BioNTech - Earnings Call - Q1 2025
May 5, 2025
Transcript
Operator (participant)
Welcome to BioNTech's first quarter 2025 earnings call. I would like to hand the call over to Michael Horowitz, Director of Investor Relations. Please go ahead.
Michael Horowicz (Senior Director of Investor Relations)
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 U.S. Securities and Exchange Commission. Forward-looking statements on this call are subject to significant risks and uncertainties and seek only, as of the date of this conference call, to be undertaken without 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 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 the call over to Ugur.
Ugur Sahin (CEO)
Thank you, Michael. 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-A antibody presented new Phase II 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 I trial evaluating BNT323 in combination with our top two targeting 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 BNT323 as a next-generation IO battery. 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 I trials evaluating BNT116, our off-the-shelf 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 II trials. Early in 2025, we published two manuscripts describing our insights from two Phase I 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-targeted 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 BioNTech 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 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 cancers, 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 drug classes that are well-suited to achieve this, following four 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.
Özlem Türeci (CMO)
Thank you, Ugur. Glad to be speaking with everyone today. Our first oncology programs are moving towards the 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 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 sent 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 IV TNBC patients face poor prognosis with a five-year survival rate around 10%. Currently, these patients, depending on their PD-L1 status, are either treated with checkpoint inhibitor 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, a manageable safety profile was observed, with no new safety signals beyond those typically described for standard-of-care chemotherapy, for anti-PD-L1, 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 III trial later this year in the first-line setting. Moving to extensive stage small cell lung cancer, an immunologically cold tumor for which high unmet need remains. With current standard-of-care treatment, the durability of responses is quite short, and 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 II 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 III clinical trial, Rosetta Lung 01. We view non-small cell lung cancer as one of our priority indications, as it is one of the most prevalent cancers 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 I 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 an 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 III 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 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 status. The study includes a Phase II part with 40 patients seeking to establish the dose for the Phase III randomized part in 942 patients. The co-primary endpoints are progression-free survival and overall survival.
Today, we are enrolling patients in the Phase II part and expect to progress to the Phase III part later this year. We will present the complete trial design for our two ongoing BNT327 global Phase III studies, Rosetta Lung O1 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 B7-H3 targeting ADC BNT324, and BNT142, our Claudin-6 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.
Jens Holstein (CFO)
Thank you, Özlem, and a warm welcome to everyone who has dialed in 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 EUR 183 million, driven mostly by the sale of our COVID-19 vaccines, compared with EUR 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 EUR 526 million for the first quarter of 2025, compared to EUR 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 EUR 121 million in the first quarter of 2025, compared to EUR 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 EUR 460 million compared to a net loss of EUR 350 million for the comparative prior year period. Our basic and diluted loss per share for the first quarter of 2025 was EUR 1.73 compared to a basic and diluted loss per share of EUR 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 cure potential.
We ended the quarter in a strong financial position with EUR 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 EUR 800 million as part of the Biotheus acquisition. It also reflects the payment made in connection with the settlement of the contractual dispute with NIH of about EUR 792 million. We expect an additional payment of EUR 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're confirming the company's financial guidance for the 2025 financial year, with revenue expected to be in the range of EUR 1.7 billion-EUR 2.2 billion. R&D expenses expected to be in the range of EUR 2.6 billion-EUR 2.8 billion. SG&A expenses expected to be in the range of EUR 650 million-EUR 750 million, and capital expenditures expected to be in the range of EUR 250 million-EUR 350 million. Our revenue guidance assumes relatively stable vaccination rates, pricing, and market shares 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. I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for our strategic outlook and concluding remarks. Thank you.
Ryan Richardson (Chief Strategy Officer)
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 II and III 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 U.S. 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 will share more details later in the year. With that, we would like to open the floor for questions.
Operator (participant)
Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. Please make sure you ask your question loudly and clearly into your microphone, and please limit yourself to one question only. To withdraw your question, please press star one and one again. We will now go to your first question. Your first question comes from the line of Tazeen Ahmad from Bank of America. Please go ahead.
Tazeen Ahmad (Senior Equity Analyst)
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? Related to that, can you remind us where manufacturing of 327 is expected to take place and if you expect any impact from those tariffs? Thanks.
Ugur Sahin (CEO)
Yeah, thank you, Tazeen. We estimate that the second-line market in endometrial cancer is about 10,000 patients in the U.S. and Europe. 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 out of 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. For the time being, we're reliant on a China-based CDMO.
Operator (participant)
Thank you.
Ugur Sahin (CEO)
Tariffs. I'll just say that, you know, maybe Jens, you can say a few things about tariffs for our broader business, but we don't anticipate at the current time significant impact, financial impact from the tariffs that have been announced. Obviously, we're continuing to track policies and responses to U.S. policy in that regard.
Operator (participant)
Thank you. We will now take the next question. Your next question comes from the line of Akash Tewari from Jefferies. Please go ahead.
Akash Tewari (Managing Director and Global Head of Biopharmaceutical Research)
Hey, thanks so much. This is more long-term. In NSCLC, let's say five years down the road, what do you think is the more likely outcome? The, you know, VEGF bispecific change standard of care in chemo combo, or you really actually needed a novel ADC along with the bispecific to beat pembrolizumab? 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.
Ugur Sahin (CEO)
Yeah, thanks, Akash. I think you're asking, just to clarify the question. You're asking in five years, how do we see the NSCLC market evolving? Do we see this evolving where an ADC will be a necessary component on top of a next-generation immunomodulator? Is that fair? We'll go with that.
Özlem Türeci (CMO)
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-1, 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.
Jens Holstein (CFO)
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, B7-H3, as well as our HER3 ADC, BNT326.
Operator (participant)
Thank you. Your next question comes from the line of Daina Graybosch from Leerink Partners. Please go ahead.
Daina Graybosch (Senior Managing Director and Senior Research Analyst)
Hi. CDC's ASIP is going to have a vote in June on the recommendation of COVID boosters. My interpretation of their pre-meeting was there is a likelihood that they narrow the U.S. recommendation to a risk base. I wonder if you could talk about that meeting, what you anticipate the vote will be, and if they do narrow it, how that might impact your COVID-19 vaccine sales in the U.S. Thank you.
Ugur Sahin (CEO)
Yeah, thanks for the question, Daina. Indeed, we. The world, not just in the United States, but also in other regions. We are expecting actually the first wave of decisions regarding strain selection and policy for the COVID season in 2025 to take place actually in the next couple of weeks in May already in some regions. We are going to be tracking that very closely. I think we will have within the next four to six weeks, we will already have some additional clarity in terms of the picture. I think in regards to the U.S. policy specifically, it has already been the case that the majority of vaccinations in the United States have gone into the older 65-plus populations, along with the immunocompromised, which together account for about 20% of the U.S. population. About 18% of the U.S.
population is 65-plus, and there's a couple more percent that take into account the immunocompromised. That's already been the majority of vaccinations in the U.S. for the last couple of years. While, of course, we're going to track the outcome of the meeting that you mentioned, we think that the market's already oriented in that direction. You know, our base scenario here is that we think that the vaccination rates in the U.S., around 20% that we've seen over the last couple of years, is still our sort of base scenario going into the end of this year.
Jens Holstein (CFO)
In addition, maybe Daina, to just add, we've seen such a development in other jurisdictions before as well. It is nothing new. What we experienced is, of course, you know, the recommendation goes for the vulnerable population, it goes for the immunosuppressive population. There will be a chunk of people that will, and that is difficult to predict, a chunk of people that will get vaccinations nonetheless, independent of the recommendation on the age. That is the experience that we had in the past to a great extent. We have to see how the implications will look like. It could have a negative implication, but it is very difficult to predict at this point in time.
Operator (participant)
Thank you. Your next question comes from the line of Cory Kasimov from Evercore. Please go ahead.
Cory Kasimov (Senior Managing Director and Fundamental Research Analyst)
Hey, good morning, guys. Thank you for taking my questions. Jens, congratulations on your retirement. I recognize it's difficult to comment on programs at another company, but I'd be interested in your perspective on Akeso's preliminary overall survival data that recently came out. I mean, is this something that's in line with your expectations? Maybe more specifically, as it relates to 327, does it have any impact at all in how you think about designing your own trials in non-small cell lung cancer? Thank you.
Özlem Türeci (CMO)
Yes, thank you, Cory, for the question. You know, we are also strong believers of the VEGF, PD-1, PD-1 bispecific concept. Therefore, we find the data which has been reported from Harmony to be 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, also this is encouraging. It has not a direct impact on our program. Rosetta Lung 02 is in a different population, and 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.
Operator (participant)
Thank you. Your next question comes from the line of Terence Flynn from Morgan Stanley. Please go ahead.
Terence Flynn (Managing Director and Senior U.S. Pharma and Biotech Analyst)
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 II portion and when we might see some of the Phase II data. Can you disclose the powering of the Phase III portion of that trial? Thank you.
Özlem Türeci (CMO)
We cannot comment at this point on the doses we are exploring. You might get more information on that later this year when we will present the trial design on conferences. The second question was, can you repeat the second question?
Terence Flynn (Managing Director and Senior U.S. Pharma and Biotech Analyst)
The timing of the data for Phase II and the powering of the Phase III portion?
Operator (participant)
Yeah. The data for Phase II, we will see some data later this year, beginning of next year. The powering for the Phase III portion is to accommodate coprimary PFS OS.
Thank you. Your next question comes from the line of Jessica Fye from JP Morgan. Please go ahead.
Jessica Fye (Managing Director and Senior Equity Research Analyst)
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 U.S. might impact BioNTech? Is currency for the U.S. market made in the U.S.? Second, can you just recap what you guys see as the key similarities or maybe, you know, more importantly, the key areas of differentiation of your development plans for 327 relative to the ivonescimab development program? Thank you.
Ugur Sahin (CEO)
Yeah, sure. Thanks, Jessica. 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 COMIRNATY currently where we have production infrastructure and capability through our partnership with Pfizer on both sides of the Atlantic. We've got the ability, we have the ability to produce that vaccine in the U.S. 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?
Jens Holstein (CFO)
No, it's just, you know, there are existing tariffs already for China, you know, 20% at this point in time that we got 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 prediction is, of course, how that will evolve over time. If pharmaceuticals will be challenged, then, you know, costs could go up for clinical trials and for research work. You know, overall, at this point in time, you know, 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 got to wait how things are evolving over time and how severe financial implications can look like.
Ugur Sahin (CEO)
With regard to your second question, Jessica, on BNT327 development strategy, I would just note that, you know, 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 have announced publicly three of those indications. A couple of those where we think we are positioned, if we can execute well, to be potentially first to market. TNBC and small cell lung cancer being two of those potential indications. Those first wave of trials are with chemotherapy backbones. We think that is the fastest path to market. The broader and longer-term strategy is to combine BNT327 with other agents, including ADCs.
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.
Özlem Türeci (CMO)
I don't have much to add. Thank you, Ryan. I think that summarizes our differentiation strategy.
Operator (participant)
Thank you. Your next question comes from the line of Evan Seigerman from BMO Capital Markets. Please go ahead.
Evan Seigerman (Managing Director and Head of Healthcare Research)
Hi, all. Thank you so much for taking my question. I wanted to take a higher-level question. You know, with varying views on mRNA technology, how are you thinking about the potential of your therapeutic vaccine franchise? You know, there's a lot of resistance building up in the U.S. Do you still see this as a core component of your strategy, or are you more focused on the bispecifics? Thank you so much.
Jens Holstein (CFO)
Definitely. We have a core interest in our mRNA therapeutics. As we have alluded 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. The same is true for the pan-tumor potential for therapeutic mRNA immunotherapies based on our neuroantigen as well as our fixed-act approach. We believe that this approach just has a huge potential, particularly in patient populations with a higher risk of relapse, either in the adjuvant setting or in the minimal residual disease setting. We also believe that the combination of both compounds, BNT327 as well as our vaccine, mRNA therapeutic vaccine, provides a huge opportunity.
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 into these technologies and further leverage our strengths here.
Operator (participant)
Thank you. Your next question comes from the line of Yaron Werber from TD Cowen. Please go ahead.
Yaron Werber (Managing Director and Senior Biotechnology Research Analyst)
Yeah, hi. Thanks for taking my question. I have a couple of interrelated questions. The first one is, you know, you've been very clear, and everything you said made a lot of sense on how you're going to develop 327, small cell, TNBC, non-small cell. What about second-line EGFR mutant? Any thoughts on that indication? Obviously, we're waiting for the Phase III from the competitor. Secondly, can you just remind us for 323 for second-line endometrial, what data are we expecting this year in filing for accelerated approval? It's going to be based on which endpoint specifically? If you can, just the powering for that study. Thank you.
Jens Holstein (CFO)
Yeah, for second-line non-small cell lung cancer, I believe you refer to the EGFR mutant population, right? We have recently published data in this population, including response and PFS data based also with differentiation into patient populations with PD-L1 positive and PD-L1 negative populations. The data are very encouraging. We have currently also running ADC trials in these populations and see encouraging data here as well. We will consider or we are considering to combine both as we expect synergistic activity here, while we also keep the option to BNT327 in the subpopulation of EGFR mutant tumors based on their PD-L1 positivity.
Ugur Sahin (CEO)
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? Alison, do you want to?
Özlem Türeci (CMO)
Yes. You are referring to our second-line endometrial cancer trial, which is a single-arm trial, which comes basically out of our basket trial across solid cancers, which we have conducted together with Duality. The endpoint is objective response rate. We are in discussion with regulatory authorities to better understand the expectations for BLA and are progressing in these discussions.
Operator (participant)
Thank you.
Özlem Türeci (CMO)
I might also add, I forgot to say that the population is across all HER2 positivity scores. It is a broader second-line endometrial cancer population.
Operator (participant)
Thank you. Your next question comes from the line of Mohit Bansal from Wells Fargo. Please go ahead.
Mohit Bansal (Managing Director and Senior Analyst)
Good. Thank you very much for taking my question and congrats on all the progress. I have two questions. One is, with Rosetta Lung 2, could you give us some timelines of when should we expect Phase II portion of the study to be over and you moving formally into Phase III? The second one, I mean, we get a lot of questions around the differences between different bispecifics, so yours, Summit, and Merus. The key difference I see, like one is that you are the only one using a PD-L1, and you also have the very heavy chain, so VHH. Could you talk a little bit about these differences and how much could they matter in the real world, especially PD-L1, given that the experience with PD-L1 antibodies has not been that fruitful? Thank you.
Ugur Sahin (CEO)
Okay. I think the first question was, when do we expect the Phase II portion of the Rosetta Lung trial to be complete?
Özlem Türeci (CMO)
The Phase II portion of Rosetta will be completed later this year, or we will have data to inform, to put it in this way, to inform the Phase III portion of the trial, defining the dose which will be then used in the Phase III portion, which will start this year. The other question I think was about the PD-L1.
Ugur Sahin (CEO)
The difference between PD-L1.
Özlem Türeci (CMO)
Yeah, the molecular differentiation between different bispecific molecules with this mode of action. We cannot comment on other molecules, obviously. We have deliberately chosen when we were assessing different external opportunities, a bispecific with a PD-L1 versus a PD-1 portion, because we expect from PD-L1 that it might be superior to PD-1 in anchoring, in particular in the tumor microenvironment where we want to have the bispecific. That was one of the reasons. Also, the molecular format with full IgG, VEGF, anti-VEGF portion, and VHH, PD-L1 portions was compelling to us because we think that we get the right pattern of cross-ligation in the tumor microenvironment.
Operator (participant)
Thank you. Your next question comes from the line of Jeff Meacham from Citigroup. Please go ahead.
Nishant Gandhi (Biopharma Analyst)
Hey, guys. This is Nishant on for Jeff, and thanks for the question. On 327, you also highlight potential to kind of combine with other modalities, including ADCs and cell therapies. I wanted to ask, what are the key factors driving the selections of these specific combinations, and what is the overall kind of rationale for these kind of combinations? Thank you.
Jens Holstein (CFO)
Yeah, I can take the question. I think we got to the combination. Our portfolio, anti-anti-cancer portfolio, has three categories of drugs which are all suitable as combination therapies. First of all, our IO pipeline. We have multiple additional bispecifics, particularly also after acquisition of BioNTech in the pipeline, including, for example, TIGIT? antibody, bispecific antibody, and other bispecific antibodies. These are we will engage into clinical trials. We have in preclinical context a mode of action synergy for these compounds. The second class, which we find very exciting, is our mRNA vaccines and mRNA immunotherapies. We believe that this modality could have the advantage not only to delay PFS and improve OS, but also help to completely eradicate residual tumor cells, which remain after checkpoint blockade.
We have been engaging into a number of preclinical studies, and our first clinical cohorts are going to start this year, later this year. We have recently demonstrated preclinical proof of concept of combinations of BNT327 with our ADC portfolio, which provides the opportunity to reduce tumor burden with ADCs to benefit from the immunogenic cell death mediated by ADCs and build on the superior effect of the bispecific combining VEGF, anti-VEGF, and PD-L1 activities.
Operator (participant)
Thank you. Your next question comes from the line of Asthika Goonewardene from Truist. Please go ahead.
Hi, this is Karina Farah at Sicklepoin. Thanks for taking the question. I have the question on the initial AACR data for BNT327, which was combined with TROP2 ADC. There was notable rate of stomatitis, which included grade 3 events. How do you plan to manage this toxicity going forward? Was this also observed with other ADCs from Duality Biologics?
Jens Holstein (CFO)
Actually, the stomatitis rate in the combination was very comparable to the stomatitis rate that is observed with BNT325, our anti-TROP2 ADC alone, which is very encouraging that we don't see additional additive toxicity.
Operator (participant)
Thank you. Your next question comes from the line of Harry Gillis from Berenberg. Please go ahead.
Harry Gillis (Senior Equity Analyst)
Hi, thank you very much for taking the questions. Could you please comment on the extent of global Phase II BNT327 data you've seen internally that informs your decision for Phase III entry in small cell lung and TNBC? Related to that, is Phase III entry in TNBC still contingent on any Phase II global data? Finally, when could we expect the Phase II global data for BNT327 in small cell or TNBC this year? Could we see it at ESMO or World Lung? Thank you.
Jens Holstein (CFO)
Yeah, yeah. As you might see from the clinical trial database, we are doing now our clinical trials in these indications in a global manner in the U.S., in Europe, in multiple centers in Turkey, and recapitulating data identified or previously presented from China patients. We are very confident that the findings of the China trials will be more or less fully recapitulated in these global trials.
Operator (participant)
Thank you. We will now take our final question for today. The final question comes from the line of John Newman from Canaccord Genuity. Please go ahead.
John Newman (Managing Director and Senior Biotechnology Equity Research Analyst)
Hi, thanks very much for taking my question. I'm just curious regarding the development of the COVID-19 vaccine with Pfizer. I wonder 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 if it were to move forward, what your strategy might be. Thanks.
Ugur Sahin (CEO)
Yeah, thanks, John. I think that I would note that the COVID-19 vaccine was first approved after a study of 43,000 participants, a very large global study where we demonstrated efficacy in that study. Obviously, we're continuing to track all potential policies out of FDA, but we don't expect that that talk is going to have a near-term impact on our COVID vaccine franchise given it's been approved for multiple years. Our expectation is that there's going to be multiple regions selecting strains for the fall 2025-2026 season. That's our focus at the moment.
John Newman (Managing Director and Senior Biotechnology Equity Research Analyst)
Absolutely.
Operator (participant)
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.