BioNTech SE Q1 FY2024 Earnings Call

Welcome to BioNTech's First Quarter 2024 Earnings Call. I would like to hand the call over to Dr. Victoria Meissner, Vice President of Strategy and Investor Relations. Please go ahead.

Good morning and good afternoon. Thank you for joining BioNTech's First Quarter 2024 Earnings Call. As a reminder, the slides we will be using on this call and the corresponding press release published this morning can be found in the Investor Relations section of our website. On the next slide, you will see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings with the U.S. Securities and Exchange Commission. Forward-looking statements in this call are subject to significant risks and uncertainties and speak only of the date of this conference call. We undertake no obligation to update or revise any of these statements. On Slide 3, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team: Ugur Sahin, Chief Executive Officer and Co-Founder; Ozlem Tureci, Chief Medical Officer and Co-Founder; Jens Holstein, Chief Financial Officer; and Ryan Richardson, Chief Strategy Officer. With this, I would like to hand over to Ugur.

A warm welcome to all those joining us today. We believe that we are entering a transformational period for BioNTech. We founded BioNTech with the vision to discover and develop scientific breakthroughs that harness the immune system to fight diseases and bring new medicines to patients. In the years following our establishment, we developed various therapeutic platforms, demonstrating the safety and clinical effectiveness of various drug candidates in early clinical trials. The period from now to 2030 is about forecasting this candidate into late-stage development and registrational trials to become a multiproduct company with the first product to be delivered by our late-stage oncology pipeline. We are continuing to execute this vision and our strategic priorities with intense focus. In the first quarter, we progressed our late-stage oncology pipeline on multiple fronts. We dosed the first patient in the pivotal Phase III clinical trial, evaluating our HER2 ADC BNT323 in HR+/HER2-low metastatic breast cancer. At the AACR annual meeting, we presented three-year follow-up data from a clinical trial evaluating our individualized mRNA cancer vaccines, autogene cevumeran in pancreatic cancer. This data showed encouraging relapse survival in certain patients with an immunogenic response to the vaccine, demonstrating the promise of our vaccine platform to induce persistent de novo neoantigen-specific T cell responses that correlate with improvements in survival. We have also taken significant steps for our first launches in oncology. Annemarie Hanekamp, an accomplished leader with a remarkable track record, is joining our team in July to drive and execute our global commercialization strategy. We appointed a General Manager in the U.S., who has commenced building out our commercial operations in the U.S. and we appointed further expertise in our global commercial team. For our COVID-19 vaccine franchise, we initiated preparations to be on track to introduce a new variant-adapted COVID-19 vaccine for the upcoming season. We have received preliminary strain selection recommendations from the World Health Organization and European Medicines Agency and plan to submit for regulatory approval later this month. Today, Ozlem and I will focus on our oncology strategy, while Jens and Ryan will provide updates on our financial and corporate progress. On Slide 6, our oncology portfolio strategy is driven by understanding the key challenges in cancer. Cancer is a genetically diverse and heterogeneous disease driven by the substantial acquisition of mutations. One consequence of this is that many treatments have an initial effect but are not associated with long-term remission or cure. Our aim is to provide solutions across the continuum of cancer disease and establish new treatment paradigms. We believe our cancer vaccine candidates are particularly suited for early intervention, while thoughtfully designed combination treatments are intended for advanced and high-volume tumors. We want to bring our therapies to as many patients as possible, and we want to use the potential power of our platforms alone and in combination. On Slide 8, our therapeutic strategy brings together synergistic mechanisms of action across three key categories. The first are novel immunomodulators, which are designed to engage the immune system, overcome cancer-mediated immunosuppression, and amplify immune responses. Second, targeted therapies, which include CAR T cell therapies and antibody-drug conjugates that can dramatically reduce the tumor burden. The third category is mRNA vaccines, which are the centerpiece of our oncology strategy. Our mRNA cancer vaccines are designed to target multiple cancer antigens in parallel and can be individualized for each patient. BioNTech was built from the very beginning as a technology-agnostic company. We do not limit ourselves to any one technology. We're interested in addressing unmet medical needs with the best possible solutions. Having a diversity of assets in our pipeline, we are positioned to pursue combination approaches that are proprietary and unique. This strategic advantage allows us to evaluate the activity of each individual compound and enables us to determine those patient populations for which monotherapy or the logistic combinations are best suited. The potential for synergy in this combination is significant, enabling us to design treatment regimens that could lead to improved patient outcomes and broaden the scope of therapeutic options. We believe that our strategy has the potential to address fundamental challenges of cancer and drive meaningful improvements in the long-term survival rates for patients. To reiterate, we are entering a transformative period for BioNTech, specifically in the development of our oncology pipeline and the formation of our oncology business, which will continue to evolve over the next few years. In 2024, we are aiming to increase the number of potential pivotal trials across our lead programs to ten or more by year-end. This trial will focus on areas of unmet medical needs, clinical indications in which we may achieve an expedited path to market. And thereafter, the first approval in the initial indication presents a high potential for expanding the market opportunity to additional indications. Starting in 2025 and continuing into the following years, we expect to enter a period rich with pivotal data that, if positive, could support regulatory submissions for marketing authorization across our pipeline. We have begun building a fully integrated oncology organization to support our transition into a global multiproduct company. This process will be accelerated this year as we bring our new Chief Commercial Officer on board. Ultimately, we are building our organization to support multiple oncology launches beginning in 2026. With that, I would like to thank you all for your ongoing support. I will now turn the call over to Ozlem.

Glad to be speaking with everyone today. As Ugur highlighted, we will focus in the next few years on increasing the number of potentially pivotal clinical trials to fuel our transition toward becoming a multiproduct company by 2030. In oncology, we have already started to execute against this goal. This is why you can see that the late-stage part of our pipeline on this slide is enriched and populated with multiple trials that feature our priority assets such as our mRNA vaccine and also our most advanced ADCs and immuno-oncologics, including those which we consider attractive backbone of unique combination treatments. To highlight recent additions to our pipeline, one is the Phase III trial in collaboration with Duality Bio, evaluating BNT323 in patients with hormone receptor-positive and HER2-low metastatic breast cancer that has progressed on hormone therapy and/or cyclin-dependent kinase 4/6 inhibitors. With BNT323, we are also planning to start a confirmatory Phase III trial this year in patients with metastatic endometrial cancer that will complement our ongoing single-arm trial in this indication. In our early-stage pipeline, we have started a Phase I/II trial in collaboration with Genmab evaluating BNT314, a bispecific antibody product candidate with EpCAM-dependent 4-1BB agonistic activity in light of solid tumors. Our aim is to continue to progress our oncology pipeline towards pivotal data readouts and submissions for regulatory approval in the next 18 months. Before highlighting some of the programs and platforms that we consider priority assets to contribute clinical progress, let me say a couple of words about execution. The coming years will be about late-stage clinical trial execution. Enrolling the patients to participate in clinical trials requires coordination across multiple functions within our company and with our partners and collaborators who are an integral part of our global trial execution approach. As we and our partners have increased the number of ongoing late-stage trials, we have also drastically increased the number of patients that participate in trials, generating data for our fully owned and partnered product candidates. Comparing the average quarterly number of patients enrolled across the last few years here on this slide, on a quarterly average, from 2022 through the first quarter of 2024, we have increased the number of patients enrolled by over 400%. On the back of this significant increase in enrollment and ongoing progress in clinical trial execution, we expect our clinical development pipeline to generate the corresponding increase in the number of data sets in the coming years. Our ultimate goal at BioNTech is to bring our database scientific breakthroughs to patients in need. Moving to our priority assets, let me start with BNT327 or PM8002, a bispecific antibody consisting of an anti-VEGF-A component fused to a humanized anti-PD-L1 scaffold being developed in collaboration with our partner, Biotheus. BNT327 combines two validated mechanisms of action. VEGF-A binding inhibits the VEGF-A/VEGF-R axis, blocking tumor angiogenesis, which leads to reduced tumor cell proliferation and survival. VEGF-A inhibition also counters the formation of the immunosuppressive tumor microenvironment, as does the PD-L1 arm of this bispecific antibody by rewarding PD-L1/PD-1 axis-mediated T-cell exhaustion. With the PD-L1 arm also anchoring this antibody to the tumor for efficient and localized scavenging of VEGF-A, this may contribute to mitigate off-tumor on-target side effects. Data from ongoing Phase I/II clinical trials across several indications in over 600 patients executed by our partner Biotheus have shown a favorable safety profile. Our partner Biotheus presented selected examples of this compound's performance in 2023, showing strong single compound activity and high response rates in combination with chemotherapy in triple-negative breast cancer and small cell lung cancer. In first-line TNBC in combination with nab-paclitaxel, there was almost an 80% objective response rate, as shown on this slide. At ASCO, there will be more data disclosures in cervical and ovarian cancer and in non-small cell lung cancer. An investigational new drug application has been accepted by the FDA for further studies in the United States and we plan to start global trials in several indications this year. One area that will see increased development activity in the coming years will be our mRNA cancer vaccine candidates. mRNA cancer vaccines are the centerpiece of our pipeline and are pivotal to our goal of developing breakthroughs for cancer patients. The aim is to develop this technology as a monotherapy in combination with standard of care and in combination with candidates from our proprietary pipeline. Our FixVac vaccines use sets of multiple antigens shared by patients across one tumor type. iNeST, our individualized vaccine program partnered with Genentech, identifies neoantigens derived from cancer mutations that are unique to an individual tumor. While iNeST and FixVac target different types of cancer cell antigens, they are based on the same mRNA and delivery technology, namely our uridine and mRNA Lipoplex platform. Its distinct mechanism of action is that the delivered antigen is presented by professional antigen-presenting cells, and lipid compartments body-wide in close proximity to T cells to be induced, coming with intrinsic adjuvanticity. These features are by design to auto-induce higher magnitude T cell immune responses that we have been detecting in all our clinical trials across tumor types and for various types of targeted cancer antigens, as shown on the right-hand side of this slide. On the next slide, you can see exemplary data from different trials in different treatment settings and tumor types in which we are evaluating our neoantigen-based individualized cancer vaccines, including several years of follow-up. Our mRNA-based neoantigen vaccine has demonstrated the ability to induce de novo neoantigen-specific polyfunctional, polyspecific, and persistent T cell responses at substantial magnitude in high proportions of treated patients, frequently against tumor antigens that were overlooked by the patient's immune system, so-called de novo immune responses. We have shown that our vaccine-induced T cells persist over years and build immunological memory. In two papers quoted on this slide, we have shown that vaccination with neoantigens encoding mRNA is associated with a reduction of recurrences in patients. The favorite setting for developing our individualized vaccines are patients that have minimal residual disease or require adjuvant treatment to reduce the probability of recurrence. Today, we have iNeST and FixVac trials in multiple disease settings and indications with data releases from several of the trials shown on the slide upland. In our FixVac program, we are evaluating four vaccine candidates, each targeting tumor-associated antigens specific to melanoma, HPV16+ head and neck cancer, prostate cancer, and non-small lung cancer, as monotherapy and in several combinations. We shared early data for all FixVac candidates in the past years and plan to present additional data within the next year. Further, we plan to start an additional trial with iNeST in the adjuvant setting with our collaborator Genentech. I would like to highlight three of these programs that are on our priority list: two programs using our individualized cancer vaccine in cancer types that have a low tumor mutational burden and are resistant to immune therapy, namely colorectal cancer and pancreatic cancer, and our non-small cell lung cancer FixVac program. Starting with CRC: The majority of patients with early-stage localized and resectable CRC undergo surgery followed by adjuvant chemotherapy as standard of care in Stage II high risk and Stage III disease. After acumen treatment, we are monitoring for recurrence, with 20% to 35% of patients experiencing a recurrence of their disease. ctDNA is a marker for minimal residual disease and identifies patients with a high risk of such recurrence. We are running a Phase II trial with our individualized vaccine in Stage II high-risk and Stage III resected CRC patients who are ctDNA positive post-surgery. After adjuvant chemotherapy, patients are randomized to either receive autogene cevumeran or an individualized vaccine or observations. We expect the first readout of this trial in the second half of 2025. Secondly, a randomized Phase II clinical trial evaluating our individualized vaccine in combination with the anti-PD-L1 agent, atezolizumab, followed by standard of care chemotherapy in patients with resected pancreatic cancer, the PTAC compared to chemotherapy alone was initiated in collaboration with Genentech in 2023 and is recruiting patients. PDAC is a high medical need tumor expected to become the second leading cause of cancer-related death, up to 85% of patients with localized pancreatic cancer that undergo surgical resection and adjuvant chemotherapy experience a recurrence of disease. This trial was initiated based on data from an investigator-initiated trial that was published last year and updated at AACR a few weeks ago. That Phase I trial showed that with our individualized vaccine combined with atezolizumab and standard of care adjuvant chemotherapy, half of the 16 treated patients developed high-magnitude vaccine-induced immune responses, and these patients had a significantly lower risk of tumor recurrence at 1.5 years of medium follow-up and continued to do so after a three-year follow-up period. Moving to our off-the-shelf tumor-associated antigen-based mRNA cancer vaccine candidate, BNT116. BNT116 is an RNA lipoplex cancer vaccine candidate comprising six mRNAs, each including a tumor-associated antigen: Mage-A3, CLDN6, KK-LC-1, PRAME, MAGE-A4, and MAGE-C1. We have selected these tumor-associated antigens based on an initial approach developed for the design of FixVac vaccines for different tumor types. Based on low or lack of expression in toxicity-relevant organs, expression in a substantial fraction of lung tumors of various histologies, immunogenicity, and tumor biological role, about 85% of NSCLC specimens express at least one of the six selected tumor-associated antigens, and more than 60% expressed at least two. BNT116 is currently being evaluated with our partner Regeneron in two clinical trials covering various non-small cell lung cancer patient populations. One is the Phase I trial investigating BNT116 in adjuvant first-line and second-line treatment settings and various treatment regimens assisted on the left side of the slide. We plan to introduce another unique combination cohort into this multi-cohort Phase I trial. The second trial is a randomized Phase II evaluating BNT116 in combination with cemiplimab in first-line treatment of patients with PD-L1 expressing non-small lung cancer shown on the right side of the slide. At AACR, we presented preliminary results from Cohort 3 of the LuCa-MERIT-1 Phase I trial evaluating BNT116 in combination with docetaxel in patients with advanced unresectable or metastatic non-small lung cancer that progressed on PD-1, PD-L1 inhibitors and platinum-based chemotherapy. Combination treatment with BNT116 and docetaxel was active with an overall response rate of 30%, a disease control rate of 85%, median progression-free survival of 4.4 months. Comparable to other FixVac candidates, BNT116 presents a manageable safety profile alone and in combination. We expect further data from these cohorts in the next 12 months that will inform further development of BNT116 in lung cancer. The ASCO Annual Meeting is right around the corner. At ASCO, we and our partners will present new clinical data for several of our programs, data that is relevant for making informed decisions about the direction of those project developments. Firstly, we and Genmab plan to present data for BNT311 from our Phase II and post-IO non-small cell lung cancer patients. BNT311 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4-1BB costimulatory activation. Second, as already mentioned, monotherapy data from Phase II trials are planned to be presented for BNT327, the bispecific anti-VEGF-A, anti-PD-L1 antibody we are developing in collaboration with Biotheus. Third, we and our partner, MediLink, plan to present first-in-human data for our free targeting ADC. We will also present epidemiologic data, including post-operative ctDNA prevalence and prognostic value from a non-interventional observational study in patients with resected high-risk Stage II, Stage III colorectal cancer that supports and informs the development of our individualized vaccine in this patient population. Lastly, for BNT211, our CAR-T cell product candidate, we plan to initiate a potentially registrational trial in patients with germ cell tumors. At ASCO, we will present real-world evidence of overall survival and treatment patterns of this patient population in the U.S. that will inform the trial design for our Phase II trial. With that, I will now pass the presentation to our CFO, Jens Holstein.

A warm welcome to everyone who has dialed into today's call. Let me begin my section with some key financial figures for Q1 2024. In the first quarter of 2024, we reported total revenues of approximately EUR 188 million driven mostly by commercial revenues from the sales of our COVID-19 vaccine. This revenue figure is consistent with our internal expectations for the period and reflects the seasonality we expect in the endemic environment for our COVID-19 vaccine. Our group revenues will continue to be driven largely by the uptake of our COVID-19 vaccines until oncology revenues are recognized. We expect to recognize approximately 90% of our full-year revenues in the last months of 2024, mostly in Q4. In terms of our operational spending, we are also in line with our internal plans and ended the first quarter with a loss before tax of EUR 332 million. We maintained our strong financial position with EUR 16.9 billion in total cash plus security investments at the end of the quarter. As mentioned by my colleagues before, we started the year making real progress across our oncology pipeline. We dosed the first patient in our second pivotal Phase III trial and are on track to start multiple additional potentially registrational trials this year. Our focus remains on our late-stage clinical trials and investing in our mRNA platform approaches that represent the core capability of BioNTech and differentiate us from others in the industry. We also continue to invest in our leading and profitable COVID-19 vaccine business. Alongside our partner, Pfizer, we are working on variant-adapted COVID-19 vaccines for the upcoming vaccination season. We are also investing in a COVID-19 flu combination vaccine candidate, which we expect to potentially drive additional demand as approved. Bolstered by our strong cash position and stringent cost discipline, we will continue to invest in our pipeline and are well-positioned to achieve future sustainable growth. I'll now be going into a little more detail on our financial results for the first quarter of 2024. As noted earlier, our total revenues reported for the first quarter of 2024 reached EUR 188 million compared with approximately EUR 1.3 billion for the first quarter of 2023. Moving to cost of sales, these amounted to EUR 59.1 million for the first quarter of 2024 compared to EUR 96 million for the comparative prior year period. Research and development expenses reached EUR 508 million for the first quarter of 2024 compared to EUR 334 million for the comparative prior year period. The increase was mainly due to progressing clinical studies for our oncology pipeline and related personnel expenses to manage those. Sales and marketing expenses of EUR 16 million appeared in the first quarter of 2024 compared to EUR 12 million in the comparative prior year period. General and administrative expenses amounted to EUR 117 million for the first quarter of 2024 compared to EUR 112 million for the comparative prior year period. The increase in SG&A was mainly due to increased expenses for IT services as well as an increase in headcount to support the scaling of our business. Income taxes were realized in the amount of EUR 16.7 million for the first quarter of 2024 compared to EUR 205.5 million of tax expenses for the comparative prior year period. The derived effective tax rate for the first quarter of 2024 was approximately 5% applicable on the negative income. For the first quarter of 2024, we reported a net loss of EUR 315 million compared to a net profit of approximately EUR 502 million for the comparative prior year period. Our loss per share for the first quarter of 2024 amounted to EUR 1.31 compared to a diluted profit per share of EUR 2.05 for the comparative prior year period. As indicated earlier this year, 2024 is a year for our company during which we will continue to invest in our long-term growth strategy. We aim to have potentially ten-plus trials running by year-end 2024, which we believe will change the picture of the company going forward. Besides having a strong franchise in infectious diseases, we aim to have multiple oncology products reaching the market by 2026 onwards. Turning to the next slide, I would like to emphasize that we have reiterated the company's financial guidance for the 2024 financial year. As mentioned previously, we expect to recognize approximately 90% of our full-year revenues in the last months of 2024, mostly in Q4. Additionally, we also reiterate our R&D and SG&A guidance from our year-end call with EUR 2.4 billion to EUR 2.6 billion for R&D and EUR 700 million to EUR 800 million for SG&A expenses. Those expenses are expected to gradually increase quarter-by-quarter until year-end. With that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our strategy outlook and concluding remarks.

We are working with Pfizer to be ready to launch our variant-adapted COVID-19 vaccine in the second half of the year upon regulatory approval. Consistent with the WHO's recommendation, we expect that the updated vaccine will encode the JN.1 variant and will be monovalent. As of April 2024, over 90% of SARS-CoV-2 genetic sequences in publicly available databases were derived from the JN. 1 variant. In 2023, we received strain inclusion recommendations from the WHO and other advisory committees in May and June and were granted approval in late August and September. This year, the timelines for strain selection and those anticipated for approval are expected to come earlier. The WHO and EMA have already received strain recommendations and expect additional regulatory updates in mid-May. We expect approval in the EU and FDA could come in late July and August, respectively. If this occurs, it could enable an earlier launch of vaccines relative to last year to support full vaccination campaigns. We are preparing to launch the variant-adapted COVID-19 vaccine in over 80 geographies worldwide. While most regions outside the U.S. will continue to be served by government contracts, we do expect some new private markets in regions like the U.K. to open in 2024. This could enable individuals who may not qualify under existing immunization recommendations to access the updated COVID-19 vaccine should they choose to do so. Turning to the next slide, our aim is to create value for patients and shareholders by delivering sustained long-term growth, and our strategy is to continue to invest in our technology platforms and diverse pipeline. We believe each of the drug classes we are investing in contains product candidates that aim to address major unmet needs and could unlock significant commercial potential. We are entering a catalyst-rich period over the next 12 to 24 months with data updates expected for more and more product candidates across each of these classes. We look forward to disclosing additional pivotal trials and more details on our go-to-market strategy for selected programs in the months ahead. To conclude on the next slide, our aim is to transform medicine through successive waves of innovation. We remain focused on our near-term goal to have ten-plus potentially registrational trials initiated by year-end 2024 and to continue to ramp up our commercial readiness activities. Over the midterm, we aim to enter the commercial stage in oncology by 2026 with our first product candidates while advancing our pipeline of late-stage and novel combination therapies. In the long term, we aim to broaden our portfolio of approved products and transform BioNTech into a diversified multiproduct immunotherapy company that is in a position to redefine medicine. We are truly excited by the potential our technologies and pipeline hold to make a difference for patients around the world. Before opening the floor for questions, I would like to highlight on the next slide, important investor events we will be holding this year. Our Annual General Meeting will take place on May 17, and our inaugural artificial intelligence and machine learning event will take place on October 1. Our main 2024 Innovation Series event is planned for November 14. We will share further details on these events in due course. With that, I would like to open the call for questions.

And your first question comes from Tazeen Ahmad from Bank of America.

For the data that you're going to be presenting at the upcoming ASCO conference as it relates to the Genmab compound, can you just remind us how many patients' worth of data to expect? And once that data is presented, can you talk to us about the next steps in the development plan for that program?

The first question was about the number of patients which we will present for the second-line non-small cell lung cancer trial with BNT311. Did I get that right?

Yes, that's right.

I cannot provide the exact numbers right now, but we expect to have around 100 patients, which represents a significant number of participants.

And also what level of detail should we expect to see?

So you will see safety data, the activity data, which we have until then, and overall response rate data.

Okay. And what is the plan moving forward with this program?

We are in the planning phase with our partner, Genmab, so that we cannot disclose any specifics at this time, but you will hear more about this program sometime later this year.

And your next question comes from Daina Graybosch from Leerink Partners.

I have another one on ASCO. So I wonder if you could talk more about the data we should expect from PM8002 at ASCO. And also, if you could talk about how this molecule compares to the competitor from Akeso Summit, which also is a bispecific of VEGF, but targeting PD-1 rather than your PD-L1. How much read-through positively can we take from the Akeso data to yours and from yours to the Akeso data for the overall approach?

So we have, at the moment, the clinical target running in multiple indications, including indications with single-arm and combination. What we are going to update at ASCO is on cervical cancer, and platinum-resistant ovarian cancer, and non-small cell lung cancer. And you will see response data and safety data in this cohort. Just to remind you, we have presented already response data on the combination in triple-negative breast cancer and small cell lung cancer, which are very encouraging, showing also responses in the PD-L1-negative or cold tumors. We expect to present similar data now for non-small lung cancer. Of course, we do not have direct comparison competitive data with Akeso, but I think the data that we are seeing goes in the same direction, and this bispecific and that means direct targeting of the PD-L1 axis plus VEGF axis appears to be associated with a better response rate as well as a better safety profile compared to anti-VEGF treatment. So we are very excited about using these compounds as a combination approach for chemotherapies and in the upcoming future for ADCs.

And your next question comes from the line of Akash Tewari from Jefferies.

This is more high level. But in the past, I know the team has tried to position BioNTech as an earnings growth story. With that in mind, what is the best estimate for BioNTech returning to consistent profitability? Is this something that should occur once the COVID flu enters the market? Or is this more tied to your oncology pipeline? And then separately, would you look to work with a large cap partner to launch your ADCs and broader oncology pipeline? Or would you look to build that commercial sales force internally?

I'll begin with the second part of your question. Strategic partnerships have historically been essential in oncology and during the COVID-19 pandemic. We will continue to assess partnerships on a case-by-case basis to determine if they can help us speed up the development of specific assets, expand their geographic reach, or assist in achieving profitability sooner, especially in situations where a partner can provide necessary infrastructure. Overall, we now have a strong balance sheet and aim to retain more financial benefits as part of our strategy. Therefore, our partnership decisions will primarily be made for each asset, while we also commit to establishing a commercial presence in oncology within major markets. This will be a priority in the coming years. I'll allow Jens to address the profitability aspect, but I want to state upfront that we believe our pipeline, which is advancing into late-stage studies, presents an opportunity for long-term growth driven by successive product launches. We have identified 2026 as a critical milestone in this strategy, though our plans extend beyond that. Our goal is to achieve 10 oncology approvals by 2030, emphasizing our belief that revenue growth can stem from multiple indication approvals and various products. Thus, our main focus is to embark on a long-term growth trajectory, while profitability remains important; our immediate priority is to establish this growth path.

Thanks, Ryan. I think you made the most important statement already. If you look into the revenue development going forward, of course, we see some potential upside when we have a COVID flu combination in the market. How big that upside could be, we are not 100% clear yet. We haven't given any guidance for '25 and the ongoing years for that combination. We're going to see how it evolves. In terms of our spend, I think we have shown that we control the costs as well as we can as it's sensible. We want to create value in investing in our oncology portfolio. And to lift it, I think Ryan made the statement already. We are looking, of course, to have some partners here and there regionally to lift the value going forward. But we are very optimistic in terms of the growth that we have in front of us as a company.

Yes. And I think what you're hearing from us, Akash, is in the very short term, we do think that the COVID combination vaccine with flu, if successful, the profitability is going to be dependent in part on COVID vaccination rates, and that's one of the near-term drivers that has the potential to bring those rates up.

Your question comes from the line of Jessica Fye from JPMorgan.

Coming back to BNT311 and the ASCO update, which regimen would you focus us on? And what element of the profile do you expect to best showcase the product's efficacy, and related to that, what's the right benchmark to compare that efficacy metric to?

So the regimen we will be presenting will be a combination of BNT311 with pembrolizumab in second-line non-small cell lung cancer and the post-CPI population to which you would then need to compare this regimen.

Maybe I'll just throw in one more. Can you recap a hypothetical list of what the 10 potentially registrational trials running by year-end might be? I imagine you contemplated a few scenarios here, but maybe you could throw out an example or two?

We are working on activating several trials, including the BNT316 trial in collaboration with OncoC4 for CTLA-4 targeting non-small cell lung cancer, which is in Phase III alongside PD-1 and PD-L1 treatments. Additionally, we have a potentially registrational trial in Phase III for HER2-low breast cancer with BNT323 that commenced earlier this year. Our priority asset list also includes trials for autogene cevumeran, the personalized vaccine we are co-developing with Genentech-Roche, such as our colorectal cancer trial anticipated for results around 2026 and an adjuvant pancreatic cancer trial. We are planning to activate trials with BNT327, the PD-L1, VEGF compound, which we mentioned earlier. Among these, one particularly exciting trial is our CLDN6 CAR-T cell trial in testicular cancer, which we hope to have active by the end of this year.

And your next question comes from the line of Yaron Werber from TD Cowen.

This is Brendan on for Yaron. I just wanted to ask for a quick update on the infectious disease pipeline. It seems we are expecting a Phase I update for the shingles vaccine sometime this year. Additionally, could you provide insights on enrollment and estimated timelines for data regarding malaria, HSV, and TB programs, as well as any updates on how you're prioritizing this segment of the pipeline?

Yes, we will provide data updates on the HSV-2, CAR-T on the TB trial and the malaria trial, which created safety and immunogenicity data in a Phase I and are proceeding now into a Phase II setting, and the data will come at various events until the end of this year.

The next question comes from the line of Etzer Darout from BMO Capital Markets.

Just another bigger picture strategy question around oncology. The fact that the early combination approaches rely on external molecules, but just curious about the strategy for moving combinations of internal assets, particularly combinations of immunotherapy and targeted therapy assets, moving those into proof-of-concept studies and when we could start seeing some of those emerge.

Yes. Excellent question. This is actually one of the strengths that we would like to activate. The first type of combination ties with internal assets is CLDN6 CAR-T cell therapy with a vaccine. We recently reported data showing synergy between the two of the combinations, increasing the persistence of T cells. We will see the start at the end of this year, the first combination trials of our ADC compounds with our IO portfolio. In fact, 2025 will be an intense year where we will do multiple combination trials dedicated to the contribution of components' price and safety assessments to bring us into the position to go into the first registrational trial in our context in the second half of 2025.

And your next question comes from the line of Terence Flynn from Morgan Stanley.

For BNT122, it sounds like it was on your list of registrational trials. So just wondering for the data next year from that Phase II CRC trial, what you'd need to show on an efficacy basis to consider filing for accelerated approval? And then again, I noticed you had an ASCO presentation on some epidemiologic data here. Again, just what are you expecting to show there at ASCO? Or what would be the key learnings?

Yes. This study is sufficiently powered Phase II study in a patient population of colorectal cancer patients who are ctDNA positive. Multiple epidemiological studies have shown that this patient population has a very poor prognosis. In fact, PFS in this patient population after surgery is around 12 months; after chemotherapy, it's around 7 months. This is an early metastatic patient population, and the clinical trial compares standard of care, which is adjuvant chemotherapy in this patient population versus standard of care followed by personalized treatment. The clinical care endpoint is disease-free survival. We expect the endpoint analysis for this trial in the second half of 2025. The trial is enrolling as expected at the moment. Of course, everything else will depend on the totality of the data.

Do you want to say a few words about the epidemiological study at ASCO?

Yes, I can do that. So what we will present at ASCO is an epidemiological study. So it's not a treatment study. We conducted this epidemiological study to better understand the prognosis of those patient populations. We have in our ongoing clinical trial with BNT122, in particular, also subpopulations which are ctDNA-positive because that further informs our ongoing clinical trial. In addition, this epidemiological trial is a prescreening trial to identify patients to recruit into our investigational trials. So you will get, in particular, epidemiological data of ctDNA positivity rates in high-risk populations in colorectal cancer and the disease-free survivals which are seen in this subpopulation.

Your next question comes from the line of Ellie Merle from UBS.

Okay, due to no response, I will go to the next question. Your next question comes from the line of Bill Maughan from Canaccord.

So as a technology-agnostic oncology company who has not yet gotten into radiotherapy, do you see the excitement recently in that field as warranted? And if so, could we expect BioNTech to potentially get some stake in radiotherapy combination or technology by partnership or just bringing it internally? It seems like a lot of the deal sizes recently could be in the range that BioNTech could look at?

Yes. So indeed, the value in immunotherapy is reaching maturity. This is one of the aspects that we are following. We are currently not looking for opportunities for in-licensing, but some of the research we are doing internally could go in that direction. We could talk about this at the end of the year when we have validation data.

And your next question comes from the line of Hartaj Singh from Oppenheimer.

I would like to inquire about the slide that shows the average quarterly patient enrollment. In recent years, companies in oncology have faced significant challenges due to the sheer number of ongoing trials in the oncology and immuno-oncology sectors when it comes to patient recruitment. However, there has been a noticeable increase in enrollment from 2022 to 2023 and into the first quarter of 2024. Could you elaborate on the factors contributing to this improvement? Are the trials receiving regulatory approvals, or are more late-stage trials progressing, possibly resulting in a higher patient recruitment rate at the sites? I would appreciate your insights on that. Additionally, how does this improvement affect your perspective on potential readouts? While it's encouraging to see the enrollment growth, how does it influence the timeline for when we might expect the readouts?

Yes. Let me take the first part of the question. In the time line of 2020 to 2022, 2023, we dealt with early clinical trials, which typically recruit a lower number of patients, defining based on those escalations of cohorts, safety assessments, biomarker assessments, and so on. We are now reaching a phase where we are multiple times in Phase II and first clinical trials in Phase III, which naturally allows us to enroll faster and ensure that we get the statistics. This is also the reason why we can now move multiple clinical trials into registration trials by the end of this year. And for all of the registrational trials, we will provide the timeline then we expect to readout. As Ryan alluded, the first readout for our first potential registration trial is in endometrial cancer, which will be next year, in the second half of next year with the opportunity to get authorization by the end of next year. We will have multiple internal readouts to present at ASCO, ESMO, and City this year on the cohorts currently running.

If I may add to that, you have pointed out quite correctly that patient recruitment becomes more and more difficult. We are in the fortunate situation that we have a richness of different assets, and thereby a design space to choose those assets and combination trials, which can give us several hits on our target to become a multiproduct oncology company by 2030. However, it was very clear to us from the very beginning that this also means we must improve our capability to execute these clinical trials. So, we have invested, and this is what this bar chart shows, we have made major efforts to mature our clinical development operations, organization, and also to grow it. We have also invested into models, such as working with partners with our partner companies to enroll into our joint trials and public-private partnerships, for example, the partnership we have with the U.K., in which we are building a cancer vaccine-launch that will mobilize large numbers of clinical sites on a national level. This is basically what these numbers reflect.

And your next question comes from the line of Ellie Merle, UBS.

Just for your HER2 ADC, where you got breakthrough designation in endometrial cancer late last year, and I think you just mentioned you expect to have the pivotal data in the second half of next year. If I heard that correctly, can you tell us a little bit more about the design of this pivotal study and also how you're thinking about the opportunity for this asset in endometrial and where it would fit in the broader landscape there?

The turning part is a single-arm trial in this population. The registration will be based on safety data and response data and durability of response data. This will be combined with a confirmatory trial for which we still are in the planning phase, and we will inform, yes, in around 3 to 4 months about the design of the complementary trial.

Your next question comes from the line of Simon Baker from Redbud Atlantic.

It's on SG&A. Your guidance implies an increase of between EUR 160 million and EUR 260 million this year. I would assume a large part of that is the global commercial footprint build-out. I'm just wondering if you could give us an idea of how that phases over this year and also '24 versus '25? Is most of the spend this year or is most of it in 2025? Some idea of the cadence of that build-out would be great.

You should expect a slight increase in sales and marketing costs and general and administrative costs quarter-by-quarter in 2024. Then in 2025, we anticipate a further increase in these expenses. Typically, hiring for commercialization occurs shortly before the product launch, and the timing of this will influence spending in 2025.

Your next question comes from the line of Yifeng Liu from HSBC.

Just one question on your HER2 ADC in breast cancer. How do you think about the biomarker selection there when you have HER2-low and HER perhaps and whether you think about HER2 ultra-low as well in the design of your pivotal study?

Yes. This is a good question indeed. The question is about HER2-low, 1 plus, 2 plus, or even ultra-low or even negative. We are considering all patient cohorts in our trial design and will make a decision on the patient population to be enrolled and the patient population to be analyzed later on in the upcoming trials and will most likely report about the clinical priority assigned at the end of this year.

And your final question comes from the line of Suzanne for Tuen from VOK.

This is Suzanne from VOK, which relates to business development and M&A. Last year, you were fairly active on the deal-making front. So can you give us an idea of what we expect going forward for this and next year? You have a lot of cash on hand, but also a lot of projects to run and many moving parts on the profitability side. I was wondering if you're continuing to pursue similar deals and assets as previously? Or did your appetite change?

I think our focus this year is more on clinical execution. That said, we will be opportunistic, and we're open to synergistic assets, but I think you can expect the general level of activity in terms of the number of deals to decrease this year.

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