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spk25: Welcome to BioNTech's First Quarter 2024 Earnings Call. I would like to hand the call over to Dr. Victoria Meisner, Vice President of Strategy and Investor Relations. Please go ahead.
spk29: Thank you. 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 will be issued 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 as of the date of this conference call. We undertake no obligation to update or revise any of these statements. On slide three, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team. Ugr Sahin, Chief Executive Officer and Co-Founder, Özlem Türeci, 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 Ugr.
spk02: Thank you, Victoria. A warm welcome to all those joining us today. We believe that we are entering a transformational period for BioNTech. We have 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, demonstrate the safety and clinical effectiveness of various drug candidates in early clinical trials. The period from now to 2030 is about progressing this candidate into late-stage development and registrational trials to become a multi-product 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 progress our late-stage oncology pipeline on multiple fronts. We dosed the first patient in the pre-votal phase 3 clinical trial, evaluating our HER2-ADC BNT3-2-3 in HR-positive HER2-low metastatic breast cancer. At the AACR annual meeting, we presented three-year follow-up data from a clinical trial evaluating our endodermic cancer vaccine, autogen-seme-vulmeran in pancreatic cancer. This data showed encouraging relatively survival in certain patients with immunogenic response to the vaccine, demonstrating the promise of our vaccine platform to induce persisting de novo neuroantigen-specific T-cell responses that correlate with improvements in survival. We have also taken significant steps for our first launches in oncology. Annemarie Harnekamp, 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, Özlem and I will focus on our oncology strategy while Jens and Ryan will provide updates on our financial and corporate progress. Our oncology portfolio strategy is driven by understanding the key challenges in cancer. Cancer is genetically diverse and heterogeneous disease driven by the sequential 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. Slide 8. Our therapeutic strategy brings together synergistic mechanisms of action across three key categories. The first are novel immune modulators, or IO, 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 BRCA nucleates, that can dramatically reduce the tumor burden. The third category are mRNA vaccines, which are the centerpiece of our oncology strategies. 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 are 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 synergistic 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 to drive meaningful improvements in the long-term survival rates for patients. Slide nine. 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 10 or more by year end. These trials will focus on areas of unmet medical needs, clinical indications in which we may achieve an expeditious path to market, and there, after the first approval in the initial indication, there's 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 multi-product company. This process will be accelerated this year as we bring our new chief commercial office 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 Özlem.
spk19: Thank you, Ugur. 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 towards becoming a multi-product 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 vaccines, and also our most advanced ADCs and IOs, including those which we consider as attractive backbones of unique combination treatments. To highlight recent additions to our pipeline, one is a phase three trial in collaboration with Duality Bio, evaluating BNT323 in patients with hormone receptor positive and her to low metastatic breast cancer that have progressed on hormone therapy and or cyclin-dependent kinase for six blockers. With BNT3-to-3, we are also planning to start a confirmatory phase three 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 GENMAP, evaluating BNT314, a bispecific antibody product candidate was outcome-dependent for 1Bb agonistic activity in multiple solid tumors. Our aim is to continue to progress our oncology pipeline towards pivotal data readouts and submissions for regulatory approvals in the next 18 months. Before highlighting some of the programs, and platforms that we consider priority assets to contribute to clinical progress, let me say a couple of words to execution. The coming years will be about late-stage clinical trial execution. Enrolling the patients to participate in clinical trials requires deep coordination across multiple functions within our company and with our partners and collaborators who are 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 quarterly average in 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 thus 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 data-based 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-VGFA SC silence IgG fused to a humanized anti-PD-L1 BHH binder being developed in collaboration with our partner, Biofears. BNT327 combines two validated mechanisms of action. VGFA binding inhibits the VGFA-BGFR axis, blocks tumor angiogenesis, which leads to reduced tumor cell proliferation and survival. VGFA inhibition also counteracts formation of the immune-suppressive tumor microenvironment, as does the PD-L1 arm of this specific antibody by reverting PD-L1-PD1 axis-mediated T-cell exhaustion. The PD-L1 arm also anchors this antibody to the tumor bed for efficient and localized scavenging of VGFA, which may contribute to mitigate of tumor on target side effects. Data from ongoing Phase I-II clinical trials across several indications in over 600 patients executed by our partner, BioHeals, have shown a favorable safety profile. Our partner Biofears 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 NAP-paclitaxel, almost 80% objective response rate as shown on this slide. At ESCO now, there will be more data disclosures in cervical, in 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 a centerpiece of our pipeline and are pivotal to our goal of developing breakthroughs for cancer patients. The aim is to develop this technology as monotherapy in combination with standard of care and in combination with candidates from our proprietary pipelines. Our 6VAC 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's tumor. While INEST and 6VAC target different types of cancer cell antigens, they are based on the same mRNA and delivery technology, namely our Uridin mRNA Lipopex platform. Its distinct mechanism of action is that the delivered antigen is presented by professional antigen-presenting cells in lymphoid compartments body-wide in close proximity to T cells to be induced, and that it comes with intrinsic adjuvanticity. These features, by design, promote the induction of high-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 set 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 magnitudes 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. And the two papers quoted on this slide, we have shown that vaccination with neoantigen encoding mRNA is associated with 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 recovery. Today, we have iNest and FIXVAC trials in multiple disease settings and indications, and data releases from several of the trials shown on this slide are planned. In our FIXVAC program, we are evaluating four vaccine candidates, which each target tumor-associated antigens specific to melanoma, HPV16-positive head and neck cancer, prostate cancer, and non-small lung cancer, as monotherapy and in several combinations. We shared early data for all fixer candidates in the past years and plan to present additional data this and 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 and cancer types that have a low tumor mutational burden and are resistant to immune therapy, namely colorectal cancer and PDAC, and our NSCLC FixVac program. Starting with CRC, with colorectal cancer. The majority of patients with early-stage localized and resectable CRC undergo surgery, followed by adjuvant chemotherapy. of care in stage 2 high risk and stage 3 disease after adjuvant treatment is watchful waiting. 20 to 35% of patients experience recurrences of their disease. CTDNA is a marker for minimal residual disease and identifies patients with high risk of such recurrence. We are running a phase 2 trial. with our individualized vaccine in stage 2 high risk and stage 3 rejected CRC patients that are CTDNA positive post-surgery. After adjuvant chemotherapy, patients are randomized to either receive autogen, sevumaran, or individualized vaccine, or observation. We expect the first readout of this trial in the second half of 2025. Secondly, a randomized phase two clinical trial evaluating our individualized vaccine in combination with the anti-PD-L1 agent, atesolizumab, followed by standard of care chemotherapy in patients with resected pancreatic cancer, PDAC, compared to chemotherapy alone, was started in collaboration with Genentech in 2023 and is recruiting patients. PDAC is a high medical need tumor expected to become the second leading cause in cancer-related death. Up to 85% of patients with localized pancreatic cancer that undergo surgical resection and adjuvant chemotherapy do experience recurrence of disease. This trial was initiated based on data from an investigator-initiated trial that were published last year and updated at AACR a few weeks ago. That phase one trial showed that with our individualized vaccine combined with adesolizumab and standard of care adjuvant chemotherapy, half of the 16 treated patients develop high magnitude vaccine-induced immune responses and that these patients have a much lower risk of tumor recurrence at 1.5 years of median follow-up and continue 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-like complex cancer vaccine candidate comprising six mRNAs, each encoding a tumor-associated antigen, mageA3, Claudine 6, KKLC1, Crane, mageA4, mageC1. We have selected these tumor-associated antigens by an in silico approach developed for design of six vaccines for different tumor types and 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 And SCLC specimens express at least one of the six selected tumor-associated antigens, and more than 60% express at least two of them. BNT116 is currently being evaluated with our partner Regeneron in two clinical trials that cover various non-small cell lung cancer patient populations. One is a phase one trial investigating BNT116 in adjuvant first-line and second-line plus settings, and various treatment regimens listed on the left side of this slide. We plan to introduce novel unique combination cohorts into this multi-cohort Phase I trial. The second trial is a randomized Phase II evaluating BNG1-16 in combination with Simiprimab in first-line treatment of patients with PD-L1-high expressing non-small cell lung cancer shown on the right side of the slide. At AACR, we presented preliminary results from cohort three of the LukaMerit phase one trial, evaluating BNT116 in combination with docetaxel in patients with advanced, unresectable, or metastatic non-small cell lung cancer that progressed on PD-1, PD-L1 inhibitor and platinum-based chemotherapy. Combination treatment with BNT116 and docetaxel was active, with an overall response rate of 30 percent, a disease control rate of 85 percent, medium progression-free survival of 4.4 months. Comparable to other six FAC candidates, BNT116 presents a manageable safety profile alone and in combination. We expect further data from these cohorts in the next 12 months, and that will inform further development of PNG 116 in Lancaster. The ESCO annual meeting is right around the corner. At ESCO, we and our partners will present new clinical data for several of our programs, data that is of relevance for making informed decisions about the direction of those projects' development. Firstly, we at GENMAP plan to present data for BNT311 from our Phase II in post-IO non-small cell lung cancer patients. BNT311 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4,1-BB co-stimulatory activation. Second, as already mentioned, monotherapy data from Phase II trials are planned to be presented for BNT327 the biospecific anti-VEGF-A, anti-PD-L1 antibody we are developing in collaboration with BioFeels. Third, we and our partner MediLink plan to present first in human data for our free targeting ADC. Then 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 2, stage 3 colorectal cancer that supports and informs the development of our individualized vaccine in this patient population. And lastly for BNT211, our CAR T-cell product candidate, we plan to initiate a potentially registrational trial in patients with At ESCO, 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 Holzstein.
spk03: Thank you, Aslam, and a warm welcome to everyone who has dialed in 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 188 million euros, 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 that we expect in an endemic environment for our COVID-19 vaccines. Our group revenues will continue to be driven largely by the uptake of our COVID-19 vaccines until oncology revenues will be recognized. We expect to recognize approximately 90% of our full year revenues in the last month 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 332 million euros. We maintained our strong financial position with 16.9 billion euros 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 three trial and are on track to start multiple additional potentially registrational trials this year. Our focus remains on our late stage clinical trials and to invest in our mRNA platform approaches that represent the core capability of BioNTech and differentiates 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 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 if approved. Both 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 €188 million, compared with approximately €1.3 billion for the first quarter of 2023. Moving to cost of sales, these amounted to €59.1 million for the first quarter of 2024, compared to €96 million for the comparative prior year period. Research and development expenses reached 508 million euros for the first quarter of 2024 compared to 334 million euros for the comparative prior year period. The increase was mainly due to progressing clinical studies for oncology pipeline and related personal expenses to manage those. Sales and marketing expenses of 16 million euros incurred in the first quarter of 2024 compared to 12 million euros in the comparative prior year period. General and administrative expenses amounted to €117 million for the first quarter of 2024 compared to €112 million for the comparative prior year period. The increase in FG&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 with an amount of €16.7 million for the first quarter of 2024. compared to 205.5 million euros of tax expenses for the comparative prior year period. The derived effective income 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 315 million euros compared to a net profit of approximately 502 million euros for the comparative prior year period. Our loss per share for the first quarter of 2024 amounted to 1 euro and 31 euro cents compared to a diluted profit per share of 2 euros and 5 euro cents 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 10 plus pivotal trials running by year end 2024, which we believe will change the picture of the company going forward. Besides having a strong franchise 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 are reiterating 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 month of 2024, mostly in Q4. Additionally, we also reiterate our R&D and SG&A guidance from our year-end call with 2.4 to 2.6 billion euros for R&D and 700 to 800 million euros 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.
spk08: Thank you, Jens. 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 JN1 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 JN1 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 fall 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, in regions like the UK to open in 2024. This could enable individuals who may not qualify under existing immunization recommendations to access updated COVID-19 vaccines 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 pipelines. We believe each of the drug classes we are investing in contain 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 from one or 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 10-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. Longer term, we aim to broaden our portfolio of approved products and transform BioNTech into a diversified, multi-product immunotherapy company that is in a position to redefine medicine. We are truly excited by the potential our technologies and pipeline holds 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 17th, and our inaugural artificial intelligence and machine learning event will take place on October 1st. Our main 2024 innovation series event is planned for November 14th. We will share further details on these events in due course.
spk09: With that, I would like to open the floor for questions.
spk25: Thank you. To ask a question, you will need to press star 1 and 1 on your telephone and wait for your name to be announced. Please limit yourself to one question only. To withdraw your question, please press star 1 and 1 again. We will now go to our first question.
spk21: One moment, please.
spk25: And your first question comes from the line of Tazeen Ahmed from Bank of America. Please go ahead.
spk18: Hi, good morning. Thanks for taking my question. For the data that you're going to be presenting at the upcoming ASCO conference as it relates to the GenMAP compounds, can you just remind us how many patients' worth of data to expect
spk15: And once that data is presented, can you talk to us about the next steps in the development plan for that program? Thanks.
spk19: Terveen, 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?
spk16: Yes, that's right. Thanks.
spk19: So that will be... I cannot... I can't tell you the specific number from the top of my head, but these will be around 100 patients, so a substantial number of patients.
spk17: And also, what level of detail should we expect to see?
spk19: So you will see safety data, the activity data, which we have until then, and ORR data.
spk18: Okay, and what is the plan moving forward with this program?
spk19: We are in the planning phase with our partner, GenMed, so that we cannot disclose any specifics at this time, but you will hear more about this program sometime later this year.
spk14: Okay, thank you.
spk25: Thank you. Once again, As a reminder, please limit yourself to one question only. We will now go to the next question. And your next question comes from the line of Dana Graybosh from Layering Partners. Please go ahead. Hi, thank you for the question.
spk28: I have another one on ASCO. So I wonder if you could talk more about the data we should expect from PM 8002 at ASCO, and also if you could talk about how this molecule compares to the competitor from Akiso 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 Akiso data to yours and from yours to the Akiso data for the overall approach? Thank you.
spk35: Hi, Diana.
spk02: So we have at the moment the clinical trial running in multiple indications, including also indications with single arm and combination. What we are going to update on ASCO is on the 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, shown also responses in the PD-L1 or cold tumors, PD-L1-negative or cold tumors. And we expect to present similar data now for non-small cell lung cancer. Of course, we do not have direct comparison, comparative data with AKESO. But I think the data that we are seeing goes into the same direction, that this bispecific, and that means direct targeting, targeting of the PD-L1 axis plus VGF axis appears to be associated with a better response rate, as well as a better safety profile. as compared to anti-BGF treatment. So we are very excited about using these compounds as combination approach for chemotherapies and in the upcoming future for ADCs.
spk25: Thank you. Thank you. We will now go to the next question. And your next question comes from the line of Akesh Tiwari from Jefferies. Please go ahead.
spk04: Hey, 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 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? Thanks so much.
spk10: Yeah, thanks, Akash, for the question. I'll start with maybe the second part of it. I think strategic partnerships have been one of the hallmarks of this approach in oncology early on and also with COVID-19. And I think we will continue to evaluate partnerships asset by asset. to see if that could help us accelerate certain assets, broaden their reach geographically, or even help us reach profitability sooner for specific assets where there might be a partner that brings infrastructure that's relevant. Generally speaking though, we do now, we have a strong balance sheet. We do wanna retain more of the economics as a general matter of strategy. So I think that those partnering decisions are gonna really be made on an asset by asset basis, while at the same time, we do commit to actually build commercial presence in oncology in the major markets. And so that is going to be a priority over the next couple of years. I'll let Jens speak a little bit to the profitability point, but I'll just say high level at the outset that we do see, as you've alluded, that there's an opportunity here with the pipeline that we're building and advancing now into late stage studies to deliver long-term sustained growth driven by successive product launches. We've indicated 2026. as a significant time point in those plans, but really the plans go beyond that. And that's why we put out the target of having 10 approvals in oncology by 2030, highlighting that we do think that that revenue growth can come from multiple indication approvals and multiple products. And so our priority is to get on that long-term growth trajectory. And of course, being profitable is important, but the focus right now is really getting on that growth trajectory.
spk03: Yeah, thanks, Ron. I think you made the most important statements already. So, I mean, if you look into the revenue development going forward, of course, you know, we see some potential upside when we have a COVID flu combination reaching the market. And how big that upside could be, we are not 100% clear yet. We haven't given any guidance for 25 in the ongoing years for that combination. We got to see how it evolves. In terms of our spend, I think we have shown that we control the cost as good as we can, as sensible as it is. 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.
spk10: Yeah, and I think, so what you're hearing from us, Akash, is, you know, in the very short term, we do think that the COVID combination vaccine with flu is 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.
spk25: Thank you. We'll now go to our next question. And your next question comes from the line of Jessica Fay from J.P. Morgan. Please go ahead.
spk27: Hey there. Thanks for taking my questions. Coming back to BNT 311 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? Thank you.
spk19: So the regimen we will be presenting will be a combination of BNT311 with pembrolizumab in second line on small cell lung cancers and the post-CPI population to which you would then need to compare this regimen.
spk26: Okay, maybe I'll just throw in one more.
spk27: Can you recap a hypothetical list of what the 10 potentially registrational trials running by year-end might be? I imagine you've contemplated a few scenarios here, but maybe you could throw out an example or two.
spk19: Probably 10 trials we are trying to activate. Do you want examples? Is this the question? So we have... Several of them activated. One example is the BNT316 trial, our cooperation with ONC-C4, an entire CTLA-4, which is in non-small cell lung cancer, in PD-1, PD-L1 experience in phase three. Another trial, which is potentially registrational, is our breast cancer trial in HER2-low. breast cancer with BNT3-2-3, also phase three, which has started early this year. Then in this priority asset list, we have trials with autogen-sebumeran, the individualized vaccine. We are co-developing with Genentech Roche. One example is our colorectal cancer trial. which will reach out in around 2026. Another example is our adjuvant pancreatic cancer trial. Additionally, we will activate trials with BNT327, so the PD-L1-BGS compound. we have talked about earlier. So these are several of the examples of potentially registrational trials we would like to activate by end of this year. One very exciting one I should also list here, which is our trial with our CAR T cell, Claudine 6 CAR T cell in testicular cancer.
spk25: Thank you. We will now go to the next question. And your next question comes from the line of Yaron Verba from TD Cowan. Please go ahead.
spk05: Hi, great. This is Brendan on for your own. Thanks for taking the question. Just a quick one from us actually on the infectious disease pipeline. It looks like, you know, we're going to have a phase one update from the shingles vaccine sometime this year. but wanted to also see where you're at with enrollment and potential timings data for maybe malaria, HSV, and TV programs, and kind of if there's any notable updates in how you're prioritizing this part of the pipeline. Thanks very much.
spk02: Yeah, we will provide data updates actually on the HSV-2 trial. on the TB trial on the malaria time which created safety and immunogenicity data in a phase one and are proceeding now into phase two settings and the data will come here at various events until end of this year.
spk21: Thank you. We will now go to the next question.
spk25: And your next question comes from the line of from BMO Capital Markets. Please go ahead.
spk32: Great. Thanks for taking the question. Just another bigger picture strategy question around oncology. looks like the early combination approaches, you know, rely on external molecules, but just curious about the strategy for moving combinations of internal assets, you know, particularly, you know, combinations of immunotherapy and targeted therapy assets, moving those into proof-of-concept studies, and when we could start maybe seeing some of those sort of emerge. Thank you.
spk02: Yeah, excellent question. This is actually one of the One of the strengths that we would like now to activate, so the first type of combination trials with internal assets is chlorine 6K T cell therapy with RNA vaccine. We have recently reported data showing indeed a synergy between the two of the combination, increasing the persistence of T cells. We will see start end of this year the first combination trials of our ADC compounds with our I.O. portfolio. And actually 2025 will be an intense year where we will do multiple combination trials dedicated to contribution of component trials and safety assessments. to bring us into the position to go into first registration of price in our convo in the second half of 2025.
spk24: Thank you.
spk25: Thank you. So we'll now go to the next question. And your next question comes from the line of Terence Flynn from Morgan Stanley. Please go ahead.
spk12: Great. Thanks for taking the question. For BNT-122, it sounds like it was on your list of registrational trials. So just wondering, for the data next year from that Phase 2 CRC trial, what you'd need to show on an efficacy basis to consider filing for an 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? Thank you.
spk02: Yeah. So this study is a sufficiently powered phase two study. It is in a patient population of colorectal cancer patients who are ctDNA positive. Multiple epidemiological studies have shown that this patient population have a very poor prognosis. Actually, the PFS in this patient population after surgery is around 12 months, after chemotherapy is around seven months. So this is actually a metastatic, early metastatic patient population, and the clinical trial compares a standard of care, which is adjuvant chemotherapy in this patient population versus standard of care followed by the personalized vaccine. The clinical trial endpoint is disease-free survival. And we expect the endpoint analysis for this trial in the second half of 2025. The trial is enrolling as expected at the moment. And of course, this is all that we can say. Everything else will depend on the totality of the data.
spk11: Do you want to say a few words about the epidemiological study at ASCO? Yeah.
spk19: Yes, I can do that. So what we will present at ESCO is an epidemiological study. So it's not a treatment study. And we have conducted this epidemiological study in order to better understand the prognosis of those patient populations we have in our ongoing clinical trial. with BNT122, in particular also of 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 trial. So you will get, in particular, epidemiological data of ctDNA positivity rates in high-risk populations in colorectal cancer and the disease-free survivors, which are seen in these subpopulations.
spk25: Thank you. Your next question comes from the line of Ellie Merler from UBS. Please go ahead.
spk21: Hello, Ellie, is your phone on mute? Ellie, is your phone on mute?
spk20: Okay, due to no response, I will go to the next question. One moment, please.
spk25: And your next question comes from the line of Bill McGann from Canaccord. Please go ahead.
spk07: Hi, and thank you. 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 a 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. Thank you.
spk02: Yeah. So, indeed, value immunotherapy is reaching our 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 that we are doing internally could go into that direction.
spk22: We could talk about this end of this year when we have first validation data.
spk20: Thank you. Thank you.
spk25: We will now go to the next question. And your next question comes from the line of Hatash Singh from Oppenheimer. Please go ahead.
spk34: Great. Thank you. Thank you for the question. You know, I just want to ask a question on the slide where you got listed the average quarterly patient enrollment. Over the last couple of years, we've seen actually, you know, real difficulty with companies in oncology just because of the vast number of trials going on in oncology and I.O. recruiting patients and you know you've seen a really nice acceleration from 2022 to 23 and the first quarter 24 so can you just put some you know color behind that or meat on the bone of what exactly are you doing is it just the ability to you know the trials getting IRB approved more trials actually moving ahead to late stage maybe spending more patients on you know recruiting trials at sites I'd love to hear that. And then how does this change your thinking on potential readouts? I mean, it's nice to see the improvement in enrollment, but how does that translate to when readouts could actually happen? Thank you.
spk02: Yes, let me take the first part of the question. So in the timeline of 2020 to 2022, 2023, of course, we dealt with early clinical ties, which are typically recruiting a lower number of patients, defining based on those escalations, of cohort safety assessment, biomarker assessment, and so on. And we are now reaching a phase where we have multiple trials in phase two and first clinical trials in phase three, which naturally allow us to enroll faster and ensure that we get the statistics. This is also the reason why we are now able to move multiple clinical trials into registration trials end of this year. And for all of the registration trials, we will provide the timeline when we expect the readout. As Ryan alluded, the first readout for our first potential registration trial is in endometrial cancer. will be next year, second half or mid-next year, with the opportunity to get an authorization end of next year. And we will have multiple interim readouts to be presented at ASCO and ESMO and CICI this year on the currently running cohort.
spk19: 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 multi-product oncology company by 2030. But it was very clear to us from the very beginning that this also means that we have to improve our capability to execute these clinical trials. So we have invested, and this is what this bar chart shows, We have invested major efforts to mature our clinical development operations organization and also to grow it. And we also have invested into models such as working with partners, with our partner companies to enroll into our joint trials and public-private partnership, for example, the partnership we have with UK in which we are building a cancer vaccine launch pad and thereby mobilizing on a national level large numbers of clinical sites. And this is basically what those numbers reflect.
spk25: Thank you. We'll now take the next question. And your next question comes from the line of Ellie Merlo, UBS. Hey, guys. Can you hear me now?
spk00: We can hear you.
spk01: Okay, perfect. Great. Thank you. Just for your HER2 ADC, where you got breakthrough-designated 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 around 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. Thanks.
spk02: The current Iranian trial 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 with a confirmatory trial for which we still are in the planning phase and we will inform in around three to four months about the design of the confirmatory trial.
spk25: Thank you. Your next question comes from the line of Simon Baker from Red Bell Atlantic. Please go ahead.
spk31: Thank you for taking my question. And it's on SG&A. Your guidance implies an increase between 160 and 260 million euros this year. I would assume a large part of that is the global commercial footprint build-out. I just wonder 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 as that build-out would be great. Thanks very much.
spk03: Yeah, thanks for the question. You should expect for 24 that we have sliding to quarter by quarter in terms of our S&M costs and the G&A costs here in 24. And then for 25, likely to have a further increase in the setup. Of course, you know, you start to hire personnel for the commercialization, you know, C4s, only shortly before you launch, and that will, you know, the timing of that will drive the Spender 25. Okay, thanks so much.
spk25: Thank you. Your next question comes from the line of Yifeng Liu from HSBC. Please go ahead.
spk30: Hello, thanks for taking my question. Just one question on your HER2 ADC in breast cancer. How do you think about the bar marker expression there when you have HER2 low and perhaps whether you think about HER2 ultra low as well in the design of your pivotal study? Thanks.
spk35: Yeah, this is a good question indeed.
spk02: The question is about HER2-1, HER2-1+, 2+, or even ultra-low, or even negative. So we are considering all patient cohorts in our trial design, and we'll make a decision on the patient population to be enrolled and the patient population to be analyzed later on for the upcoming trials. And we'll most likely report about the clinical trial design end of this year.
spk33: Thanks.
spk25: Thank you. We will now take our final question for today. And your final question comes from the line of Suzanne van Fortuytsen from VLK.
spk06: Please go ahead. Hi there, this is Suzanne from VLK. Thanks for taking my question, which relates to business development and M&A. Last year you were fairly active on the deal-making front, so can you give some context of what we expect going forward for this and next year? um you have a lot of cash on hand but also a lot of projects to run and many moving parts on the profitability side so i was wondering if you're continuing to pursue similar deals and assets as previously or does your appetite change thank you yeah thanks suzanne um i think our our focus this year is more on clinical execution that said um we will be opportunistic uh and if we were open
spk10: to synergistic assets, but I think you can expect the general level of activity in terms of number of deals to be decreased this year.
spk25: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Thank you. Thank you. you Thank you.
spk33: Bye. Bye. you Thank you.
spk21: Good morning and good afternoon.
spk29: 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 we issued 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 as of the date of this conference call. We're going to take no obligation to update or revise any of these statements. On slide three, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team. Ugur Zahin, Chief Executive Officer and Co-Founder, Aslim 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.
spk02: Thank you, Victoria. A warm welcome to all those joining us today. We believe that we are entering a transformational period for BioNTech. We have 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 demonstrate the safety and clinical effectiveness of various drug candidates in early clinical trials. The period from now to 2030 is about progressing this candidate into late-stage development and registration trials to become a multi-product 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 progress our late-stage oncology pattern on multiple fronts. We dose the first patient in the pre-votal phase three clinical trial, evaluating our HER2-ADC BNT3-2-3 in HR-positive HER2-low metastatic breast cancer. At the AACR annual meeting, we presented three-year follow-up data from a clinical trial evaluating our endogenous mRNA cancer vaccine, autogen-seam, in pancreatic cancer. This data showed encouraging relapsing survival in certain patients with immunogenic response to the vaccine, demonstrating the promise of our vaccine platform to induce persisting 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, Özlem and I will focus on our oncology strategy while Jens and Ryan will provide updates on our financial and corporate progress. Slide six. Our oncology portfolio strategy is driven by understanding the key challenges in cancer. Cancer is genetically diverse and heterogeneous disease driven by the sequential 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. Slide 8. Our therapeutic strategy brings together synergistic mechanisms of action across three key categories. The first are novel immune modulators, or IO, 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 chronicates that can dramatically reduce the tumor burden. The third category are mRNA vaccines, which are the centerpiece of our oncology strategies. 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 are 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 synergistic 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 to drive meaningful improvements in the long-term survival rates for patients. Slide nine. 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 10 or more by year end. These trials will focus on areas of unmet medical needs, clinical indications in which we may achieve an expeditious path to market, and there, after the first approval in the initial indication, there's 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 multi-product company. This process will be accelerated this year as we bring our new chief commercial office 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 Özlem.
spk19: Thank you, Ugo. Glad to be speaking with everyone today. As Uwe highlighted, we will focus in the next few years on increasing the number of potentially pivotal clinical trials to fuel our transition towards becoming a multi-product 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 vaccines, and also our most advanced ADCs and IOs, including those which we consider as attractive backbones of unique combination treatments. To highlight recent additions to our pipeline, one is a phase three trial in collaboration with Duality Bio, evaluating BNT323 in patients with hormone receptor positive and her to low metastatic breast cancer that have progressed on hormone therapy and or cyclin-dependent kinase for six blockers. With BNT3 to three, we are also planning to start a confirmatory phase three trial this year in patients with metastatic endometrial cancer that will complement our ongoing single arm trials in this indication. In our early-stage pipeline, we have started a Phase I-II trial in collaboration with GENMAP, evaluating BNT314. The bispecific antibody product candidate was outcome-dependent for 1Bb agonistic activity in multiple solid tumors. Our aim is to continue to progress our oncology pipeline towards pivotal data readouts and submissions for regulatory approvals in the next 18 months. Before highlighting some of the programs, and platforms that we consider priority assets to contribute to clinical progress, let me say a couple of words to execution. The coming years will be about late-stage clinical trial execution. Enrolling the patients to participate in clinical trials requires deep coordination across multiple functions within our company and with our partners and collaborators who are 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 quarterly average in 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 thus progress in clinical trial execution, we expect our clinical development pipeline to generate a corresponding increase in the number of data sets in the coming years. Our ultimate goal at BioNTech is to bring our data-backed scientific breakthroughs to patients in need. Moving to our priority assets, let me start with BNT327 or PMH002, a bispecific antibody consisting of an anti-VGF-A SC-silenced IgG fused to a humanized anti-PD-L1 BHH binder being developed in collaboration with our partner, BioFeels. BNT327 combines two validated mechanisms of action. VGFA binding inhibits the VGFA-BGFR axis, blocks tumor angiogenesis, which leads to reduced tumor cell proliferation and survival. VGFA inhibition also counteracts formation of the immune-suppressive tumor microenvironment, as does the PD-L1 arm of this specific antibody by reverting PD-L1-PD1 axis-mediated T-cell exhaustion. The PD-L1 arm also anchors this antibody to the tumor bed for efficient and localized scavenging of VGFA, which may contribute to mitigate of tumor on target side effects. Data from ongoing Phase I-II clinical trials across several indications in over 600 patients executed by our partner, BioHeals, have shown a favorable safety profile. Our partner Biofears 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 NAP-paclitaxel, almost 80% objective response As shown on this slide. At ESCO now, there will be more data disclosures in cervical, in 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 a centerpiece of our pipeline and are pivotal to our goal of developing breakthroughs for cancer patients. The aim is to develop this technology as monotherapy in combination with standard of care and in combination with candidates from our proprietary pipelines. Our six 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's tumor. While INEST and FixVac target different types of cancer cell antigens, they are based on the same mRNA and delivery technology, namely our Uridin mRNA LipoPEX platform. Its distinct mechanism of action is that the delivered antigen is presented by professional antigen-presenting cells in lymphoid compartments body-wide in close proximity to T cells to be induced, and that it comes with intrinsic adjuvanticity. These features by design promote the induction of high-end-of-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 set 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 magnitudes 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. And the two papers quoted on this slide, we have shown that vaccination with neoantigen encoding mRNA is associated with 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, and data releases from several of the trials shown on this slide are planned. In our FIXVAC program, we are evaluating four vaccine candidates, which each target tumor-associated antigens specific to melanoma, HPV 16 positive head and neck cancer, prostate cancer, and non-small lung cancer, as monotherapy and in several combinations. We shared early data for all FICSAC candidates in the past years and plan to present additional data this and 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 and cancer types that have a low tumor mutational burden and are resistant to immune therapy, namely colorectal cancer and PDAC, and our NSCLC FixVac program. Starting with CRC, with colorectal cancer, the majority of patients with early-stage localized and resectable CRC undergo surgery, followed by adjuvant chemotherapy. Standard of care in stage two high risk and stage three disease after adjuvant treatment is watchful waiting. 20 to 35% of patients experience recurrences of their disease. CTDNA is a marker for minimal residual disease and identifies patients with high risk of such recurrence. We are running a phase two trial with our individualized vaccine in stage 2 high risk and stage 3 resected CRC patients that are CTDNA positive post-surgery. After adjuvant chemotherapy, patients are randomized to either receive autogen, sevumaran, or individualized vaccine, or observation. We expect the first readout of this trial in the second half of 2025. Secondly, a randomized phase two clinical trial evaluating our individualized vaccine in combination with the anti-PD-L1 agent, atesolizumab, followed by standard of care chemotherapy in patients with resected pancreatic cancer, PDAC, compared to chemotherapy alone, was started in collaboration with Genentech in 2023 and is recruiting patients. PDAC is a high medical need tumor expected to become the second leading cause in cancer-related death. Up to 85% of patients with localized pancreatic cancer that undergo surgical resection and adjuvant chemotherapy do experience recurrence of disease. This trial was initiated based on data from an investigator-initiated trial that were published last year. and updated at AACR a few weeks ago. That phase one trial showed that with our individualized vaccine combined with adesolizumab and standard of care adjuvant chemotherapy, half of the 16 treated patients develop high magnitude vaccine-induced immune responses and that these patients have a much lower risk of tumor recurrence at 1.5 years of median follow-up and continue 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-like complex cancer vaccine candidate comprising six mRNAs, each encoding a tumor-associated antigen, mageA3, Claudine 6, KKLC1, Crane, mageA4, mageC1. We have selected these tumor-associated antigens by an in silico approach developed for design of six vaccines for different tumor types and 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 And SCLC specimens express at least one of the six selected tumor-associated antigens, and more than 60% express at least two of them. BNT116 is currently being evaluated with our partner Regeneron in two clinical trials that cover various non-small cell lung cancer patient populations. One is a phase one trial investigating BNT116 in adjuvant first-line and second-line plus settings, and various treatment regimens listed on the left side of this slide. We plan to introduce novel unique combination cohorts into this multi-cohort Phase I trial. The second trial is a randomized Phase II evaluating BNG1-16 in combination with Simiprimab in first-line treatment of patients with PdL1-high expressing non-small cell lung cancer shown on the right side of the slide. At AACR, we presented preliminary results from cohort three of the LUCA MERIT phase one trial, evaluating BNT1-16 in combination with doxetaxel in patients with advanced, unresectable, or metastatic non-small cell lung cancer that progressed on PD-1, PD-L1 inhibitor 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%, medium progression-free survival of 4.4 months. Comparable to other SIGSEG candidates, BNT116 presents a manageable safety profile alone and in combination. We expect further data from these cohorts in the next 12 months, and that will inform further development of PNG 116 in Lancaster. The ESCO annual meeting is right around the corner. At ESCO, we and our partners will present new clinical data for several of our programs, data that is of relevance for making informed decisions about the direction of those projects' development. Firstly, we at GENMAP plan to present data for BNT311 from our Phase II in post-IO non-small cell lung cancer patients. BNT311 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4,1-BB co-stimulatory activation. Second, as already mentioned, monotherapy data from Phase II trials are planned to be presented for BNT327 the biospecific anti-VEGF-A, anti-PD-L1 antibody we are developing in collaboration with BioFeels. Third, we and our partner MediLink plan to present first in human data for our free targeting ADC. Then 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 2, stage 3 colorectal cancer that supports and informs the development of our individualized vaccine in this patient population. And lastly, for BNT211, our CAR T-cell product candidate, we plan to initiate a potentially registrational trial in patients with germ cell tumors. At ESCO, 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 Holzstein.
spk03: Thank you, Aslam, and a warm welcome to everyone who has dialed in 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 188 million euros, 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 that we expect in endemic environment for our COVID-19 vaccines. Our group revenues will continue to be driven largely by the uptake of our COVID-19 vaccines until oncology revenues will be recognized. We expect to recognize approximately 90% of our full year revenues in the last month 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 332 million euros. We maintained our strong financial position with 16.9 billion euros 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 three trial and are on track to start multiple additional potentially registrational trials this year. Our focus remains on our late stage clinical trials and to invest in our mRNA platform approaches that represent the core capability of BioNTech and differentiates 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 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. Boasted 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 188 million euros, compared with approximately 1.3 billion euros for the first quarter of 2023. Moving to cost of sales, these amounted to 59.1 million euros for the first quarter of 2024 compared to 96 million euros for the comparative prior year period. Research and development expenses reached 508 million euros for the first quarter of 2024 compared to 334 million euros for the comparative prior year period. The increase was mainly due to progressing clinical studies for our oncology pipeline and related personal expenses to manage those. Sales and marketing expenses of 16 million euros incurred in the first quarter of 2024 compared to 12 million euros in the comparative prior year period. General and administrative expenses amounted to 117 million euros for the first quarter of 2024 compared to 112 million euros for the comparative prior year period. The increase in FG&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 with an amount of 16.7 million euros for the first quarter of 2024, compared to 205.5 million euros of tax expenses for the comparative prior year period. The derived effective income 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 €315 million compared to a net profit of approximately €502 million for the comparative prior year period. Our loss per share for the first quarter of 2024 amounted to €1.31 compared to a diluted profit per share of €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 10-plus pivotal 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 are reiterating 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 month of 2024, mostly in Q4. Additionally, we also reiterate our R&D and SG&A guidance. from our year-end call with 2.4 to 2.6 billion euros for R&D and 700 to 800 million euros 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.
spk08: Thank you, Jens. 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 JN1 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 JN1 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 fall vaccination campaigns. We are preparing to launch the variant-adapted COVID-19 vaccine in over 80 geographies worldwide. While most regions outside the US will continue to be served by government contracts, we do expect some new private markets in regions like the UK to open in 2024. This could enable individuals who may not qualify under existing immunization recommendations to access updated COVID-19 vaccines 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 pipelines. We believe each of the drug classes we are investing in contain 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 from one or 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 10-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. Longer term, we aim to broaden our portfolio of approved products and transform BioNTech into a diversified, multi-product immunotherapy company that is in a position to redefine medicine. We are truly excited by the potential our technologies and pipeline holds 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 17th, and our inaugural artificial intelligence and machine learning event will take place on October 1st. Our main 2024 innovation series event is planned for November 14th.
spk09: We will share further details on these events in due course. With that, I would like to open the floor for questions.
spk25: Thank you. To ask a question, you will need to press star 1 and 1 on your telephone and wait for your name to be announced. Please limit yourself to one question only. To withdraw your question, please press star 1 and 1 again. We will now go to our first question.
spk21: One moment, please.
spk25: And your first question comes from the line of Tazeen Ahmed from Bank of America. Please go ahead.
spk18: Hi, good morning. Thanks for taking my question. For the data that you're going to be presenting at the upcoming ASCO conference as it relates to the GenMAP 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?
spk15: Thanks.
spk19: 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?
spk16: Yes, that's right. Thanks.
spk19: So that will be... I cannot... tell you the specific number from the top of my head, but these will be around 100 patients, so a substantial number of patients.
spk17: And also, what level of detail should we expect to see?
spk19: So you will see safety data, the activity data, which we have until then, and ORR data.
spk18: Okay, and what is the plan moving forward with this program?
spk19: We are in the planning phase with our partner, GenNet, so that we cannot disclose any specifics at this time, but you will hear more about this program sometime later this year.
spk14: Okay, thank you.
spk25: Thank you. Once again, As a reminder, please limit yourself to one question only. We will now go to the next question. And your next question comes from the line of Dana Graybosh from Layering Partners. Please go ahead. Hi, thank you for the question.
spk28: 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 Akiso 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 Akiso data to yours and from yours to the Akiso data for the overall approach? Thank you.
spk35: Hi, Diana.
spk02: So we have at the moment the clinical trial running in multiple indications, including also indications with single arm and combination. What we are going to update on ASCO is on the cervical cancer and platinum-resistant ovarian cancer and non-small cell lung cancer. trial, 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 or cold tumors, PD-L1-negative or cold tumors. And we expect to present similar data now for non-small cell lung cancer. Of course, we do not have direct comparison, comparative data with AKESO. But I think the data that we are seeing goes into the same direction, that this bispecific, and that means direct targeting, targeting of the PD-L1 axis plus VGF axis appears to be associated with a better response rate, as well as a better safety profile. as compared to anti-BGF treatment. So we are very excited about using these compounds as combination approach for chemotherapies and in the upcoming future for ADCs.
spk25: Thank you. Thank you. We will now go to the next question. And your next question comes from the line of Akash Tiwari from Jefferies. Please go ahead.
spk04: Hey, 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 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? Thanks so much.
spk10: Yeah, thanks, Akash, for the question. I'll start with maybe the second part of it. I think strategic partnerships have been one of the hallmarks of this approach in oncology early on and also with COVID-19. And I think we will continue to evaluate partnerships asset by asset. to see if that could help us accelerate certain assets, broaden their reach geographically, or even help us reach profitability sooner for specific assets where there might be a partner that brings infrastructure that's relevant. Generally speaking, though, we do now have a strong balance sheet. We do want to retain more of the economics as a general matter of strategy. So I think that those partnering decisions are going to really be made on an asset-by-asset basis, while at the same time, we do commit to actually build commercial presence in oncology in the major markets. And so that is going to be a priority over the next couple of years. I'll let Jens speak a little bit to the profitability point, but I'll just say high level at the outset that we do see, as you've alluded, that there's an opportunity here with the pipeline that we're building and advancing now into late-stage studies to deliver long-term sustained growth driven by successive product launches. We've indicated 2026. as a significant time point in those plans. But really, the plans go beyond that. And that's why we put out the target of having 10 approvals in oncology by 2030, highlighting that we do think that that revenue growth can come from multiple indication approvals and multiple products. And so our priority is to get on that long-term growth trajectory. And of course, being profitable is important. But the focus right now is really getting on that growth trajectory.
spk03: Yeah, thanks, Ron. I think you made the most important statements already. So, I mean, if you look into the revenue development going forward, of course, you know, we see some potential upside when we have a COVID flu combination reaching the market. And how big that upside could be, we are not 100% clear yet. We haven't given any guidance for 25 in the ongoing years for that combination. We got to see how it evolves. In terms of our spend, I think we have shown that we control the cost as good as we can, as sensible as it is. 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.
spk10: Yeah, and I think, so what you're hearing from us, Akash, is, you know, in the very short term, we do think that the COVID combination vaccine with flu is 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.
spk25: Thank you. We'll now go to our next question. And your next question comes from the line of Jessica Fay from JP Morgan. Please go ahead.
spk27: Hey there. Thanks for taking my questions. Coming back to BNT 311 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? Thank you.
spk19: So the regimen we will be presenting will be a combination of BNT311 with pembrolizumab in second line on small cell lung cancers and the post-CPI population to which you would then need to compare this regimen.
spk26: Okay, maybe I'll just throw in one more.
spk27: Can you recap a hypothetical list of what the 10 potentially registrational trials running by year-end might be? I imagine you've contemplated a few scenarios here, but maybe you could throw out an example or two.
spk19: Probably 10 trials we are trying to activate. Do you want examples? Is this the question? So we have... Several of them activated. One example is the BNT316 trial, our cooperation with ONC-C4, an entire CTLA-4, which is in non-small cell lung cancer in PD-1 and PD-L1 experience in phase three. Another trial, which is potentially registrational, is our breast cancer trial in HER2 low. breast cancer with BNT3-2-3, also phase three, which has started early this year. Then in this priority asset list, we have trials with autogen-sebumeran, the individualized vaccine. We are co-developing with Genentech Roche. One example is our colorectal cancer trial. which will reach out in around 2026. Another example is our adjuvant pancreatic cancer trial. Additionally, we will activate trials with BNT327, so the PD-L1BGS compound. we have talked about earlier. So, these are several of the examples of potentially registrational trials we would like to activate by end of this year. One very exciting one I should also list here, which is our trial with our CAR T cell, Claudine 6 CAR T cell in testicular cancer.
spk20: Thank you.
spk25: We will now go to the next question. And your next question comes from the line of Yaron Verba from TD Cowan. Please go ahead.
spk05: Hi, great. This is Brendan on for your own. Thanks for taking the question. Just a quick one from us actually on the infectious disease pipeline. It looks like, you know, we're going to have a phase one update from the shingles vaccine sometime this year. but wanted to also see where you're at with enrollment and potential timings data for maybe malaria, HSV, and TB programs, and kind of if there's any notable updates in how you're prioritizing this part of the pipeline. Thanks very much.
spk02: Yeah, we will provide data updates actually on the HSV-2 trial. on the TB trial on the malaria time which created safety and immunogenicity data in a phase one and are proceeding now into phase two settings and the data will come here at various events until end of this year.
spk21: Thank you. We will now go to the next question.
spk25: And your next question comes from the line of from BMO Capital Markets. Please go ahead.
spk32: Great. Thanks for taking the question. Just another bigger picture strategy question around oncology. Looks like the early combination approaches, you know, rely on external molecules, but just curious about the strategy for moving combinations of internal assets, you know, particularly, you know, combinations of immunotherapy and targeted therapy assets, moving those into proof of concept studies and when we could start maybe seeing some of those sort of emerge. Thank you.
spk02: Yeah, excellent question. This is actually one of the strengths that we would like now to activate. So the first type of combination trials with internal assets is chlorine 6-car T-cell therapy with RNA vaccine. We have recently reported data showing indeed a synergy between the two of them. the combination increasing the persistence of T cells. We will see start end of this year the first combination trials of our ADC compounds with our IO portfolio. And actually 2025 will be an intense year where we will do multiple combination price dedicated to contribution of components price and safety assessment to bring us into the position to go into first registration of price in our combos in the second half of 2025.
spk24: Thank you.
spk25: Thank you. We will now go to the next question. And your next question comes from the line of Terrence Flynn from Morgan Stanley. Please go ahead.
spk12: Terrence Flynn, Morgan Stanley, Great. Thanks for taking the question. For BNT-122, it sounds like it was on your list of registrational trials. So just wondering for the data next year from that Phase 2 CRC trial, what you'd need to show on an efficacy basis to consider filing for an 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? Thank you.
spk02: Yeah. So this study is a sufficiently powered phase two study. It is in a patient population of colorectal cancer patients who are ctDNA positive. Multiple epidemiological studies have shown that this patient population have a very poor prognosis. Actually, PFS in this patient population after surgery is around 12 months. After chemotherapy is around 7 months. So this is actually a metastatic, early metastatic patient population. And the clinical trial compares a standard of care, which is adjuvant chemotherapy in this patient population versus standard of care followed by the personalized vaccine. The clinical trial endpoint is disease-free survival. And we expect the endpoint analysis for this trial in the second half of 2025. The trial is enrolling as expected at the moment. And of course, this is all that we can say. Everything else will depend on the totality of the data.
spk11: Do you want to say a few words about the epidemiological study at ESCO?
spk19: Yes, I can do that. So what we will present at ESCO is an epidemiological study. So it's not a treatment study. And we have conducted this epidemiological study in order to better understand the prognosis of those patient populations we have in our ongoing clinical trial with BNT122, in particular also of 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 trial. So you will get, in particular, epidemiological data of ctDNA positivity rates in high-risk populations in colorectal cancer and the disease-free survivors, which are seen in these subpopulations.
spk25: Thank you. Your next question comes from the line of Ellie Merler from UBS. Please go ahead.
spk21: Hello, Ellie, is your phone on mute? Ellie, is your phone on mute?
spk20: Okay, due to no response, I will go to the next question. One moment, please.
spk25: And your next question comes from the line of Bill McGann from Canaccord. Please go ahead.
spk07: Hi, and thank you. 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 a 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. Thank you.
spk02: Yeah. So, indeed, value immunotherapy is reaching our 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 that we are doing internally could go into that direction.
spk22: We could talk about this end of this year when we have first validation data.
spk21: Thank you.
spk20: Thank you.
spk25: We will now go to the next question. And your next question comes from the line of Hatash Singh from Oppenheimer. Please go ahead.
spk34: Great. Thank you. Thank you for the question. You know, I just want to ask a question on the slide where you got listed the average quarterly patient enrollment. Over the last couple of years, we've seen actually, you know, real difficulty with companies in oncology just because of the vast number of trials going on in oncology and I.O., recruiting patients. And, you know, you've seen a really nice acceleration from 2022 to 23 and the first quarter of 24. So can you just put some, you know, color behind that or meat on the bone of what exactly are you doing? Is it just the ability to, you know, the trials getting IRB approved, more trials actually moving ahead to late stage, maybe spending more patients on, you know, recruiting trials at sites? I'd love to hear that. And then how does this change your thinking on potential readouts? I mean, it's nice to see the improvement in enrollment, but how does that translate to when readouts could actually happen? Thank you.
spk02: Yes, let me take the first part of the question. So in the timeline of 2020 to 2022, 2023, of course we dealt with early clinical ties, which are typically recruiting a lower number of patients, defining based on those escalations, of cohort safety assessment, biomarker assessment, and so on. And we are now reaching a phase where we have multiple trials in phase two and first clinical trials in phase three, which naturally allow us to enroll faster and ensure that we get the statistics. This is also the reason why we are now able to move multiple clinical trials into registration trials end of this year. And for all of the registration trials, we will provide the timeline. Then we expect a readout. As Ryan alluded, the first readout for our first potential registration trial is in endometrial cancer. will be next year, second half of, or mid-next year, with the opportunity to get an authorization end of next year. And we will have multiple interim readouts to be presented at ASCO and ESMO and CITSE this year on the currently running cohort.
spk19: 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 multi-product oncology company by 2030. But it was very clear to us from the very beginning that this also means that we have to improve our capability to execute these clinical trials. So we have invested, and this is what this bar chart shows, We have invested major efforts to mature our clinical development operations organization and also to grow it. And we also have invested into models such as working with partners, with our partner companies to enroll into our joint trials and public-private partnership, for example, the partnership we have with UK in which we are building a cancer vaccine launch pad and thereby mobilizing on a national level large numbers of clinical sites. And this is basically what those numbers reflect.
spk25: Thank you. We'll now take the next question. And your next question comes from the line of Ellie Merlo, UBS. Hey, guys. Can you hear me now?
spk00: We can hear you.
spk01: Okay, perfect. Great. Thank you. Just for HER2-ADC, where you got breakthrough-designated 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 around 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. Thanks.
spk02: The current Iranian trial 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 with a confirmatory trial for which we still are in the planning phase and we will inform in around three to four months about the design of the confirmatory trial.
spk25: Thank you. Your next question comes from the line of Simon Baker from Red Bell Atlantic. Please go ahead.
spk31: Thank you for taking my question. And it's on SG&A. Your guidance implies an increase between 160 and 260 million euros this year. I would assume a large part of that is the global commercial footprint build-out. I just wonder 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 as that build-out would be great. Thanks very much.
spk03: Yeah, thanks for the question. You should expect for 24 that we have sliding to quarter by quarter in terms of our S&M costs and the G&A costs there in 24. And then for 25, likely to have a further increase in the setup. Of course, you know, you start to hire personnel for the commercialization, you know, C4s, only shortly before you launch and that will, you know, the timing of that will drive the standard 25.
spk24: Okay, thanks very much.
spk25: Thank you. Your next question comes from the line of Yifeng Liu from HSBC. Please go ahead.
spk30: Hello, thanks for taking my question. Just one question on your HER2 ADC in breast cancer. How do you think about the biomarker reflection there when you have HER2 low and perhaps whether you think about HER2 ultra low as well in the design of your pivotal study? Thanks.
spk35: Yeah, this is a good question indeed.
spk02: The question is about HER2 low 1+, 2+, or even ultra low, or even negative. So we are considering all patient cohorts in our trial design. And we'll make a decision on the patient population to be enrolled and the patient population to be analyzed later on for the upcoming price. And we'll most likely report about the clinical trial design end of this year.
spk33: Thanks.
spk25: Thank you. We will now take our final question for today. And your final question comes from the line of Suzanne van Fortuusen from VLK.
spk06: Please go ahead. Hi there. This is Suzanne from VLK. Thanks for taking my question, which relates to business development and M&A. Last year, you were fairly active on the deal-making front. So can you give us some context of what we expect going forward for this and next year? um you have a lot of cash on hand but also a lot of projects to run and many moving parts on the profitability side so i was wondering if you're continuing to pursue similar deals and assets as previously or does your appetite change thank you yeah thanks suzanne um i think our our focus this year is more on clinical execution that said um we will be opportunistic uh and if we were open
spk10: to synergistic assets, but I think you can expect the general level of activity in terms of number of deals to be decreased this year.
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