Welcome to the BioNTech First 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..

Good morning and good afternoon, and thank you for joining us today to review BioNTech's first quarter 2022 clinical and operational and financial results. A few housekeeping items before we start.

Please view the slides that accompanied the webcast in the first quarter 2022 press release, both were issued this morning and can be found in the Investors section of our website. As outlined on Slide 2, today's presentation, we'll be making several forward-looking statements.

These forward-looking statements include, but are not limited to, our current COVID-19 vaccine revenues as they 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, 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 and reporting of data from our preclinical studies and our clinical trials, the timing of and our ability to obtain and maintain regulatory approval for our product candidates and other risks described in our filings made with the U.S.

Securities and Exchange Commission, including our most recent annual report on Form 20-F. As 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 and 4 provide detailed and important safety information regarding our COVID-19 vaccine. Finally, you can see the agenda for today's call on Slide 5. It's my pleasure to introduce the members of BioNTech's management team participating in today's call.

I'm 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..

Thank you, Sylke. Good morning and good afternoon, and a warm welcome to all participants and thank you for your continued support. Today, I'm happy to provide you an overview about the key highlights from the first quarter and objectives for the year. Our team will provide further details, and then we will open the call for questions.

Starting on Slide 6. Let me remind everyone about a few features of our company. Our vision is to harness the immune system to fight human diseases. Our response to the COVID-19 pandemic provided us with the unique opportunity to help protect well over 1 billion people with our first approved product.

It provided us also a historic chance to accelerate our progress towards our long-term vision to bring the next generation of immunotherapy to patients.

With a fully integrated spectrum of competencies for biopharmaceutical drug development covering discovery, translational research, development, GMP manufacturing and commercial capabilities, we are well positioned for success.

We are pursuing a technology-agnostic solution-focused multi-platform strategy and have built an innovation engine that covers various emerging technologies. We are advancing a diversified product pipeline of immunotherapies that aim to address high unmet medical needs in oncology and multiple infectious disease indications.

We are building a centrally immunotherapy powerhouse with a mission anchored to our strong sense of global social responsibility. We seek to make a positive impact on global health and democratize access to cutting-edge medicines. Highlights for the first quarter are summarized on Slide 7.

Our solid performance continued in the first quarter of 2022, following a strong fourth quarter in 2021. In the first quarter, we reported total revenues of €6.4 billion. We signed our first pandemic preparedness contract with the Federal Republic of Germany that runs through 2027.

The framework agreement is aimed at pandemic preparedness, including development, manufacturing and supply of mRNA vaccines in emerging situations in Germany. During the first quarter, we also engaged into collaborations that complement our internal innovation engine.

The Matinas collaboration combines our mRNA vaccine development expertise and Matinas nanocrystal delivery platform technology to advance novel formulations for mRNA vaccines, including a potential formulation for oral vaccines.

With Regeneron, we plan to jointly conduct clinical trials, evaluating candidate BNT116 in combination with for the treatment of advanced non-small cell lung cancer. Our impact on human health and economy around the globe continued in 2022.

We have invoiced approximately 750 million doses of our COVID-19 vaccines globally in 2022 and to end of the first quarter. In terms of expanding our broader population, we recently received certain approvals. This includes a first dose in adults aged 50 and over as well as in certain types of immunocompromised patients aged 30 years and older.

Our pediatric indications now includes vaccinations in children, aged 5 and over as well as booster for those and up in multiple geographies. On the oncology front, our first fibroma program, BLT141 entered a first in-human study in solid tumors in January. BNT141 is an mRNA included IgG antibody targeting CLDN18.2.

In April, we presented a promising preliminary clinical data from 14 evaluable patients in our Phase I/II trial of BNT211, our next-generation Claudin 6 targeting CAR T cells in solid tumors at the AACR Annual Meeting.

We documented first antitumor effects even at the lowest CAR T cell dose in heavily treated patient population pointing to an encouraging activity of targeting Claudin 6 and our CARVac approach. Slide 8.

Since the start of the pandemic, we have delivered nearly 3.4 billion doses of to people located in more than 175 countries and regions, demonstrating our strong global position in the fight against COVID-19. We remain on track to achieve our pledge to deliver a total of more than 2 billion doses to low and middle income countries by the end of 2022.

To stay ahead of COVID-19, we continue to innovate and optimize our vaccine. This year, we have introduced a ready-to-use formulation that does not require and received approval for a shelf life extension from 9 to 12 months when stored at minus 90 to minus 60 Celsius.

To further expand the label to pediatric populations, we have filed for the approval of boosters in children 5 to under 12 years old. The filings were supported by recent positive data demonstrating that at first dose increase neutralizing antibodies sixfold in this age group.

We are also evaluating a dose primary regimen in children 6 months to under 5 years old and expect data in the coming weeks. As part of our approach to pandemic preparedness, we are collaborating this in study on an early warning system that analyzes globally available sequencing data and predict high rest variance of SARS-CoV-2.

This warning system allows us to rapidly adapt our vaccine product candidate in a data guided way. As part of our preemptive approach to variance, we have an ongoing comprehensive development program where we are evaluating several follow-on and next-generation COVID-19 vaccines, including variant adapted vaccines.

We also have initiated research program to study the immune profile after vaccination booster and flu infection. This research program is informing our vaccine development strategy.

To conclude my opening remarks, as shown on Slide 9, we are building a differentiated pipeline that we believe could usher in a new era of immunotherapy to multiple ways of innovation.

Our COVID-19 vaccine program is enabling a transformation of our company that will position us to broaden and accelerate our pipeline towards the market, consistent with our vision to transform medicine. In oncology, we have 16 programs in 20 ongoing clinical trials, including 5 randomized Phase II trials.

In infectious diseases, we have 1 ongoing Phase I program and more than 10 preclinical programs, 4 of which we expect to bring into the clinic this 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 our current core disease pillar of oncology and infectious diseases.

There's multiple programs underway in new disease areas that are in the lead candidate selection phase, advancing our technology into these new areas expand the future for BioNTech and will support our vision in the long term. With that, I will turn the call over to Ozlem..

landscape research, product research and product development. Our landscape research elucidates how the virus evolves within the context of vaccine and infection-induced immunity. We are studying how immunity is being shaped over time by iterations of vaccinations ongoing boosters and infections with different variants of concern.

The data we are continuously generating will inform our evolving response to the pandemic. A recent research study has added to our understanding and may be crucial in the development of next-generation vaccines. These data have been submitted for peer review in a hiring journal and published on a preprint server.

In the study, we evaluated the sera of individuals who had breakthrough infections with Omicron after either 2 or 3 doses of original vaccine to determine the impact of Omicron infection on immunity.

We found that the exposure to Omicron spike by Omicron breakthrough infection of vaccinated individuals strongly enhanced with not only neutralizing activity against Omicron BA1, but broadly augments immunity, including against Omicron BA2, previous SARS-CoV-2 variants of concern and even Omicron breakthrough infection mediated abroad B-cell recall primarily for expanded memory that recognize antigen shared broadly by different variants rather than inducing new B cells against strictly Omicron-specific antigen.

Taken together, these results suggest that despite possible imprinting of immune response by previous vaccination, the preformed B-cell memory can be refocused and quantitatively remodeled by exposure to spike proteins from different strains.

We believe this may allow neutralization of variants that previously established neutralizing antibody response.

The observation also may suggest that a vaccine adapted to Omicron's spike put similarity reshape the B-cell memory repertoire and therefore, may be more beneficial than an extended series of boosters with the existing vaccines directed against the original strain.

We believe that the data may also suggest that exposure of ancestor strain vaccine experience individuals to an Omicron spike mono vaccine could provide similar cross-train immunity.

To be prepared for future challenges we may face with further involvement of the virus, we have been engaged since the approval of BNT162b2 in a very robust product research effort to explore various follow-on and novel next-generation vaccines to prevent COVID-19.

These are currently in development and several projects may move into the clinic this year. We are evaluating mono and multivalent vaccine, T cell-enhancing approaches and pan-coronavirus covering vaccine concepts.

Our landscape research helps our product development strategy that currently focuses on responding to the need for vaccine adaptation due to the emergence of Omicron and its top lineages. Our clinical program evaluating the safety, tolerability and immunogenicity of various variant adaptive vaccines in multiple clinical trials is advanced.

Emerging data from these trials will be reviewed and discussed with regulators in the coming weeks to determine the appropriate regulatory path forward for either monovariant or bivariant adapted vaccine product candidates. As a reminder, Slide 12 shows our comprehensive clinical response strategy to the Omicron variant.

We are investigating different dose schedules of a monovarient Omicron adaptive vaccine, for example, in individuals aged 18 to 55 years and evaluating bivariant approaches as well. We expect data from these studies will be available in the coming weeks.

While there is currently no regulatory consensus on the benefit of Omicron adapted vaccines, we anticipate regulatory developments as clinically meaningful data become available.

As we await the data, we remain prepared to adapt our technology and manufacturing processes to ensure that our vaccine provides robust protection against current and emerging variants of COVID-19. Slide 13 highlights our expensive oncology pipeline. That is a result of our comprehensive innovative multi-modality toolbox.

And our focus execution throughout 2021 and 2022. We have multiple assets in development across different immune therapeutic modalities with the possible potential to using complementary strategies, either by targeting tumor cells directly or by modulating the immune response against the tumor.

Many of our product candidates can be combined with our pipeline assets. Our oncology pipeline includes the total of 16 product candidates across 4 different drug classes in 20 ongoing clinical trials, 5 of which are randomized Phase II clinical trials.

We expect continued pipeline advancement and expansion as well as further data readout from the ongoing trials in 2022. We believe that this will be a year of focused execution across our 5 Phase II clinical trials in multiple tumor types, as shown on Slide 14.

First, we have 2 Phase II trials ongoing that are evaluating FixVac, our off the shelf mRNA vaccine immune therapy platform. BNT111, which is being evaluated in anti-PD-1 refractory relapsed advanced melanoma and tumor antigens that cover greater than 90% of cutaneous melanoma patients.

Our approach may have the potential to improve outcomes when used in combination with anti-PD-1. We have received FDA fast track and orphan drug designations for this program. BNT113, which includes HPV 16 oncoprotein E6 and E7 is being evaluated in HPV 16 positive PD-L1-positive head and neck cancer in combination with anti-PD1.

Next, we have with our partner, Genentech, 2 individualized neoantigen-based vaccine programs, iNeST programs, evaluating Autogene cevumeran or BNT122 in Phase II trials, 1 in frontline melanoma and 1 in colorectal cancer in the adjuvant setting.

If our melanoma trial is successful and accepted by regulators, we would unlock the possible use of iNeST as a frontline therapy in combination with anti-PD-1 in anti-PD-1 naive advanced cancers. In colorectal cancer, we aim to address the residual cancer cells that remain after treatment with standard therapy, a key driver of relapse.

Finally, BNT311, our bispecific antibody that we are developing with our partner is in an ongoing Phase II study in refractory or recurrent non-small cell lung cancer.

This next-generation immunotherapy uses conditional 4-1BB co-stimulation concurrent with PD-L1 blockade with the goal of tumor-targeted enhancement of T cells and natural killer cell function. Turning now to Slide 15.

We recently presented promising efficacy and safety data for BNT211, our next-generation CAR T cell program at the AACR annual conference.

BNT211 combines 2 of our platforms that we believe have complementary modes of action, CLDN6 CAR-T cells and a CAR T cell amplifying or vaccine called CARVac based on our technology used in other cancer vaccine programs.

CLDN6 CAR T cells are equipped with a second-generation chimeric androgen receptor of high sensitivity and specificity for the passing of embryonic, tumor-specific antigen CLDN6. CLDN6 is heavy adult tissue, yet frequently expressed in high medical need cancers, making this tumor-antigen an ideal candidate for CAR-T cell therapy.

In preclinical studies, we demonstrated that CARVac drives in vivo expansion of transferred CAR-T cells, increasing their persistence and efficacy. BNT211 aims to overcome CAR-T cell in patients with solid tumors.

The ongoing test in human Phase I/II trial is evaluating the safety and efficacy of CLDN6 CAR-T cells as monotherapy and in combination with CARVac in patients with CLDN6 positive relapsed or refractory advanced solid tumors.

We are testing 3 dose levels of CLDN6 of CAR T cells as monotherapy dose escalation as well as in combination with fixed dose of mRNA vaccine. The subsequent dose expansion cohorts will include patients with ovarian, testicular and endometrial cancer as well as other rare CLDN6-positive cancer types, such as sarcoma.

Slide 16 provides a summary of AACR data.

The presentation included data from 16 heavily pretreated patients who received CLDN6 CAR-T cells alone at 2 dose levels, 1x10 to the 7 and 1x10 to the 8 all combined with CARVac after tumor indications included 8 testicular cancer patients, 4 ovarian cancer patients and 1 patient each for endometrial cancer, fallopian tube cancer, glaucoma and gastric cancer.

The results demonstrated a tolerable safety profile for both the CAR T cells as monotherapy and when combined with CARVac as 8 patients experienced cytokine release syndrome Grade I to II, which was manageable with tocilizumab with no signs of neurotoxicity seen.

So far, 2 dose-limiting toxicities were observed manageable and patients fully recovered. One was [indiscernible] observed in the combination part at dose level 2, the other observed in the monotherapy cohort at dose level 2 was prolonged cytopenia in testicular cancer patient with a recent release on high-dose chemotherapy and autologous patient.

A new cohort with reduced lymphodepletion chemotherapy was subsequently opted to avoid prolonged cytopenia in testicular cancer patients with a history of The maximum tolerated dose has not yet been reached.

The preliminary efficacy data showed encouraging signs of clinical activity with an overall disease control rate of 86% and an overall response rate of 43%, with partial response observed in patients with testicular and ovarian cancer.

Five patients with test secular cancer were treated at 1 to 10 to the 8 CAR T dose levels and showed encouraging responses with an objective response rate of 80% and a disease control rate of 100%. One patient had a complete response, 3 had partial responses and 1 had stable disease.

This sub-analysis includes 1 additional patient with partial response that received a reduced patient regimen. The addition of CARVac supported CAR-T engraftment and mediated physiological expansion plus upgrade regulation of survival pathways in patients receiving the combination.

We also observed deepening of responses over time and continuing long-term persistence of CAR-T in some patients with CAR-T participants lasting beyond 150 days post infusion.

Slide 17 shows the CAR-T engraftment, all 16 patients showed robust CAR T cell engraftment with peak expansion 10 to 17 days after infusion, reaching cell frequencies above 10 to 8, total cell count at the 10 to the 8 dose level.

We observed that incremental improvement of CAR-T cell expansion, either through a higher dose level or by adding the CARVac vaccine translated into clinical activity and risk. Slide 18 provides an overview of the preliminary signs of clinical activity. 14 patients were evaluable for efficacy assessment with at least 1 scan 6 weeks post infusion.

Six patients showed partial responses and an additional 5 patients had stable disease with shrinkage of target lesions as shown in gray diamonds with green outline. One patient had no change from baseline and 2 patients had no signs of clinical activity, both of which were rapidly progressing prior to adoptive set transfer.

This resulted in an objective response rate of 43% and a disease control rate of 86% across all patients. At 12 weeks, 4 of the 6 patients with a partial response showed deepening and durability of responses with 1 patient reaching a complete response 18 weeks after infusion.

All 4 testicular cancer patients in the higher dose levels had disease control and 3 of these patients showed objective responses. In addition, 1 testicular cancer patient showed a partial response after infusion of the lowest CAR-T dose level in combination with CARVac.

At the very bottom of the slide under the gray bar, we wanted to share 1 further test secular cancer patient who has shown a partial response after a reduced lymphodepletion regimen. That patient is not included in the 14 evaluable patients we discussed previously.

In summary, and most encouragingly, all initial partial responses showed deepening at the second assessment and 1 partial response patient transition to a complete response.

The waterfall plot on the left of Slide 19 shows the best response for those 4 testicular and 2 ovarian cancer patients who responded focusing on the testicular cancer patients, you see a tighter plot on the right depicting the duration of the responses.

Besides 1 patient that only received the lower 10 to 7 dose levels without CARVac, all other patients showed a clinical benefit. All achieved responses showed signs of continuing response durability. This includes the patient whose initial partial response deepened to an ongoing complete response 18 weeks after infuse.

Slide 20 shows of 2 testicular cancer patients with tumor regression. Both patients had multiple prior treatments and relapses before receiving BNT211. Patient 1 is a 61-year-old male diagnosed in 2008. He had previously received 6 lines of treatment and shortened response after CAR-T treatment at dose level 2 without CARVac.

The large lung metastasis was completely eliminated over time, and the patient remained tumor-free as of latest scan with a serum tumor marker at normal values 6 months after infusion. Patient 2 is a 56-year-old male testicular cancer patient diagnosed in 2020, who received dose level 1 and was additionally treated with CARVac.

Treatment translated into a robust response, as you can see in those scans with substantial shrinkage of more than 15 metastasis. Following the week 12 scan, the patient had new lesions. As the on treatment biopsy showed positivity for CLDN6, the patient was redose with CAR-T cells on this 197, and we have seen a tumor marker response already.

We are very encouraged by the safety and activity data and another data update from the ongoing Phase I/II trial is expected in the second half of 2022. I'd now like to turn over the call to Jens Holstein, who will cover our financial results..

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 first quarter of 2022, which you can find on Slide 22. The first quarter of 2022 has been an extraordinary one, which also becomes visible by looking at our key financial highlights.

Our total revenues reported for the first quarter of 2022 reached €6.4 billion, reflecting a record figure for the company since its inception. As a consequence of this top line number, we ended the first quarter with an operating result of €4.8 billion and generated earnings per share on a fully diluted basis of €14.24.

In respect of cash, we ended the first quarter of 2022 with €6.2 billion of cash and cash equivalents as well as trade receivables of around €12.7 billion. The trade receivables are mainly derived from our collaboration with Pfizer and many remained outstanding due to the contractual settlement of the gross profit share under the collaboration.

From our outstanding trade receivables as of March 31, 2022, we had already collected €5.2 billion in cash by mid-April 2022, improving our cash and in turn, reducing our trade receivable position subsequent to the end of Q1 2022. Continuing with Slide 23, I want to point out how strong our first quarter in 2022 has been.

As mentioned before, we have recognized approximately €6.4 billion of COVID-19 vaccine revenues during the first quarter of 2022. This has been the result of an increased order volume initially placed in late 2021 following the then emerging Omicron variant. Let me give you some more details on our revenue stream.

As a reminder, on our COVID-19 vaccine collaborations, territories have been allocated between us, Pfizer and Fosun Pharma based on marketing and distribution. Our COVID-19 vaccine revenues included €4.6 billion revenues related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners territories.

These revenues already represent a net figure, meaning that 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.

Our COVID-19 vaccine revenues during the first quarter of 2022 comprised approximately €1.2 billion revenues from direct COVID-19 vaccine sales to customers in our territory, which is significantly driven by the orders that we placed in late 2021 following the then emerging Omicron variant.

Also included in our COVID-19 vaccine revenues during the first quarter of 2022 were €0.6 billion from sales to our collaboration partners. Again, we started the year very strong, which we believe gives us a solid foundation for achieving our previously announced guidance for the 2022 financial year.

We expect the following quarters to be lower than Q1 given the current situation of the pandemic. I'll be moving to our financial results for the first quarter of 2022, as shown on Slide 24. Having explained our revenues on the previous slide, let me move now to the cost of sales.

that reached approximately €1.3 billion in the first quarter of 2022 compared to €0.2 billion for the comparative period in 2021.

The increase in cost of sales resulted mainly from the recognition of costs related to our COVID-19 vaccine revenues in our own territories that include the share of gross profit that we owe to our collaboration partner, Pfizer.

This increase in cost of sales is additionally attributed to expenses arising from inventory write-offs and for production capacities derived from contracts contract manufacturing organizations.

Research and development expenses were approximately €0.3 billion for the first quarter of 2022 compared to around €0.2 billion for the comparative period in 2021.

The increase was mainly due to the recognition of costs related to the production of prelaunch Omicron vaccine products as research and development expenses in the period incurred as well as increase in headcount.

The increase was partly offset by lower research and development expenses related to our COVID-19 vaccine program as compared to the prior year period. General and administrative expenses reached €90.8 million for the first quarter of 2022 compared to €38.9 million for the comparative period in 2021.

The increase in G&A was mainly due to the increased expenses for purchased management consulting and legal services as well as an increase in headcount. Income taxes were accrued in an amount of €1.3 billion tax expenses for the first quarter of 2022 compared to €0.5 billion tax expenses for the comparative period in 2021.

The derived effective income tax rate for the first quarter of 2022 was 26.3% and is expected to be around 28% for the full year. For the first quarter of 2022, net profit reached €3.7 billion compared to €1.1 billion for the comparative period in 2021.

Our diluted earnings per share for the first quarter of 2021 amounted to €14.24 compared to €4.39 for the comparative period in 2021. Moving to Slide 24, that shows that we reiterate our outlook for the 2022 financial year.

We started very strong with Q1 2022 and reiterate our full year guidance though we have to acknowledge the uncertainty derived from the course of the pandemic and the political uncertainties of the recent months.

Considering the unchanged order book of approximately 2.4 billion doses for delivery during the 2022 financial year, we are confirming our estimated COVID-19 vaccine revenues of approximately €13 billion to €17 billion for the full year 2022.

For 2022, we also reiterate our planned expenses and CapEx as well as the estimated annual effective 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 and concluding remarks. Thank you..

Thank you, Jens. Turning to Slide 27 and our priorities for the remainder of the year. We continue to focus on supply of our COVID-19 vaccine and the development of our pipeline of next-generation vaccines.

Earlier this year, we announced a multiyear pandemic preparedness contract with the German government and discussions with other governments are underway. In oncology, we expect our first readout from a randomized Phase II trial in addition to data updates from our ongoing Phase I/II trial of BNT211, our CAR-T cell program for solid tumors.

We continue to prepare for the initiation of multiple registrational trials across our pipeline in the next 12 months, and we'll provide further updates on those plans later in the year.

In infectious disease, we plan to initiate first-in-human clinical trials for 4 additional mRNA vaccine programs in 2022 and in addition to building out our expanding preclinical portfolio.

Additionally, we are accelerating the expansion of our platforms into new therapeutic areas, such as autoimmune disease, regenerative medicine and cardiovascular disease and expect to make lead candidate selections for several programs.

To support our focused execution against these goals, we are investing in our foundation, particularly in building out our digital and AI capabilities as well as our global development team to support further pipeline expansion, which we envision in the coming years.

On Slide 28, our COVID-19 vaccine order book for the year stands at approximately 2.4 billion doses with approximately 750 million doses invoiced by the end of the first quarter.

We expect multiple BNT162b2 data updates throughout the rest of the year, including data for a 3-dose regimen in children ages 6 months to 5 years, which we expect in the coming weeks. We are evaluating a fourth dose in adults ages 6 and older as part of a comprehensive variant adaptive vaccine program.

In addition, we expect to disclose safety and immunogenicity data for our Omicron adaptive and bivalent vaccines in the coming weeks, which will inform our ongoing regulatory discussions. Moving to Slide 29 and our expected pipeline milestones for 2022.

We expect to initiate 7 first-in-human trials this year, including for our mRNA vaccines for shingles, tuberculosis, HSV2 and malaria. In January, we dosed the first patient for our BNT141 RiboMab program, the first program from this exciting new platform.

We anticipate our second RiboMab program, BNT142, which includes the CD3 CLDN18.2 bispecific antibody will enter the clinic in the coming months.

BNT116 our FixVac program for non-small cell lung cancer, which will be evaluated in combination with Libtayo as part of our expanded Regeneron collaboration is also expected to enter the clinic in the second half of the year. We expect data updates from 3 further programs this year, BNT161 and influenza mRNA vaccine partnered with Pfizer.

And in the second half of 2022, we expect to have a data update from BNT122, our iNeST program being evaluated in combination with pembrolizumab as a frontline treatment for melanoma. Finally, we expect further data updates this year for our BNT211 CAR-T cell program which Ozlem highlighted.

Before concluding on Slide 30, I would like to remind investors that we will have our Annual General Meeting on June 1 for which detailed information can be found on our website. and we will host our first virtual Capital Markets Day on Wednesday, June 29.

I would like to thank our shareholders for their continued support, and we'll now open the floor for questions..

[Operator Instructions]. Your first question today comes from the line of Matthew Harrison from Morgan Stanley..

I guess maybe if you could just give us a little bit more detail on your current thinking around what regulatory discussions you need to have in terms of boosters and what the regulatory pathway, especially in the U.S. is going to look like here.

Is your expectation that you can just run a simple bridging study? Or might it be more complicated than that?.

So I think I can take the question and maybe Ozlem can complement. With the regulatory path towards authorization of a variant adaptive vaccine is not clearly defined yet.

We had a number of meetings with regulatory authorities, including FDA and EMA and they propose to see the data on monovalent vaccines as well as bivalent vaccines and would like to make the decision based on the data.

As you might have heard, the FDA is planning a meeting end of June, where they indicated that they would provide a more clearer guidance about the vaccines, vaccines that are preferred for the next season.

A similar statement was made by the EMA and both authorities seem to prefer an authorization of vaccines in the time frame of August, September, October. So that the process is ongoing.

We are generating data for monovalent and different biovalent vaccines, including lower and higher doses and will have the data available for discussion with the authorities. I hope that answers the question.

The next question?.

Your next question comes from the line of Cory Kasimov from JPMorgan..

I wanted to follow up on this general line of thinking, recognizing that there's data from various COVID programs anticipated over the coming weeks and an uncertain regulatory pathways you just discussed.

I'm just curious as to your views on how you see the relative value proposition between an Omicron specific booster compared with a bivalent 1 over both the short and the longer term..

Yes. So what we already know and I refer to published data with regard to antibody titers after Omicron 1 infection. And this data clearly indicated in pre-vaccinated individuals, and we have generated data for individuals who have received our vaccine with 2 vaccinations or 3 vaccinations and we evaluated what is happening of the Omnicon exposure.

And what we see is that Omnicon BA1 exposure result not only an increase in antibody types against the Omnicon variant, but also against all other variants, including the Delta, alpha and the original wild-type variant. So an Omnicon exposure in vaccinated individuals really boost both antibody response.

And this is -- this was meanwhile, we published that in the meantime, other groups showed the same effect.

What is important is that an exposure to an Omicron infection, and we expect this is going to happen also in vaccinated individuals primarily boost memory responses, preestablished memory responses and naive immune responses will likely take additional months until naive B cells are generated.

We do not see a rational advantage combining the moment an Omnicon vaccine and another vaccine. But at the end of the day, data count. So that means they are generating data in different individuals.

And we will compare the antibody neutralization titers not only against the prior Omicron variant, but also the newly emerging the BA4 and BA5 variants as well as former SARS-CoV-2 variants, regardless whether they have there might have an impact or not in the future..

Your next question comes from the line of Christopher Zopf from Goldman Sachs..

Congratulations on the quarter. Following up again on the same topic. Based on the conversation that happened earlier that started to lay out the framework for this decision, can you give us a sense of what data do you think they're looking for to try to make this decision.

You talked a little bit about kind of neutralizing titers against different variants. Is it that simple? Or are they going to be looking for kind of other aspects of safety, of course.

And once these data on Omicron specific vaccine in hand, do you anticipate this may have an impact on other regulatory discussions like in China as well?.

Yes, of course, safety is regarded -- will be evaluated and the safety evaluation happens in a few hundreds of subjects who received the booster vaccine. So we don't expect that this is a larger price will be needed also based on the feedback from the regulatory authorities.

I can't say -- as already stated, we had a number of conversations with the authorities. And every time they asked for the same data sets, they would like to see monovalent data and bivalent data, but they did not refer what kind of vaccine monovalent or bivalent is preferred by them.

I assume that this is a topic for the VERPAC discussion end of June. And I would be -- I don't think that we are going to be surprised by the request of non-expected data set in addition to what we are already generating..

I will go to the next question. Your next question comes from Akash Tewari from Jefferies..

So it seems like you and Moderna have been talking up different approaches for an Omnicom booster. Maderna seems to be talking of bivalent while you and Pfizer have been topping up more of a modified spike for patients who aren't naive.

Can you talk about how antibody titers for both of these approaches may differ, especially at day 28 where Moderna has mentioned there may not be a big difference between wild-type boosters and an Omnicon booster, while you've already shown higher antibodies at 28, at least with your And then given the uncertainty around the regulatory path forward, in a scenario where you would need robust BE data to get onto the market, could there be a scenario where we don't get an Omicron-specific booster in 2022?.

So let me just face the overall situation in which we are regardless now of the sinking of different companies. We have a situation there where with an ongoing Omicron pandemic, so 99.8% or 99.9% of all infections are mediated by Omicron sub variants. We have a situation that currently multiple Omicron sub variants exist with different escape profile.

And so in Europe, we are seeing sub variants like Omnicon 2.9 or 2.12.1. And from Africa and in the East, we are seeing the BA4 and BA5 variants, which appear to have even higher loss of neutralization titers. And any decision of a seasonal vaccine must be in line with the actual variants, which are circulating at the moment.

And we and Moderna and other companies started to evaluate Omicron adaptive vaccine, including monovalent and bivalent vaccine. So that means all companies will generate this data. And we have to match this data, which has been generated with evaluating of neutralization titers against the actual variance.

And based on that, we have to come to conclusions. That's the way to go. I can't say what is now going to happen in the next few weeks, where new variants will emerge. But I am pretty sure that any decisions they make by an authority must reflect what is ongoing with regard to the sub variants that are currently in circulation..

Your next question comes from the line of Daina Graybosch from SVB..

I'm going to ask another one on this, but maybe a slightly different direction. You mentioned that the paper that you published showing memory B cell responses against some conserved epitopes, after Omicron infection, I think there was a similar one published, I think, from some scientists at Rockefeller.

But you looked pretty soon after that breakthrough infection, I think, 40 to 50 days.

And I wonder what gives you confidence that those broader B cells and neutralizing antibodies are going to be as durable as maybe neutralizing antibodies more specific against the variant spikes that have some longer durability, as we know from previous vaccination..

Daina, the durability of antibodies in my opinion, is primarily driven by the initial antibody titer. So that is what is happening in the body fluid compartments, including plasma and in the new surfaces. Then we have a second reaction ongoing, which is the continued memory B cell maturation process.

Directly after infection, we will have the memory B cell response, as we have shown in our paper, is dominated by preestablished memory B cells, but they will be new naive memory B cells joining into the action. But this naive memory B cells will have less mutations and lower affinity antibodies.

And this will require several weeks, up to 3 months, until the maturation is established. And then a second booster might have to really generate high affinity antibodies against novel epitope. That is what immunology taught us and that is what we are going to expect. That means antibody titers will decline.

But on the other side, we will generate novel memory B cells which are better adapted to the new epitopes coming from with the Omicron variant..

Your next question comes from the line of Zhiqiang Shu from Berenberg..

Congrats on the strong quarter. I'd like to ask about the capital allocation. You have €19 billion on the balance sheet as of Q1. How do you think about spending that cash, in particular on the backdrop of the depressed biotech evaluation here thinking about BD and M&A opportunity. A quick one on the CLDN18.2 mRNA program.

Given where your history on that target, how do you see that approach differentiated from antibody approach?.

Thanks very much for the question. Let me start, and then I'll pass on to Ugur. We have reiterated the guidance, as you've seen, so €13 billion to €17 billion is the figure. After the first quarter, we feel very, very good about it.

I mean the €6.4 billion that we have reported in revenues and the profitability supports that we confirm that guidance as stated at our year-end call, the main focus of our investments remain to invest in our research and development activities and going forward.

But as you remember, we also have announced that we will invest €1.5 billion in the share buyback program that we just had kick off very recently and that we also will give our shareholders that have stayed with us for a long time in the past, we gave shareholders €500 million of a dividend payment in the course of this year.

going forward in terms of M&A activities, et cetera, we have, of course, looked and continuously look into additions in terms of transactions that we can make, collaborations, all kinds of things.

That we are intending to proceed as we did in the past, but we can give you a closer guidance on where and when we will invest in how much we got to see how things are evolving. But we feel good about the cash position. You've heard from me earlier that our cash position increased. We collected another €5.2 billion mid of April.

So we're in the ballpark of around about €10 billion or above €10 billion at this point in time. So we feel good about our cash position, and that gives us the opportunity to invest money in the years to come.

Ugur? Ugur, do you want to take over the second question?.

I can take over the second question, which was about our CLDN18.2 RiboMab development.

As you have already pointed out, we have experience with clinical activity of an entire -- of CLDN18.2 directed antibody and using mRNA to encode the entire body and circumvent the production, the need for producing the antibody as a recombinant protein comes with many opportunities, and we want to leverage these opportunities for using our repo map as a single-agent therapy, but also for combining it with other modalities..

We will take one further question. And the last question comes from Ellie Merle from UBS..

This is Sarah on for Ellie.

I guess in terms of BNT211 and sort of moving into later-stage development, what are you looking for? And what's your expectation that would make you confident in moving forward? And then on a larger scale, I guess, where do you see this fitting in, in terms of the other treatment options available and what line of therapy?.

With BNT211, our CAR-T cell therapy directed against CLDN6, we are still in the dose escalation stage. So we have even not reached high dose, we actually wanted to administer, yet we see already encouraging and promising clinical activity in particular, in testicular cancer as well as in ovarian cancer.

So what we want to do is to continue to collect the data and decide based on aggregate data, how to proceed. CAR-T cell therapy would be something which we would like to position in later lines of treatment.

We think that in those indications in which we assess CLDN6 CAR-T cells, namely advanced metastatic testicular cancer, ovarian cancer, endometrial cancer, rare cancers such as sarcoma, there is considerable medical need and how exactly we will position will depend on the aggregate data will produce in dose escalation and dose expansion parts of this initial trial..

I will now hand the call back Sylke for closing remarks..

Thank you for joining us today. We look forward to speaking with you in the future. Thank you, and bye-bye..

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