Participants

Michael Horowicz; Associate Director, Investor Relations and Strategy; Biontech SE

Ugur Sahin; Chief Executive Officer, Member of the Management Board; Biontech SE

Oezlem Tuereci; Chief Medical Office, Member of the Management Board; Biontech SE

Jens Holstein; Chief Financial Officer; Biontech SE

Ryan Richardson; Chief Strategy Officer, Member of the Management Board; Biontech SE

Daina Graybosch; Analyst; Leerink Partners

Akash Tewari; Analyst; Jefferies

Chris Shibutani; Analyst; Chris Shibutani

Tazeen Ahmad; Analyst; BofA Global Research

Terence Flynn; Analyst; Morgan Stanley

Harry Gillis; Analyst; Berenberg

Cory Kasimov; Analyst; Evercore ISI

Sadia Arman; Analyst; Wells Fargo

Asthika Goonewardene; Analyst; Truist Securities

Yaron Werber; Analyst; TD Cowen

Jessica Fye; Analyst; JPMorgan

Presentation

Operator

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.

Michael Horowicz

Thank you. Good morning and good afternoon. Thank you for joining BioNTech's Foirter 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 3, 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; Jan Holstein, Chief Financial Officer; and Robin Richardson, Chief Strategy Officer.
With this, I would like to hand over to Ugur.

Ugur Sahin

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 are fully interpreted bio pharmaceutical 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 of patients by fully harnessing the power of the immune system to fight immune 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 aligned 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 this program across various cancer types, building up commercial functions for the future commercialization in key markets and enhancing manufacturing capabilities to support both clinical type 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 a vigorous 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 clinical 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. For our mRNA immunotherapies, we initiated the third Phase 2 trial, evaluating autogene cevumeran in adjuvant setting, namely in bladder cancer.
In early 2025, we also published two manicures describing our insights from two Phase 1 trials for autogene cevumeran. For three of the FixVac programs, we reported data, including the announcement that FixVac candidate BNT111 met the randomized Phase 2 trial in patients with anti-PD-1 with refractory melanoma.
We presented multiple data sets for our next-generation IO, BNT327 at PD-L1 VEGF bispecific antibody, an initiated Phase 3 and Phase 3 trials in small cell lung cancer and non-small cell lung cancer. We plan to initiate a Phase 3 pile in triple-negative breast cancer this year.
We announced our intention to acquire to secure global control over BNT327 and expand our immunotherapy capabilities. This transaction closed earlier this year, and we are thrilled to welcome BioFire as a new arm of our operations in China.
With regard to our COVID-19 vaccine, we and maintained our leading market share globally. We also continued to progress several other programs in our early-stage infectious disease pardon. 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 immuno therapies including neoantigens for application primarily for the early stage, including adjuvant setting and our FixVac at immunotherapies targeting tumor-associated tensions in combination with checkpoint immunotherapy, respectively.
Second, our PD-L1 biospecific antibody BNT327 which we believe has the potential to become a next-generation I-O backbone for the treatment of advanced cancers. We believe that both programs have panned tumor potential and could be combined with different modalities to address large patient population 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 We are excited to now formally welcome team to BioNTech, having worked for a year with the highly skilled and dedicated team at 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. This acquisition of biosis, we have now a fully integrated antibody manufacturing network in China. The sites supplies antibodies for clinical trials and could potentially support initial commercial supply for market launches.
Lastly, 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.

Oezlem Tuereci

Thank you, Ugur. Glad to be speaking with everyone today. Before talking about our focus 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, in particular, our ADCs.
As Ugur mentioned, 2025 will be an important year for both of our priority programs. BNT327 by localizing the blockade of PD-L1 and VEGF-A signaling to the tumor is designed to deliver superior antitumor 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 therapy. 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 road map 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 chemophierapy 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 free registrational clinical trial.
Our second wave of development with BNT327 reflects that I-O 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, B7-H3 from our partnerships with and and informed by a robust database of single-agent data for 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 tumor types to broaden our global clinical development program with BNT327.
With this focused clinical development program, we aim to leverage BNT327's 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 data sets will come later this month at the European Lung Cancer Congress and trials in small cell lung cancer.
Small cell lung cancer is a tumor type with notable incidents worldwide and an immunologically cold tumor for which high unmet need remains with current standard of care treatment with durability of responses is quite short and 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 is one of our priority indications for BNT327.
We plan to present free data sets 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 data sets continue to support our enthusiasm for evaluating the 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 immune therapy platform, iNeST and FixVac are the other cornerstone of our oncology portfolio. Ortogensirumaran, a.k.a. 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 three 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 manageable safety profile where by used as single agent in combination with anti-PD-1, PD-L1 inhibitors or with chemotherapy.
Crucially, our data also indicate that these immunotherapies are highly effective at inducing and expanding high magnitude, functional and longest 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 in particular, 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 antitumor immune risk.
Our mRNA cancer immunotherapy approach aims to significantly increase these antitumor 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 two order of magnitude amplification of existing neoantigen-specific T cells. Furthermore, in several patients, we detected newly induced antitumor T cells infiltrating the tumor of treated patients. These findings demonstrate the potent immunogenicity of autogene cevumeran even in patients with advanced rapidly progressing cancers, which is a requisite for clinical activity.
In our ongoing Phase 2 clinical trials we aim to confirm these data and evaluate in which treatment setting and indications for 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 the Phase 1 trial was conducted in heavily pretreated resistant refractory fast-growing advanced cancer.
We recently also received top line data from the MCODE-001 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 versus alone as first-line treatment for patients with metastatic or advanced melanoma.
This trial is part of the broader study program initiated in 2017 by our partner Genentech and us, designed to identify optimal treatment settings and patient populations for individualized mRNA cancer immunotherapies including early and late-stage cancers. initial data 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 and overall survival. The combination of autogenerumuran with PD-1 blockade was well tolerated with adverse events consistent with the known safety profiles of the individual treatment.
We are continuing to analyze the results, including exploratory endpoints and biomarker correlation. We and our partner, Genentech, will share this 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 pretreated resistant refractory fast-growing advanced cancers and provides valuable insights. Patients in the first-line metastatic melanoma setting has 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, reconfirm our strategic focus on using iNeST in the adjuvant setting, where patients have resectable cancer 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 without sufficient time for the vaccine-induced immune response to develop and mature. Also in earlier disease stages, mechanisms of resistance, clonal heterogeneity, and an immunosuppressive tumor microenvironment are typically less established.
Patients in the adjuvant setting often have healthier immune systems and less compromised T cell function increasingly likelihood of a clinically meaningful response. This rationale is the reason why we strategically focused our advanced iNeST program on the adjuvant setting.
We currently have three ongoing randomized Phase 2 trials of autogene cevumeran, one in colorectal cancer that is enrolling stage two high-risk in Stage III CRC patients who are ctDNA positive after surgical resection and standard of care chemotherapy.
These patients are at high risk of recurrence, often within the year. We continue to anticipate initial data from the 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 control Phase 2 trial in bladder cancer was initiated in the fourth quarter of last year. We believe individualized cancer immunotherapies have a potential to change the current standard of care and improve overall survival by delaying or preventing recurrence of cancer metastases. 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 why we are evaluating novel I-O combination 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.

Jens Holstein

Thank you, Ozlem, and a warm welcome to everyone who has done in today's call. I'll start with our fourth quarter and full year results 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 expectations.
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 well 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 to the amount of approximately USD800 million and payments derived from the settlement of the contractual disputes with NIH at the University of Pennsylvania to the amount of USD792 million and USD467 million, respectively. We expect that the acquisition payment and the NIH payment totaling approximately USD1.6 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 USD535 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 a lower COVID-19 vaccine market demand. In addition, 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 as compared to negative EUR188 million in 2023. This was mainly due to payments and expenses related to the above-mentioned contractual disputes with NIH UPenn, net of aforementioned related reimbursement 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 to 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. VTB's 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 for 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 vacillation rate, 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 territory.
We also expect revenues related to our service business 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 influenced 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, namely BNT327, our mRNA cancer immunotherapies 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 disrupted pan-tumor technologies.
In summary, 2025 will be another year of continued transition for BioNTech with the aim to become a multiproduct 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.

Ryan Richardson

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 are 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 an 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 in 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.

Question and Answer Session

Operator

(Operator Instructions) Daina Graybosch, Leerink Partners.

Daina Graybosch

You had 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 road map of any particular ones that we should pay attention to that you think could have outcomes decided in the next quarters in this year.

Jens Holstein

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 20-F.

Ryan Richardson

Yes. I think, David, just to add to that. I think as we've said in the 20-F as well that we're confident in the strength of our IP estate and some of the -- sometimes these processes can go through multiple appeals processes, but we think we're in a good position and are going to continue to defend our IP estate, along with our partner, Pfizer.

Daina Graybosch

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

Oezlem Tuereci

Thank you for the question. I'm not sure whether I got it correctly. So the question was with regard to our melanoma FixVac BNT11, right, where we have reported top line results that we have that it was a successful trial and that we have achieved the end point -- we will have data presentations on this later this year on one of the conferences and are also preparing a manuscript. So there will be more information about that.
As you pointed out, yes, we observed it for our iNeST first line setting. It seems that it's not the right one. So metastatic setting with advanced cancers and tumor -- higher tumor burden is not optimal. And which actually is not surprising. I have described the reasons for this which can explain a couple in my talk today.
That's also why we are focusing our iNeST approach, our individualized cancer approach on the adjuvant setting and have initiated three trials in this setting. We believe that here of probability of getting robust clinical benefit is much higher due to simply the biology of adjuvant cancer.

Ugur Sahin

Daina, the key differences between the iNeST approach and FixVac approach is that FixVac can be applied immediately without any delay. And for the iNeST approach at the time point of the clinical price we had a turnaround times in the range of six to eight weeks, which is in a metastatic setting, really difficult because the tumors tend to progress, particularly by explanations ongoing and immune responses are built.
So based on that, we early on adapted our strategy and went into the adjuvant stage the patients before they progress have been 6, 9, 12 months before events occur.

Operator

Akash Tewari, Jefferies.

Akash Tewari

Just on 327, I know in the past, your teams alluded to 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 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?

Ryan Richardson

Yes. Thanks, Akash. I'll start with that. So we're proceeding right now on our own. And actually, we think we have the capabilities to execute against 327 in these initial trials that we've started, and that's really the focal point this year.
So non-small cell lung cancer, small cell lung cancer and triple-negative breast cancer being the first indications, but we are looking at a much broader set of additional indications, including the ADC combinations, as we've alluded to in our prepared remarks. So that's really the focus for 2025.
What we have said though is that we recognize that with such a broad potential IO backbone therapy. The combinations with other companies agents could prove useful down the road. And indeed, we have been approached by different companies who are interested in potentially combining with BNT327.
And so we are evaluating those potential collaborations and nothing to announce at this point. But I think given the broad applicability, it is plausible and actually probably likely that we'll enter into some combination partnerships over the next 12 to 18 months.
I won't comment beyond that at this point, but we do think that it's worth -- given the breadth of the program potential that it's -- that it makes sense for us to evaluate all opportunities to potentially speed up and expand the program.

Operator

Chris Shibutani, Goldman Sachs.

Chris Shibutani

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 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.

Ryan Richardson

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 for 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 and 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 --

Ugur Sahin

No. I guess, just -- it's really about the execution of the piles if you really consider the full spectrum will take many years in multiple indications. So then you revisit what has happened in the I-O also anti-PD-1 treatment -- and this is also process which went and is still ongoing in the last 10 years. And this is something which we expect also for the next generation of an anti-PD-1 blockade with the bispecific antibody.
So this is something where we see in the next year, the need to start multiple clinical sites in multiple indications, but not only do the trials in combination with standard of care, but also consider combinations with novel compounds that can help to differentiate the efficacy seen by BNT327 alone.

Chris Shibutani

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

Oezlem Tuereci

We don't see anything specific. I mean you know that clinical trial enrollment in particular, 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 effect on our trials and have actually very good enrollment, in particular, into the 327 trials, which seems to be a compound where investigators are very enthusiastic about.

Operator

Tazeen Ahmad, Bank of America Securities.

Tazeen Ahmad

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 I wanted to follow up on that previous question a few minutes ago about partnership. How are you thinking about building out commercial organization versus waiting to partner.

Ryan Richardson

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?

Tazeen Ahmad

Yes.

Ugur Sahin

Yes. So as you know, endometrial cancer as an indication where patients can be categorized into two and HER2 low tumors. And based on that, we expect efficient efficacies in the range of ADCs that have been evaluated in this indication. It's a single-arm study. The standard of care chemotherapy with a very short PFS and OS.
As you know, the compound receive breakthrough designation in this indication. So we are confident that the results will fulfill the requirements for potential registration.

Ryan Richardson

Yes. And to Ugur's point, I mean we've seen within HER2 response rates are 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 20% range.

Operator

Terence Flynn, Morgan Stanley.

Terence Flynn

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?

Ryan Richardson

So I think in the first instance, I'll start and Ozlem or Ugur can join. So we've already published some data in small cell lung cancer where we showed response rates in the 70% range or with a combination with chemotherapy. We're expecting that these data sets that are coming are to an extent going to further validate and expand on that and further justify our decision to move aggressively into pivotal trials in small cell.
I think one of the unique things here is that we are going to be coming out with both data and first line and also additional data in second line. And so that's is going to build on the previous data sets that we put out there.

Oezlem Tuereci

Yes. And there would be a data report this year, which will, on the one hand, be follow-up and update on an ongoing clinical trial, which has been presented last year. So you will get follow-up data, but also new data from our dose justification clinical trials, which we have initiated.

Operator

Harry Gillis, Berenberg.

Harry Gillis

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 US vaccination rates and any impacts from Sanofi's commercialization of the --

Jens Holstein

Yes, thanks very much. Happy to take the question. So of course, as you pointed out, we -- our revenue guidance assumes relatively stable vaccination with some market share as we've seen 2024. We have, though, to include as a company, if you think about prices guidance that we have some write-offs to reflect, product returns write-offs consist out of write-offs of material like we've seen in '24.
We had one. We had KP2 variants and for us, and we had to face some write-offs here because Pfizer was producing it, and we, of course, have to take half of it. So it goes in our gross profit share. That's point number one.
The second is that we also took into account some minor price and volume effect in the US in 2025, reflecting a little bit potential competitive pressure here to your point of Sanofi. And thirdly, there is potentially also some risk that the EU is moving a little bit of a volume towards from 2025, contractually towards 2026, they're contractually having the opportunity to do so.
And to some extent, we also have reflected that. And that explains why we are at the midpoint at this range.

Operator

Cory Kasimov, Evercore.

Cory Kasimov

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 comp at this stage?

Oezlem Tuereci

So we will have PFS data. I cannot say from the top of my head, what would follow up time within this study is that we are even PFS data on our small cell lung cancer slide. And emerging data -- no, median OS, but emerging OS.

Ryan Richardson

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

Oezlem Tuereci

POR3 trial as a benchmark of web.

Operator

Mohit Bansal, Wells Fargo.

Sadia Arman

This is [Sadia Arman] on for Mohit. So another question on 327. With the 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?

Ugur Sahin

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

Operator

Asthika Goonewardene, Truist Securities.

Asthika Goonewardene

Ozlem, you mentioned that you started recruiting patients with 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 related to this, guys, could you maybe comment on the statistical analysis of the study? And I believe you're considering the nonsquamous and squamous population separately, which is different from how your competitors Summit is doing their analysis of HARMONY3. So why do you prefer your method?

Oezlem Tuereci

So what is the question, the size of our study. There were several questions. I think regarding the non-small cell lung cancer study. As Ugur has pointed out business in principle, like two studies in one because we want to explore in our Phase 2/3, both non-squamous squamous and so small cell lung cancer across all PD-1 status setting. That means with these different patient populations covered.
We have a center size, which is around 950-plus patients -- and we expect, based on earlier data, we have seen that all these histologies and also different PD-L1 strata can benefit from the BNT327, this is why we have been all covered in our study.

Ugur Sahin

And we discussed also all options how to structure this clinical trial, including also having a single big cohort based on the discussion also with the FDA, we decided and to have two indications, particularly with the observations and recently reset in some of the clinical trials, they are nonsmall cell lung cancer and squamous -- non-squamous and squamous did show different type of results for some of the compounds is now more attention on the different sheets.

Asthika Goonewardene

Got it. Guys, 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.

Oezlem Tuereci

So 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 center size. And this is equally ditributed across non-squamous and squamous non-small cell lung cancer studies, so to say. We will not as you can imagine, is about further optimizing the dose or justifying the dose. So it's not a technical part of the development.

Operator

Yaron Werber, Cowen.

Yaron Werber

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

Ryan Richardson

Yes. Thanks, Yaron. Not too much to say at this stage.Obviously, we're following very closely to 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.

Operator

Jessica Fye, JPMorgan.

Jessica Fye

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 of listed on the slide, but it just says 2025-plus.

Oezlem Tuereci

So the question was about next upcoming BNT327 data after small cell lung cancer. One data package will be TNBC in which we also have a Phase 2 study ongoing and follow-up data on a previous study, which we have presented last year at the San Antonio conference, where we -- you will learn a bit more about further maturing OS.
Additional report could be about other indication cohorts we have with 327, including also the first cohort where we combined with our ADCs, specifically our trial where we combined 327 with 325 or top two ADCs.

Operator

Thank you.