BioNTech SE Price & Performance (BNTX)

Good morning and good afternoon. Thank you for joining BioNTech's fourth quarter and full year twenty twenty four earnings call. As a reminder, the slides we will be using during this call a corresponding press release we issued this morning can be found 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. We undertake no obligation to update or revise any of these statements. On Slide three, you can find the agenda for today's call. Today, I'm joined by the following members of Biontech's management team. Huber Zaheem, Chief Executive Officer and Co Founder Ozlem Tarechi, Chief Medical Officer and Co Founder Ian Solstein, Chief Financial Officer and Ryan Richardson. Chief Strategy Officer.

With this, I would like to hand over to Ugar.

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. [indiscernible] Before we do so, I want to speak briefly about our original vision, and the strategy to become an immuno tab powerhouse and a fully integrated biopharmaceutical company with multiple approved products. BioNTech has evolved significantly since its founding in '28, 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 path of patients who participated in our clinical trials. With a clear focus, we will continue to invest in our technologies and drug candidates that has 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, six SAC and INEST, and our bispecific anti PD L1 anti VQF antibody interviewed seven. 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 this program across various cancer types. Building up commercial functions for their future commercialization in key markets and enhancing manufacturing capabilities to support both [indiscernible] and commercial supply. In the infectious disease sector, we are advancing the development of our next generation COVID-nineteen and combination vaccines. Our infectious disease product strategy focuses on sustainable value creation with active pipeline prioritization and the 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 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 third Phase two trial evaluating autogen serum Iran adjuvant setting [indiscernible] namely in bladder cancer. In early twenty twenty five, we also published two manuscripts describing our insights from two Phase one trials [indiscernible] For three of the SHAFZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZZ data including the announcement that six track candidate 111 met the primary endpoint in a randomized Phase two trial in patients with anti PD-one relapse.

Refractory melanoma. We presented multiple data sets for our next generation IO BNT327, the PD L1 VGF bispecific antibody and initiated Phase three and Phase two trials in small cell lung cancer and non small cell lung cancer. We plan to initiate a Phase III trial in triple negative breast cancer this year. We announced our intention to acquire BioThios to secure global control over BNT-three twenty seven and expand our immunotherapy capabilities. This transaction closed earlier this year and we are thrilled to welcome Biofios as a new arm of our operations in China. With regard to our COVID-nineteen 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. 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 immunotherapy including mutant neoantigens for application primarily for the early stage including adjuvant setting and our fixed back immunotherapies targeting tumor associated TENSIONS in combination with checkpoint immunotherapy respectively.

Second, our PD L1 VGF bispecific antibody BNT4use seven which we believe has the potential to become a next generation IO backbone for the treatment of advanced cancers. We believe that both programs have planned 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 We are excited to now formally welcome BioPhiSios team to BioNTech. Having worked for a year with the highly skilled and dedicated team at BioNTech, 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 BMT-three 27. However, there are other factors of this acquisition which are also strategically important for us. [indiscernible] 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 preclinical development and decision making allowing us to bring other programs into late stage and global development.

With the acquisition of BioThios, we have now a fully integrated antibody manufacturing network, China. The sites supplied antibodies for clinical trials and could potentially support initial commercial supply for market launches. Lastly, BioThouse 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 Esther. Thank you, Ugoa. Glad to be speaking with everyone today. Before talking about our focus programs introduced by Ugo, 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 II and III 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 Ugo pointed out, our mRNA immuno therapies and our BN T327 centered clinical development program are dominantly represented in our pipeline and particularly so in the advanced clinical stages with BNT-three twenty seven becoming our platform for unique combinations with several of our other assets, in particular, our ADCs.

As Ugo mentioned, 2025 will be an important year for both of our priority programs. BNT327 by colocalizing the blockade of PD L1 and VGFA 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 VGFA. With the potential to minimize adverse events associated with systemic anti VGFase therapy. With the anti PD L1 and anti VEGFA mechanisms, being validated across numerous tumor types and in some cases in combination we have a roadmap for development. We have made strong progress over the past few months across all three waves of our 27 clinical development. Program. The first wave is focused on lung cancer in TNBC as key indications to establish BNT-three twenty seven combined with standard of care chemotherapy therapy with first approvals in first line settings of these indications. We have completed enrollment in our global Phase two 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 three trial. In key MBC, we will start a global registrational study later this year. In non small cell lung cancer, we have begun enrolling patients patients in our global Phase II pre registrational clinical trial.

Our second wave of development with BNT-three twenty seven reflects that IO plus ADC combos are an emerging treatment paradigm in oncology. We have started exploring combinations BNT-three twenty seven with four ADCs directed against DROP-two HERF HER3, B7H3 from our partnership with Duality and MediLink and informed by a robust database of single agent data for these ADCs. A BNT twenty seven ADC combination study with our TROC-two ADC BNT-three twenty five is already enrolling patients. In the coming months, we expect to dose the first patients combining BNT-three twenty seven with our HER2 ADC three twenty three and our B7H380. Throughout this year, we will evaluate the data from these initial combination trials and will start additional novel combinations across two more types: to broaden our global clinical development program with BNT327. With this focused clinical development program, we aim to leverage BNT-three twenty seven full potential. As previously mentioned, we expect 2025 to be a data rich year across our whole pipeline and especially for BNP three twenty seven. The first of these data sets will come later this month at the European Lung Cancer Congress and feature our trials in small cell lung Small cell lung cancer is a tumor type type with notable incidence worldwide and an immunologically code tumor for which high unmet need remains.

With current standard of care treatment, the durability of is quite short and five year survival rate for extended stage small cell lung cancer is only three percent. [indiscernible] Based on our emerging data, we believe that PNT-three twenty seven has the potential to improve clinical outcomes for patients At ESMO twenty twenty three, data were presented which show encouraging activity of BNT-three twenty seven 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 BNT-three twenty seven. We plan to present three data sets from trials in small cell lung cancer this year, including data from two separate single arm Phase two trials. Evaluating BNT-three twenty seven 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 NT-three twenty seven for the potential treatment of first line small cell lung cancer in our ongoing global Phase three trial. As Ryan will cover later, we expect to share additional important clinical data updates throughout the year. Our mRNA cancer immune therapy platforms, INEST and six FACT are the other cornerstone of our oncology portfolio. [indiscernible] [indiscernible] twenty two developed in partnership with Genentech is based on the INIS blood Ines targets neoantigens unique tumor specific mutations and is FICC, in contrast, targets shared non mutated tumor antigen and is an off the shelf approach.

Both platforms utilize our proprietary uroden 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 INAS and FIGFAC trials across various tumor types These data consistently demonstrate that urothelin mRNA LTX based immune of Europeese have manageable safety profile whereby used as single agent. In combination with anti PD-one, PD L1 inhibitors or with chemotherapy. Crucially, our data also indicate that these immunofuruppies are highly effective at inducing and expanding high magnitude functional and long lived T cell risk in a significant proportion of patients. This robust immune response is a prerequisite for clinical activity. We have multiple trials with both Fyxtleg 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 one clinical trial of autogen zavumoram published in Nature Medicine which included over two hundred patients with resistant refractory advanced and metastatic solid tumors. This trial evaluated autogenerzivumorant both with and without the checkpoint inhibitor atezolizumab.

It is known that only a small fraction one percent to two percent of cancer mutations spontaneously elicit an antitumor immune response. Our mRNA cancer immunotherapy approach aims to significantly increase these anti tumor immune responses. In this Phase one trial, autogenerzivumiran successfully induced T cell responses across multiple cancer types converting a high portion of patients [indiscernible] The majority of these responses were fully epitopic directed against multiple mRNA encoded neoentes And these responses were de novo, meaning they were newly generated against the encoded neoantigens and did not exist higher to treatment. In some patients, we observed up to a two order of magnitude amplifications. Of existing neoantigen specific T cells. [indiscernible] Furthermore, in several patients, we detected newly induced anti tumor T cells infiltrating the tumor of treated patients. These findings demonstrate the potent immunogenicity [indiscernible] even in patients with advanced rapidly progressing cancers. Which is a prerequisite for clinical activity. In our ongoing Phase two 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 one trial, we observed modest signals of clinical activity.

Which was expected given that the Phase one trial was conducted in heavily pretreated resistant refractory fast growing advanced cancers. We recently also received top line data from the IMCODE-one Phase II trial marked here on this slide. This was the first randomized proof of concept Phase II trial of an INES candidate evaluating all pembrolizumab versus pembrolizumab alone. As first line treatment for patients with metastatic or advanced melanoma. [indiscernible] This trial is part of a broader M code 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. By the initial data confirm our observations that autogen Rumoran 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 autogenerzalumoram with PD-one 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 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 one 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 timeframe 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 INESTS 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. Etrovant 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 immune suppressive tumor microenvironment are typically best 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 INS program on the adjuvant setting. We currently have three ongoing randomized Phase two trials of autogenerate, one in colorectal cancer that is enrolling Stage II high risk and Stage three CRC patients who are ctDNA positive after surgery resection and standard of care chemotherapy. These patients are at high risk of recurrence often within a year. Continue to anticipate initial data from this study either late this year or in early twenty twenty six. These data will be critical for informing the next stages of development and regulatory discussion. We are also evaluating Autogen's Rumoran as an adjuvant treatment for pancreatic cancer. This Phase two is informed by a small Phase one trial in which we showed strong immune responses induced by autogen sevumoram and their correlation with significant improvement of recurrent three survival. A randomized controlled Phase two trial in bladder cancer was initiated in the fourth quarter of last year. We believe individualized cancer immunof therapies have a 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, Jensal Staatsch.

Thank you, Arthim, 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 €2,800,000,000 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 €678,000,000 a diluted loss per share of €2.77 Our cash position, including cash equivalents and investments, and securities, amounted to €17,400,000,000 at the end of twenty twenty four. This leaves us financially well positioned to continue with the Please note that this year end cash position has not yet reflected the closed acquisition of BioPheas, to the amount of approximately US800 million dollars in and payments derived from the settlement of the contractual disputes with NIH at the University of Pennsylvania to the amount of $792,000,000 and $467,000,000 respectively. We expect that the BioThieves acquisition payment and the NIH payment totaling approximately US1.6 billion dollars will be reflected in our first quarter twenty twenty five financial position. We expect that the University of Pennsylvania settlement payment will be reflected in our second quarter twenty twenty five financial position.

With respect to the settlements, we also expect the reimbursement of approximately US538 million dollars 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 12/31/2024, we recognized total revenues of approximately €1,200,000,000 compared to approximately €1,500,000,000 in the prior year period. For the full year, we recognized around €2,800,000,000 compared to around €3,800,000,000 in 2023. The reduction was primarily driven by a lower COVID-nineteen market demand. In addition, write downs by our collaboration partner Pfizer reduced our gross profit share and hence negatively influenced our revenues for 2020 Research and development expenses reached €612,000,000 for the fourth quarter of twenty twenty four compared to €578,000,000 for the comparative period in 2023. For 2024, R and D expenses amounted to approximately EUR 2,300,000,000.0 compared to roughly EUR 1,800,000,000.0 in 2023. The increase was mainly influenced by the planned advancing of our priority programs including BNT-three 27 towards late stage development. SG and A expenses amounted to approximately €132,000,000 for the fourth quarter of twenty twenty four, compared to €142,000,000 in the same period of the previous year.

For the 2024 financial year, SG and A expenses amounted to approximately €599,000,000 compared to €558,000,000 in 2023. The increase in SG and 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 €671,000,000 for the 2024 financial year as compared to negative €188,000,000 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 reimbursement, by our collaboration partner Pfizer. [indiscernible] For the fourth quarter of twenty twenty four, we reported a net profit of approximately €260,000,000 compared to around €458,000,000 for the comparative period in 2023. For the full year 2024, we reported a net loss of €665,000,000 compared to a net profit of €930,000,000 in the prior year. Our diluted earnings per share for the fourth quarter of twenty twenty four amounted to €1.08 compared to €1.88 in the comparative period in 2023. For the 2024 financial year, our diluted loss per share amounted €2.77 compared to €3.83 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 full year 2024 revenue guidance of €2,500,000,000 to €3,100,000 During our third quarter twenty twenty four 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 and D, we reported roughly €3,000,000,000 in expenses for 2024 slightly below the low end of our full year 2024 financial guidance range of €400,000,000 to €2,600,000,000 This was in part driven by our active portfolio management and the shifting of some registrational study costs from 2024 into 2025. On SG and A and capital expenditures for operating activities, we ended at the lower end of our 2024 expectations from our last earnings call. ATV's lower guidance ranges is the 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 EnergyE We expect total revenues in the range of €1,700,000,000 to €2,200,000,000 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-nineteen 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 Brexit vaccines and mRNA technology in The United States and or elsewhere could also negatively influence BioNTech's COVID-nineteen vaccine revenues and financial results. Turning to operating expenses. In 2025, we expect R and D expenses to be in the range of €2,600,000,000 to €2,800,000,000 As compared to 2024, we expect to see an increase in investment into our priority late stage programs in 2025. 27 our mRNA cancer and monotherapy and our AEC pipeline. Consistent with our portfolio prioritization strategy, we'll also expect to decrease our R and 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 and A. We expect SG and A expenses to be in the range of EUR650 million to EUR750 million. We're 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 €250,000,000 to €350,000,000 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 disrupt In summary, 2025 will be another year of continued transition for BioNTech with the aim to become a multiproduct commercial and colo chip company. We will continue to diligently invest in our long term growth strategy. While maintaining strict financial discipline. With that, we remain focused on achieving long term sustainable growth and generating value for patients and shareholders. Now I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for our strategic outlook and concluding remarks. Thank you. Thank you, Jens.

I would like to end our prepared remarks with a summary of our priorities for 2025, our key anticipated upcoming clinical and regulatory milestones for our oncology pipeline. This year, our focus will remain on executing on two BNT-three 27 and our mRNA cancer immunotherapies. Each of these programs are in Phase II or Phase III 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 In infectious disease, we will continue to invest to maintain our and Pfizer's global leadership position in the COVID-nineteen vaccine market while continuing to advance next generation and combination vaccines in the clinic.

We expect to provide multiple updates from our early stage infectious disease pipeline over the course of the year. We are in a catalyst rich period for BioNTech. We plan to share multiple clinical updates across our focus programs throughout 2025, including at upcoming oncology conferences in March and April. In addition to the data for 27, we plan to share data updates for our mRNA cancer immunotherapies iNest and FixPACK. And with regards to our first potential oncology product in HER2ADC BNT-three twenty three, [indiscernible] plan to share Phase two data from a single arm registrational trial in 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. 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 and D Day on November 18. [indiscernible] will share further details on both events later With that, we would like to open the floor for questions.

Thank you. We will now take the first question.

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

Thanks, Dana, 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. [indiscernible] Yes.

I think, Dana, 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 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.

And maybe one more because that was quick. On the fixed pack, data that you're going to share this year of simlopumab, Can you just remind us of the context going into that? Recall that that was a top line success. So how we should be thinking about a vaccine in relapsedrefractory melanoma in context of, Azam, you sharing that the personalized vaccine didn't work in a metastatic melanoma setting? Thank you. Hi. Thank you for the question. I'm not sure whether I got it correctly. So the question was with regard to our [indiscernible] Right, where we have reported a that it was a successful trial and that we have a achieved the endpoint. We will have data presentations on this later this year on one of the conferences and also preparing a manuscript. So there will be more information about that. As you pointed out, yes, we observed that for our eye mass 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 probability of getting robust clinical benefit is much higher due to SYNTHOVIOLOGY. Of adjuvant cancer. And then one of the key differences between between the INS approach and fixed back approach is fixed back can be applied immediately without any delay and for the IVAC approach at the time from the clinical trial 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 vial vaccinations ongoing in immuno responses are built. So based on that, we early on adapted our strategy and went into the adjuvant stage. [indiscernible] patients, patients before they progress have three, six, nine, twelve months before PFS event is approved.

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

Hey, thanks so much.

Just on 03/27, I know in the past your teams alluded to kind of the cost associated with developing an agent like this. Across different tumor types and certainly Merck is talking about running a lot of different Phase three trials. Over time And you guys have hinted at a potential fifty-fifty partnership. Where does Blanta currently stand on the partnership question? On 03/27? And what clinical or commercial capabilities would you be looking at for an external partner? Thank you.

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 03/27 in these initial trials that we've started and that's really the focal point this year. So on small cell lung cancer, small cell lung cancer and triple negative breast cancer being the first indications. But 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, that combinations with other companies' agents could could prove useful down the road. And indeed, we have been approached by different companies who are interested in potentially combining with BNT-three twenty seven. 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 twelve to eighteen 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 makes sense for us to evaluate all opportunities to potentially speed up and expand the program.

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

Good morning. Thank you so much.

With your plan for 03/27, obviously, the scope of opportunity is considerable. And as we think about the other leading player developing Summit Akizo, 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 CNBC, but is there some sort of strategic overlay, whether it's thinking about PD L1 agnosticism, geographies, something that helps discern how your approach may be differentiated to ultimately also demonstrate differentiated clinical data?

Thank you.

So I can start and maybe Renal 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 tumor indications, also different patient segments within tumor indications. Both for PD-one, PD L1 therapies have been successful. But also potentially in in patient segments where PD-one, PD-one 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 that we've disclosed so far. But down the road, as we've also mentioned, 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 also cancer vaccines that we have. That could enable such novel combinations. I don't know who would you want to No, no. Just it's really about about the execution of this price.

If you really consider the full spectrum. Tech many years in multiple indications. So then you revisit what has happened in the IO CF and IPV1 treatments And this was a process which went and is still ongoing in the last ten years. And this is something something which we expect also for the next generation of an entire three d one blockade with the bispecific antibody. So this is something where we see in the next year the need to to start multiple clinical trials and multiple indications but not only do the trials in combination with standard of care but also consider consider combinations with novel compounds that can help to differentiate the efficacy seen by ENTY301 alone.

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?

We don't see anything specific. I mean, you know that clinical trial enrollment in particular to 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 three twenty seven trials, which seems to be a compound where investigators are very enthusiastic about.

Thank you. I appreciate the follow-up.

Thank you. We will now take the next question from the line of Tassin Afmat from Bank of America Securities. Please go ahead. Hi, good morning. Thanks for taking my question.

Can I just ask you what you're expecting the bar for efficacy to need to be for three twenty three 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 three twenty three, if in fact you're able to do so in 2026? And maybe I wanted to follow-up on that previous question How are you thinking about building out commercial organization versus waiting to partner?

Thanks. [indiscernible] Yes. Thanks, Tazeen. So on the first question, I just to clarify, I think you're asking the efficacy bar for BNT-three twenty three and endometrial cancer, correct?

Yes.

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

Yes. And to Ubers' point, I mean, we've seen within HER2 response rates around fifty percent. 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 brebacizumab plus chemo, we're seeing response rates far lower than that.

Terms of standard of care. So in the sort of twenty percent range.

Thank you. Could you just repeat the second question, please?

My God, I mean, this is crazy.

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

Hi. Thanks for taking the question. Know you mentioned you're going to have some three twenty seven Phase two data for small cell lung cancer here over the next month or so. Just wondering if you can help frame expectations there in terms of what you're hoping to see in actually how much data we'll get, will we get anything with respect to PFS, etcetera? Thank you.

So I think in the first instance, I'll start and Alvin Nougher can join.

We've already published some data in small cell lung cancer where we showed response rates in the seventy percent range with a combination with chemotherapy. We're expecting that these data sets that are coming to an extent going to to further validate and expand on that. And further justify our decision to move aggressively into a pivotal trial in small cell. I think one of the neat 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 been built on previous data sets that we put out there.

Yes. And there will 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 our dose justification clinical trials, which we initiated. Thank you. We will now take the next question. From the line of Harry Gillis from Berenberg. Please go ahead.

Thank you for taking the question.

Just on the 2025 revenue guidance, you talk about relative stability in vaccination rates, pricing and market share. 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 NovoFaxx Thank you.

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 the market share seen it 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 part returns or write offs that consist out of write offs on material like we've seen in '24. We had JAN1. We had KP2 variants. In 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 in 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 a little bit potential competitive pressure here.

So to your point of Finofi. And thirdly, there is potentially also some risk that the EU is moving a little bit of a volume towards 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 why we are at the midpoint at this range.

Thank you.

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

Hey guys. Thanks for taking the question.

I wanted to follow-up on Terence's question regarding setting the stage for the update later this month at ELCC. Are you able to comment on how much follow-up you will have at the meeting? And what do you see as the appropriate comp at this stage? Thank you. [indiscernible] we will have PFS data. I cannot say from the top of my head what would follow-up time within the study is, but we have we will have CFS data. On our small cell lung cancer trial. [indiscernible] And emerging OS data. And emerging OS data, yes, no medium OS, but emerging OS data.

Yes. And the in terms of the standard of care, it continues to be in the first line setting. It continues to be to centric plus chemotherapy. With the benchmark.

Great. Thank you.

Thank you.

EMPOWAT-one 33 trial as a benchmark of that test?

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

Hi.

This is Sadia Arman on for Mohit. Thanks for taking our questions. So another question on 03/27, was it would the competitor expected to read out their OS data in lung cancer later this year. How would you view read through from those seven? 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. [indiscernible] Our North American Lung Cancer study is actually actually two studies in one study. Addressing complete population of of AGA negative first lung cancer patients That means the PD L1 high, PD L1 low and PD L1 negative population. In squamous and non squamous patients. Our competitor is [indiscernible] Plus chemotherapy. And treatment group received PNT-three twenty seven plus chemotherapy and endpoints are as usual PFS. And OS.

Thank you.

We will now take the next question. From the line of Arshtikar Gunwardenet from Tuohy Securities. Please go ahead.

Hi, guys. Thanks for taking my question. Aslam, you mentioned that you started recruiting patients who have Phase twothree trial in non small cell lung cancer. Could you give a little bit more color on the size of that Phase two cohort? And if you plan on reporting that data and maybe a little bit of guidelines on expectations for enrolling that that Phase two portion? And then sort of related to this, guys, could you maybe comment on the statistical analysis of the 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 Harmony three. So why do you prefer your method? Thank you.

So was the question the size of our study? [indiscernible] regarding the non small cell lung cancer study, as U. K. Has pointed out, this is in principle like two studies in one because we want to both non squamous and squamous small cell lung cancer. Across all PD L1 status is [indiscernible] That means with these different patient populations covered, we have center 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 PDL-1s and strata can benefit from the end [indiscernible] three twenty seven. This is why we have all covered in our study.

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

Skamos and Skamos did show different type of results. For some of the compounds. It's now more more attention on the different histologies.

Got it. Guys, but can I also just double click into this a little bit, please? Because the study, the Phase twothree, recruiting nine eighty something patients. What proportion of that target enrollment is specifically for the Phase two component?

For the Phase two component is around 40 patients. The Phase three component is 940 something. So I was basically reflecting the Phase three component. With the central size.

And this is, equally distributed across non squamous and squamous non small cell lung cancer sub studies. So to say?

Got it. Thanks so much for the color.

Thank you. We will now take as you can imagine is about further optimizing the dose or just a justifying the dose. So it's It's more a technical part of the development. We will now take the next question from the line of Yaron Werber from TD Cohen. Please go ahead.

Great. I have a quick question.

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

Thank you.

Yes. Thanks, Yaron. Not too much to say at this stage. Obviously, we're following very closely the policy environment for COVID-nineteen 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. Thank you.

We will now take the next question from the line of Jessica Fye from JPMorgan. Please go ahead.

Hey guys, good morning. Thanks for taking my questions. So beyond the small cell lung data, coming up imminently for three twenty seven, can you just take us through what specifically the next 03/27 data releases will be? And where we should look out for them? I realize there's number listed on the slide, but it just says 2025 plus.

Thank you.

So the question was about next next upcoming BNT-three twenty seven. Data after small cell lung cancer. One data package will be TNBC in which we also have a Phase two.

So study ongoing and follow-up data on a previous study, which we have presented last year at the Antonio conference, where you will learn a bit more about further maturing OS Additional reports could be about other indication cohorts we have with three twenty seven including also the first cohorts where we combine with our ABCs, specifically our trial where we combine three twenty seven with three twenty five, our top two ADC.

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

Two,