Welcome to BioNTech's First Quarter 2025 Earnings Call. I would like to hand the call over to Michael Horowicz, Director, Investor Relations. Please go ahead.

Thank you. Good morning, and good afternoon. Thank you for joining BioNTech's first quarter 2025 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 3, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team: Ugur Sahin, Chief Executive Officer and Co-Founder; Özlem Türeci, Chief Medical Officer and Co-Founder; Jens Holstein, Chief Financial Officer; and Ryan Richardson, Chief Strategy Officer. With this, I'd like to hand the call over to Ugur.

Thank you, Michael. A warm welcome to all those joining us today. As BioNTech has grown and evolved significantly over the years, our vision has remained unchanged: to translate science into survival by building an immunotherapy powerhouse and becoming a fully integrated biopharmaceutical company with multiple approved products. In today's call, we will provide updates on key achievements from this quarter related to our strategic goals. In oncology, we presented new clinical data for our two pan-tumor priority programs, our bispecific immunomodulator BNT327 and our mRNA cancer immunotherapies at recent medical meetings. For BNT327, our bispecific anti-PD-L1 anti-VEGF antibody, we've presented new Phase 2 data in small-cell lung cancer at the European Lung Cancer Congress with preliminary overall survival data in the first-line setting. At AACR, we reported the first data from our Phase 1 trial evaluating BNT327 in combination with our top two targets in ADC BNT325, signaling that this combination appears to have a manageable safety profile and may have synergistic clinical efficacy. This data strengthened our conviction in BNT327 as a next-generation IO-backbone. We will continue to drive its clinical development with the aim to establish a new standard of care for cancer patients who are currently treated with approved checkpoint inhibitors and for some that are currently not. For our mRNA cancer immunotherapies, we reported data from ongoing Phase 1 trial evaluating BNT116, our off-the-shelf FixVac mRNA immunotherapy candidate in combination with cemiplimab in PD-L1 positive frail patients with non-small cell lung cancer. The data indicate that our off-the-shelf mRNA immunotherapy may be synergistic with checkpoint inhibition. Likewise, we are progressing our individualized mRNA cancer immunotherapy autogene cevumeran in randomized Phase 2 trials. Early in 2025, we published two manuscripts discovering our insights from two Phase 1 trials, which demonstrate the polyspecific induction of long-term neoantigen-specific T cell responses and strongly support the anticipated mode of action of our individualized mRNA therapy approach in multiple cancer indications. We are also advancing towards commercialization in oncology with the first BLA submission for BNT323. Our HER2 ADC planned by the end of 2025, pending regulatory feedback. Regarding our COVID-19 vaccine franchise, we initiated preparations to be on track to roll out a variant-adapted COVID-19 vaccine for the upcoming season. During the quarter, we closed the Biotheus acquisition and now hold global control over BNT327. We were able to achieve all this while maintaining a strong financial position. Leveraging our COVID-19 vaccine business and our strong financial position, we are significantly investing in the clinical development of our priority oncology programs across key tumor indications. Before I continue with our strategy in oncology, I would like to provide an update regarding our Management Board. Today, we announced our new Chief Financial Officer. We will welcome Ramón Zapata on July 1, 2025. Ramón is an accomplished leader with deep finance experience who will be taking over from Jens at an exciting phase. He will join BioNTech from Novartis, a global biomedical research organization, where he has been serving as CFO since 2022. He will introduce himself in the next analyst and investor call in August. With this, and as previously shared, our current CFO, Jens Holstein, will retire at the end of his term at the end of June as planned. Dear Jens, thank you for your excellent financial leadership and your significant contributions to BioNTech's successful trajectory. We wish you continued success and fulfillment in the next chapter of your journey. Now coming back to our oncology strategy. One of our first convictions for cancer immunotherapy is that we believe that future cancer treatment, and particularly the desire to increase cure rates in human cancer, will be driven by combination therapy, exploiting compound classes with potentially synergistic modes of action. Driven by our vision, we want to address the full continuum of cancers across different states, from resected cancers, which are in the adjuvant stage and have a high risk for relapse, to early-stage metastatic cancers, as well as the late-stage cancers, which are refractory to different types of treatment. We have built a pipeline with compounds from different classes that are well-suited to achieve this, following for novel-novel combinations of immunomodulators with targeted therapies and mRNA cancer immunotherapies. With 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. We believe that our two priority pan-tumor programs, our mRNA cancer immunotherapies, FixVac and iNeST, and our bispecific anti-PD-L1 anti-VEGF antibody BNT327, have disruptive potential and are aligned well with our vision. If successfully developed and approved, we believe these programs could establish a new standard of care and enhance patients' 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 the future commercialization in key markets, and enhancing manufacturing capabilities to support both clinical trials and commercial supply. I will turn the call over to Özlem to provide more details on select clinical programs.

Thank you, Ugur. Glad to be speaking with everyone today. Our first oncology programs are moving towards commercial stage. We continue to advance toward our first BLA submission in oncology with BNT323 in HER2 expressing second-line endometrial cancer. Alongside BNT323 and our mRNA cancer immunotherapies, BNT327 is a key program in our development pipeline, with first global pivotal clinical trials in triple-negative breast cancer, small cell, and non-small cell lung cancer. BNT327 by co-localizing the blockade of PD-L1 and VEGF-A signaling to the tumor is being developed with the aim to deliver superior anti-tumor immunomodulatory and anti-angiogenic effects compared to individual targeting of PD-L1 and VEGF-A, and with the potential to minimize adverse events associated with systemic anti-VEGF-A therapy. We now have data from over 1,000 patients across indications, which further strengthens our conviction in this asset. With the anti-PD-L1 and anti-VEGF-A mechanisms being validated across numerous tumor types and, in some cases, in combination, we have a clear roadmap for development. The first wave is focused on small cell and non-small cell lung cancer and TNBC as key indications to establish BNT327 combined with standard-of-care chemotherapy, with first approvals then for the first-line settings of these indications. We have made continuous progress over the past months in researching these key indications. 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 novel ADC candidates informed by single-agent data for these ADCs. The last wave aims at further broadening our global clinical development program with BNT327 through additional novel combinations across tumor types. As mentioned, triple-negative breast cancer is a priority indication for BNT327 based on the unmet need we see for patients and based on the clinical profile observed to date. Stage 4 TNBC patients have a poor prognosis with a five-year survival rate around 10%. Currently, these patients, depending on their PD-L1 status, are either treated with checkpoint inhibitors in combination with chemotherapy or with chemotherapy alone. PD-L1 positive patients have a median overall survival of 23 months, while PD-L1 negative patients have a median overall survival of 15.2 months, as observed in the KEYNOTE-355 study. Data from a study in first-line metastatic triple-negative breast cancer showed that BNT327 in combination with chemotherapy has an encouragingly high objective response rate of 73.8%, irrespective of PD-L1 status. We also observed in the trial encouraging landmark overall survival rates, such as 69.7% at 18 months for BNT327 in this setting, suggesting that effective control of disease can translate into improved overall survival. In addition to the encouraging efficacy data, the manageable safety profile was observed with no new safety signals beyond those typically described for standard-of-care chemotherapy, for anti-PD-1/PD-L1, and anti-VEGF-A monotherapies. Based on these data, we believe that BNT327 has the potential to become a first-line treatment option for triple-negative breast cancer patients, including those not currently treated by existing IO therapies. We also plan to start a Phase 3 trial later this year in the first-line setting. Moving to extensive-stage small cell lung cancer, an immunologically cold tumor for which a high unmet need remains. With current standard-of-care treatment, the durability of responses is quite short, and the five-year survival rate is only 3%. Today, these patients are treated with a combination of atezolizumab and chemotherapy and experience a median overall survival of 12.3 months, as observed in the IMpower133 clinical trial. Based on our emerging data, we believe that BNT327 has the potential to improve clinical outcomes for patients with small cell lung cancer. At the European Lung Cancer Congress, we disclosed interim data from a Phase 2 clinical trial evaluating BNT327 in combination with chemotherapy as a first-line treatment for patients with extensive-stage small cell lung cancer. Beyond the response rate of 85.4% and median progression-free survival of 6.9 months, the ELCC data also included for the first time median overall survival data with a median overall survival of 16.8 months. In addition, a manageable safety profile was observed with no new safety signals beyond those typically described for chemotherapy agents and anti-PD-L1 and anti-VEGF monotherapies. While these data are still immature, we are encouraged by the findings. These data support our decision to evaluate BNT327 in combination with chemotherapy in the ongoing global randomized Phase 3 clinical trial, ROSETTA Lung-01. We view non-small cell lung cancer as one of our priority indications as it's the number one most prevalent cancer globally. Over 80% of patients are diagnosed at late stages. Long-term outcomes depend on PD-L1 status and histology, but overall remain poor despite improvements in care by checkpoint inhibitors. At the ASCO Annual Meeting last year, we presented data from the Phase 1 trial evaluating BNT327 as a monotherapy first-line treatment in metastatic PD-L1 positive non-small cell lung cancer. BNT327 monotherapy treatment resulted in an overall response rate of 47%, a DCR of 100%, and mPFS of 13.6 months. In summary, BNT327 indicated encouraging anti-tumor activity and manageable safety in this patient population. Safety events were consistent with those described for anti-PD-L1 and anti-VEGF monotherapy. These data support our decision to start our global Phase 3 trial in non-small cell lung cancer, which is named ROSETTA Lung-02. ROSETTA Lung-02 is designed to evaluate the potential of BNT327 dosed in combination with chemotherapy to improve on survival outcomes when compared to standard-of-care pembrolizumab in combination with chemotherapy as a first-line therapy for non-small cell lung cancer patients without actionable genomic alterations. This trial is enrolling both non-squamous and squamous histologies in two separately powered sub-studies, and each sub-study will enroll patients across all PD-L1 statuses. The study includes a Phase 2 part with 40 patients seeking to establish the dose for the Phase 3 randomized part in 942 patients. The co-primary endpoints are progression-free survival and overall survival. Today, we are enrolling patients in the Phase 2 part and expect to progress to the Phase 3 part data this year. We will present the complete trial design for our two ongoing BNT327 global Phase 3 studies, ROSETTA Lung-01 and ROSETTA Lung-02, which are evaluating BNT327 dosed in combination with chemotherapy in first-line small cell and non-small cell lung cancer at the ASCO Annual Meeting at the end of this month. We plan to have a significant presence at the ASCO Annual Meeting, including five clinical data updates across our oncology pipeline, featuring not only our immunomodulator BNT327, but also our anti-CTLA-4 BNT316, our B7H3 targeting ADC BNT324, and BNT142, our CLDN6 T-cell engager RiboMab. We look forward to this and other conferences this year, during which we plan to share more data updates across our investigational oncology pipeline as we continue our progress toward becoming a multi-product oncology company. To conclude, as I highlighted at the beginning of my section, we remain strongly convinced that our combination-based pipeline offers the potential to positively impact the future outcomes for patients in key indications such as in breast and lung cancers. With that, I will now pass the presentation to our CFO, Jens Holstein.

Thank you, Özlem, and a warm welcome to everyone who has dialed into today's call. Let me begin my section with our Q1 2025 financial results. In the first quarter of 2025, we reported total revenues of approximately €183 million, driven mostly by the sale of our COVID-19 vaccines, compared with €188 million for the first quarter of 2024. This revenue figure is consistent with our expectations and reflects the seasonality that we expect in an endemic COVID-19 environment. Research and development expenses reached €526 million for the first quarter of 2025, compared to €508 million for the comparative prior-year period. The increase was mainly driven by progressing late-stage clinical studies for pipeline candidates, including BNT327 in our ADC portfolio. SG&A expenses amounted to approximately €121 million in the first quarter of 2025, compared to €133 million in the comparative prior-year period. The decrease was primarily driven by a reduction in external services. For the first quarter of 2025, we reported a net loss of €416 million compared to a net loss of €315 million for the comparative prior-year period. Our basic and diluted loss per share for the first quarter of 2025 was €1.73 compared to a basic and diluted loss per share of €1.31 in the comparative prior-year period. As indicated in our full-year earnings call in March, 2025 will be a year of transition for BioNTech with the aim of becoming a multi-product oncology company. We will continue to invest with discipline in our long-term growth strategy, namely by advancing BNT327 and our mRNA cancer immunotherapies. We believe that these two programs have disruptive and tumor potential. We ended the quarter in a strong financial position with €15.9 billion in total cash plus security investments. Among other things, the reduction compared to the year-end figure is due to the payment of approximately US$800 million as part of the Biotheus acquisition. It also reflects the payment made in connection with the settlement of a contractual dispute with NIH of about US$792 million. We expect an additional payment of US$400 million associated with the settlement with the University of Pennsylvania to be reflected in our second quarter 2025 financial position. With respect to both these settlements, we expect to be reimbursed partially by our partner, Pfizer, during 2025 and 2026. Building on our strong cash position and track record of financial discipline, we will continue to invest in our pan-tumor oncology programs, which we believe position us well to achieve sustainable growth. Turning to the next slide, we are confirming the company's financial guidance for the 2025 financial year, with revenue expected to be in the range of €1.7 billion to €2.2 billion; R&D expense is expected to be in the range of €2.6 billion to €2.8 billion; SG&A expense is expected to be in the range of €650 million to €750 million; and capital expenditure is expected to be in the range of €250 million to €350 million. Our revenue guidance assumes relatively stable vaccination rates, pricing, and market share as compared to 2024. We anticipate a revenue phasing similar to last year, with the last three to four months of the year driving the full year revenue figure. Please note that potential changes in law or government policy, including tariffs and public health policy, and evolving public sentiment around vaccines and mRNA technology worldwide could further negatively impact our anticipated COVID-19 vaccine revenues and expenses. While it is premature to comment specifically on the potential impact of tariffs on the pharmaceutical industry at this stage, we're actively monitoring the situation and evaluating potential risk mitigation strategies. 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 the Pfizer 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. We continue to diligently invest in our long-term growth strategy while maintaining financial discipline. We remain focused on achieving long-term sustainable growth and generating value for patients and shareholders. Today, I will close my section on a personal note. As Ugur mentioned, I will retire from my executive role at BioNTech at the end of June and will focus on Non-Executive Board roles in the future. As this is my last earnings call as CFO of BioNTech, I would like to take this opportunity to thank the investor and analyst community for their trust. I also thank my colleagues on the supervisory and management board as well as my teams for their dedication and collaboration during this remarkable growth journey. It has been a privilege to be part of the development of BioNTech into one of the largest global biotechnology companies. I'm confident that BioNTech is well-positioned for continued success. And with that, 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 will close our prepared remarks with a brief summary of our 2025 strategic priorities. We are continuing to focus on executing against two pan-tumor product opportunities, BNT327 and our mRNA cancer immunotherapies, FixVac and iNeST. Both of these programs are currently in multiple ongoing Phase 2 and 3 trials, reflecting our strategy to bring novel combinations to patients. We expect to generate additional meaningful data for these programs throughout this year. We are also continuing to build out our commercial capabilities in oncology to support our goal of becoming a fully integrated biopharmaceutical company. These include a US general manager and broader global commercial leadership team with the goal of commercial readiness to support our transition to the commercial stage in oncology, starting with the potential launch of BNT323 as early as 2026, if approved. In infectious diseases, we will continue to invest to maintain our and Pfizer's global leadership position in the COVID-19 vaccine market, while advancing next-generation and combination vaccines in the clinic. We expect to provide multiple updates from our early-stage infectious disease pipeline this year. In closing, 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 16th. We also plan to hold our Innovation Series event in the fall, and we'll share more details later in the year. With that, we would like to open the floor for questions.

Thank you. We will now go to our first question. The first question comes from Tazeen Ahmad from Bank of America. Please go ahead.

Hello, good morning. Thank you for taking my question. As you prepare for your first launch for endometrial cancer, can you talk to us about how big you think that particular addressable population is? And then, related to that, can you remind us where the manufacturing of 327 is expected to take place? And if you expect any impacts from those tariffs? Thanks.

Yeah. Thank you, Tazeen. So, we estimate that the second line market in endometrial cancer is about 10,000 patients in the US and Europe. So, it is a sizable potential market opportunity. In regards to manufacturing, we licensed this program, BNT323, as you know, from Duality Biologics. Manufacturing is currently supplied from China, and we are in the process of diversifying our supply base, and our plans over the next couple of years are to establish multiple supply nodes, including outside of China. But for the time being, we are reliant on a China-based CDMO.

Thank you.

I would like to mention that perhaps Jens can provide some insights into tariffs related to our broader business, but as of now, we do not expect any significant financial impact from the announced tariffs. We are, of course, monitoring the policies and responses to US policy in this area.

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

Hey, thanks so much. So, just more long-term, in NSCLC, let's say, five years down the road, what do you think is the more likely outcome? The VEGF bispecifics changed standard of care in chemo combo or you really actually needed a novel ADC along with the bispecific to beat pembro chemo? And then, kind of as an add-on, how do you expect the safety profile of 327 to evolve in chemo combo versus some of the early data you've seen with the TROP2 ADC? Thanks.

Thanks, Akash. To clarify your question, you want to know how we envision the NSCLC market five years from now. Are we anticipating that an ADC will be an essential part of a next-generation immunomodulator? Is that accurate? Let's go with that.

I think that was the question. Akash, we think that actually both will be the case. On the one hand, we, as you know, are developing our bispecific 327 in combination with chemotherapy to replace first-generation CPIs in non-small cell lung cancer. However, we expect that the clinical benefit threshold to be reached will be moving over time, and, therefore, also ADCs in combination with our bispecifics or with such PD-1, PD-L1 VEGF bispecifics will also have a role. That's the reason why we are following both streams of development in a sort of sequential manner.

Yeah. And with regard to the ADCs, as you know, we have several ADCs that in principle can be combined in the non-small cell lung cancer indication, including our TROP2 ADC, B7H3, as well as our HER3 ADC, BNT326.

Thank you. Your next question comes from the line of Daina Graybosch from Leerink Partners. Please go ahead.

Hi. The CDC's ACIP is set to vote in June on the recommendation for COVID boosters. From their pre-meeting, it seems likely that they may narrow the US recommendation to be based on risk. Could you discuss that meeting, what you expect the vote outcome to be, and how a possible narrowing might impact your COVID-19 vaccine sales in the US? Thank you.

Thank you for the question, Daina. We are monitoring not only the situation in the United States but also in other regions. We expect the first decisions regarding strain selection and policy for the COVID season in 2025 to occur in the next few weeks, as early as May in some areas. We will be monitoring this closely, and we anticipate gaining more clarity within the next four to six weeks. In terms of US policy, most vaccinations have been administered to individuals aged 65 and older, as well as the immunocompromised, who together represent about 20% of the US population. About 18% of the population is 65 and older, with a small percentage more being immunocompromised. This demographic has accounted for the majority of vaccinations in the US over the past couple of years. While we will follow the outcomes of the meeting you mentioned, we believe the market is already moving in that direction. Thus, our expectation is that vaccination rates in the US will remain around the 20% level we have observed over the last couple of years as we approach the end of this year.

Additionally, we have observed similar developments in other regions in the past. This situation is not unique. The recommendations primarily target the older and immunosuppressed populations, but we anticipate that some individuals will still choose to be vaccinated regardless of age guidelines. This has been our experience historically. We will need to assess the potential implications, which may be negative, but predicting them accurately at this moment is challenging.

Thank you. Your next question comes from the line of Cory Kasimov from Evercore. Please go ahead.

Good morning, everyone. Thank you for taking my questions. Jens, congratulations on your retirement. I understand it's challenging to comment on another company's programs, but I would like your opinion on Akeso's recent preliminary overall survival data. Is this in line with your expectations? More specifically regarding the 327, does it influence how you approach designing your own trials for non-small cell lung cancer? Thank you.

Yes. Thank you, Cory, for the question. We are also strong believers in the VEGF PD-1/PD-L1 bispecific concept. Therefore, we find the data which has been reported from HARMONi-2 very encouraging. The PFS, which was the primary endpoint, speaks for itself. The OS trend, which is based on a premature analysis of an immature information fraction with very low alpha, is also encouraging. It has no direct impact on our program. ROSETTA Lung-02 is in a different population. It's in combination with chemotherapy. However, as I said, seeing that the concept as such is producing encouraging data and clinical benefit is also very positive for us.

Thank you. Your next question comes from the line of Terence Flynn from Morgan Stanley. Please go ahead.

Great. Thanks for taking the question. Two-part for me on 327. Thanks for the details on the ROSETTA Lung-02 study. I was just wondering if you could elaborate in terms of the doses that are being studied exactly in the Phase 2 portion and when we might see some of the Phase 2 data? And then, can you disclose the powering of the Phase 3 portion of that trial? Thank you.

We cannot comment on the doses we are exploring at this time. You may receive more information later this year when we present the trial design at conferences. Could you please repeat the second question?

The timing of the data for Phase 2 and the powering of the Phase 3 portion?

Yeah. So, the data for Phase 2, we will see some data later this year, beginning of next year. And the powering for the Phase 3 portion is to accommodate a co-primary PFS OS.

Thank you. Your next question comes from the line of Jessica Fye from JPMorgan. Please go ahead.

Hey, guys. Good morning. Thanks for taking my question. Ryan, I think earlier in the call, you mentioned minimal impact from current tariffs, but can you speak to how the potential implementation of future biopharma tariffs in the US might impact BioNTech? Is commodity for the US market made in the US? And second, can you just recap what you guys see as the key similarities or, maybe more importantly, the key areas of differentiation of your development plans for 327 relative to the Ivonescimab development program? Thank you.

Yeah, sure. Thanks, Jessica. So, on the tariff point, my reference to limited near-term financial impact was related mainly to the fact that we've got one commercial-stage product in commodity currently where we have production infrastructure and capability through our partnership with Pfizer on both sides of the Atlantic. So, we've got the ability. We have the ability to produce that vaccine in the United States. We also have the ability to produce it in Europe, and we have sufficient capacity to manage that accordingly. I don't know, Jens, would you add anything?

No. Just there are existing tariffs already for China, 20% at this point in time that we need to cover, and the financial implications so far have been really minor. For us, going forward, that makes life a little bit difficult in terms of predictions, of course, how that will evolve over time and if pharmaceuticals will be challenged, then costs could go up for clinical trials and for research work, but overall, at this point in time, we would estimate that as not being really critical for us. We can't talk for anyone else, of course. I mean, we've seen a lot of statements from other companies in terms of the tariffs. We've got to wait on how things evolve over time and how severe financial implications can look like.

And with regard to your second question, Jessica, on BNT327 development strategy. I would just note that our strategy is based on a couple of key pillars. The first of which is to establish BNT327 as an approved therapy in a number of solid tumor indications. We've announced publicly three of those indications. A couple of those where we think we're positioned if we can execute well to be potentially first to market. So, TNBC and small cell lung cancer being two of those potential indications. Those first wave of trials are with chemotherapy backbones. We think that's the fastest path to market. But the broader and longer-term strategy is to combine BNT327 with other agents, including ADCs. And there, we think we have a differentiated strategy by virtue of our broad pipeline and the ADCs and other therapies that we have in-house that could be combined with it.

I don't have much to add. Thank you, Ryan. I think that summarizes our differentiation strategy.

Thank you. Your next question comes from the line of Evan Seigerman from BMO Capital Markets. Please go ahead.

Hi, all. Thank you so much for taking my question. I wanted to take a higher-level question. With varying views on mRNA technology, how are you thinking about the potential of your therapeutic vaccine franchise? There's a lot of resistance building up in the United States. Do you still see this as a core component of your strategy? Are you more focused on the bispecifics? Thank you so much.

Definitely, we have a core insight in our mRNA therapeutics. As we have alluded to today, we have two pan-tumor opportunities with BNT327, which gives us the opportunity to develop the product as a potential new IO backbone in multiple indications. And the same is true for the pan-tumor potential for therapeutic mRNA immunotherapies based on our neoantigen as well as our FixVac approach. We believe that this approach has huge potential, particularly in patient populations with a higher risk of relapse either in the adjuvant setting or in the minimal residual disease setting. But we also believe that the combination of both compounds, BNT327 as well as our mRNA therapeutics vaccines, provides a huge opportunity. So, the science is clearly stating that mRNA therapeutics are going to be a disruptive platform of the future, and we believe it's even more the time to invest in the technologies and further leverage our strengths here.

Thank you. Your next question comes from the line of Yaron Werber from TD Cowen. Please go ahead.

Yeah, hi. Thanks for taking my question. I have a couple of interrelated questions. The first one is, you've been very clear, and everything you said made a lot of sense on how you're going to develop 327 in small cell TNBC, non-small cell. What about second-line EGFR mutant? Any thoughts on that indication? Obviously, we're waiting for the Phase 3 from the competitor. And then secondly, can you just remind us for 323 for second-line endometrial, what data are we expecting this year and filing for accelerated approval is going to be based on which endpoints specifically, and if you can, just the powering for that study? Thank you.

For second-line non-small cell lung cancer, I believe you are referring to the EGFR mutant population. We have recently published data in this group, which includes response and progression-free survival data, differentiated by patient populations with PD-L1 positive and PD-L1 negative statuses. The data is very encouraging. We are also currently conducting ADC trials in these populations and are seeing positive data in this area as well. We are considering combining both approaches as we anticipate a synergistic effect, while also keeping the option to use 327 in the subgroup of EGFR mutant tumors based on their PD-L1 status.

And I think in regards to your second question, which I believe was what are the endpoints in the data package that we expect for BNT323 later this year. Ozlem, do you want to comment?

Yes. You are referring to our second-line endometrial cancer trial, which is a single-arm trial derived from our basket trial involving solid cancers that we are conducting with Duality. The endpoint is the objective response rate. We are in discussions with regulatory authorities to gain a clearer understanding of the expectations for the BLA, and we are making progress in these discussions. I might also add, I forgot to say, that the population is across all HER2 positivity scores, so it's a broader second-line endometrial cancer population.

Thank you. Your next question comes from the line of Mohit Bansal from Wells Fargo. Please go ahead.

Good day. Thank you for taking my question, and congratulations on your progress. I have two questions. First, regarding ROSETTA Lung-02, can you provide some timelines on when we can expect the Phase 2 portion of the study to be completed and when you will officially transition into Phase 3? Second, we receive many questions about the differences between your bispecific antibodies and those from Summit and Merck. One key distinction is that you are the only one utilizing PD-L1, along with your very heavy chain, VHH. Could you elaborate on these differences and their potential impact in real-world scenarios, particularly regarding PD-L1, considering the mixed results with PD-L1 antibodies in the past? Thank you.

Okay. So, I think the first question was, when do we expect the Phase 2 portion of the ROSETTA Lung trial to be complete?

The Phase 2 portion of ROSETTA will be finished later this year, providing us with data to guide the Phase 3 part of the trial in determining the dose to be used, which is set to begin this year. The other question was about the...

The difference between PD-L1...

We have identified molecular differences between various bispecific molecules with this mechanism. While we cannot comment on other molecules, we intentionally selected a bispecific that targets PD-L1 compared to PD-1 because we believe PD-L1 may perform better in anchoring, particularly within the tumor microenvironment where we aim to apply this bispecific. This was one motivating factor. Additionally, the molecular structure, which includes a full IgG VEGF anti-VEGF component and a VHH PD-L1 component, was appealing to us because we anticipate it will provide the right balance of cross-mitigation in the tumor microenvironment.

Thank you. Your next question comes from the line of Geoff Meacham from Citigroup. Please go ahead.

Hi, everyone. This is Nishant filling in for Geoff, and I appreciate the question. Regarding 327, you mentioned the potential to combine with other therapies, such as ADCs and cell therapies. I would like to know what factors are influencing the choice of these specific combinations, and what is the overall reasoning behind these combinations? Thank you.

Certainly. Regarding the combination aspect of our portfolio, our cancer products fall into three categories, all of which are compatible with combination therapies. First, we have our IO pipeline, which includes multiple bispecific antibodies, especially following the acquisition of Biotheus. This pipeline will be engaged in clinical trials, and we have established a mode of action synergy for these compounds in the preclinical setting. The second category, which we find very promising, consists of our mRNA vaccines and mRNA immunotherapies. We believe this approach may not only delay progression-free survival and enhance overall survival but could potentially eradicate tumor cells that persist after checkpoint blockade. We are currently conducting several preclinical studies, and our first clinical cohorts will start this year. Recently, we demonstrated preclinical proof of concept for combining BNT327 with our ADC portfolio, which offers the possibility of reducing tumor burden through ADCs, benefiting from the immunogenic cell death they induce, and building on the enhanced effects of the bispecifics that target both anti-VEGF and PD-L1.

Thank you. Your next question comes from the line of Asthika Goonewardene from Truist. Please go ahead.

Hi. This is Karina for Asthika. Thank you for the question. I would like to inquire about the initial AACR data for BNT327, which was combined with the top two ADCs. There was a significant rate of stomatitis, including Grade 3 events. How do you intend to manage this toxicity in the future? Was this also observed with other ADCs from DualityBio?

Actually, the stomatitis rate in the combination was very comparable to the stomatitis rate that is observed with this BNT325, our anti-TROP2 ADC alone, which is very encouraging that we don't see additional additive toxicity.

Thank you. Your next question comes from the line of Harry Gillis from Berenberg. Please go ahead.

Hi, thank you very much for taking the questions. Could you please comment on the extent of global Phase 2 BNT327 data you've seen internally that informs your decision for Phase 3 entry in small cell lung and TNBC? And then related to that, is Phase 3 entry in TNBC still contingent on any Phase 2 global data? And finally, when could we expect the Phase 2 global data for BNT327 in small cell or TNBC this year? Could we see it at ESMO, World Lung? Thank you.

We are conducting our clinical trials for these indications globally, including in the US, Europe, and multiple centers in Turkey, and we are reiterating data previously presented from patients in China. We are very confident that the results from the China trials will be largely confirmed in this global trial.

Thank you. We will now take our final question for today. And the final question comes from the line of John Newman from Canaccord Genuity. Please go ahead.

Hi, thanks very much for taking my question. I'm just curious regarding the development of the COVID-19 vaccine at Pfizer. Wondering if you have any thoughts on some of the recent comments coming out of FDA regarding the possibility of looking at randomized studies for the yearly strain updates. I'm wondering if you think that's feasible or likely, and if it were to move forward, what your strategy might be. Thanks.

Thanks, John. I want to point out that the COVID-19 vaccine was initially approved after studying 43,000 participants in a significant global study where we showed its efficacy. We are closely monitoring any potential policies from the FDA, but we do not anticipate that these discussions will impact our COVID vaccine business in the short term, as it has been approved for several years. We expect that multiple regions will choose strains for the fall '25, '26 season, and that is our current focus.

Absolutely.

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