BioNTech Se (BNTX) Q4 2024 Earnings Call Transcript

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BioNTech Se (NASDAQ: BNTX)
Q4 2024 Earnings Call
Mar 10, 2025, 8:00 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

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 -- Vice President, Strategy and Investor Relations

Thank you. Good morning and good afternoon. Thank you for joining BioNTech's fourth quarter and full year 2024 earnings call. As a reminder, the slides we will be using during this call and the corresponding press release we issued this morning can be found in the investor relations section of our website.

On the next slide, you will see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings with the U.S. 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.

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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: Uğur Şahin, chief executive officer and co-founder; Ozlem Tureci, chief medical officer and co-founder; Jens Holstein, chief financial officer; and Ryan Richardson, chief strategy officer. With this, I would like to hand over to Ugur.

Uğur Şahin -- Co-Founder and Chief Executive Officer

Thank you, Michael. A warm welcome to all those joining us today. We will spend today's call on our key areas of focus for this year. Before we do so, I want to speak briefly about our original vision and the strategy to become an immunotherapy powerhouse and a fully integrated biopharmaceutical company with multiple approved products.

While BioNTech has evolved significantly since its founding in 2008, our vision has remained steadfast: to translate science into survival for patients by fully harnessing the power of the immune system to fight human diseases, particularly cancer. In 2024, we made significant progress on this vision, thanks to the excellent work and dedication of our BioNTech team, our collaboration partners, and the trust of patients who participated in our clinical trials. We have a clear focus. We will continue to invest in our technologies and drug candidates that have the potential to improve outcomes for patients across a wide range of tumor types.

In oncology, we have identified two key pan-tumor programs: our mRNA cancer immunotherapies FixVac and iNeST and our bispecific anti-PD-L1, anti-VEGF antibody BNT327. We believe that these programs have disruptive potential and align with our vision. If successfully developed and approved, these programs could establish a new standard of care and enhance patient outcomes in multiple cancer indications globally. We are significantly investing in the clinical development of these programs across various cancer types, building up commercial functions for their future commercialization in key markets, and enhancing manufacturing capabilities to support both clinical trials and commercial supply.

In the infectious disease sector, we are advancing the development of our next-generation COVID-19 and combination vaccines. Our infectious disease product strategy focuses on sustainable value creation, with active pipeline prioritization and rigorous opportunity assessment based on strategic fit and operational efficiency. Consequently, as outlined in our 20-F filing today, we are prioritizing areas with disruptive potential for value generation. Moreover, we are planning to adjust our resources in manufacturing, administrative functions, and preclinical research over the next three years to further solidify efficient execution.

Let me continue with a look back at what we have achieved in 2024. For our mRNA cancer immunotherapies, we initiated the first phase 2 trial evaluating autogene cevumeran in adjuvant setting, namely in bladder cancer. In early 2025, we also published two manuscripts describing our insights from two phase 1 trials for autogene cevumeran. For our three off-the-shelf FixVac programs, we reported data, including the announcement that FixVac candidate BNT111 met the primary end point in a randomized phase 2 trial in patients with anti-PD-1 relapsed or refractory melanoma.

We presented multiple datasets for our next-generation IO BNT327 PD-L1/VEGF bispecific antibody and initiated phase 3 and phase 2/3 trials in small cell lung cancer and non-small cell lung cancer. We plan to initiate a phase 3 trial in triple-negative breast cancer this year. We announced our intention to acquire Biotheus to secure global control over BNT327 and expand our immunotherapy capabilities. This transaction closed earlier this year, and we are thrilled to welcome Biotheus as a new arm of our operations in China.

With regard to our COVID-19 vaccine, we and Pfizer maintained our leading market share globally. We also continued to progress several other programs in our early stage infectious disease pipeline. Lastly, we were able to achieve all this while maintaining our strong financial position. We believe these achievements positions us well for further progress in 2025.

As already pointed out, in oncology, we are focused on the development of candidates addressing the full spectrum of solid tumors with a focus on two pan-tumor programs. First, our personalized mRNA cancer immunotherapies encoding mutant neoantigens for application primarily for the early stage, including adjuvant setting; and our FixVac immunotherapies targeting tumor-associated antigens in combination with checkpoint immunotherapy, respectively. Second, our PD-L1/VEGF bispecific antibody BNT327, which we believe has the potential to become our next-generation IO-backbone for the treatment of advanced cancers. We believe that both programs have pan-tumor potential and could be combined with different modalities to address large patient 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 Biotheus. We are excited to now formally welcome Biotheus team to BioNTech.

Having worked for a year with the highly skilled and dedicated team at Biotheus, we had decided to plan for an acquisition of the company. Now, as one company, we have the capabilities to accelerate and expand the global development of BNT327. However, there are other factors of this acquisition which are also strategically important for us. We are going to build a strong and experienced clinical development organization in China that can help us to further accelerate the development across programs and tumor types.

We believe this will facilitate more streamlined clinical development and decision-making, allowing us to bring other programs into late-stage and global development. With the acquisition of Biotheus, we have now a fully integrated antibody manufacturing network in China. The site supplies antibodies for clinical trials and could potentially support initial commercial supply for market launches. Lastly, Biotheus comes with leading antibody engineering technology and expertise.

With their capability, they have very quickly built a diverse pipeline of programs that we are evaluating and which we believe could offer additional value in the coming years. With that, I will turn the call over to Ozlem.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

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 colocalizing the blockade of PD-L1 and VEGF-A signaling to the tumor, is designed to deliver superior anti-tumor immunomodulatory and anti-angiogenic effects compared to the individual targeting of PD-L1 and VEGF-A, with the potential to minimize adverse events associated with systemic anti-VEGF-A therapy.

With 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 chemotherapy with first approvals in first-line settings of these indications. We have completed enrollment in our global phase 2 dose optimization studies in small cell lung cancer and TNBC.

In small cell lung cancer, we have begun enrolling patients in the global randomized phase 3 trial. In TNBC, we will start a global registrational study later this year. In non-small cell lung cancer, we have begun enrolling patients in our global phase 2/3 registrational clinical trial. Our second wave of development with BNT327 reflects that IO plus ADC combos are an emerging treatment paradigm in oncology.

We have started exploring combinations of BNT327 with four ADCs directed against TROP2, HER2, HER3, B7-H3 from our partnerships with Duality and MediLink and informed by a robust database of single-agent data for these ADCs. The 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 B7-H3 ADC. Throughout this year, we will evaluate the data from these initial combination trials and we'll 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 datasets will come later this month at the European Lung Cancer Congress and feature our trials in small cell lung cancer. Small cell lung cancer is a tumor type with notable incidence worldwide and an immunologically cold tumor for which high unmet need remains.

With current standard-of-care treatment, the durability of responses is quite short, and five-year survival rate for extended-stage small cell lung cancer is only 3%. Based on our emerging data, we believe that BNT327 has the potential to improve clinical outcomes for patients with small cell lung cancer. At ESMO 2023, data were presented, which show encouraging activity of BNT327 in combination with standard-of-care chemotherapy in second-line small cell lung cancer that has motivated us to pursue small cell lung cancer as one of our priority indications for BNT327. We plan to present three datasets from trials in small cell lung cancer this year, including data from two separate single-arm phase 2 trials evaluating BNT327 plus chemotherapy as a first- or second-line treatment for extensive-stage small cell lung cancer.

These datasets continue to support our enthusiasm for evaluating BNT327 for the potential treatment of first-line small cell lung cancer in our ongoing global phase 3 trial. As Ryan will cover later, we expect to share additional important clinical data updates throughout the year. Our mRNA cancer immunotherapy platforms, iNeST and FixVac, are the other cornerstone of our oncology portfolio. Autogene cevumeran, aka BNT122, developed in partnership with Genentech, is based on the iNeST platform.

iNeST targets neoantigens' unique tumor-specific mutations and is manufactured on demand for each individual patient. FixVac, in contrast, targets shared non-mutated tumor antigens and is an off-the-shelf approach. Both platforms utilize our proprietary uridine mRNA LPX delivery technology. The discovery of these two different types of target antigens is one of our core competencies.

Over the past several years, we've accumulated substantial data from iNeST and FixVac trials across various tumor types. These data consistently demonstrate that uridine mRNA LPX-based immunotherapies have manageable safety profile, whether used as single agents, 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 long-lived T-cell responses in a significant proportion of patients. This robust immune response is a prerequisite for clinical activity.

We have multiple trials with both FixVac and iNeST ongoing and have had multiple data reports in the past years and, 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 anti-tumor immune response. Our mRNA cancer immunotherapy approach aims to significantly increase these anti-tumor immune responses. In this phase 1 trial, autogene cevumeran successfully induced T-cell responses across multiple cancer types, converting a high portion of patients into immune responders. The majority of these responses were poly epitopic directed against multiple mRNA-encoded neoantigens, and these responses were de novo, meaning they were newly generated against the encoded neoantigens and did not exist prior to treatment.

In some patients, we observed up to a two order of magnitude amplification of existing neoantigen specific T cells. Furthermore, in several patients, we detected newly induced anti-tumor T cells infiltrating the tumor of treated patients. These findings demonstrate the potent immunogenicity of autogene cevumeran even in patients with advanced rapidly progressing cancers, which is a prerequisite for clinical activity. In our ongoing phase 2 clinical trials, we aim to confirm these data and evaluate in which treatment setting and indications were immune responses translate best into clinical activity.

While we saw strong immune responses in this phase 1 trial, we observed modest signals of clinical activity, which was expected given that this phase 1 trial was conducted in heavily pretreated resistant refractory fast-growing advanced cancers. We recently also received top-line data from the IMCODE001 phase 2 trial marked here on this slide. This was the first randomized proof of concept phase 2 trial of an iNeST candidate evaluating autogene cevumeran in combination with pembrolizumab versus pembrolizumab alone as first-line treatment for patients with metastatic or advanced melanoma. This trial is part of a broader IMCODE study program initiated in 2017 by our partner Genentech and us, designed to identify optimal treatment settings in patient populations for individualized mRNA cancer immunotherapies, including early and late-stage cancers.

While the 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 end point of a statistically significant improvement in progression-free survival. However, we did observe a numerical trend favoring the combination arm in overall survival. The combination of autogene cevumeran with PD-1 blockade was well tolerated, with adverse events consistent with the known safety profiles of the individual treatments. We are continuing to analyze the results, including exploratory end points and biomarker correlations.

We and our partner Genentech will share these data with the scientific community at an upcoming medical conference. The outcome confirms what we have observed in our phase 1 trial in patients with heavily pretreated resistant refractory fast-growing advanced cancers and provides valuable insights. Patients in the first-line metastatic melanoma setting have a substantial tumor burden and rapid disease progression. An effective immune response, even a potent one, requires time to develop, typically six to eight weeks, based on our data.

This time frame may be insufficient to control the 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 cancers and minimal residual disease. We believe this setting offers a strong biological rationale for success due to several reasons. Adjuvant therapy targets a much smaller number of residual tumor cells.

After surgery, the slower disease progression in the adjuvant setting allows sufficient time for the vaccine-induced immune response to develop and mature. Also, in earlier disease stages, mechanisms of resistance, clonal heterogeneity, and an immune suppressive tumor microenvironment are typically less established. Patients in the adjuvant setting often have healthier immune systems and less compromised T-cell function, increasing the likelihood of a clinically meaningful response. This rationale is the reason why we strategically focused our advanced iNeST program on the adjuvant setting.

We currently have three ongoing randomized phase 2 trials of autogene cevumeran: one in colorectal cancer that is enrolling Stage 2 high-risk and Stage 3 CRC patients who are ctDNA positive after surgical resection and standard-of-care chemotherapy. These patients are at high risk of recurrence, often within a year. We continue to anticipate initial data from this study either late this year or in early 2026. These data will be critical for informing the next stages of development and regulatory discussions.

We are also evaluating autogene cevumeran as an adjuvant treatment for pancreatic cancer. This phase 2 is informed by a small phase 1 trial in which we showed strong immune responses induced by autogene cevumeran and their correlation, with significant improvement of recurrence-free survival. A randomized controlled phase 2 trial in bladder cancer was initiated in the fourth quarter of last year. We believe individualized cancer immunotherapies have the potential to change the current standard of care and improve overall survival by delaying or preventing recurrence of cancer metastasis.

2025 will be an important year for BioNTech. We are intensely focused on the execution of our late-stage trials, particularly in the adjuvant setting, where we believe our individualized mRNA immunotherapy approach has the greatest potential for clinical impact while we are evaluating novel IO combinations for the treatment of advanced rapidly progressing high volume tumors. We look forward to providing updates on our progress. With that, I will now pass the presentation to our CFO, Jens Holstein.

Jens Holstein -- Chief Financial Officer

Thank you, Ozlem, and a warm welcome to everyone who has dialed 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 2.8 billion euros in revenues, meeting the approximate midpoint of our full year 2024 revenue guidance and with this slightly better than our previously announced expectation.

Driven by effective cost management, we limited our full year 2024 losses before taxes to approximately 678 million euros and a diluted loss per share of 2.77 euros. Our cash position, including cash equivalents and investments and securities, amounted to 17.4 billion euros 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 Biotheus to the amount of approximately $800 million and payments derived from the settlement of the contractual disputes with NIH and the University of Pennsylvania to the amount of $792 million and $467 million, respectively.

We expect that the Biotheus acquisition payment and the NIH payment totaling approximately $1.6 billion will be reflected in our first quarter 2025 financial position. We expect that the University of Pennsylvania settlement payment will be reflected in our second quarter 2025 financial position. With respect to the settlements, we also expect a reimbursement of approximately $535 million from our partner Pfizer during 2025 and 2026. I'll be moving now to the summary of our financial results for the fourth quarter and full year of 2024, as shown on the next slide.

For the three months ended December 31, 2024, we recognized total revenues of approximately 1.2 billion euros, compared to approximately 1.5 billion euros in the prior-year period. For the full year, we recognized around 2.8 billion euros, compared to around 3.8 billion euros 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 612 million euros for the fourth quarter of 2024, compared to 578 million euros for the comparative period in 2023. For 2024, R&D expenses amounted to approximately 2.3 billion euros, compared to roughly 1.8 billion euros in 2023. The increase was mainly influenced by the planned advancing of our priority programs, including BNT327, toward late-stage development. SG&A expenses amounted to approximately 132 million euros for the fourth quarter of 2024, compared to 142 million euros in the same period of the previous year.

For the 2024 financial year, SG&A expenses amounted to approximately 599 million euros, compared to 558 million euros 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 671 million euros for the 2024 financial year, as compared to negative 188 million euros in 2023. This was mainly due to payments and expenses related to the above-mentioned contractual disputes with NIH and UPenn, net of aforementioned related reimbursements for our collaboration partner Pfizer.

For the fourth quarter of 2024, we reported a net profit of approximately 260 million euros, compared to around 458 million euros for the comparative period in 2023. For the full year 2024, we reported a net loss of 665 million euros, compared to a net profit of 930 million euros in the prior year. Our diluted earnings per share for the fourth quarter of 2024 amounted to 1.08 euros, compared to 1.88 euros in the comparative period in 2023. For the 2024 financial year, our diluted loss per share amounted to 2.77 euros, compared to 3.83 euros 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 2.5 billion euros to 3.1 billion euros. 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 U.S. On R&D, we reported roughly 2.3 billion euros in expenses for 2024, slightly below the low end of our full year 2024 financial guidance range of 2.4 billion euros to 2.6 billion euros. This was in part driven by our active portfolio management and the shifting of some registrational study costs from 2024 into 2025. On SG&A and capital expenditures for operating activities, we ended at the lower end of our 2024 expectations from our last earnings call.

Meeting these lower guidance ranges is a result of our continued cost monitoring 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 1.7 billion euros to 2.2 billion euros for 2025. Our revenue guidance assumes relatively stable vaccination rates, pricing, and market share as compared to 2024.

We also anticipate a revenue phasing similar to last year with the last three to four months driving the full year revenue figure. In addition, we estimate some inventory write-downs and other charges in the range of roughly 15% of BioNTech's share of gross profit from COVID-19 vaccine sales in Pfizer's territory. We also expect revenues related to our service 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 influence BioNTech's COVID-19 vaccine revenues and financial results.

Turning to operating expenses. In 2025, we expect R&D expenses to be in the range of 2.6 billion euros to 2.8 billion euros. 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 650 million euros to 750 million euros. 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 250 million euros to 350 million euros. With these investments, we're paving the way for multiple potential product launches. Investments include manufacturing expansion projects and investment in commercial IT systems to support portfolio growth and build capacity for the development and commercialization of our potentially disruptive pan-tumor technologies. In summary, 2025 will be another year of continued transition for BioNTech, with the aim to become a 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 -- Chief Strategy Officer

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 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 16th. We are excited to once again host two innovation series events this year. The first will be another AI event on October 1st. The second will be our R&D Day on November 18th.

We will share further details on both events later in the year. With that, we would like to open the floor for questions.

Questions & Answers:

Operator

Thank you. [Operator instructions] We will now take the first question from the line of Daina Graybosch from Leerink Partners. Please go ahead.

Daina Graybosch -- Leerink Partners -- Analyst

Hi. Thank you for the question. You had few charges related to legal events that you talked about, Jens. There's a lot more IP cases going on, and they seem to be accelerating and coming to some conclusions.

And I wonder if you could just help give us an overview or road map of any particular ones that we should pay attention to that you think could have outcomes decided in the next quarters and this year. Thank you.

Jens Holstein -- Chief Financial Officer

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

Ryan Richardson -- Chief Strategy Officer

Yeah. I think, Daina, just to add to that, you know, 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 these -- 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 -- Leerink Partners -- Analyst

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

Ozlem Tureci -- Co-Founder and Chief Medical Officer

Hi. Thank you for the question. I'm not sure whether I got it correctly. So, the question was with regard to our melanoma FixVac BNT111, 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 that for our iNeST, the 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, the probability of getting robust clinical benefit is much higher due to simply the biology of adjuvant cancer.

Uğur Şahin -- Co-Founder and Chief Executive Officer

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

Daina Graybosch -- Leerink Partners -- Analyst

Great. Thank you.

Operator

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

Akash Tewari -- Jefferies -- Analyst

Hey. Thanks so much. Just on 327, I know, in the past, your teams alluded to kind of the costs associated with developing an agent like this across different tumor types; and certainly, Merck's talking about running a lot of different phase 3 trials over time. And you guys have hinted at a potential 50-50 partnership.

Where does BioNTech currently stand on the partnership question on 327 and what clinical or commercial capabilities would you be looking at for an external partner? Thank you.

Ryan Richardson -- Chief Strategy Officer

Yeah. 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 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 very -- such a broad potential IO-backbone therapy, that 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

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

Chris Shibutani -- Analyst

Good morning. Thank you so much. With your plan for 327, obviously the scope of opportunity is considerable. And as we think about the other leading player developing, Summit/Akeso, they're mapping out a pretty broad plan.

Can you clarify how you see what you think would be differentiating in your approach? I think, preliminarily, we noticed that you have maybe further along with TNBC. But is there some sort of strategic overlay, whether it's thinking about PD-L1 agnosticism, geographies, something that helps discern how your approach may be differentiated to ultimately also demonstrate differentiated clinical data? Thank you.

Ryan Richardson -- Chief Strategy Officer

So, I can start and Ugur and Ozlem can add. So, I think the first point to mention, Chris, is that, you know, 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 add?

Uğur Şahin -- Co-Founder and Chief Executive Officer

No, just it's really about the execution of these trials. If we really consider the full spectrum, it will take many years in multiple indications. So then you revisit what has happened in the IO field for anti-PD-1 treatments, and this was a process which went and is still ongoing in the last 10 years. So -- and this is something which we expect also for the next generation of an entire PD-1 blockade with the bispecific antibody.

So, this is something where we see in the next years the need to start multiple clinical trials 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 -- Analyst

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? Thank you.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

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

Chris Shibutani -- Analyst

Thank you. I appreciate the follow-up.

Operator

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

Tazeen Ahmad -- Analyst

Hi. Good morning. Thanks for taking my question. Can I just ask you what you're expecting the bar for efficacy to need to be for 323 for the endometrial data that you're expecting this year that would be able to support a 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 were you thinking about building out commercial organization versus waiting to partner? Thanks.

Ryan Richardson -- Chief Strategy Officer

Yeah. 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 -- Analyst

Yes.

Uğur Şahin -- Co-Founder and Chief Executive Officer

Yeah. So, as you know, endometrial cancer is an indication where patients can be categorized into HER2+ and HER2 low tumors. And based on that, we expect efficiency -- efficacy in the range of ADCs that have been evaluated in this indication as a single-arm study, the standard-of-care chemotherapy with a very short PFS and OS. As you know, the compound BNT323 received breakthrough designation in this indication.

So, we are confident that the results will fulfill the requirements for potential registration.

Ryan Richardson -- Chief Strategy Officer

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

So, in the sort of 20% range.

Operator

Thank you.

Ryan Richardson -- Chief Strategy Officer

Could you just repeat the question, please?

Unknown speaker -- -- Analyst

My God. I mean, this is crazy.

Operator

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

Terence Flynn -- Analyst

Hi. Thanks for taking the question. I know you mentioned you're going to have some 327 phase 2 data for small cell lung cancer here over the next month or so. 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, etc.? Thank you.

Ryan Richardson -- Chief Strategy Officer

So, I think in the first instance -- I'll start and maybe Ozlem and Ugur can join. So, we've already published some data in small cell lung cancer where we showed response rates in the 70% range for -- with the combination with chemotherapy. We're expecting that these datasets 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 in first line and also additional data in second line.

And so, that's going to build on the previous datasets that we put out there.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

Yes. And there will be a data report this year, which will, on the one hand, been -- be a 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

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

Harry Gillis -- Berenberg Capital Markets -- Analyst

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

vaccination rates and any impacts from Sanofi's commercialization of the Novavax vaccine? Thank you.

Jens Holstein -- Chief Financial Officer

Yeah. Thanks very much. Happy to take the question. So, you know, of course, as you pointed out, we -- our revenue guidance assumes relatively stable vaccination rates and market share as we've seen in -- for 2024.

We have, though, to include as a company, if you think about Pfizer's guidance, that we have some write-offs to reflect product returns or write-offs that consist out of write-offs on material like we've seen in '24. We had JN.1, we had KP.2 variants and produce -- 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 into our gross profit share. That's part number one. The second is that we also took into account some minor price and volume effect in the U.S.

in 2025, reflecting, you know, a little bit potential competitive pressure here, so to your point on Sanofi. And thirdly, you know, there is potentially also some risk that the EU is moving a little bit of the volume toward -- from 2025 contractually toward 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

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

Cory Kasimov -- Analyst

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

Ozlem Tureci -- Co-Founder and Chief Medical Officer

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

Uğur Şahin -- Co-Founder and Chief Executive Officer

And emerging OS data.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

And emerging OS data. Yeah.

Uğur Şahin -- Co-Founder and Chief Executive Officer

Yeah.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

No median OS but emerging OS data.

Uğur Şahin -- Co-Founder and Chief Executive Officer

Yeah. Then --

Ozlem Tureci -- Co-Founder and Chief Medical Officer

Yeah.

Ryan Richardson -- Chief Strategy Officer

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

Cory Kasimov -- Analyst

Great. Thank you.

Operator

Thank you.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

But IMpower133 trial as the benchmark, if that helps.

Operator

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

Sadia Rahman -- Wells Fargo Securities -- Analyst

Hi. This is Sadia Rahman on for Mohit. Thanks for taking our questions. So, another question on 327.

With a competitor expected to read out their OS data in lung cancer later this year, how would you view read-through from those results to 327 in lung cancer? And can you discuss any differences in how you're approaching development, specifically in non-small cell lung cancer, from the competitor? Just any differences or similarities that you would highlight. Thank you.

Uğur Şahin -- Co-Founder and Chief Executive Officer

OK. Our non-small lung cancer study is 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 non-squamous patients. Our comparator is pembrolizumab plus chemotherapy.

The treatment group will receive BNT327 plus chemotherapy, and end points are, as usual, PFS and OS.

Operator

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

Asthika Goonewardene -- Analyst

Hi, guys. Thanks for taking my question. Ozlem, you mentioned that you started recruiting patients to the 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 in that phase 2 portion? And then sort of related to this, guys, could you maybe comment on the statistical analysis of this study? And I believe you're considering the non-squamous and squamous populations separately, which is different from how your competitor Summit is doing their analysis of HARMONi-3.

So, why do you prefer your method? Thank you.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

So, what's 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, this is, in principle, like two studies in one because we want to explore in our phase 2/3 both non-squamous and squamous small cell lung cancer across all PD-L1 status as setting. That means with these different patient populations covered, we have a sample size, which is around 950-plus patients. And we expect, based on earlier data we have seen, that all these -- that these histologies and also different PD-L1 strata can benefit from the BNT327.

This is why we have them all covered in our study.

Uğur Şahin -- Co-Founder and Chief Executive Officer

And we discussed also all kind of options how to structure this clinical trial, including also having a single big cohort. Based on the discussion also with the FDA, we decided to have two indications, particularly with the observations and recently in some of the clinical trials there non-small cell lung cancer and squamous --

Ozlem Tureci -- Co-Founder and Chief Medical Officer

Non-squamous and squamous.

Uğur Şahin -- Co-Founder and Chief Executive Officer

Non-squamous and squamous did show different types of results for some of the compounds. There is now more attention of -- on the different histologies.

Asthika Goonewardene -- Analyst

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

Ozlem Tureci -- Co-Founder and Chief Medical Officer

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

Asthika Goonewardene -- Analyst

Got it. Thanks so much for the color.

Operator

Thank you. We will now take --

Ozlem Tureci -- Co-Founder and Chief Medical Officer

And the phase [Inaudible] as you can imagine is about further optimizing the dose or justifying the dose. So, it's more technical part of the development.

Operator

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

Yaron Werber -- Analyst

Great. I have a quick question. Actually, I want to maybe shift to the ACIP's latest decision not to hold an ACIP meeting. This time it was for flu.

Just curious, I know it's kind of early, but how would you handle this? Would you, at the end of the day, with Pfizer just use the World Health Organization recommendation for the COVID strains? And I don't know whether you have any sort of communication so far sort of what to expect. Thank you.

Ryan Richardson -- Chief Strategy Officer

Yeah. Thanks, Yaron. Not too much to say at this stage. Obviously, we're following very closely the policy environment for COVID-19 vaccines in the United States.

Our expectation is that there will eventually be a strain selected, and we're going to be in a position to respond very quickly, as we have done over the last couple of years. But I'm afraid that, at this point, that's pretty much all we can say.

Operator

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

Jessica Fye -- Analyst

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

Thank you.

Ozlem Tureci -- Co-Founder and Chief Medical Officer

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 reports could be about other indication cohorts we have with 327, including also the first cohorts where we combine with our ADCs, specifically our trial where we combine 327 with 325, our top two ADCs.

Jessica Fye -- Analyst

Thank you.

Operator

[Operator signoff]

Duration: 0 minutes

Call participants:

Michael Horowicz -- Vice President, Strategy and Investor Relations

Uğur Şahin -- Co-Founder and Chief Executive Officer

Ozlem Tureci -- Co-Founder and Chief Medical Officer

Jens Holstein -- Chief Financial Officer

Ryan Richardson -- Chief Strategy Officer

Daina Graybosch -- Leerink Partners -- Analyst

Akash Tewari -- Jefferies -- Analyst

Chris Shibutani -- Analyst

Tazeen Ahmad -- Analyst

Unknown speaker -- -- Analyst

Terence Flynn -- Analyst

Harry Gillis -- Berenberg Capital Markets -- Analyst

Cory Kasimov -- Analyst

Sadia Rahman -- Wells Fargo Securities -- Analyst

Asthika Goonewardene -- Analyst

Yaron Werber -- Analyst

Jessica Fye -- Analyst

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