Welcome to BioNTech's Fourth Quarter and Full-Year 2024 Earnings Call. I would like to hand the call over to Michael Horowicz, Director of Investor Relations. Please go ahead.

Thank you. Good morning and good afternoon. Thank you for joining BioNTech's fourth quarter and full-year 2024 earnings call. As a reminder, the slides we will be using during 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 US Securities and Exchange Commission. Forward-looking statements on 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'm joined by the following members of BioNTech's management team: Ugur Sahin, Chief Executive Officer and Co-Founder; Ozlem Tureci, Chief Medical Officer and Co-Founder; Jens Holstein, Chief Financial Officer; and Ryan Richardson, Chief Strategy Officer. With this, I would like to hand over to Ugur.

Thank you, Michael. A warm welcome to all those joining us today. We will spend today's call on our key areas of focus for this year. Before we do so, I want to speak briefly about our original vision and the strategy to become an immunotherapy powerhouse and a fully-integrated biopharmaceutical company with multiple approved products. While BioNTech has evolved significantly since its founding in 2008, our vision has remained steadfast to translate science into survival for patients by fully harnessing the power of the immune system to fight human diseases, particularly cancer. In 2024, we made significant progress on this vision. Thanks to the excellent work and dedication of our BioNTech team, our collaboration partners and the trust of patients who participated in our clinical trials. We have a clear focus. We will continue to invest in our technologies and drug candidates that have the potential to improve outcomes for patients across a wide range of tumor types. In oncology, we have identified two key pan-tumor programs. Our mRNA cancer immunotherapy FixVac and iNeST and our bispecific anti-PD-L1/anti-VEGF antibody BNT327. We believe that these programs have disruptive potential and align with our vision. If successfully developed and approved, these programs could establish a new standard of care and enhance patient outcomes in multiple cancer indications globally. We are significantly investing in the clinical development of these programs across various cancer types, building up commercial functions for their future commercialization in key markets and enhancing manufacturing capabilities to support both clinical and commercial supply. In the infectious disease sector, we are advancing the development of our next-generation COVID-19 and combination vaccines. Our infectious disease product strategy focuses on sustainable value creation with active pipeline prioritization and rigorous opportunity assessment based on strategic fit and operational efficiency. Consequently, as outlined in our 20-F filing today, we are prioritizing areas with disruptive potential for value generation. Moreover, we are planning to adjust our resources in manufacturing, administrative functions and preclinical research over the next three years to further solidify efficient execution. Let me continue with a look back at what we have achieved in 2024. So for our mRNA cancer immunotherapies, we initiated the third Phase 2 trial evaluating autogene cevumeran in the adjuvant setting, namely in bladder cancer. In early 2025, we also published two manuscripts describing our insights from two Phase 1 trials for autogene cevumeran. For three off-the-shelf FixVac programs, we reported data including the announcement that FixVac candidate BNT111 met the primary endpoint in a randomized Phase 2 trial in patients with anti-PD-1 relapsed or refractory melanoma. We presented multiple datasets for our next-generation IO BNT327, a PD-L1/VEGF bispecific antibody and initiated Phase 3 and Phase 2 trials in small cell lung cancer and non-small cell lung cancer. We plan to initiate a Phase 3 trial in triple-negative breast cancer this year. We announced our intention to acquire Biotheus to secure global control over BNT327 and expand our immunotherapy capabilities. This transaction closed earlier this year and we are thrilled to welcome Biotheus as a new arm of our operations in China. With regard to our COVID-19 vaccine, we and Pfizer maintained our leading market share globally. We also continued to progress several other programs in our early-stage infectious disease pipeline. Lastly, we were able to achieve all this while maintaining our strong financial position. We believe these achievements position us well for further progress in 2025. As already pointed out, in oncology, we are focused on the development of candidates addressing the full spectrum of solid tumors with a focus on two pan-tumor programs. First, our personalized mRNA cancer immunotherapies encoding mutant neoantigens for application primarily for the early stage, including adjuvant setting and our FixVac immunotherapies targeting tumor-associated antigens in combination with checkpoint immunotherapy, respectively. Second, our PD-L1/VEGF bispecific antibody BNT327, which we believe has the potential to become a next-generation IO backbone for the treatment of advanced cancers. We believe that both programs have pan-tumor potential and could be combined with different modalities to address large patient populations with high unmet medical need. 2025 will be an important year for these priority programs. We expect to generate and share new clinical data that will help inform our development strategy. I want to take a moment to highlight our recently completed acquisition of Biotheus. We are excited to now formally welcome Biotheus team to BioNTech. Having worked for a year with the highly skilled and dedicated team at Biotheus, we have decided to plan for an acquisition of the company. Now as one company, we have the capabilities to accelerate and expand the global development of BNT327. However, there are other factors of this acquisition, which are also strategically important for us. We are going to build a strong and experienced clinical development organization in China, that can help us to further accelerate the development across programs and tumor types. We believe this will facilitate more streamlined clinical development and decision-making, allowing us to bring other programs into late-stage and global development. With the acquisition of Biotheus, we now have a fully-integrated antibody manufacturing network in China. The site supplies antibodies for clinical trials and could potentially support initial commercial supply for market launches. Lastly, Biotheus comes with leading antibody engineering technology and expertise. With their capability, they have very quickly built a diverse pipeline of programs, that we are evaluating and which we believe could offer additional value in the coming years. With that, I will turn the call over to Ozlem.

Thank you, Ugur. Glad to be speaking with everyone today. Before talking about our focused programs introduced by Ugur, I wanted to take a minute to show our pipeline progress in 2024. If you compare our oncology pipeline today to previous years, you can see that we have significantly increased the number of Phase 2 and 3 trials that are ongoing, both as a total number and as a percentage of the total trials we are running. When choosing which programs to move forward into late-stage trials, we maintain a high bar for prioritization, which is guided by clinical data, unmet medical need and commercial potential. As Ugur pointed out, our mRNA immunotherapies and our BNT327 centered clinical development program are dominantly represented in our pipeline and particularly so in the advanced clinical stages with BNT327 becoming our platform for unique combinations with several of our other assets, particularly our ADCs. As Ugur mentioned, 2025 will be an important year for both of our priority programs. BNT327, by co-localizing the blockade of PD-L1 and VEGF-A signaling to the tumor is designed to deliver superior anti-tumor, immune modulatory and anti-angiogenic effects, compared to the individual targeting of PD-L1 and VEGF-A with the potential to minimize adverse events associated with systemic anti-VEGF-A therapy. With anti-PD-L1 and anti-VEGF-A mechanisms being validated across numerous tumor types and in some cases in combination, we have a roadmap for development. We have made strong progress over the past few months across all three waves of our BNT327 clinical development program. The first wave is focused on lung cancer and TNBC as key indications to establish BNT327 combined with standard-of-care chemotherapy with first approvals in first-line settings of these indications. We have completed enrollment in our global Phase 2 dose optimization studies in small-cell lung cancer and TNBC. In small-cell lung cancer, we have begun enrolling patients in the global randomized Phase 3 trial. In TNBC, we will start a global registrational study later this year. In non-small cell lung cancer, we have begun enrolling patients in our global Phase 2 registrational clinical trials. Our second wave of development with BNT327 reflects that IO plus ADC combos are an emerging treatment paradigm in oncology. We have started exploring combinations of BNT327 with four ADCs directed against TROP2, HER2, HER3, and B7H3 from our partnerships with Duality and MediLink and informed by a robust database of single-agent data for these ADCs. A BNT327 ADC combination study with our TROP2 ADC BNT325 is already enrolling patients. In the coming months, we expect to dose the first patients combining BNT327 with our HER2 ADC, 323 and our B7H3 ADC. Throughout this year, we will evaluate the data from these initial combination trials and will start additional novel combinations across two more types to broaden our global clinical development program with BNT327. With this focused clinical development program, we aim to leverage BNT327 full potential. As previously mentioned, we expect 2025 to be a data-rich year across our whole pipeline and especially for BNT327. The first of these datasets will come later this month at the European Lung Cancer Congress and feature our trials in small cell lung cancer. Small cell lung cancer is a tumor type with notable incidence worldwide and an immunologically cold tumor for which high unmet need remains. With current standard-of-care treatment, the durability of responses is quite short, and the five-year survival rate for extended-stage small cell lung cancer is only 3%. Based on our emerging data, we believe that BNT327 has the potential to improve clinical outcomes for patients with small cell lung cancer. At ESMO 2023, data were presented, which show encouraging activity of BNT327 in combination with standard-of-care chemotherapy in second-line small cell lung cancer that has motivated us to pursue small cell lung cancer as one of our priority indications for BNT327. We plan to present additional datasets from trials in small cell lung cancer this year, including data from two separate single-arm Phase 2 trials, evaluating BNT327 plus chemotherapy as the first or second-line treatment for extensive-stage small cell lung cancer. These datasets continue to support our enthusiasm for evaluating BNT327 for the potential treatment of first-line small cell lung cancer in our ongoing global Phase 3 trial. As Ryan will cover later, we expect to share additional important clinical data updates throughout the year. Our mRNA cancer immunotherapy platforms, iNeST and FixVac, are the other cornerstones of our oncology portfolio. Autogene cevumeran, also known as BNT122, developed in partnership with Genentech, is based on the iNeST platform. iNeST targets neoantigens, unique tumor-specific mutations and is manufactured on demand for each individual patient. FixVac, in contrast, targets shared non-mutated tumor antigens and is an off-the-shelf approach. Both platforms utilize our proprietary uridine mRNA LPX delivery technology. The discovery of these two different types of target antigens is one of our core competencies. Over the past several years, we've accumulated substantial data from iNeST and FixVac trials across various tumor types. These data consistently demonstrate that uridine mRNA LPX-based immunotherapies have a manageable safety profile, when used as single agents in combination with anti-PD-1/PD-L1 inhibitors or chemotherapy. Crucially, our data also indicates that these immunotherapies are highly effective at inducing and expanding high-magnitude functional and long-lived T cell responses in a significant proportion of patients. This robust immune response is a prerequisite for clinical activity. We have multiple trials with both FixVac and iNeST ongoing and have had multiple data reports in the past years, and particularly in 2024. Today, I would like to focus on iNeST and recent data we have obtained in the trial highlighted here from which we recently published data in Nature Medicine. This is our first Phase 1 clinical trial of autogene cevumeran published in Nature Medicine, which included over 200 patients with resistant refractory advanced and metastatic solid tumors. This trial evaluated autogene cevumeran both with and without the checkpoint inhibitor atezolizumab. It is known that only a small fraction, 1% to 2% of cancer mutations spontaneously elicit an anti-tumor immune response. Our mRNA cancer immunotherapy approach aims to significantly increase these anti-tumor immune responses. In this Phase 1 trial, autogene cevumeran successfully induced T cell responses across multiple cancer types, converting a high portion of patients into immune responders. The majority of these responses were fully epitopic directed against multiple mRNA-encoded neoantigens. And these responses were de novo, meaning they were newly generated against the encoded neoantigens and did not exist prior to treatment. In some patients, we observed up to a two-order of magnitude amplification of existing neoantigen-specific T-cells. Furthermore, in several patients, we detected newly induced anti-tumor T cells infiltrating the tumors of treated patients. These findings demonstrate the potent immunogenicity of autogene cevumeran even in patients with advanced rapidly progressing cancers, which is a prerequisite for clinical activity. In our ongoing Phase 2 clinical trials, we aim to confirm these data and evaluate the treatment settings and indications where immune responses translate best into clinical activity. While we saw strong immune responses in this Phase 1 trial, we observed modest signals of clinical activity, which was expected given that this Phase 1 trial was conducted in heavily pre-treated resistant refractory fast-growing advanced cancer. We recently also received top-line data from the IMCODE001 Phase 2 trial marked here on this slide. This was the first randomized proof-of-concept Phase 2 trial of an iNeST candidate, evaluating autogene cevumeran in combination with pembrolizumab versus pembrolizumab alone, a first-line treatment for patients with metastatic or advanced melanoma. This trial is part of a broader IMCODE study program initiated in 2017 by our partner Genentech and us, designed to identify optimal treatment settings in patient populations for individualized mRNA cancer immunotherapies, including early and late-stage cancers. According to the initial data, we confirm our observations that autogene cevumeran induces high-magnitude immune responses against encoded neoantigens in this advanced treatment setting. Here in patients with advanced and metastatic melanoma, the trial did not meet its primary endpoint of a statistically significant improvement in progression-free survival. However, we did observe a numerical trend favoring the combination arm in overall survival. The combination of autogene cevumeran with PD-1 blockade was well-tolerated with adverse events consistent with the known safety profiles of the individual treatments. We are continuing to analyze the results, including exploratory endpoints and biomarker correlation. We and our partner, Genentech, will share these data with the scientific community at an upcoming medical conference. The outcome confirms what we have observed in our Phase 1 trial in patients with heavily pre-treated resistant refractory fast-growing advanced cancers and provides valuable insights. Patients in the first-line metastatic melanoma setting have a substantial tumor burden and rapid disease progression. An effective immune response, even a potent one, requires time to develop, typically six to eight weeks based on our data. This time frame may be insufficient to control rapidly growing advanced disease and may require treatment combinations with other modalities. This experience combined with our extensive translational data reinforces our strategic focus on using iNeST in the adjuvant setting, where patients have resectable cancers and minimal residual disease. We believe this setting offers a strong biological rationale for success due to several reasons: adjuvant therapy targets a much smaller number of residual tumor cells after surgery, the slower disease progression in the adjuvant setting allows sufficient time for the vaccine-induced immune response to develop and mature. Also, in earlier disease stages, mechanisms of resistance, clonal heterogeneity, and an immune-suppressive tumor microenvironment are typically less established. Patients in the adjuvant setting often have healthier immune systems and less compromised T cell function increasing the likelihood of a clinically meaningful response. This rationale is the reason why we strategically focused our advanced iNeST program under the adjuvant setting. We currently have three ongoing randomized Phase 2 trials of autogene cevumeran, one in colorectal cancer that is enrolling Stage 2 high-risk and Stage 3 CRC patients, who are ctDNA positive after surgical resection and standard-of-care chemotherapy. These patients are at high risk of recurrence, often within a year. We continue to anticipate initial data from this study either late this year or in early 2026. These data will be critical for informing the next stages of development and regulatory discussions. We are also evaluating autogene cevumeran as an adjuvant treatment for pancreatic cancer. This Phase 2 is informed by a small Phase 1 trial, in which we showed strong immune responses induced by autogene cevumeran and their correlation with significant improvement of recurrence-free survival. A randomized controlled Phase 2 trial in bladder cancer was initiated in the fourth quarter of last year. We believe individualized cancer immunotherapies have the potential to change the current standard of care and improve overall survival by delaying or preventing recurrence or cancer metastasis. 2025 will be an important year for BioNTech. We are intensely focused on the execution of our late-stage trials, particularly in the adjuvant setting, where we believe our individualized mRNA immunotherapy approach has the greatest potential for clinical impact, while we are evaluating novel IO combinations for the treatment of advanced rapidly progressing high-volume tumors. We look forward to providing updates on our progress. With that, I will now pass the presentation to our CFO, Jens Holstein.

Thank you, Ozlem, and a warm welcome to everyone who has dialed into today's call. I'll start with our fourth quarter and full-year results for 2024. Then I'll share our 2025 financial guidance. In terms of our financial results, we executed the year according to our plans. We recognized around EUR2.8 billion in revenues, meeting the approximate midpoint of our full-year 2024 revenue guidance and with this slightly better than our previously announced expectation. Driven by effective cost management, we limited our full-year 2024 losses before taxes to approximately EUR678 million and a diluted loss per share of EUR2.77. Our cash position, including cash equivalents and investments in securities, amounted to EUR17.4 billion at the end of 2024. This leaves us financially positioned to continue with the execution of our strategy in 2025. Please note that this year-end cash position has not yet reflected the closed acquisition of Biotheus to the amount of approximately $800 million and payments derived from the settlement of the contractual disputes with NIH and the University of Pennsylvania amounting to $792 million and $467 million, respectively. We expect that the Biotheus acquisition payment and the NIH payment totaling approximately $1.6 billion will be reflected in our first quarter 2025 financial position. We expect that the University of Pennsylvania settlement payment will be reflected in our second quarter 2025 financial position. With respect to the settlements, we also expect a reimbursement of approximately $535 million from our partner Pfizer during 2025 and 2026. I'll be moving now to the summary of our financial results for the fourth quarter and the full year of 2024 as shown on the next slide. For the three months ended December 31, 2024, we recognized total revenues of approximately EUR1.2 billion, compared to approximately EUR1.5 billion in the prior year period. For the full year, we recognized around EUR2.8 billion, compared to around EUR3.8 billion in 2023. The reduction was primarily driven by lower COVID-19 vaccine market demand. Additionally, write-downs by our collaboration partner Pfizer reduced our gross profit share and hence negatively influenced our revenues for 2024. Research and development expenses reached EUR612 million for the fourth quarter of 2024, compared to EUR578 million for the comparative period in 2023. For 2024, R&D expenses amounted to approximately EUR2.3 billion, compared to roughly EUR1.8 billion in 2023. The increase was mainly influenced by the planned advancing of our priority programs, including BNT327 towards late-stage development. SG&A expenses amounted to approximately EUR132 million for the fourth quarter of 2024, compared to EUR142 million in the same period of the previous year. For the 2024 financial year, SG&A expenses amounted to approximately EUR599 million, compared to EUR558 million in 2023. The increase in SG&A expenses is primarily attributable to the build-out of our commercial organization. With respect to the company's other operating results, we reported negative EUR671 million for the 2024 financial year, compared to negative EUR188 million in 2023. This was mainly due to payments and expenses related to the above-mentioned contractual disputes with NIH and UPenn, net of the aforementioned related reimbursements by our collaboration partner, Pfizer. For the fourth quarter of 2024, we reported a net profit of approximately EUR260 million, compared to around EUR458 million for the comparative period in 2023. For the full year 2024, we reported a net loss of EUR665 million, compared to a net profit of EUR930 million in the prior year. Our diluted earnings per share for the fourth quarter of 2024 amounted to EUR1.08, compared to EUR1.88 in the comparative period in 2023. For the 2024 financial year, our diluted loss per share amounted to EUR2.77, compared to EUR3.83 for the prior year. Let's now continue with the next slide. As depicted on the slide, we executed well against our 2024 financial guidance update that was provided in our third quarter earnings call in November. Starting from the top, we achieved roughly the midpoint of our full-year 2024 revenue guidance of EUR2.5 billion to EUR3.1 billion. During our third quarter 2024 earnings call, we stated that we expected full-year 2024 revenues to be at the low end of the guidance range. In the final month of the year, we experienced stronger-than-expected sales outside the US. On R&D, we report roughly EUR2.3 billion in expenses for 2024, slightly below the low end of our full-year 2024 financial guidance range of EUR2.4 billion to EUR2.6 billion. This was in part driven by our active portfolio management and the shifting of some registrational study costs from 2024 into 2025. On SG&A and capital expenditures for operating activities, we ended at the lower end of our 2024 expectations from our last earnings call. Meeting these lower guidance ranges is a result of our continued cost, monetary and financial discipline. Turning to the next slide, let me highlight now some key aspects of the company's outlook for the 2025 financial year. We expect total revenues in the range of EUR1.7 billion to EUR2.2 billion for 2025. Our revenue guidance assumes relatively stable vaccination rates, pricing and market share, as compared to 2024. We also anticipate a revenue phasing similar to last year with the last three to four months driving the full-year revenue figure. In addition, we estimate some inventory write-downs and other charges in the range of roughly 15% of BioNTech's share of gross profit from COVID-19 vaccine sales in Pfizer's territory. We also expect revenues related to our service businesses as well as revenues from the German pandemic preparedness agreement to contribute to our overall group revenues. Please note that potential changes in law or government policy at the state or national level and evolving public sentiment around vaccines and mRNA technology in the United States and/or elsewhere could also negatively influence BioNTech's COVID-19 vaccine revenues and financial results. Turning to operating expenses. In 2025, we expect R&D expenses to be in the range of EUR2.6 billion to EUR2.8 billion. As compared to 2024, we expect to see an increase in investment into our priority late-stage programs in 2025, mainly BNT327, our mRNA cancer immunotherapy and our ADC pipeline. Consistent with our portfolio prioritization strategy, we also expect to decrease our R&D spend outside of our priority areas. We will continue to follow the data generated by our pipeline to ensure we are investing appropriately to drive innovation and create value. Next, SG&A. We expect SG&A expenses to be in the range of EUR650 million to EUR750 million. We are anticipating an increase compared to 2024 as we continue our commercial build-out for oncology and prepare for our first oncology launch. Lastly, capital expenditures for the 2025 financial year are expected to be in the range of EUR250 million to EUR350 million. With these investments, we're paving the way for multiple potential product launches. Investments include manufacturing expansion projects and investment in commercial IT systems to support portfolio growth and build capacity for the development and commercialization of our potentially disruptive pan-tumor technologies. In summary, 2025 will be another year of continued transition for BioNTech with the aim to become a multi-product commercial oncology company. We will continue to diligently invest in our long-term growth strategy while maintaining strict financial discipline. With that, we remain focused on achieving long-term sustainable growth and generating value for patients and shareholders. Now I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for our strategic outlook and concluding remarks. Thank you.

Thank you, Jens. I would like to end our prepared remarks with a summary of our priorities for 2025 and our key anticipated upcoming clinical and regulatory milestones for our oncology pipeline. This year, our focus will remain on executing on two pan-tumor product opportunities, BNT327 and our mRNA cancer immunotherapies. Each of these programs is in Phase 2 or Phase 3 trials and will generate data updates over the course of the year. We will continue to build out our commercial capabilities in oncology to support our goal of becoming a fully integrated biopharmaceutical company. In infectious disease, we will continue to invest to maintain our and Pfizer's global leadership position in the COVID-19 vaccine market while continuing to advance next-generation and combination vaccines in the clinic. We expect to provide multiple updates from our early-stage infectious disease pipeline over the course of the year. We are in a catalyst-rich period for BioNTech. We plan to share multiple clinical updates across our focus programs throughout 2025, including at upcoming oncology conferences in March and April. In addition to the data for BNT327, we plan to share data updates for our mRNA cancer immunotherapies, iNeST and FixVac. And with regards to our first potential oncology product and HER2 ADC BNT323, we plan to share Phase 2 data from a single-arm registrational trial in HER2 expressing endometrial cancer, as we prepare for a potential BLA submission later this year. In closing, I would like to highlight, on the next slide, important investor events we will be holding throughout the year. Our Annual General Meeting will take place on May 16. We are excited to once again host two innovation series events this year. The first will be another AI event on October 1. The second will be our R&D Day on November 18. We will share further details on both events later in the year. With that, we would like to open the floor for questions.

Thank you. We will now take the first question from Daina Graybosch from Leerink Partners. Please go ahead.

Hi, thank you for the question. You had a few charges related to legal events that you talked about, Jens. There's a lot more IP cases going on and they seem to be accelerating and coming to some conclusions. And I wonder if you could just help give us an overview or roadmap of any particular ones that we should pay attention to that you think could have outcomes decided in the next quarters and this year. Thank you.

Thanks, Daina, for the question. I mean, it's very difficult to predict the timing of certain events in such legal disputes. I would like to refer to the 20-F where we have explained the circumstances in detail, and I can't comment more than what we have published in the 20-F.

Yes, Daina, to add to that, I believe we have indicated in the 20-F that we are confident in the strength of our IP statement. While some of these processes may involve multiple appeals, we believe we are in a strong position and will continue to defend our IP estate alongside our partner, Pfizer.

Great. And maybe one more because that was quick. On the FixVac data that you're going to share this year of cemiplimab, can you just remind us of the context going into that? I recall that that was a top-line success. And so, how we should be thinking about a vaccine in relapsed/refractory melanoma in the context of, Ozlem, you sharing that the personalized vaccine didn't work in a metastatic melanoma setting? Thank you.

Thank you for the question. I'm not sure if I completely understood it. So, to clarify, the question was about our melanoma FixVac, BNT111, where we have reported that we achieved the endpoint with top-line results. We will present more data later this year at one of the conferences and are preparing a manuscript, so further information will be available. As you noted, we did observe that our iNeST approach in the first-line setting does not appear to be suitable. Specifically, in the metastatic setting with advanced cancers and higher tumor burden, it is not optimal, which is not surprising. I have explained some of the reasons for this in my talk today. This is why we are concentrating our iNeST approach on the adjuvant setting and have started trials there. We believe that in this setting, the likelihood of achieving significant clinical benefit is much higher due to certain underlying biological factors associated with adjuvant cancer.

And Daina, one of the key differences between the iNeST approach and the FixVac approach is that FixVac can be applied immediately without any delay. And for the iNeST approach at the time point of the clinical trial, we had turnaround times in the range of six to eight weeks, which is really difficult in a metastatic setting, because the tumors tend to progress particularly while vaccination is ongoing and immune responses are built. So based on that, we early on adapted our strategy and went into the adjuvant stage where the patients before they progress have three, six, nine, or 12 months before PFS events occur.

Great. Thank you.

Thank you. We will now take the next question from the line of Akash Tewari from Jefferies. Please go ahead.

Hey, thanks so much. Just on 327, I know in the past, your teams alluded to kind of the costs associated with developing an agent like this across different tumor types. And certainly, Merck is talking about running a lot of different Phase 3 trials over time. And you guys have hinted at a potential 50-50 partnership. Where does BioNTech currently stand on the partnership question on 327 and what clinical or commercial capabilities would you be looking at for an external partner? Thank you.

Yes, thank you, Akash. I’ll begin with that. We are currently moving forward independently, and we believe we have the capability to execute on BNT327 in the initial trials we’ve started, which is our main focus this year. The first indications include non-small cell lung cancer, small cell lung cancer, and triple-negative breast cancer, but we are also considering a wider range of additional indications, including ADC combinations, as mentioned in our prepared remarks. This will be a key focus for 2025. We’re aware that with such a broad potential for IO backbone therapy, combining with other companies' agents could be beneficial in the future. We have indeed been contacted by various companies interested in exploring potential combinations with BNT327, and we are assessing those collaboration opportunities. There’s nothing to announce at this moment, but we believe it’s important, given the extensive potential of the program, to evaluate all opportunities to accelerate and expand it.

Thank you. We will now take the next question from the line of Chris Shibutani from Goldman Sachs. Please go ahead.

Good morning. Thank you so much. With your plan for 327, obviously, the scope of opportunity is considerable. And as we think about the other leading player developing Summit Akeso, they're mapping out a pretty broad plan. Can you clarify how you see what you think will be differentiating in your approach? I think preliminarily, we noticed that you have maybe further along with TNBC, but is there some sort of strategic overlay, whether it's thinking about PD-L1 agnosticism, geographies, something that helps discern how your approach may be differentiated to ultimately also demonstrate differentiated clinical data? Thank you.

So I can start, and Ugur and Ozlem can add. So, I think the first point to mention, Chris, is that because we see such a broad potential therapeutic opportunity here for this product in terms of many different tumor indications, also different patient segments within tumor indications, both where PD-1/PD-L1 therapies have been successful, but also potentially in patient segments where PD-1/PD-L1 historically has not been successful. Given that potential breadth, we think that the most important element of strategy is actually going to be clinical development strategy, targeting the right patient groups and executing against those initial set of trials. The initial batch of trials are likely to involve chemotherapy combinations and you see that with the three indications that we've disclosed so far. But down the road, as we've also mentioned, we think a further angle of differentiation is going to be other combinations, including with ADCs. And I think there, BioNTech is uniquely situated given the broad portfolio of both ADCs and also cancer vaccines that we have that could enable such novel combinations. I don't know, Ugur, do you want to add to that?

It's really about the execution of this trial. If you consider the full spectrum, it will take many years across multiple indications. Looking back at what has happened in the IO field for anti-PD-1 treatments, this has been an ongoing process over the last ten years. We expect a similar trajectory for the next generation of PD-1 blockade with the bispecific antibody. In the coming year, we anticipate the need to initiate multiple clinical trials across various indications, not only in combination with standard-of-care treatments but also exploring combinations with novel compounds to enhance the efficacy of BNT327 alone.

Can I follow-up with a quick related question? Are you seeing any issues with the enrollment of trials or competing for sites for the enrollment of patients? Thank you.

We don't see anything specific. I mean, you know that clinical trial enrollment, in particular, in those high medical need indications like non-small cell lung cancer and breast cancer and so on is, generally speaking, very competitive because there is a lot going on. But we don't see any specific effects on our trials and we have actually very good enrollment in particular into the 327 trials, which seems to be a compound where investigators are very enthusiastic about.

Thank you. I appreciate the follow-up.

Thank you. We will now take the next question from the line of Tazeen Ahmad from Bank of America Securities. Please go ahead.

Hi, good morning. Thanks for taking my question. Can I just ask you what you're expecting the bar for efficacy to need to be for 323 for the endometrial data that you're expecting this year that would be able to support the filing this year? And then related to that, maybe the second part of the question is for Ryan. How are you preparing for the launch of 323 if in fact you're able to do so in 2026? And maybe one follow-up on that previous question a few minutes ago about partnerships. How are you thinking about building out the commercial organization versus waiting to partner? Thanks.

Yes, thanks, Tazeen. So on the first question, just to clarify, I think you're asking the efficacy bar for BNT323 in endometrial cancer, correct?

So as you know, endometrial cancer is an indication where patients can be categorized into HER2+ and HER2-low tumors. Based on that, we expect efficiencies in the range of ADCs that have been evaluated in this indication. It's a single-arm study, the standard of care therapy with a very short PFS and OS. As you know, the compound BNT323 received breakthrough designation in this indication. So we are confident that the results will fulfill the requirements for potential registration.

Yes. And to Ugur's point, I mean, we've seen within HER2 response rates around 50%, but increasingly we're expecting in HER2 to move into the first line. And if we look at the other second-line therapies that are available, including bevacizumab plus chemo, we're seeing response rates far lower than that in terms of standard of care, so in the sort of 20% range.

Thank you.

Could you just repeat this question, please?

Oh my god. I mean, this is crazy.

Sorry, we will now take the next question from the line of Terence Flynn from Morgan Stanley. Please go ahead.

Hi, thanks for taking the question. I know you mentioned you're going to have some 327 Phase 2 data for small cell lung cancer here over the next month or so. I was just wondering if you can help frame expectations there in terms of what you're hoping to see and actually how much data we'll get? Will we get anything with respect to PFS, et cetera? Thank you.

In the beginning, I will start, and Ozlem or Ugur might join me. We have already shared some data on small cell lung cancer, where we reported response rates around 70% for the combination with chemotherapy. We anticipate that the upcoming datasets will further validate and expand on those findings, reinforcing our decision to proceed vigorously into pivotal trials for small cell. A unique aspect is that we will be presenting data for both first-line and additional second-line treatments, which will enhance the previous datasets we released.

Yes. This year, there will be a data report that will provide a follow-up and update on an ongoing clinical trial that was presented last year. You will receive follow-up data as well as new data from our dose justification clinical trials that we have initiated.

Thank you. We will now take the next question from the line of Harry Gillis from Berenberg. Please go ahead.

Hi, thank you for taking the question. Just on the 2025 revenue guidance, you talked about relative stability in vaccination rates, pricing and market share. I was just wondering if you could provide maybe some quantification or details on what those metrics look like at the low and high end of your guidance? And perhaps specifically, what you're factoring into your forecast for U.S. vaccination rates and any impacts from Sanofi's commercialization of the known FixVac? Thank you.

Thank you for your question. Our revenue guidance for 2024 assumes stable vaccination rates and market share as we see it. However, we also need to consider Pfizer's guidance, which includes some write-offs related to product returns and material from the variants produced, specifically JN.1 and KP.2. We are accounting for these write-offs in our gross profit share. Additionally, we have factored in some minor changes in price and volume in the U.S. for 2025, which may reflect some competitive pressure, particularly from Sanofi. Lastly, there is a possibility that the EU may postpone some volume to 2026, and we have taken that into account as well, which helps explain our position at the midpoint of our guidance range.

Thank you. We will now take the next question from the line of Cory Kasimov from Evercore. Please go ahead.

Hey, guys. Thanks for taking the question. I wanted to follow-up on Terence's question regarding setting the stage for the update later this month at ELCC. Are you able to comment on how much follow-up you will have at the meeting? And what do you see as the appropriate comparison at this stage? Thank you.

So, we will have PFS data. I cannot say from the top of my head what the follow-up time within the study is, but we will have PFS data on our small cell lung cancer trial.

And emerging OS data.

Yes. No median OS, but emerging OS data, yes.

Yes. Then...

In terms of the standard of care, it continues to be in the first-line setting and continues to be Tecentriq plus chemotherapy with the benchmark.

Great. Thank you.

Thank you. We will now take the next question from the line of Mohit Bansal from Wells Fargo. Please go ahead.

Hi, this is Sadia Rahman on for Mohit. Thanks for taking our questions. So, another question on 327 with a competitor expected to read out their OS data in lung cancer later this year, how would you view read-through from those results to 327 in lung cancer? And can you discuss any differences in how you're approaching development, specifically in non-small cell lung cancer from the competitor? Just any differences or similarities that you would highlight? Thank you.

Okay. Our non-small lung cancer study is actually two studies in one study addressing the complete population of AGA negative first lung cancer patients. That means the PD-L1, high PD-L1, low and PD-L1 negative population in squamous and non-squamous patients. Our comparator is pembrolizumab plus chemotherapy, and the treatment group received BNT327 plus chemotherapy. The endpoints are as usual PFS and OS.

Thank you. We will now take the next question from the line of Asthika Goonewardene from Truist Securities. Please go ahead.

Hi, guys. Thanks for taking my question. Ozlem, you mentioned that you started recruiting patients for a Phase 2/3 trial in non-small cell lung cancer. Could you give a little bit more color on the size of that Phase 2 cohort? And if you plan on reporting that data, and maybe a little bit of guidelines on expectations for enrolling that Phase 2 portion. And then sort of related to this, could you maybe comment on the statistical analysis of this study? And I believe you're considering the non-squamous and squamous populations separately, which is different from how your competitor Summit is doing their analysis of HARMONi-3. So why do you prefer your method? Thank you.

The question was about the size of our study. There were several inquiries, particularly regarding the non-small cell lung cancer investigation. As Ugur mentioned, this study essentially functions as two studies in one because we aim to investigate both non-squamous and squamous small cell lung cancer across all PD-L1 status settings in our Phase 2/3 trial. With these varied patient populations included, our sample size stands at around 950 patients. Based on previous data, we believe that these different histologies and various PD-L1 strata can benefit from the BNT327, which is why we have incorporated them all into our study.

And we discussed also all kinds of options on how to structure this clinical trial, including also having a single big cohort based on discussions with the FDA, we decided to have two indications, particularly with the observations in some of the clinical trials where non-small cell lung cancer and squamous did show different types of results for some compounds. There is now more attention on the different histologies.

Got it. Guys, but can I also just double click into this a little bit, please? Because the study, the Phase 2/3 recruiting 980 something patients, what proportion of that target enrollment is specifically for the Phase 2 component?

So the Phase 2 component is around 40 patients. The Phase 3 component is 940 something. So I was basically reflecting the Phase 3 component with the sample size, and this is equally distributed across non-squamous and squamous non-small cell lung cancer sub-studies, so to say.

Got it. Thanks so much for the color.

Thank you. We will now take the next question from the line of Yaron Werber from TD Cowen. Please go ahead.

Great. I have a quick question. Actually, I want to maybe shift to the ACIP latest decision not to hold an ACIP meeting, this time it was for flu. Just curious, I know it's kind of early, but how would you handle this? Would you, at the end of the day, with Pfizer just use the World Health Organization recommendation for the COVID strains? And I don't know whether you have any sort of communications so far, sort of what to expect? Thank you.

Yes, thank you, Yaron. Not too much to say at this stage. Obviously, we're following very closely the policy environment for COVID-19 vaccines in the United States. Our expectation is that there will eventually be a strain selected and we're going to be in a position to respond very quickly as we have done over the last couple of years. But I'm afraid that, at this point, that's pretty much all we can say.

Yes. Thank you. We will now take the next question from the line of Jessica Fye from JP Morgan. Please go ahead.

Hey, guys, good morning. Thanks for taking my question. So beyond the small-cell lung data coming up imminently for 327, can you just take us through what specifically the next 327 data releases will be and where we should look out for them? I realize there's a number listed on the slide, but it just says 2025 plus. Thank you.

The question was about the upcoming data for BNT327 following the small cell lung cancer results. One of the upcoming data sets will cover triple-negative breast cancer, where we have an ongoing Phase 2 study and additional follow-up data from a previous study presented last year at the San Antonio Conference, which will provide insights into overall survival. We may also release additional reports regarding other indication cohorts for BNT327, including initial cohorts that combine it with our antibody-drug conjugates, particularly our trial that involves combining BNT327 with BNT325, our leading two ADCs.

Thank you. That's all the time we have for questions today. This concludes today's conference call. Thank you for participating. You may now disconnect.