up to another 195 million doses, bringing the potential total to 300 million doses. Upon delivery of the initial 105 million doses, we and Pfizer will receive $3.2 billion. We also have an order for more than 650 million doses to be delivered to EC Member States this year. We amended the contract to re-phase deliveries towards the fourth quarter. This re-phasing will not change the total doses expected to be delivered in 2022. With the expected launch of our Omicron variant adaptive vaccines, we anticipate that shipment volumes will increase in the late fall should we receive regulatory authorization.

We also continue to prioritize equitable access to our medicines. As shown on Slide 29, we are making substantial progress towards our commitment to provide 2 billion doses of our COVID-19 vaccine to low and middle income countries, having shipped over 1.5 billion doses as of July 17, 2022. At the end of June, we also broke ground and started construction of our first BioNTainer site in Kigali, Rwanda. This is the first note in the decentralized manufacturing network of at least three sites on the African continent. Additional sites are planned for Senegal and South Africa. Once fully operational, each BioNTainer unit will have the capacity to manufacture up to 50 million doses per year.

On Slide 30, we highlighted select pipeline milestones for the year. We plan to begin testing the immunogenicity and safety of an Omicron BA.4/5 adapted bivalent vaccine in August. We anticipate advancing additional next-generation vaccines into the clinic during the second half of the year and plan to provide further data updates on our expanding COVID-19 vaccine portfolio in the second half. Also in the second half of the year, we intend to begin dosing patients with our shingles vaccine, partnered with Pfizer. We also anticipate initiating clinical trials for our Herpes Simplex 2 virus vaccine BNT162, in the second half as well as for our tuberculosis and malaria vaccines, BNT164 and 165, respectively, also in the second half of the year or early 2023. Based on encouraging results demonstrated by BNT161, our Pfizer partnered modified mRNA seasonal influenza vaccine. Pfizer plans to initiate a Phase 3 clinical trial in the second half of the year.

In oncology, and together with our collaboration partner, Genmab, we plan to start a first-in-human Phase 1/2 clinical trial in the second half for our CD27 targeted antibody, BNT313. We also expect to provide data updates later this year for our Claudin 6 positive CAR T-cell candidate, BNT211, which is in trials in multiple solid tumors. We anticipate disclosing data from our ongoing Phase 2 trial evaluating our INS candidate, BNT122, in first-line melanoma in combination with pembrolizumab in the first half of 2023.

Concluding on Slide 31, we remain focused on executing against our strategic objectives for the remainder of the year. We are in a strong position to continue our COVID-19 leadership with the potential launch of our first variant adapted vaccines later this fall, alongside the continued development of multiple next-generation product candidates. We will also continue to broaden and accelerate our oncology pipeline development with the planned initiation of multiple registrational and first-in-human trials. In infectious disease beyond COVID-19, we plan to initiate multiple first-in-human vaccine trials by year-end. And we also continue to progress more than 10 preclinical stage mRNA vaccine and precision antibacterial programs.

We expect continued corporate development activity in the second half as well. We are currently evaluating a wide range of opportunities, which could complement and expand both our pipeline and technology toolkit. And we continue to add capability and scale to our organization as we expand our footprint in Europe, United States, Asia and Africa. We are investing in human capital, bringing on the people and expertise needed to further transform our global research and development and commercial organization to support our growing pipeline and long-term vision. We remain as focused as ever on creating true long-term value for patients, shareholders and society.

With that, I would like to thank our shareholders for their continued support and would now open the floor for questions.

[Operator]

[Operator Instructions] And the first question comes from the line of Matthew Harrison from Morgan Stanley. Your line is open. Please ask your question.

[Matthew Harrison, Morgan Stanley]

Great. Good morning. Thanks for taking my question. Ryan, I guess I just wanted to follow-up on one of the comments you made towards the end about size and scope of the opportunities that you are evaluating. How you think about broadly uses of cash here? And should investors be expecting that you would consider deals that are quite sizable, or should we be thinking much more about smaller bolt-on technology deals? Thanks very much.

[Ryan Richardson, Chief Strategy Officer]

Yes. Thanks for the question, Matt. So, we are looking at a wide range of opportunities. But for the most part, Matt, we are looking really at bolt-on acquisitions and/or strategic partnerships. Our focus is going to continue to be on organic R&D and scaling that up over the coming years. And as we get into more registrational trials with our own pipeline, we think we will have a better ability, say, over the next 24 months or so to be able to deploy capital into those pivotal trials that could deliver products for launches over the next 3 years to 5 years, as Ugur laid out. So, really, it’s about complementing that organic strategy, and that includes expanding our pipeline in either early or mid-stage pipeline in complementary ways. We are really looking for programs and technologies that synergize with what we are already doing, and that may include extending our RNA platforms into new verticals or new white space or bolstering our cell therapy pipeline. Does that answer your question?

[Matthew Harrison, Morgan Stanley]

It does. Thank you, Ryan.

[Operator]

Thank you. Now we are going to take our next question, please standby. And the next question comes from the line of Tazeen Ahmad from Bank of America. Your line is open. Please ask your question.

[Tazeen Ahmad, Bank of America]

Okay. Thank you. Thanks for my question. Ryan, maybe I also want to ask you about some of the prep comments that you made about deliveries for the rest of the year. So, for this quarter, when you mentioned that some deliveries have been pushed out, are you just referring to the portion of delivery that BioNTech is responsible for or would it also have applied to some of what Pfizer was delivering in the U.S.? And then same topic, how should we think about your capacity to deliver doses for the rest of the year once you get to full-scale production for the new variants. Basically, do you have a sense of how many doses you would have capacity to deliver between now and year end? Thanks.

[Ryan Richardson, Chief Strategy Officer]

Thank you, Tazeen. I will start with that and then also ask Jens Holstein to weigh in as well. On your first question with regard to the shift in doses towards the end of the year, that is a – that does reflect both our and Pfizer scheduled deliveries. I think namely, it includes the orders for delivery to the European Union. We had announced during the quarter that some of those deliveries would be shifted into the back end of the year. And that’s a pretty sizable number of orders. It’s actually our largest order for this year and extends into next year. So, that’s a big component of the shift to Q4, but we also see that in other markets as well. The U.S. is less about shifting because the orders – the original contract orders went through April. And then as we mentioned on the call today, we had an additional order, which we expect will be delivered over the second half of the year, likely heavily weighted in Q4. Maybe before we go to the capacity point, Jens, do you want to add to that?

[Jens Holstein, Chief Financial Officer]

Yes. Thank you, Ryan. But you basically gave the answer already. Maybe a bit to add here, I mean we have, of course, in other countries also some delays, specifically if we look at Europe or not too late, we have some shifts from Q2 and Q4. And Ryan was alluding to this in his speech that we have 650 million doses that we expect to be delivered in the course of this year. I mean all of this, of course, is heavily influenced and we have seen that throughout the year so far by the dynamic of the pandemic, and of course, specifically, how the timing will be for approval from the FDA and EMA and that will influence the total amount that we are able to deliver to our customers at the end of the day. So, there is – that’s the main reason why we have been cautious in terms of looking at our guidance of 18 to 17. I think overall, if you look at the 9.6 billion that we have reported for the first six months, I mean we feel very, very good about it. And just to maybe allude also to what we said in the Q1 call on the basis of 2.4 billion doses we said, we will end up somewhere in the middle of that range. So, of course, there are some fluctuations that we have seen already last year when that delivery moved from one month into the next month that can happen over the end of the quarter, over the end of the year as well, of course. So, in all this, just keeps us with the guidance that we have given to you on 13 to 17. But we are overall very optimistic that we will see a good year 2022.

[Ryan Richardson, Chief Strategy Officer]

Yes. And Tazeen, on your capacity question, I would just say that, of course, we – our objective is to deliver the full order book, the full 2.5 billion doses that are scheduled for delivery this year. This year, I think one factor that will – that could impact that would be the timing of the various authorizations that we do expect in the fall for the Omicron variant vaccine. I think we do have to manage inventory as we have alluded to here on the call, we have produced different vaccines at risk in order to be able to supply readily. We do feel confident that we will be able to supply to meet demand. But of course, as mentioned, these things are dynamic. The demand is dynamic and will be following regulatory authorizations, should they occur. So, we feel good about the position, but there is always a chance, of course, that the planned deliveries will shift as we move throughout the year. And we just have to – and we have been operating under those assumptions for 1.5 years now and have to continue to do so.

[Tazeen Ahmad, Bank of America]

Okay. That’s a lot of color. Thank you.

[Operator]

Thank you. Now, we are going to take our next question, please stand by. And the next question comes from the line of Daina Graybosch from SVB Securities. Your line is open. Please ask your question.

[Daina Graybosch, SVB Securities]

Alright. Thank you all for the question. I have one, sort of a three-parter under fall booster. So, we have talked about the EMA and U.S. and whether they want BA.1 versus BA.4/5, can you give us a breakdown of the rest of the world and your expectation for which of these versions they will guide to or want? And the second part is, do you think there will be enough use of both versions for us to understand the relative vaccine effectiveness as you compare across countries using BA.1 versus BA.4/5? And finally, is your BA.4/5, does it have spikes from both the BA.4/5 or have you selected one? Thank you.

[Ugur Sahin, Chief Executive Officer and Co-Founder]

Hi, Daina, this is Ugur. Thanks for the question. So, with regard to the BA, so you are aware that the FDA expects a BA.4/5 vaccine, whereas the EMA appears to be open to both BA.1 as well as BA.4/5. And based on that, we are preparing ourselves to manufacture and supply both vaccine compositions both as a bivalent vaccine. With regard to the rest of the world, we have to see how the static pandemic is will continue. Currently, it appears to be that the dominating sub-lineages are based on the BA.2 and BA.4/5 sub-lineages. And if this continues, we anticipate that the BA.4/5 vaccine, yes, which has higher similarity to the BA.2 lineage will produce a stronger neutralizing antibody response against both BA.4/5 as well as BA.2. There is some evidence from preclinical data that we have generated and in part presented already, and there is also evidence from ongoing studies in humans with full infection indicating that BA. 2 or BA.4/5 vaccine could have a border neutralization. And with regard to BA.4/5 spike, you know that BA.4/5 in the original sequence share the same spike sequence and therefore, we always refer to be BA.4/5.

[Daina Graybosch, SVB Securities]

Great. Thank you.

[Operator]

Thank you. Now, we are going to take our next question, please standby. And the next question comes from the line of Chris Shibutani from Goldman Sachs. Your line is open. Please ask your question.

[Unidentified Analyst]

Hi. Good morning. This is Steven [ph] on for Chris. Thank you for taking our question. I had one on cost of sales. It was noted that this was affected by inventory write-offs. We were just wondering if you could provide some context around these write-offs maybe quantify the impact and then related to know how we should be thinking about margins on a forward basis? Thank you.

[Jens Holstein, Chief Financial Officer]

Yes. Steven, thanks for the question. So, indeed, we have some write-offs in Q2. You will see that in the filing document, we talked about around about €400 million that have impacted negatively our cost figure. If you look – if you take that out, the gross margin is in the range of what we have seen in previous quarters, despite the fact that the increase in terms of volume that went into low-income countries and middle-income countries actually slightly increased in Q2. So that is something that we have to swallow in Q2, depending on how much forward it will take or something that this will remain a topic that we have to keep a view on in the quarters, depending on how the pandemic evolves.

[Unidentified Analyst]

Got it. Okay. Thank you very much.

[Operator]

Thank you. Now, we are going to take our last question, please standby. And the last question comes from the line of Zhiqiang Shu from Berenberg. Your line is open. Please ask your question.

[Zhiqiang Shu, Berenberg]

Hi. Thanks for taking my questions. I would like to ask about the next-generation vaccine approaches. In particular, with regard to the T-cell enhancing vaccines, I mean Ugur, can you talk about the advantage of this vaccine? And regarding the pan-SARS-CoV-2 vaccine, I was wondering if you can talk about the feasibility here? Whether you could – this vaccine will include multiple strains or – and including some of the appreciation stability approaches you are taking there? And as a quick follow-up on BNT122 maybe for Ozlem in terms of the first-line melanoma, I noticed the data release is shifted to first half ‘23. Can you talk about some of the considerations there?

[Ugur Sahin, Chief Executive Officer and Co-Founder]

Okay. So, I am happy to take both questions. So, first of all, with regard to our strategy for next-generation vaccines. We have a number of ongoing preclinical programs and decided to bring two clinical programs into – two preclinical programs into clinical testing. One is related to next-generation vaccines, aiming to increase the neutralizing antibody titers and broaden the neutralizing antibody titers by modification of the spike put in. And the second approach, so this is about strengthening the B-cell response. And the second approach aims for the development of boldly active T-cell vaccine. As you know, the spike protein is the target of strong evolution and has a high mutation rate. And the concept of the T-cell vaccine is to strengthen the cellular immunity against COVID-19. It is and now established that cellular immunity has a paramount effect on preventing severe disease. And we see here the opportunity to identify epitopes that are conserved among all, last two variants. And this is an approach where we will share more information in the coming weeks, how this development would relate to the already existing vaccine approaches. With regard to BNT122, so we shifted read-out for the Phase 2 to next year and the background is here that the recruitment of patients into the study was delayed also related to the pandemic and post-pandemic effects, and therefore, the read-out is shifted to 2023.

[Zhiqiang Shu, Berenberg]

Got it. Thank you very much.

[Operator]

Thank you. There are no further questions. Sylke, over to you.

[Sylke Maas, Vice President, Investor Relations and Strategy]

Thank you. Thank you all for joining us today and we look forward to speaking with you in the future. Thank you and stay safe.

[Operator]

That does conclude our conference for today. Thank you for participating. You may all disconnect. Have a nice day.