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 an 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 the company 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 two, 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 these 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 US 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 three and four provide detailed and important safety information regarding our COVID-19 vaccine. Finally, today's agenda can be found on slide five. 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..

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 four 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 Multi-Pronged innovation strategy to respond to the evolving pandemic and improve upon our vaccines with next-generation approaches that generates broader and more durable immunity.

We have successfully delivered our first variant adaptive vaccines to address Omicron BA.1 and BA 4-5 vaccines. We believe that our vaccine has potential to be combined with a original flu vaccine. Across many parts of the world, people are currently receiving the Omicron adapted vaccine boostersat the same timeas their flu shot.

Health agencies, including the US CDC now recommend co-administration 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 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 five and older in the US. In the EU, we received a marketing authorization for individuals age12 and older. Submission for ages five 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 six months to four 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 edge groups. Slide 15 highlights the positive data in the ages 18 and older cohort reported from the ongoing Phase 2/3 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 volunteer's each stress and order, all of whom had already received at least three doses of an approved COVID-19 vaccine. The adults who did received either 30 or 60 micrograms of a BA.4/5-adapted bivalent booster over original vaccine as a comparator.

Adolescence age 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 bivalent vaccine COVID.

The comparator group included 40 individuals over 55 years of age who will received original vaccine. The data showed that the safety and tolerability profile of bivalent booster which remains favorable and similar to the original vaccine.

On Slide 16, you can see the titers of neutralizing antibodies broken down by age group and by pre-vaccination 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 titles, whereas the individuals who were negative at baseline experienced 28.3 fold increase.

These responses were higher than that -- 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 arm.

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 [indiscernible] continue to be the dominant circulating strains.

These data provide strong evidence offer 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 vaccines built on BioNTech’ validated mRNA technology.

The Phase 1 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 3 trial was initiated by Pfizer in September.

In the combination trial, the quadrivalent influenza vaccine candidate contain a 2 type A strains and 2 type B strains that have been selected for the current seasonal traditional flu vaccine.

180 people aged 18 to 64 will be enrolled across six trial arms to test various combinations of the influenza vaccine candidate and the Omicron adapted vaccine at 30 and 60 microgram doses. The influenza vaccine candidate individually understand that licensed influenza vaccine as a comparator arm.

Slide 18 details our two development tracks to create next-generation vaccine. One track includes our engineered spike protein vaccine candidate designed to elicit more broad neutralizing antibodies protection against the vast array of variants, including those, which have not yet evolved.

The other track are vaccines candidates designed to enhance the T cell response against SARS-CoV-2 [ph], our first-testing candidate for this program BNT162b4, targets might have highly conserved non-spike protein 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 start 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 choice in-human trials of our mRNA vaccine candidates over the coming months. This includes our Shingles and HSV-2 vaccine candidate, 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 2023, and our tuberculosis vaccine candidates expected to dose the first patient in early 2023. These programs built on our validated platform of nucleoside-modified mRNA LNP 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 products candidates across four different drug classes in 24 ongoing clinical trials, five of which are randomized Phase 2 trials.

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

In the third quarter of 2022, preclinical programs advanced to Phase 1 clinical testing. This includes our FixVac candidate BNT116 for second-line treatment of non-small cell lung cancer and our bispecific RiboMab product candidate, BNT142 for solid tumor.

In collaboration with Genmab, we recently initiated a Phase 1 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 2 trial of our FixVac program, BNT113. This trial is evaluating BNT113 in combination with pembrolizumab in patients with first plan HPV16+, PDL1+ head and neck cancer carcinoma.

The other is preliminary efficacy and safety data from another Genmab collaboration, the Phase 1 trial of BNT312, a CD40×4-1BB dual body in advance solid tumors. Finally, we have BNT211, our next-generation CAR-T therapy product can be designed to overcome first generation CAR-T cell therapy mutations in patients with solid tumors.

We recently presented follow-on data for BNT211 at the ESMO annual contract. The Phase 1 dose escalation data continue 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 Car-T cell amplifying mRNA vaccine called CARVac encoding Claudin. CARVac 6 is based on neurogen mRNA-lipoplex technology with another cancer vaccine candidate programs.

Claudin-6 CAR-T cells with a second-generation chimeric antigen receptor of high sensitivity and specificity for to carcinoembryonic tumor-specific antigen Claudin-6. Claudin-6 is absent in heavy adult issue, 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 resets or refractory advanced solid tumors.

Our dose escalation study has been three dose levers of Claudin-6 CAR-T cells, as monotherapy, as well as in combination with the six dose of the RNA vaccine. The expansion cohorts into 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 we Claudin-6 CAR-T cells at two dose levels, 10⁷ and 10⁸, alone or in combination with CARVac. Patients received lymphodepletion with 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 one [indiscernible] dose toxicities were observed in two patients, both were manageable, and the patients fully recovered.

One was thrombocytopenia in the dose level two monotherapy group in a patient with testicular cancer after lymphodepletion. The second was [indiscernible] doses in the dose level two combination group prior to application 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, six partial responses and seven patients with stable disease.

We are particularly encouraged by the observed activity in patients with testicular cancer, receiving the 10 CAR-T dose levels after lymphodepletion. Of seven evaluable testicular cancer patients, included in the analysis, one had a confirmed complete response.

We 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 our 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- 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 10 to the 8th CART-T dose level. The disease control rate was 85% at 10 to the 8th CAR-T dose level.

One patient at the 10 to the 8th CAR T dose level was assessed by the investigator as having a complete response at 12 weeks. This complete response continue and was confirmed at the 18-week and 52-week time point. We are very encouraged by the safety and clinical activity data from the strong BNT program.

Turning now to Slide 25, and our next-generation immune modulators partnered with Genmab. These programs, which aim to prime and activate anti-tumor T cell and Natural Killer cell function are continuing to advance. Abstract to cover this conference were just announced earlier today.

We will present a post highlighting preclinical results supporting BNT311, our bispecific antibody designed to Conditional 4-1BB co-stimulation concurrent with PD-L1 blockade. Additionally, an abstract of preclinical data demonstrating the mechanism of action of BNT313 has been accepted for post presentation at FixVac [ph].

BNT313 is an anti-CD27 antibody that carries a Hex summarization enhancing domain to support antibody Hex summarization transformation that drives the CD27 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 with [indiscernible].

As previously mentioned, for our BNT312 program, an abstract has been accepted for a presentation at the ESMO Immuno-Oncology Conference 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 €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 €2.4 billion and generated earnings per share on a fully diluted basis of €6.98.

With respect to the company's liquidity position, we ended the third quarter of 2022 with €13.4 billion of cash and cash equivalents as well as trade receivables of around €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 €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 €3.4 billion of COVID-19 vaccine revenues during the third quarter and €12.9 billion during the first nine months. Revenues for the first nine 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 €2.5 billion for the third quarter and €9.1 billion for the first nine 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 two companies and therefore, reduced BioNTech's revenue figure, but not those of our partner, Pfizer.

Our COVID-19 vaccine revenues from direct COVID-19 vaccine sales to customers in our territory were €0.6 billion for the third quarter and €2.3 billion for the first nine 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 €0.3 billion for the third quarter and €1.5 billion for the first nine 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 nine 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 €0.8 billion in the third quarter of 2022, compared to €1.2 billion for the comparative prior year period.

For the first nine months of 2022, the cost of sales reached approximately €2.8 billion, compared to €2.3 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, 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 €34.8 million for the third quarter of 2022, compared to €260.4 million for the comparative prior year in 2021.

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

General and administrative expenses reached €141 million for the third quarter of 2022, compared to €68.2 million for the comparative period in 2021. For the first nine months of 2022, general and administrative expenses reached €361.8 million, compared to €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 €0.7 billion for the third quarter of 2022, compared to €1.5 billion for the comparative period in 2021.

For the first nine months of 2022, income taxes were accrued with an amount of €2.6 billion compared to €3.2 billion for the comparative prior year period. The derived effective income tax rate for the first nine months of 2022 was 26.8%.

In the third quarter of 2022, net profit reached €1.8 billion compared to €3.2 billion for the comparative period in 2021. In the first nine months of 2022, net profit reached €7.2 billion compared to €7.1 billion for the comparative prior year period.

Our diluted earnings per share for the third quarter of 2022 amounted to €6.98 compared to €12.35 for the competitive period in 2021. For the first nine months of 2022, our diluted earnings per share was €27.70 compared to €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, €16 billion to €17 billion from €13 billion to €17 billion previously.

The narrowed guidance reflects delivery of the Omicron-adapted bivalent vaccine booster, 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’ll 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 two 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 US$1 billion and began on May 2, 2022, and ended October 10, 2022. As shown on the slide, a total of 6,945,530ADSs were repurchased at an average price of US$143.98, representing 2.8% of the shares issued as of April 30, 2022.

In addition, we had paid out a dividend of approximately €0.5 billion to shareholders in 2022. In November, the second tranche of the repurchase program worth of value of up to $0.5 billion has been approved, commencing on December 7 this year. All 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..

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 our variant-adapted B4B5 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 variant-adapted 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 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 file 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 two 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-adapted vaccines. 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 five new clinical trials starts in infectious diseases. Turning to slide 35.

In oncology, alongside the first patient dosed in the Phase 1 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 1 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. [Audio Gap] 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..

Thank you. [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. Please, go ahead..

Hello. Good morning. Thanks for taking my question. Can I just give 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 and BQ.1.1.

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. Would those be delayed until later next year? Do the parties that have ordered it have the right to delay shipment for a newer version of the vaccine? Thanks..

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. The -- 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?.

Yeah. 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 is 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 conversely served by again, either the current vaccine or future vaccines if a future variant vaccines needed..

Okay. Great. Thanks for the color..

Thank you. 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. Thanks for taking my question. 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? Thank you..

So just to clarify the question, you referenced the PCV.

So you're talking about the IMS program?.

In melanoma, yes..

Yeah.

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

Yes, yes. Thank you..

Okay.

Ugur Sahin, do you want to address that?.

Yes. I think this is too early to give to define a threshold. We are working with hazard 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 first-line melanoma, yeah.

We have to align this understanding also with the progress that we have made in the manufacturing of our IMS platform. So we in the meantime, improved algorithm and reduce 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 focus and can just use the study to expand the clinical trial for a potential accelerated approval or do a confirmatory trial..

Thank you..

Thank you. We will now go to our next question. And your next question comes from the line of Chris Shibutani from Goldman Sachs. Please go ahead..

Yes. Thank you very much.

Recent media reports suggest the potential for distribution of your COVID vaccine in China with the initial target population being ex-Pats, as we're trying to better understand the potential scope of this opportunity, thinking in terms of units and pricing, can you, number one, give us any updates on development when perhaps your vaccine might be approved in China? Number two, 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? Thank you..

Yeah. 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 ex pat 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..

Thank you. We will go to our next question. And your next question comes from Jessica Fye from JPMorgan. Please go ahead..

Hey there. Good morning. Thanks so much for taking my questions. 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 COVID vaccine volumes could trail that 500 million, 600 million range next year, but then increase in 2024 and beyond to something closer to the flu range? Thank you..

Yes. Maybe I'll start -- this is Jens Holstein with answering the question and then Ryan might chime in or -- I think we all know that the pandemic has evolved throughout 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 -- death 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 the disease. 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, with -- in such an endemic scenario 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 positions and we have been able, over the time, to the 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 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 combined to create the multi-billion long-term market opportunity that we expect that, Ugur just outlined..

Thank you. We'll now go to our next question. And your question comes from Daina Graybosch from SVB Leerink. Please go ahead. Your line is open..

Hi. Thanks for the question. I want to ask about some academic applications that were posted as preprint from the broken lab recently and they were on their own looking at immunogenicity of the bivalent boosters versus another boost of a 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, and 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? Thank you..

Hi, Daina. Thank you for the question. So first of all, to the preprint of course, we have studied the preprint. 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 our 4-fold neutralization titers and – as compared to those who have been – who had prior infections.

And so our data, we have published a seven-day data and one-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 few 4-fold higher increase in neutralization titers as compared to the wild-type vaccine. And we are talking here about -- about the immediate antibody response.

What we have also to consider is that every vaccination is 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 three-plus months.

So we believe that -- we believe 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 wild-type vaccine.

Just to also repeat findings that were generated with the wild-type vaccine, even the booster with the wild-type vaccine reduces the severe disease state and reduces the mortality. So that means, regardless whether we are immunizing, boosting with wild-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 neutralization titers appeared to be significantly higher with the wild-type..

Thank you. We will now go to our next question. And your next question comes from the line of Akash Tewari from Jefferies. Please go ahead. Your line is open..

Hey, good morning. And this is Avi [ph] on for Akash. Thanks for taking our question. 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? Consensus models 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? Thanks..

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 US, existing US 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 of 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, you want to add to that?.

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 2023 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..

Got it. Thanks..

Thank you. We'll now go to our next question. And the next question comes from Yaron Werber from Cowen. Please go ahead. Your line is open..

Hi. This is Brandon [ph] on for Yaron. Thanks very much for taking the questions. Congrats on the 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 the 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, 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 two 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 all this consistent for all variant-adapted vaccines.

And the second aspect is that we found that pre-clinical data and clinical data and breakthrough -- subjects with breakthrough 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 and 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..

Okay, great. Thanks very much..

Thank you. We WILL now go to our next question. And the question comes from Ellie Merle from UBS. Please go ahead. Your line is open..

Hey guys, thanks so much for taking the question.

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? Thanks..

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 documentation 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 2023 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..

Got it. Thanks..

Thank you. We will now go to the next question. And your next question comes from the line of Simon Baker from Redburn. Please go ahead. Your line is open..

A question on pricing, if I may. You very helpfully gave us the list price range for the US of around $1.10 to $1.30 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, you also 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 US for 2023? Thanks very much..

Yeah. 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 US 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 Ron just said. I mean you read what Pfizer said to the topic, that pricing has been set given or in relation to what sort of benefit, and 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 US 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 main 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..

Got it. Thank you very much..

Thank you. We will take one more question. And the question comes from the line of [indiscernible] Shu from Berenberg. Please go ahead. Your line is open..

Great. Thanks for taking the question. 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 this modality will play as the most significant role.

And a quick follow-up to 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? Thanks very much..

Yes. Thank you, Tian. So, let's start with the cancer vaccine question, and Ozlem will take the question related to the encoding 6 CARV [ph]. 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 or -- and the best indication and clinical setting for cancer vaccines is post surgery, where tumors are in a micrometastatic manner left. So this is a 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 two to three ears after surgery.

In triple-negative best cancer, this is also in the range of 30% to 40% the first four years after surgery, and pancreatic cancer is 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, showing 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 two dose levels or three 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..

Thank you very much..

Thank you. 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..