BioNTech SE

NASDAQ:BNTX

Earnings Call Transcript 2023-Q1

[Operator]

Welcome to the BioNTech First Quarter 2023 Update Call.

I would like to hand the call over to Dr. Victoria Meissner, Vice President of Strategy and Investor Relations. Please go ahead.

[Dr. Victoria Meissner]

Good morning and afternoon. My name is Victoria Meissner, and I'm the new Head of Investor Relations at BioNTech. I'm a medical doctor by training and have recently joined BioNTech from Healthcare Investment Banking at Jefferies.

I look forward to working with you on the corporate side. Thank you for joining us today for BioNTech's first quarter 2023 earnings call. As a brief reminder, the slides that accompany this call and the first quarter 2023 press release that was issued this morning can be found in the Investors section of our website.

As outlined on Slide 2, you can see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings made with the U.S. Securities and Exchange Commission. Forward-looking statements on the call are subject to substantial risks and uncertainties, speak only as of called original date, and we undertake no obligation to update or revise any of the statements.

On Slides 3 and 4, you can see detailed safety information regarding our COVID-19 vaccine. On Slide 5, you can find the agenda for today's call.

Today, I'm joined by the following members of BioNTech's management team: our CEO and Co-Founder, Ugur Sahin; Ozlem Tureci, our Chief Medical Officer and Co-Founder; Jens Holstein, our Chief Financial Officer; and Ryan Richardson, our Chief Strategy Officer.

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

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

Thank you, Victoria. Good morning, and good afternoon, and warm welcome to all the call participants. We appreciate your continued support. Today, I will summarize our first quarter 2023 highlights and priorities before I pass the call over to my team to provide further details.

Let me reiterate our strategic goals for 2023 and highlight our first quarter and recent achievements. First, to expand and sustain our leadership in COVID-19 with Pfizer by advancing our next-generation vaccine candidate, developing combination vaccines and advancing key Comirnaty features.

This quarter, we maintained our strong COVID-19 vaccine market position, supported by key label expansions in regions around the world. This month, we published preclinical data in the Journal Cell on our next-generation vaccine component in combination is coming out.

Our second goal is to accelerate our oncology pipeline and initiate multiple potentially registrational products. Our new collaborations with DualityBio and OncoC4 complement our pipeline with multiple mid- to late-stage clinical programs that will help us to achieve this goal in the near term.

Our third and final strategic goal is to initiate and accelerate clinical programs with high unmet medical need in infectious diseases. In the first quarter, we initiated new clinical vaccine programs namely for shingles and tuberculosis. The first quarter was a strong start to 2023. We plan to continue execution against these strategic goals to continue our development into a fully integrated global multiproduct biotechnology company and divesting medical needs worldwide.

Cancer remains one of the key unmet medical needs. Our long-term oncology strategy is to expand the treatment options available for cancer patients and become a multiproduct company in the next year. In order to best serve the needs of tumor patients, we aim to address the full continuum of cancer treatment, being novel party to market for patients with adjuvant and late-stage cancer and combining our platforms and programs to translate our science into survival.

Key elements in our oncology pipeline are mRNA cancer vaccines, cell therapies, next-generation checkpoint immune modulators and antibiotic conjugate. We believe that these classes have the potential to drive improved outcomes for solid tumor patients across multiple lines of treatment and tumor types.

Our most advanced oncology assets are currently in development for a range of solid tumors at all stage of treatment. We believe that this asset has first-in-class or best-in-class potential and may enable us to drive meaningful change in the treatment of many cancers.

How are we planning to achieve this? Our technology-agnostic innovation engine leverages modular technology platforms, both developed internally and accessed via collaboration partnerships, to produce novel product candidates.

In the first quarter, we announced two new collaborations to give us access to assets and platforms that we believe may be important in how solid tumors are treated in the future. One of those which I'm particularly excited about is the new collaboration with Duality Biologics, the Company focused on the discovery and development of next-generation antibody drug conjugates.

In the last few years, advancements in ADC technology has resulted in a potent use for the treatment of solid tumors. We believe that ADCs have the potential to replace highly toxic chemotherapy regimens as the cytotoxic backbone to cancer treatment. ADCs consists of three main components: antibody lincoln payload, each of these components has an impact on ADC's pharmacological and clinical properties.

ADC is a precision medicine, allowing for targeted graft delivery, particularly to tumor cells with high specificity and potent in use with the benefit of reduced off-target events. When the monoclonal antibody binds to the target antigen specifically expressed on the tumor cell, the ADC is internalized, allowing for the release of the cytotoxin, which leads to cell death.

Slide 11. Under the terms of the exclusive worldwide licensing collaboration agreement with DualityBio, excluding Mainland China, Hong Kong region and Macau region, we will gain access to two programs: dB-1303 targeting HER2 and DB-1311.

Driven by Duality Biotech platform and novel cleavable linker and payload technologies, this third-generation ADCs have demonstrated pharmacokinetic properties that may contribute to an increased third-party window compared to other ADC platforms.

ADCs offer a bold combination potential, especially with various IO agents. A Phase 1/2 clinical trial for DB-1303 is ongoing, which we plan to expand into further tumor indications, and we aim to rapidly advance clinical development of this program.

Slide 12. I want to end where I started, our vision. With our new collaboration, we now have 27 programs. We plan to start multiple potentially registrational products in the coming years. Within the next years, we aim to become a multiproduct global biotechnology leader, aiming to contribute and address the world's most pressing health challenges with pioneering disruptive technologies delivered at scale.

With that, I would like to thank you all for your confidence in our success and your continued support. I will now turn the call over to Ozlem.

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

Thank you, Ugur. I'm delighted to speak with everyone today and provide our pipeline update.

Starting on Slide 14. Not only since BioNTech's founding, we have firmly believed in the potential for mRNA cancer vaccines to have a place in the future of cancer treatment. We have built our personalized and offer share platforms and initiated a broad clinical program to evaluate the full utility of our approaches.

Today, we have a broad cancer vaccine development program with four ongoing randomized Phase 2 clinical trials in both the adjuvant and metastatic disease settings. The iNeST program includes clinical studies, the Phase 2 clinical trial with autogene cevumeran, BNT122 monotherapy in adjuvant CRC started in 2020 and is recruiting patients with CTDNA positive resected Stage 2 high-risk and Stage 3 colorectal cancer.

Data from an investigator initiated Phase 1 clinical trials evaluating BNT122, autogene cevumeran, and onetime dosing of atezolizumab in adjuvant pancreatic ductal adenocarcinoma were presented at ASCO last year. A Phase 2 clinical trial in this patient population is planned to start in 2023. A randomized Phase 2 clinical trial evaluating our agent in combination with pembrolizumab in first-line melanoma patients has finished enrollment. Analysis of PFS as primary endpoint will be triggered event-based.

Data from a Phase 1 clinical trial with BNT122 autogene cevumeran, a single agent and in combination with articllezumab in patients with locally advanced disease and metastatic disease across multiple tumor types was presented previously. We are preparing a manuscript summarizing the Phase 1 data for publication.

In our fixed program that is comprised of four different indication-specific product candidates, we have ongoing clinical studies. We have a first-in-human Phase 1/2 clinical trial, evaluating BNT112 monotherapy and in combination with cemiplimab in two cohorts of patients, namely with metastatic castration-resistant prostate cancer and with high-risk localized prostate cancer who are eligible for treatment with androgen deprevation Europe is ongoing.

A randomized Phase 2 clinical trials evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with PD-L1 positive unresectable recurrent or metastatic HPV-16 positive head neck squamous cell carcinoma is ongoing.

A randomized Phase 2 clinical trial evaluating BNT111 in combination with cemiplimab, whereas both agents as monotherapy in patients with refractory/relapsed unresectable Stage 3 or 4 melanoma is ongoing, conducted in collaboration with Regeneron. Data from the first-in-human open-label Phase 1 clinical trial evaluating BNT111 in patients with advanced melanoma have been published and presented.

A Phase 1 clinical trial evaluating BNT116 alone and in combination with cemiplimab in patients with non-small cell lung cancer in various settings is ongoing. For example, patients who have progressed on prior PD-1 inhibitor treatment or are not eligible for chemotherapy and in combination with the docetaxel in patients who have received prior platinum-based chemotherapy.

The second trial is planned to start this year to evaluate the combination of BNT116 and cemiplimab and cemiplimab alone as first-line treatment of patients with non-small cell lung cancer. Based on the data collected from these trials, we plan to continue the clinical trial advancement and expansion of both our mRNA cancer vaccine program.

I'd like to put our first quarter pipeline advancements and additions into the broader context of our clinical stage pipeline, which is depicted on Slide 15. In the first quarter, we added to our pipeline the new assets Ugur already mentioned. The HER2 targeting ADC, DB-1303 developed by our colleagues at DualityBio, which has recently started the Phase 2 portion of the ongoing Phase 1/2 clinical trial.

Also in the first quarter, we added ONC-392 to our pipeline, the PH sensitive anti-CTLA4 antibody developed by our partner, OncoC4. ONC-392 is being tested in two ongoing clinical trials, the first in multiple tumors as monotherapy and in combination with pembrolizumab; and the second trial in platinum-resistant ovarian cancer patients in combination with pembrolizumab. We are excited about accelerating and broadening the clinical development for both of these programs based on the data we've seen in the pre-clinic and clinic.

On Slide 16, I want to briefly highlight the mechanism of action and clinical data of ONC-392. CTLA-4 recycles continuously between the sales service and the endosomes as it does not undergo the some degradation. Interruption of this process is associated with the development of autoimmunity. Autoimmunity and immune-related store events are a major limitation of approved anti-CTLA-4 antibodies, such as ipilimumab that disrupts CTLA-4 recycling by promoting lysosomal degradation of these important immune checkpoint markers.

ONC-392 does not interpret with the recycling it dissociates from the CTLA4 molecule in the endosome and allows normal recycling of both the antibody and the CTLA-4 molecule, and thus is designed for stronger cancer therapeutic effect and less immune-related adverse effects. ONC-392 is being tested in the trial that investigated dose escalation, a single agent and in combination with pembrolizumab. Multiple indications, such as I/O naïve and resistant non-small cell lung cancer and melanoma are being treated with RP2D. Preliminary data shows that ONC-392 is well tolerated with no DLTs, and the RP2D was determined to be 10 mg per kg without MTDs being reached.

Severe immune-related grade-free adverse event rate in the combo dose escalation was 23%, which is considered lower than what was reported for comparable IO/IO combination. The RP2D dose for combination is 6 mg per kg. In summary, ONC-392 dose as monotherapy or in combination was well tolerated, and the safety profile appears to allow higher dosing for a longer duration of treatment as compared to ipilimumab.

Early efficacy data as monotherapy in platinum-resistant ovarian cancer patients and in combination with pembrolizumab in multiple solid tumors were promising. Presentation of the first data from the NSCLC expansion cohort of the Phase 1/2 PRESERVE 001 study is planned at ASCO next month.

Building on this data, we are planning to start a Phase 3 clinical trial in non-small cell lung cancer patients without driver mutations, who have progressed following anti-PD-1. After progressing on an anti-PD-1 treatment, non-small cell lung cancer patients have 8 to 11 months median overall survival and 3 to 4.5 months progression-free survival with a response rate of around 10% when treated with the second-line standard of care docetaxel.

With ONC-392, we hope to offer a promising new second-line treatment option for these patients. The randomized open-label controlled multicenter Phase 3 PPRESERVE 003 study is planned to treat IO resistant non-small cell lung cancer patients in the dose confirmation part we and NC4 plan to assess the efficacy and safety of ONC-392 given at two dose levels in comparison to docetaxel. In the subsequent part of the trial, we intend to assess the safety and efficacy of ONC-392 at the collective dose regimen versus docetaxel.

Patients with Stage 4 non-small cell lung cancer who progressed on prior IO treatment with or without chemotherapy and ECOG status of zero or one can be enrolled. IO/IO therapy is allowed. A total of about 600 patients are planned to be enrolled and randomized 1:1 to receive either on ONC-392 or docetaxel in this two-stage study. The primary endpoint is overall survival with objective response rate, PFS and safety as secondary endpoints. The study is planned to start enrolling patients within the next few weeks. The trial in progress poster will be presented at the 2023 ASCO Annual Meeting.

Moving to our collaboration with our partner, DualityBio, on Slide 18. As part of the collaboration, we will gain access to DualityBio's lead candidate, DB-1303, a HER2 targeting ADC comprised of the trastuzumab biosimilar covalently linked to a proprietary DNA topoisomerase I inhibitor P1003 via [indiscernible] L101. Approved ADCs have shown antitumor activity and clinical benefits and multiple types of cancer. While current generations of anti-HER2 ADCs have an improved overall therapeutic index, more efficacious and safer HER2 ADC, for example, regarding potential lung toxicity, such as the severe life-threatening or fatal interstitial lung disease, including pneumonitis may add further clinical benefit.

The first data for DB-1303 were presented at the EORTC and IACR conference last October and describe the significantly improved therapeutic window of DB-1303 pre-clinically as compared to DS-8201a or TDM-1 analogs to trastuzumab, deruxtecan and trastuzumab emtansine, respectively. In red monkey and human plasma, DB-1303 demonstrated high drug to antibody ratio and outstanding plasma stability.

In HER2-positive and HER2 negative mixed cell cultures, DB-1303 inhibited the proliferation of both cell types, demonstrating its bi-standard effect. Pharmacokinetic and pharmacodynamic analysis of DB-1303 and xenograft mouse models showed targeted delivery of the toxin into tumor tissue. Further in vivo studies in monkeys showed a superior stability of DB-1303 and rapid systemic clearance of the toxin. These pharmacokinetic properties result in maintenance of efficacy and reduction of systemic toxicity in animal models, which are shown on the next slide.

Slide 19, DB-1303 exhibited potent antitumor activity in both HER2-positive and HER2-low tumor models, potentially expanding the benefit population of HER2-targeted therapy. Preclinical studies in monkeys demonstrated an improved safety profile compared to DS-8201 with the highest non-severely toxic dose of 80 mg per kg. Further, DB-1303 showed lower risk of causing lung inflammation with no ILD-like lung toxicity. The pharmacokinetic properties of DB-1303 may contribute to a superior safety profile observed in monkeys.

Slide 20. The program has received Fast Track Designation from the FDA and is currently being evaluated in a Phase 1/2 clinical trial for HER2-positive advanced solid tumors. The study is enrolling pretreated patients with advanced or metastatic HER2-positive or HER2-expressing solid tumors. Data from this study will be presented at ASCO this year.

After determination of the recommended Phase 2 dose, further dose expansion cohorts are planned, including tastuzumab-treated HER2 gastric or the gastric adenocarcinoma, esophageal carcinoma and CRC to over-expressing and HER2-low endometrial carcinoma, hormone receptor positive HER2 low breast cancer as well as HER2-positive breast cancer and non-small cell lung cancer with activating HER2 mutations.

Slide 21 highlights our infectious disease pipeline. In December of last year, we initiated the first clinical trials, investigating an mRNA-based vaccine for malaria prevention. Consistent with our 2023 strategic priorities, we started first in human clinical trials testing new mRNA vaccine candidates in the first quarter of 2023. One is a vaccine against tuberculosis and the other with our partner, Pfizer, a vaccine for shingles.

These programs built on our validated platform of mRNA LNPs that have a backbone optimized design and our new nucleoside modified to address diseases with a significant global need. The World Health Organization estimates that about 25% of the world population is latently infected with mycobacterium tuberculosis, the bacterium responsible for the tuberculosis disease. 10.6 million people developed active tuberculosis in 2021 and a total of 1.6 million people died of tuberculosis worldwide.

There are limited prophylactic treatment options for tuberculosis and cases of multidrug-resistant mycobacterium tuberculosis strains are increasing worldwide. The only licensed tuberculosis vaccine is the mycobacterium bovis derived and attenuated BCG, which was first introduced in the 1920s and is still routinely administered to newborns in most tuberculosis endemic countries.

While BCG provides time protection from severe forms of tuberculosis in childhood, the high number of pulmonary tuberculosis cases that emerge every year illustrates the limited durability and protective efficacy of BCG against tuberculosis disease and transmission in adolescents and adults. Vaccine technology advances are seen as important to ending with tuberculosis epidemic by 2030, which is the United Nations Sustainable Development Goal.

Given the major global unmet medical need for tuberculosis vaccines, we and the Bill and Melinda Gates Foundation are working on multi-antigen mRNA-lipid nanoparticle vaccine candidates against tuberculosis. The target population of a BNT164 program will include gram-negative and positive BCG and vaccinated healthy adults. The clinical program in Germany and South Africa, thereby including a non-endemic and endemic country, will investigate with safety, reactogenicity and tolerability of the BNT164 vaccine candidates.

The Phase 1 program is intended to have select for optimal mRNA vaccine candidate and the dose level for advancement to Phase 2. The vaccine may prevent infection and subsequent transmission, and when applied to a large enough proportion of the target population that constitutes the infectious reservoir, could enable interruption of transmission and that bring us closer to the elimination of tuberculosis. We believe that even a vaccine that is only 50% efficacious would be a critical intervention and a success in contributing to the WHO tuberculosis elimination target by 2030.

Slide 23. Dynamic evolution of COVID-19 strain requires care vaccine adaptations and innovative next-generation vaccines. We are pursuing several next-gen vaccine concepts. One of these is a T-cell string vaccine component aka BNT162b4. As shown on the left-hand side, along the evolution of and particularly pronounced in the omicron sub-lineages, there has been progressive loss of concert by protein neutralizing antibody sites.

In contrast, HLA Class 1 and 2 presented T cell epitopes of the spike protein remained mostly across the virus evolution. This is not surprising. Indeed, a fundamental difference of T cell versus B cell-mediated immunity is that owing to their very nature, T cell epitopes are less likely to be impacted by mutations. And the T cell mediated layer of immunity is more robust against immune aviation.

T-cell response is likely to remain much less impacted than neutralizing antibodies by new variants of concern and may contribute to prevention or limitation of severe COVID-19 manifestation. Based on this rationale, we are developing BNT162b4, an mRNA that encodes variant conserve immunogenic segment of non-spike proteins of SARS-CoV-2, mainly of nuclear captured membrane and OFAB proteins with binding to diverse HLA alleles. For design of this strength, we have built on our platforms and skills developed in the context of designing thematic mutation-based cancer vaccines.

Our BNT162b4 T-cell string vaccine component is designed to enhance T-cell immunity and is intended to be combined with variant adapted. We believe we can improve immunity that is variant independent. Our preclinical data was recently published in cells. In a mouse animal, we demonstrated that mice immunized with BNT162b4, which is Comirnaty with our without BNT162b4, which is the T-cell string on strong polyfunctional and polyepitopic CD4 and CD8 T cell responses to the M and of O 1 AB proteins of SARS-CoV-2, thus broadening the T cell response beyond the spike protein.

Data from Syrian hamsters that were immunized with BNT162b4 alone or in combination with BNT162b2 and then challenged with white type SARS-CoV-2 of the delta variants demonstrate that BNT162b4 alone and in combination protect animals from severe disease and enhances viral clearance. The clinical study investigating this next-generation COVID-19 vaccine component can be date in combination with Comirnaty is ongoing.

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.

[Jens Holstein, Chief Financial Officer]

Thank you, Ozlem, and a warm welcome to everyone who dialed in today's call. I'll start my section with the key highlights for the first quarter of 2023, which you can find on Slide 26.

The first quarter of 2023 started strong and fully to our expectations. The quarter was driven by seasonal and some carryover effects from the previous year. As an example, we generated revenues from sales in countries with late approvals of our BA.4/5 adapted by COVID-19 vaccine. For the rest of the year, we are expecting an increase in vaccine sales towards the Northern Hemisphere winter season in the countries which are our key markets. As a consequence, we expect the second quarter to be the weakest quarter in 2023.

Overall, we reiterate our COVID-19 vaccine revenue guidance of around €5 billion for the full 2023 financial year. I would now like to dive into some key financial figures that underline our successful first quarter. Our total revenues reported for the first quarter of 2023 reached €1.3 billion, mainly related to our share of gross profit from COVID-19 vaccine sales in the collaboration partner territories. These revenues represent a net figure, meaning that we generate a 100% gross margin on those.

As a reminder, under our COVID-19 vaccine collaboration, territories have been allocated between us, Pfizer and Fosun Pharma based on marketing and distribution rights. Please keep in mind that Pfizer's fiscal quarter for subsidiaries outside the United States differs from our financial reporting cycle. Hence, Pfizer's international operations from December 2022 will be reflected in their Q1 2023 earnings, whereas we have included the respective estimate already in our Q4 2022 financial figures.

This creates a deviation between the numbers of our partner Pfizer publishers versus our numbers on a quarterly and a full year basis. With €1.3 billion in revenues, we ended the first quarter with an operating result of €654.4 million and generated earnings per share on a fully diluted basis of €2.05.

With respect to the Company's financial position, we ended the first quarter of 2023 with €12.8 billion, comprising €12.1 billion cash and cash equivalents as well as €0.7 billion security investment with a longer time horizon, which we made as part of our investment strategy.

When looking at our cash burn during the first quarter of 2023, the cash movement was negatively impacted, for example, due to a onetime payment settling our wage tax liability incurred in the context of our 2022 share-based payment settlement significant tax prepayments relating to the full financial year of 2023 as well as amounts spent as part of our share repurchase program.

Subsequent to the end of the quarter, in April 2023, we have received approximately €4 billion in cash from our collaboration partner, Pfizer, settling our gross profit share for the fourth quarter of 2022.

Our M&A activities and recent collaboration license agreements announced in the first quarter did not lead to cash outflows during the quarter. In connection with the planned acquisition of InstaDeep and the upfront payments of the collaboration and license agreements with OncoC4 and Duality Biologics, we expect approximately €0.8 billion to be invested in cash and by exchanging shares in the course of 2023. Please note the final institute purchase price will be determined on closing and the mentioned amount for M&A does not comprise future earnout and milestone payments.

I'll be moving to our financial results for the first quarter of 2023, as shown on Slide 27. Having explained our revenues on the previous slide, let me move to cost of sales that amounted to €0.1 billion in the first quarter of 2023 compared to €1.3 billion for the comparative prior year period. The drop was mainly due to the decrease in COVID-19 vaccine sales.

Research and development expenses reached €334 million for the first quarter of 2023 compared to €285.8 million for the comparative prior year period. The increase was mainly due to higher expenses incurred from progressing the clinical studies for pipeline candidates. The increase was further driven by an increase in wages, benefits and social security expenses resulting from an increase in headcount.

General and administrative expenses amounted to €119.4 million for the first quarter of 2023 compared to €90.8 million for the comparative prior year period. The increase in G&A was mainly due to increased expenses for IT consulting and IT services as well as an increase in wages, benefits and social security expenses, resulting mainly from an increase in headcount.

Income taxes were accrued with an amount of €205.5 million for the first quarter of 2023 compared to €1.3 billion for the comparative prior year period. The derived effective income tax rate for the first quarter of 2023 was approximately 29%, which is expected to decrease over the 2023 financial year to be in line with our guidance.

For the first quarter of 2023, net profit reached €502.2 million compared to €3.7 billion for the comparative prior year period. Our diluted earnings per share for the first quarter of 2023 amounted to €2.05 compared to €14.24 for the comparative prior year period.

Now turning to Slide 28, I would like to emphasize that we are reiterating the Company's outlook for the 2023 financial year. Please note the following number reflects current base case projections and are calculated based on the constant currency rate. As stated before, we reiterate our estimated COVID-19 vesting revenues of around €5 billion for the full 2020 financial year.

Our capital allocation strategy includes a strong investment in M&A transactions to the extent disclosed. They have been, as far as known, reflected in the R&D expenses and will be updated as needed. Overall, we maintain our guidance for client expenses and growth and maintenance CapEx for operating activities as well as the estimated annual effective income tax rate, which we have summarized for you on the slide.

And with that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our strategic outlook for 2023 and concluding remarks. Thank you.

[Ryan Richardson, Chief Strategy Officer]

Thank you, Jens. To wrap up our prepared remarks, I'll provide a brief summary of the commercial outlook for our COVID-19 vaccine franchise before concluding with a few important dates to mark on your calendars.

In 2023, we aim to develop, manufacture and deploy a seasonal adapted Comirnaty vaccine. We expect a recommendation from governmental authorities regarding vaccine strain composition midyear with a potential approval for an adaptive vaccine by the end of the summer. Broad vaccination is planned to start early fall.

In addition, we aim to introduce a single-dose, ready-to-use vial, and will continue to improve key Comirnaty features such as shelf stability. In addition, we plan to advance our next-generation COVID-19 vaccine candidates throughout the year. We expect that COVID demand in 2023 will continue to come from a broad range of regions globally.

Since the beginning of the first quarter, we have shipped COVID-19 vaccine doses to more than 70 countries and regions. Since the start of the year, our deliveries to middle-income and low-income countries have increased. We have also seen a greater contribution from the pediatric segment so far this year.

For the full year 2023, we expect global demand to be driven by existing signed government contracts, which we anticipate will be augmented by the opening of a commercial market in the U.S. in the second half. In the midterm, we see multiple potential growth drivers for our COVID-19 vaccine franchise. These include the potential for volume growth as the seasonal market is established, particularly in high-risk population segments.

In addition, we believe continued innovation from variant adaptive vaccines, next-generation vaccines and possible respiratory combination vaccines have the potential to support future franchise growth. The transition to private markets in certain regions is likely to take several years. We believe the shift to commercial pricing will provide further midterm growth potential.

We and our partner, Pfizer, believe in the value that our COVID-19 vaccines provide both to individuals and health systems, and we will continue to invest to maintain our leadership position in the market.

The next slide summarizes our pipeline news flow for 2023. Some of these points have been covered, so I won't go through them in detail again here. What is clear is that our pipeline of 27 clinical-stage programs is expected to produce several readouts throughout the year across a range of technologies. We expect data updates for our CAR-T cell program, targeting Claudin-6, our anti-CTLA-4 program and our new HER2 antibody neoconjugate at ASCO, in addition to multiple further updates for other programs later in the year.

Before concluding and opening up the floor for questions, I would like to reiterate that we will hold our AGM on May 25 and our next innovation series event on November 7. We'll provide further details in the coming weeks on both events.

With that, I'd like to thank our shareholders for their continued support, and I'll conclude our remarks and open up the floor for questions.

[Operator]

[Operator Instructions] And your first question comes from the line of Tazeen Ahmad from Bank of America. Please go ahead.

[Tazeen Ahmad, Bank of America]

I have one pipeline as it relates to the partnership with Pfizer. On the iNeST program for first-line melanoma, can you give us a sense of when exactly this year that data could be presented, if it's still this year? And what level of data we should expect at the top line? And then I have a follow-up.

[Ryan Richardson, Chief Strategy Officer]

Yes, sure. Thank you, Tazeen. I'll start and maybe Ugur, you want to add. So, we've retained our guidance for an update in the first-line melanoma setting for this year. And we've also -- we've stated previously, and it's still the case, that our expectation is that the update would speak to both ORR and also PFS.

Ugur, anything you'd like to add?

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

No, that's it. Thank you.

[Tazeen Ahmad, Bank of America]

Okay. And then as it relates to HER2 with your ADC program, so this is competitive space, there's multiple candidates that are in development. Can you just talk to us about how you think your program could be differentiated and how you're thinking about the general competitive landscape and what indications could that serve?

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

Yes, maybe I can take this question. So the generation of ADCs, particularly HER2 provided a massive improvement on existing ADC compounds. We believe that there is still room for improvement, and we also believe that there is room for multiple lines of development, including, for example, to oncological tumors like ovarian cancer, endometrial cancer, HER2-positive non-small cell lung cancer, but even in the breast cancer space, with a compound that comes with a differentiated safety profile. That could add additional safety features and tolerability features.

I would like to mention that we will have a poster at ASCO, which would provide data generated in a larger breast cancer cohort. And that -- and this data could be informative about how this product could be positioned.

[Operator]

We will now go to our next question. And the next question comes from the line of Daina Graybosch, SVB Securities. Please go ahead.

[Daina Graybosch, Securities]

I have -- I'll take two questions, too. The first one, I wonder if you could talk about the payload in the immunity -- sorry, in the DualityBio programs, and whether you think that this payload will be as synergistic with IO as some of the other payloads that we've seen late-stage clinical trials? And how -- whether its synergy is great or less great, how that will impact your development in combination with your other programs? And then I have a follow-up.

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

Yes, Daina, thank you for the excellent question. Actually, you bring up a key point by we are interested in these ADCs. So, the payload is based on topoisomerase inhibitor. The linker technology is differentiated, providing a more stable linker with even more reduced release of the spontaneous release of the toxin. And yes, the key aspects of bringing in this new compound class is that we believe that these new compounds would be highly synergistic with our IO pipeline, including the next-generation immune modulators and bispecific antibodies as well as our personalized vaccines and FixVac applications.

[Daina Graybosch, Securities]

Great. And then my second question is on the flu vaccine. And I wonder how much degree of freedom there was and is in designing an mRNA-based flu vaccine? And essentially, I'm trying to get at, how similar or different should we expect Pfizer BioNTech vaccine from the Moderna vaccine in its outcome?

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

So, there is always flexibility. If you use this mRNA technology, there's a lot of flexibility in having a vaccine with a differentiated profile. As you know, there are challenges in the field of influenza vaccines, particularly if you address the question of influenza A versus B immune responses. Therefore, I believe that the design of these vaccines could provide additional features that can overcome limitations in the field.

[Operator]

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

[Unidentified Analyst]

This is Ivy on for Akash. We have two actually. First is for COVID. So for your new government orders, I guess, how many doses have been delivered so far? Because the tracker we use to suggest there's around 900 million that has been delivered, but now it's only showing around 700 million BioNTech Pfizer doses delivered, with around like 200 million unknown categories. So I guess, any clarification you can give you will be super helpful. Then I have a follow-up question on your IMS program.

[Jens Holstein, Chief Financial Officer]

Yes. Yes, thanks for the question. I mean, as you know, we are currently in discussions with the EU regarding the renegotiation of the contract. And given that we're in the middle of these discussions, we don't want to give any details on this. We don't want to put any burden on those discussions. So please bear with us. We expect that we have some more clarity on the discussions in the course of Q2. That's our expectation, and then we're happy to share the results on those negotiations with you, of course.

[Unidentified Analyst]

Got it. So my second question is for BNT122. So melanoma data readout this year, I guess you just reiterate that this will be limited to PFS or. Is there any specific reason on why there won't be any OS data? Does that imply a potential longer duration of result?

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

I can take this question. The maturation of the data is -- will most likely not allow to generate OS readout.

[Operator]

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

[Chris Shibutani, Goldman Sachs]

Some clarifying questions in terms of how we should think about your results and financials through the year, if I could. The reiteration of the €5 billion of guidance, can you tell us what does that take into account embedded in your base case assumption here, particularly as I recognize that you have the EC contract negotiations are going through? You did mention the second quarter has been a delight, but then the deliveries, again, in the assumption for the €5 billion through the balance of the year.

Similarly to the financials on the R&D-related expense, you have the outlining of the full year level in the first quarter. It was quite a bit less than we had been expecting and I believe consensus as well. Help us with the sort of the cadence and the shape of spending through the year. And then I have one other follow-up.

[Jens Holstein, Chief Financial Officer]

Yes, Chris, happy to take that question, and Ryan will chime in. Maybe starting with the top line guidance, we reiterated the guidance, as I stated in my speech, before we had a good start in Q1. We believe, Q2, and that's not a surprise to you, will be weaker. I mean it's not really the season for vaccinations as we see it for flu. We assume that the development in terms of how people will get vaccinated is comparable to some extent to what we see in flu. So specifically looking at the Northern Hemisphere, so our expectations for Q3 and Q4 is that these will be the two quarters of relevance for us for the full year.

We have, of course, seen already before we went out with the guidance that the discussions with the EU will be discussions where we might have to face, and we stated that when we went out with the guidance that we might have to face some reduction in the total volume for '23 versus what has been negotiated before that we might have some other implications in some other countries potentially as well, and we try to reflect this accordingly.

I would like to reiterate that if you compare the Pfizer guidance of $13.5 billion, if you take that, I think they're also reflected those discussions in the bushes ongoing. And if you translate that, taking into account the currency implication, taking into account that Pfizer reflects their December revenue figure of 2022 in their Q1 figure, and December 2022 has been a very strong month, we -- whereas we have to reflect this month in our full year figures for 2022, so we have from January to December, our revenue figures were at Pfizer for the international part is just looking at November to November.

So, these things caused some differences, quite significant differences in our estimation, if you compare the December 2022 versus our expectation for December 2023. So, there is a big impact coming from this. And if you then take this into account, we feel that the €5 billion that we have reiterated today is something that we can live with. It could be that -- and that has been our assumption that there might be a new variant that we will adapt the existing vaccine that we produce. That's our assumption to reach the €5 billion. And we're -- our assumption in that respect remains valid at this point in time. I hope that helps you.

[Ryan Richardson, Chief Strategy Officer]

And maybe -- I would just add, and maybe you can come back as well to the R&D point.

[Jens Holstein, Chief Financial Officer]

Yes, I'll come back to the R&D just to add.

[Ryan Richardson, Chief Strategy Officer]

Two points to that. So first is actually the volumes, while we're not disclosing volumes in the first quarter, we were shipping to quite a broad range of countries in the first quarter, over 70 countries we mentioned. There's still some carryover there to pandemic contracts. And so, as I mentioned in the prepared remarks, we did see some significant volumes in particular to low and middle income countries in the first quarter.

[Jens Holstein, Chief Financial Officer]

Yes. And then maybe to add on the R&D costs, Chris, so the first quarter has been relatively light if you see the EUR4 billion that we have booked for if you put that into relation of the €2.4 billion to €2.6 billion of our guidance. But this is, to a great extent, some sort of phasing application to a great extent, also coming from our various programs that we have together with our collaboration partner, Pfizer.

So, I wouldn't read too much into this. I would -- we reiterated that guidance. Please also take into account that we have reflected under already in there and to a great extent, Duality, spending for our clinical studies here. So, we feel comfortable with the €2.4 billion to €2.6 billion in the course of the next quarters.

[Chris Shibutani, Goldman Sachs]

And then to follow on, Pfizer during their meeting in December outlined their vision for what the vaccines for COVID could look like usage, particularly in the U.S. out for the next three or four years. There was a factor in there in terms of potential for combination with flu. Can you talk to what the BioNTech house view is? Were you involved with these projections, if there's any fundamental differences in your point of view where might they lie?

[Ryan Richardson, Chief Strategy Officer]

Yes, thanks for the question. So yes, we're very involved with Pfizer on an operational level and also on the commercial planning level globally as a co-commercialization partner. I think it's fair to say that Pfizer has taken the driver's seat in the U.S. commercial sphere. We've been very involved in Europe and also in other geographies. I think how we look at this is that it's a little too early to be precise and prescribe a factor to the contribution from combinations at this point.

I think we need to see more data. I think what we outlined today is that we do see combinations, respiratory combination specifically as a potential, one of multiple potential growth drivers over the mid- to longer term for the franchise. So that is something that we're looking very closely at with our partner, multiple angles there. And I think Pfizer brings a lot to the table there, but so do we in terms of thinking about how combinations could be best deployed to meet patient need.

[Chris Shibutani, Goldman Sachs]

Great. Thanks. We'll look for the data as it progresses. Thank you.

[Operator]

We will now go to our next question. And your next question comes from the line of Yaron Werber from Cowen. Please go ahead. As there is no response, I will go to the next question, and your next question comes from the line of Karen Flynn, Morgan Stanley. Please go ahead.

[Karen Flynn, Morgan Stanley]

Just had a follow-up on the iNeST vaccine program. I was wondering if you can just discuss high level about how you're thinking about likelihood of success in the adjuvant versus the metastatic setting. I think Merck and Moderna have focused more on the adjuvant setting, but obviously, you're taking a more broader approach. So just wondering, if you could elaborate there?

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

Yes, I can take this question. The question is a very important one. With regard for the development, we have an early adjuvant study in melanoma, and we have initiated two additional adjuvant stage trials, one in triple-negative breast cancer, for which we do not yet have reports; and the second one in pancreatic cancer, which we have reported at ASCO last year and where we are expecting a publication in the next few weeks.

And in the adjuvant setting, the clear understanding is that we have as compared to the metastatic setting, a higher immunogenicity rate even though using the same vaccine platform. And in the melanoma and now previously reported cancer study, we have shown that immune responses are correlated, this prevention of relapses or with a reduced relapse rate in this patient population.

We have also reported the metastatic study, Phase 1 study, which yielded also immunogenicity, but to a much weaker extent than the actual setting. And based on this, we can clearly say that at least in the setting, how the vaccines are used so far, we see an improved activity in the action stage.

There are other reasons why adjuvant-stage cancers could be more eligible. This is, first of all, the lack of heavily established tumor micro environment, the lower tumor load and most importantly in the adjuvant setting, there is a window of opportunity, so the tumors do not progress in the first six to -- or in the first three months, giving the opportunity to build an immune response, which can then deal with the tumor.

So, in the totality, we believe that the adjuvant stage is the type of diseases to go. We have, as you know, randomized clinical trial in colorectal cancers running since 2019. We expect here readout data from the randomized colorectal cancer trial in 2024, yes. And we are planning a Phase 2 study based -- randomized Phase 2 study in pancreatic cancer based on the data that we have observed.

[Operator]

We will now go to our next question. And your next question comes from the line of Yaron Werber, Cowen. Please go ahead.

[Yaron Werber, Cowen]

I got a quick question on Pfizer and your flu vaccine, 161. The 25,000 patients -- I'm sorry, U.S. healthy adult study is ongoing. Any sense as to when you think we might be able to see data this year? Is it -- are you thinking sort of in the fall? And is that sufficient to follow? Do you need to run an additional study potentially in the rest of the world or even in the Southern Hemisphere? And then secondly, my understanding that's the quadrant modified RNA vaccine. Any update on the self-amplifying mRNA vaccine for flu as well?

[Ryan Richardson, Chief Strategy Officer]

Yes, Yaron, I'll start and, Ugur, you may want to add to this. But I think it's -- just to start off, it's important to reiterate that we licensed that program in 2018 to Pfizer. So they're really in the driver's seat in terms of development. We do have rights to royalties and milestones upon success. And so of course, we're tracking that with them and working with them broader program. But I think Pfizer has guided to an update this year. I don't think they've specified and that we don't want to contradict what they put out. So I'll leave it at that. And the same goes, Yaron, for the self-amplifying program, both are -- fall under our collaboration agreement with Pfizer.

[Yaron Werber, Cowen]

So Ryan, maybe just a follow-up, when for the flu-COVID combo, can you give us any sense at all as to whether your royalty is going to be sort of a blended between your low teens, let's say, for flu and you're 50-50 for COVID?

[Ryan Richardson, Chief Strategy Officer]

Yes, it's a great question. And I think blended is the right way to think about it. We haven't disclosed with Pfizer the specific economics, but I think it's fair to assume it would be a blend. As you know, we have a 50% gross profit share on the COVID-19 vaccine, and we do have a royalty on flu. And so, there are still ongoing discussions about that, but I think we'll leave that for now until we can present some data and discuss next steps for the program.

[Operator]

We will now go to our next question. And your next question comes from the line of Jessica Fye from JPMorgan. Please go ahead.

[Unidentified Analyst]

This is Nasan on for Jessica Fye. I think I want to ask about the FixVac program and the progress there and when we might get to see initial data on that program. And then whether like in light of the comment on metastatic versus adjuvant setting, how you're thinking about the development for FixVac?

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

Maybe I'll take the second question on, Ryan, if you could take the first question would be great. Yes. So for FixVac, we have generated data in the metastatic setting in patients with melanoma, particularly with a high proportion of patients who did process under existing PD-1 therapy and have seen in objective responses and high rate of immunogenicity objective responses in combination with anti-PD1 in the range of 35% to 40% with vaccine alone in the range of 20%.

The key advantage of FixVac as compared to the customized new adjuvant vaccine is the availability of the vaccine directly after patient inclusion. So that means we do not have this four to six weeks of waiting time until patients can be dosed. Therefore, in principle, FixVac could be an option for patients with advanced metastatic disease. But again, here, it's a question of the combination compound. And this is something that is now in the focus of our upcoming studies evaluating the use of this vaccine in combination with our checkpoint immune model later, for example, the bispecific BNT312 and BNT311 molecules, but as well as our RiboCytokine molecules, the modified IL-2 as well as the IL-2 approach.

[Ryan Richardson, Chief Strategy Officer]

Yes. And in terms of the time lines, we haven't guided any FixVac updates this year. So I would say that 2024 is the most likely. And as you know, we have multiple trials ongoing, multiple trials, so recruiting in NSCLC in refractory melanoma, head neck carcinoma in a few, likely 2024.

[Operator]

We will now go to our next question. And your next question comes from the line of Bill Maughan from Canaccord.

[Bill Maughan, Canaccord]

So, I have two on the broader strategy. So first of all, some of the more recent BD, the partnerships our focused look more on late-stage clinical programs and less on massive paradigm shifting earlier stage programs. So, is there an internal push to reach profitability on some certain time line on the non-COVID portfolio? And then second related question is, are there any other technology platforms that you want to get into that you don't have that technology yet?

[Ryan Richardson, Chief Strategy Officer]

Yes, thank you. So maybe I'll take the first one and then, Ugur, if you want to speak to the technology platforms piece. In terms of the rationale for the recent deals, I think what we have been is clear about our intention to go commercial in the oncology portfolio by 2026 onwards. And so we have multiple internal programs that if successful in late-stage trials could give us opportunities around that time period to bring products to market.

And so what you've seen us do with these BD deals is basically add depth, further depth to that sort of wave one of oncology programs that have potential is successful to get to market around that same time frame.

In addition, we've gone for programs that can serve as backbones. So we've really tried to maximize synergy rather than solving for profitability near term, mid- to long-term synergy with our own pipeline. And so, you see that with the anti-CTLA-4 molecule. You see that also with the HER2 ADC with ADC modalities in general. Again, programs and technologies that we think could combine very well with our existing pipeline.

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

Yes. Thank you, Ryan. With regard to technologies, no, we are not looking to any disruptive technology. We have a number of disruptive technologies in-house. But what we are clearly doing is we are evaluating technology modules and that could close gaps in our technology platforms or further augment the activity of our technology platforms.

[Operator]

We will now go to our next question. And your next question comes from the line of Zhiqiang Shu from Berenberg. Please go ahead.

[Zhiqiang Shu, Berenberg]

I have two. First, I wanted to ask about the FixVac, BNT116. I think you mentioned you're going to start a Phase 2 program in first-line lung cancer. I wonder if you can comment on any signals from Phase 1 that gives you the confidence to start a Phase 2.

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

Short answer, no, we do not have any updates so far from the running clinical type that is expected end of the season.

[Zhiqiang Shu, Berenberg]

Got it. And then a quick follow-up on the -- your ADC deal. Can you talk about the, I guess, the comparison in top one payload versus microtubule inhibitors payload in terms of the combination with IO differences and severities there?

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

Yes. I think the most important aspect is for getting ADC technologies that we believe that in the next six, seven, eight years, this ADC technologies will more or less complete the -- completely replace chemotherapy. So that means any type of combination therapy, which requires chemotherapy backbone might end up in an ADC approach.

With regard to the currently evaluated compounds and TOP2 inhibitors come with a profile allowing sustainable and also long-term application and we have also seen now in several studies that they are ideally suited as backbone for combinations with IO compounds.

We do not exclude that we could be -- we might be also interested in microtubule inhibitors, but several of the microtubular inhibitors have been in the past, at least in the Shamatha project setting associated with PolyNovo [indiscernible] [pages] and we believe that this new compound class should give the opportunity to develop treatments which do not come with dose-limiting toxicity with regard to repeated application.

[Operator]

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