BioNTech SE

NASDAQ:BNTX

Earnings Call Analysis

BioNTech Reports Strong Q3 2024 Results and Oncology Pipeline Advances

In Q3 2024, BioNTech reported revenues of EUR 1.245 billion, a rise from EUR 895 million in Q3 2023, primarily driven by early COVID-19 vaccine approvals. The company posted a net income of EUR 198 million and diluted EPS of EUR 0.81. Despite robust revenues, BioNTech anticipates a loss for the full year and has adjusted SG&A expense guidance down to EUR 600-700 million, reducing capital expenditure guidance to EUR 300-400 million. Their oncology pipeline, highlighted by the promising BNT327 antibody, is poised for multiple product launches by 2030, demonstrating a 74% objective response rate in trials for triple-negative breast cancer.

Strong Revenue Growth in Q3 2024

BioNTech reported total revenues of approximately EUR 1.245 billion for the third quarter of 2024, significantly up from EUR 895 million in Q3 2023. This notable increase is largely driven by early approvals of COVID-19 vaccines targeting new variants, reflecting the ongoing demand in high-income markets.

R&D Investment Continues Amid Growing Costs

Research and development expenses rose to EUR 550 million from EUR 498 million year-over-year, driven by active clinical trials in oncology. The company is committed to advancing its late-stage oncology pipeline despite rising costs in R&D.

Financial Discipline & Guidance Adjustments

As BioNTech navigates substantial shifts in market demand, it has adjusted its financial guidance. For the full year 2024, the revenue is now expected to be at the lower end of the provided range, between EUR 2.5 billion and EUR 3.1 billion, due to lower demand in some geographic areas. Additionally, potential write-downs related to collaborations and ongoing legal disputes may affect revenues by an estimated 10%.

Operational Efficiency and Cost Management

In response to shifting market conditions, BioNTech has reduced its estimated SG&A expenses for 2024 by EUR 100 million to a range of EUR 600 million to EUR 700 million. Capital expenditure guidance was similarly lowered by EUR 100 million, now projected between EUR 300 million to EUR 400 million.

Oncology Pipeline Progress and Strategic Focus

The company illustrated robust activity in its oncology pipeline, with multiple Phase II and III trials ongoing. Specifically, BNT327 (a bispecific antibody) is prioritized for registration trials in small cell lung cancer and triple-negative breast cancer. Data updates for various pipeline candidates are expected in 2025, including from mRNA cancer vaccine platforms and additional cancer immunotherapy developments.

Future Expectations and Clinical Updates

Looking ahead, BioNTech anticipates generating clinical data updates from its ongoing trials within the next 18 months. Upcoming results will include data from both its personalized mRNA cancer vaccines and the bispecific antibody BNT327, which is seen as key to enhancing treatment efficacy across several cancer types.

COVID-19 Vaccine Responsibilities and Market Sustainability

With robust demand for COVID-19 vaccines, BioNTech continues to expect sustainable market opportunities. The partnership with Pfizer will allow the company to maintain a lean cost structure while enhancing cash flow generation. This model is seen as favorable for future growth, especially in light of ongoing global vaccination efforts.

Earnings Call Transcript 2024-Q3

[Operator]

Welcome to BioNTech's Third Quarter 2024 Earnings Call. I would like to hand the call over to Michael [ Horowicz ] Director, Investor Relations. Please go ahead.

[Unknown Executive]

Thank you. Good morning and good afternoon. Thank you for joining BioNtech's Third Quarter 2024 Earnings Call. As a reminder, the slide that 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 comments 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 in this call are subject to significant risks and uncertainties and speak only as of the date of this conference call. We undertake no obligation to update or revise any of these statements.

On Slide 3, you can find the agenda for today's call. Today, I am joined by the following members of Biotech's management team: Ugur Sahin, 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.

[Ugur Sahin, executive]

Thank you, Michael. Welcome to all with us today. I will be keeping my introduction rather brief today. We made significant achievements during the third quarter, including advancements across our oncology pipeline and a strong start to the season for our COVID-19 vaccine franchise. Our progress in this quarter based on what has already been an impactful year. I would like to highlight achievements in three areas. First, with regard to our COVID-19 vaccine leadership. We have successfully launched updated vaccines targeting the latest variance, distribution now underway in multiple regions globally.

In oncology, we have presented our progress in two strategic priority areas, namely our bispecific immunomodulated BNT327, partnered with [ Biocell ] and our mRNA cancer vaccine portfolio. As part of our pipeline progress, we shared numerous clinical updates across our oncology pipeline at the ESMO Congress. [indiscernible], our partner bios has kicked off the board global development of BNT327, our bispecific antibody targeting PD-L1 and [ VGFA ]. The data sets presented at ESMO [ a ] conferences earlier this year, support the cancer potential of this priority asset and support our clinical development plans that we will touch on today and discuss in greater detail at our innovation series next week. We took significant steps forward in the execution of our clinical development plan this quarter and dosed the first patients in two optimization studies in small cell lung cancer and triple [indiscernible] breast cancer to inform the pivotal studies than in both indications.

With regard to our mRNA vaccine portfolio, we announced earlier in the quarter that our off-the-shelf FixVac mRNA cancer vaccine candidate, BNT111, met the primary endpoint in the ongoing randomized two trials evaluating BNT111 in combination with a general anti-PD-1 agent [ cemiplimab ] in patients with Stage 3 and Stage 4 cutaneous melanoma. This preliminary result has caused our belief in the transformative potential of our proprietary mRNA vaccine technology, which is a key pillar of our oncology strategy. Moreover, we have taken another step to broaden our personalized mRNA cancer vaccine development program. We and our partner, Genentech have initiated a new randomized controlled Phase II clinical trial evaluating our personalized cancer vaccine candidate in patients with bladder cancer in the [indiscernible] setting in combination with immune checkpoint inhibition. Our personalized vaccine program now includes four ongoing Phase II clinical trials.

In addition, during Q3, we had our [ in-house covert AI day ] where we highlighted our in-house AI company, InstaDeep and provided an overview of BioNtech's collective AI capabilities. This was an exciting event where we showcased our commitment to building state of the art AI.

Before turning over to [ Ozlem ] for more detailed coverage of these achievements, let me remind you our overarching strategy for oncology. Biotech was established the ambition to revolutionize cancer treatment to the development of mRNA-based immunotherapies particularly to personalized cancer vaccines. This approach remains at the forefront of our efforts to pioneer next wave of cancer treatments, aiming to tailor therapies to the individual genetic makeup of each patient's tumor. Building on this foundation, we have systematically assessed next-generation immune modulator with a focus on bispecific molecules that can engage more than 1 target. BNT327, our bispecific antibody targeting PD-L1 and VGFA has emerged as a key molecule in our pipeline. We believe that BNT327 has the potential to serve as a foundational component in the treatment of aliments from multiple cancer types, enhancing the effectiveness of our Terra project mRNA cancer vaccines and other therapies to its dual targeting mechanism. Complementing these mechanisms of action we have recently expanded our portfolio to include targets immunotherapies such as antibody drug [ cone new ] gates and CAR-T cell therapies. These modalities offer precise mechanisms for attacking cancers, providing new avenues for combination therapies, particularly for fighting large metastatic tumors.

Our integrated long-term approach will combine the synergistic therapeutics platform to optimize cancer treatment. Our strategy aims not only to address the existing challenges in cancer care, but also to significantly long-term survival rates even in patients with advanced disease state. By continually evaluating the effectiveness of usual compounds and innovative combinations, we can better identify the most promising treatment strategies for specific patient populations. Today, as [indiscernible] discussed in more detail our progress on BNP327 and our outstanding efforts on our therapeutic mRNA cancer vaccine fund, two profit key pillars of our strategy. Before handing over, I would like to thank you all for your ongoing support. We entered a truly exciting period for BioNTech and progress towards our founding vision. Thank you.

[Özlem Türeci, executive]

Thank you, Ugur. Glad to be speaking with everyone today. I will begin with our COVID-19 franchise. Ahead of this vaccination season, regulatory and public health authorities at five vaccine manufacturers to revise the antigen composition for the authorized COVID-19 vaccines in line with tenants epidemiologic data. The continuous evolution of SARS-CoV-2 and the emergence of variants have led to regionally different recommendations for the [indiscernible] strain selection. We have been able to rapidly meet these different requirements due to the flexibility of our mRNA technology, which enables us to adapt our construct on relatively short notice. .

In Europe, less than 3 weeks after the regulatory of our year, we commented the use of JN1 spike antigen in the COVID-19 vaccine toward '24, '25 season we were able to submit our application to a European regulator and we began rolling out our update shortly after appropriate [indiscernible] are ready to live. Anticipating the regional differences, we followed up with development and submission for our [indiscernible] KP2 adapted vaccine.

In the U.K., the regulator posted our JN1 adapted COVID-19 vaccine in July and our KP2 adapted COVID-19 in early October. In the United States and Canada, regulatory authorities, recommended the use of KP2 as a preferred [indiscernible] for the presence [indiscernible]. Less than 2 weeks after recommendation, we initiated our rolling submission with the U.S. FDA has received approval of our KP2 adaptive vaccine in August.

In Japan, we received our JN1 approval in early August. These early strain recommendations and approval have allowed for the timely delivery and earlier availability of vaccines for four vaccination campaign.

Execution at such speed was enabled by our continued surveillance and analysis of areas of concern by the strength of our mRNA technology, which allows for scalable rapid production and due to our expertise in navigating the regulatory landscape on a global scale. We will continue to monitor our evolving epidemiology of COVID-19 and remain prepared to develop vaccines with adapted antigenic composition in line with regulatory recommendations. COVID-19 transitions to an endemic infection pattern. -- data on a weekly new hospital admission due to infections caused by [indiscernible] and [indiscernible] influenza show different patterns of seasonality. This past season, like in the prior year, COVID-19 disease related hospitalization had two primary peaks, one in the winter and an additional one in summer. In contrast, for influenza, we predominantly see increases in hospitalizations in the winter. The emergence of new variants, coupled with a weighing of both vaccine and infection induced in immunity indicates that the susceptibility to COVID-19 infection remains a concern after the winter vaccination season. These different patterns of seasonality of Influenza and COVID-19 may have an impact on regulatory guidelines to facilitate protection throughout the year.

Recently, U.S. authorities recommended order and immunocompromised individuals received an additional COVID-19 vaccine dose administration of additional doses, [indiscernible] season could contribute to improved vaccine coverage over time, mitigating the risks associated with evolving COVID-19 variance. Given our current understanding of COVID-19 seasonality its burden on health care systems, we are proud that our vaccine can contribute to mitigate severe infection and protect people around the world from COVID-19 replacement hospitalizations index.

Turning now to our oncology pipeline. Our multi-platform immuno-oncology clinical pipeline is continuing to advance, and it is a rich source from a strategically planned novel-novel combinations that we consider a key pillar of our vision for oncology. As you can see, two of our modalities, namely mRNA and immune non-ocular [ data IO ] are dominant year represented in our pipeline, and particularly so in the advanced clinical stages. This is a testament to our drive towards mid- to late-stage clients as part of our position to achieve multiple product launches in oncology by 2030. It is [indiscernible] a special focus on our mRNA cancer vaccine portfolio and our BNT327 setup clinical development program with the latter becoming our platform for unique combinations with several of our other assets, in particular [OIDC ].

BNT327 is a bispecific antibody candidate that targets both PD-L1 and VGFA that's combined two complementary functions. The binding of BNT327 to PD-L1 tumor stores effectors [indiscernible] of tumor cells and enrich the GLA non-neutralization within the tumor micro environment to create a cycle of ventricular normalization, improved blood flow and reduce hypoxia with the tumors. BNT327 also reverses the negative effect of the GFA signaling on the infiltration and activation of immune cells inter-tumor microenvironment. By co-localizing the blockade of PD-L1 and VGFA signaling to the tumor, BNT327 is designed to deliver superior anti-tumor compared to individual targeting of PD-L1 and VGFA with the potential to minimize worth events associated with systemic anti VGFA [indiscernible]. With the entire PD-L1 and VGFA antagonistic mechanisms being navigated across numerous tumor types and in some cases, in combination, we have a role for a development of BNT327.

We and our partner [indiscernible] have treated over 700 patients in clinical trials across a wide range of clinical indications with BNT327 either as monotherapy or in combination with various standard of care [indiscernible]. In these early studies, BNT327 demonstrated encouraging activity as mono and combo therapy with a favorable safety profile that was shown to be generally well manageable and in line with worst events and immune related to work observed with other purity targeted PD-L1.

The data also indicates robust single-agent activity for BNT327 and in combination with standard of care chemotherapy across tumor type and treatment plans. This extensive data collection provides us with the foundation for making data-driven decisions on potential indications and patient cohorts for future potentially registrational study. One of the indications we have selected for further development in triple-negative breast cancer, TNBC, the type of breast cancer with the poorest outcomes. In first sign metastatic TNBC, we have observed a high objective response rate with encouraging responses and long progression-free survival for BMT327 in combination with [indiscernible]. As now this year, we presented updated efficacy and safety findings from the ongoing Phase I/II study in this indication across the 10 to 3 population of 42 patients, we observed a confirmed objective response rate of 74%. Importantly, which posted were shown clinically meaningful irrespective of PD-L1 status. In patients with PD-L1 combined positive score of CPS smaller than one confirmed of objective response rate was 76.9% in patients with PD-L1 CPS between one and 10, the confirmed objective response was 52%. And in patients with tier 1 CPS higher, the control of trend rate was 100%.

We also served record tumor shrinkage with a median time to response of 1.9 months and an encouraging median duration of response of 11.7 in the intense treat population. Treatment-related adverse events of Grade 3 or [indiscernible] occurred in 57% of patients leading to treatment less continuation in 4.8%.

In summary, we are encouraged by the potential of BNT327 in combination with chemotherapy to offer clinically meaningful antitumor activity regard to of PD-L1 status and by manageable toxicity. We have prioritized the planning of global trials in TNBC where unmatched needs remains high, particularly for the with PD-L1 negative tumors, if they are not eligible for current anti-PD-1 treatment.

We will be presenting additional data in first line TNBC at the San Antonio Breast Cancer Conference next month. We believe that BNT327 and this [indiscernible] class at large are showing a single validated mechanism of action, where dose optimization price in the U.S. initiated recently allow us to create a robust scientific data package to inform the global development of [indiscernible] and tick off three waves of focus development.

We plan to execute [indiscernible] and move broadly into three ways. First, we are investigating the BNT327 combination in standard of care chemotherapies as an [indiscernible] fast-to-market approach. The data generated by our partner, [indiscernible], that have driven our decision to prioritize the planning of registrational trials in small cell lung cancer, TNBC and non-[indiscernible] lung cancer due to start in the next few months. Second, we plan to evaluate BNT327 with our ADC isolate tumor types and additional key indications. The first exploratory trial evaluating novel BNT327 commissions was started earlier this year with our proprietary TROP2, ADC '23, '25. These non combinations may open up new areas of activity for BNT327. We plan to initiate additional trials evaluating other proprietary combinations of BNT327 with before year-end and over the next 12 months.

Lastly, we aim to expand with standard of care chemotherapy and moral combinations beyond ADCs across [indiscernible] and treatment settings. It is a strategic goal for us to explore BNT327 as part of normal and other combinations.

Given our experienced clinical development team, which has an increasingly global footprint, our strong financial position and unique pipeline. We are confident that we are well positioned to efficiently execute on this comprehensive clinical development strategy. Now to the other cornerstone of our oncology portfolio, our mRNA cancer vaccine platform, IMS and [indiscernible]. [indiscernible] target neoantigens necrosometic mutations in cancer cells that are unique to the individual tumor. I see our investigational vaccines that are being codeveloped with our partner Genentech and are manufactured on-demand and personalized to win with your patients. FixVac vaccines target mitosis non-mutated tumor antigens shared by the majority of patients with a given tumor type and are also shared cancer vaccine chemicals. The computational approaches to discovering and testing these to different types of target antigens of our core company IMS and FixVac both use the same vaccine and delivery technology minor proprietary MRAS platform. Today, we have ongoing trials in multiple disease settings and indications across on we have reported relation in clinical data over the last couple of years and future data updates from multiple trials shown on this plan. aggregate data that we have reported in the past across IMS and FixVac trials indicate that Urogen mRNA LPS-based vaccines are a manageable and much we might safety profile as single agents in combination with anti-PD-1, PD-L1 compound and in combination with chemotherapy. Our data also indicates that our uridine mRNA LP based vaccine platform is highly proficient in inducing and expanding high magnitude functional and longest T cell responses in the majority of patients, which is a prerequisite for clinical activity.

Furthermore, our data from small [indiscernible] patient cohorts indicates clinical activity alone and in combination with [indiscernible] PD-L1 and PD-1 treatment. In our fixed back program, I would like to highlight two vaccine candidates for which we have important updates during the quarter. For BNT113, our mRNA vaccine candidate against HPV16-positive cancer, we presented data from [indiscernible] at the ESMO conference. One data set was from the safety run in cohort of or potentially registrational Phase II randomized trial and had merit. This trial evaluates BNT113 in combination with emporium net versus payroll alone in first-line HPV16-positive PD-L1 positive had in net came sarcolemma. The data supports the tolerability of BNT113 and clinical activity in combination with pembro and the induction of higher magnitude de novo T cell responses against HPV16 antigens encoded in this vaccine. In summary, we are encouraged by the data in the safety cohort.

The second data set from investigator initiated Phase I/II trials, exploring the NT1 person as single agent in patients localized in metastatic [indiscernible] and [indiscernible] other HPV16 driven carcinoma, further confirmed positive safety and immunogenicity finding. We have reported top line findings for BNT111, which is being investigated in patients with anti-1 relapsed or refractory melanoma BNT111 includes four melanoma associated antigens, which collectively cover more than 90% of melanoma patients and are highly immunogenic. In the randomized two clinical trial conducted in collaboration with Regeneron, BNT111 is being evaluated in combination with their anti-PD-1 contain. The trade in more 184 patients with PD-L1 refractory unresectable Stage 3 or 4 for and comprises prearm of which one evaluates the combination and the other to measure the activity of BNT111 alone or simply map. The trial met its primary endpoint, achieving a statistically significant improvement in ORR objective response rate in BNT111 similar combination as compared to a historical control of anti-PD-1 monotherapy in relapsed refractory patients based on live-stage chemical trials that established make business ORR for monotherapy checkpoint inhibitors in this setting for patient population.

The results we saw in the Phase II study are consistent with results seen and we're proceeding on two trial in patients with advanced melanoma who have exhausted frequent option. BNT111 a lower oil combination with anti-PD-1 compound induced high magnitude T-cell responses against at least one targeted tumor related antigen in all analyzed patients, most of which were not detected prior to losing [indiscernible]. We plan to present the full data from the primary levers at a medical conference.

The various FixVac data updates provided in Q3 are a proof of concept in three dimensions. Firstly, for our mRNA cancer vaccine technology that uses uridine mRNA chemistry. A noncoding [indiscernible] that is engineered for commercialization performance and our proprietary like formulation for systemic delivery, which we are using in both IMS and FixVac vaccine.

Secondly, for our computational approaches for the activities and targets for our indication specific fixed red program candidates. Now see a proof of concept for our strategy to combine synergistic modalities in the case of BNT111 and [indiscernible] with established immune [indiscernible] inhibitor treatment.

Moving to [ Outogen Saunoral ], also BNT122, our individualized mRNA cancer vaccine candidate based on our IMS platform in development with our partner Genentech. We consider individualized cancer vaccines as a potential medical breakthrough is addressing by high under medical need of resectable cancer and acumen or minimal disease treatment setting. We have demonstrated that our individualized vaccine can be deduced in patients with atomic pancreatic cancer can induce de novo responses that are specific to the individual muting tumor neoantigens and that the risk of recurrence of cancer for patients when they're being induced immune responses was reduced over a 3-year follow-up period. We have two active randomized Phase II price evaluating our individual cancer vaccine in the [indiscernible] setting. Mainly pancreatic factors, adenocarcinoma aqueduct and in colorectal cancer. The 5 years elaborate in [indiscernible] after resection is 10% and up to 75% of patients with PDP relapse even though the [indiscernible] within 5 years after adjuvant treatment.

For high-risk colorectal cancer, about 35% of patients elect within 5 years after resection and accelerate. So to summarize, we aim to bring endometrial cancer vaccine into [indiscernible] treatment setting in tumor tracts where unmet medical need is [indiscernible]. As such, we have expanded into a new indication with the start of a Phase II trial evaluating our individualized cancer vaccine candidate in the active treatment master-invasive urothelial carcinoma, which has started screening patients.

The current treatment includes neutrals chemotherapy followed by cystectomy and for eligible patients. This is followed by actual treatment with an induced checkpoint inhibitor. The [indiscernible] survival among issues with metastatic greater cancer is about 8% Excellent treatment of master evasive disease is an important opportunity to potentially avoid recurrent metastases and improve overall survival. The randomized [indiscernible] multi-cite Phase I clinical trials into they make [ autogenounoran ] as an adjuvant treatment with the on checkpoint in [indiscernible] patients with [indiscernible]. The trial is expected to enroll about 360 patients to evaluate the efficacy of BNT122 in combination with novo compared to [indiscernible], the standard of care product indication in the U.S. The primary point for study is investigator-assessed disease suite provider secondary objectives include our survival and safety.

Lastly, as a final note, I would like to invite you to our upcoming innovation period day next week, where we will share additional details on needs and other programs of our PRP pipeline. With that, I will now pass the presentation to our CFO, Jens Holstein.

[Jens Holstein, executive]

Thank you, Ozlem, and a warm welcome to everyone who have done in today's call. Let me start by reviewing our financial results for the 3 -- ended September 30, 2024. The total revenues reported for the period were approximately EUR 1.245 billion. mostly recorded in September compared to approximately EUR 895 million for the third quarter of 2023. The increase compared to the same period last year can be largely attributed to early approvals of our variant adapted COVID-19 vaccines this year versus last year.

Moving to cost of sales. Cost of sales amounted to approximately EUR 179 million for the third quarter of 2024 compared to approximately EUR 162 million for the comparative prior year period. Research and development expenses were approximately EUR 550 million for the third quarter of 2024 compared to approximately EUR 498 million for the comparative prior year period. These expenses were mainly influenced by progressing clinical trials for our late-stage oncology pipeline candidates.

Sales, general and administrative expenses amounted to approximately EUR 151 million for the third quarter of 2024 compared to about EUR 164 million for the comparative prior year period. SG&A expenses were primarily driven by personnel expenses. The company's other operating results amounted to approximately negative EUR 355 million in the third quarter of 2024 compared to negative EUR 9 million for the comparative prior year period. The other operating result was primarily influenced by accruals for contractual disputes.

Income taxes were realized with an amount of about EUR 39 million in the third quarter of 2024 compared to approximately EUR 67 million of accrued tax expenses for the comparative prior year period.

For the third quarter of 2024, we reported a net income of approximately EUR 198 million compared to about EUR 161 million for the comparative prior year period. Our diluted earnings per share for the third quarter of 2024 amounted to EUR 0.81 compared to EUR 0.66 for the comparative prior year period. As of September 30, 2024, our cash and cash equivalents plus security investments reached approximately EUR 17.8 billion.

Our strong balance sheet allows us to invest in future value creation. Consequently, we will continue to invest in maintaining a lean cash generative COVID-19 vaccine business. In the development of our [indiscernible] therapies and in our core capabilities to sort additional late-stage trials and potential commercialization of our most encouraging oncology assets. We will continue to assume a rigorous go/no-go decision-making across all development stages as part of our portfolio prioritization strategy. This allows us to maintain our focus on materializing the value in our pipeline.

Turning to the next slide, we see financial guidance for the full year of 2024. We saw a strong quarter in terms of revenues, which included certain revenues that we previously anticipated in the last quarter of 2024. With this, we expect full 2024 financial year revenues to be at the low end of the guidance range provided in our outlook. Our guidance reflects some risk of write-downs and other charges by our collaboration for the Pfizer, which we estimate to approximately 10% of company revenues. We will continue to monitor the risk of potential write-downs to determine the full scope of charges related to the 2024, 2025 vaccination season. In line with our disclosure earlier in the year, we expect to report a loss for the 2024 financial year as we continue to invest in our most differentiating assets and technologies.

We are committed to responsible and sustainable growth. And with this, updating our full 2024 financial year expenses guidance to indicate a decrease in estimated SG&A expenses and capital expenditures. Reflecting our focus on continued investment in our pipeline, we're maintaining our R&D expense guidance. We have lowered the initial full 2024 financial year SG&A expense guidance by EUR 100 million from EUR 700 million to EUR 800 million to now EUR 600 million to EUR 700 million. We also reduced our capital expenditures guidance by EUR 100 million from the initial 2024 guidance range of between EUR 400 million and EUR 500 million to between EUR 300 million and EUR 400 million.

Please note that these guidance update for SG&A expenses and CapEx do not reflect any M&A, collaborational licensing transaction that we may enter into in the future, nor any potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activities such as judgments or settlements or other extraordinary items all of which may have a material effect on our results of operations and cash flows. In summary, we remain focused on executing the company strategy highlighted by the progress across our pipeline. We have advanced and started new dose optimization and potentially registrational trials and have shared encouragingly [indiscernible] has to demonstrate the potential of our product candidate.

In our oncology portfolio, our focus remains on investing in our innovative technologies that we believe can have the greatest impact on medical practice while progressing our late-stage programs efficiently towards potential approvals. Our cash position and financial discipline allows us to continue to invest in those assets with the highest disruptive potential and focus on generating value for patients and our shareholders. With that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for our strategic outlook and concluding remarks.

[Ryan Richardson, executive]

Thank you, Jens. Starting with COVID-19, we continue to execute on our successful launch of this season's JN1 and KP2 variant adaptive vaccines in more than 40 countries and regions around the world. In September, we began distribution of our KP2 variant adaptive vaccine in Europe following the initial rollout of JN1 vaccines in July. We expect additional markets including the U.K. that received initial shipments of JN1 vaccine to transition to KP2 deliveries in November.

In the United States, we continue to expect vaccination rates this year that are generally comparable to last year. with potential for slightly higher volumes due in part to the earlier approval and rollout of vaccines and supported by ACIP's recommendation in October for a second dose of COVID-19 vaccine for individuals who are 65 or older or immunocompromised.

Internationally, we have seen the opening up of several private meets in countries like the U.K., Japan, Switzerland, Australia, South Korea, Singapore and Brazil. This year, we have also increased our supply of prefilled syringes in a number of international markets. The epidemiology of COVID-19 over the last 2 years and the associated global demand for vaccination continue to support our view that COVID-19 vaccines will be a sustainable market for the foreseeable future. We expect to maintain or even gain market share in [indiscernible] key markets this year. versus last year and believe that we are likely to enter a period with improved visibility into vaccine demand. One of the unique features of our COVID-19 vaccine business is its lean cost structure.

Our partnership with Pfizer allows us to leverage its manufacturing infrastructure and global commercial capabilities, which we will continue to enable us to limit the OpEx flowing through our P&L. These features create the potential for us to generate significant cash flow from our COVID-19 business, a feature we expect to benefit from in the future.

Turning to the next slide. We are entering a catalyst-rich period for our company, in particular, for our oncology portfolio. Today, we have more than 10 Phase II and III trials ongoing across multiple tumor types. In the next 18 months, we expect multiple clinical data updates from these trials, and we'll initiate several additional trials with registrational potential. Data is expected in 2025 from both our mRNA cancer vaccine platforms, FixVac and iNeST. We also expect data updates for BNT327, our anti-PD-L1 VGFA bispecific antibody and BNT323, our HER2 ADC.

Before we conclude our planned remarks, I would like to invite everyone to watch our annual Innovation Series event on November 14. This will include a deeper dive into our oncology strategy, including plans for BNT327 and our mRNA cancer vaccine candidates. We look forward to engaging with you later this month to share more on our plans to create value for patients, society and shareholders. With that, we would like to open the floor for questions.

[Operator]

[Operator Instructions]. We will now take the first question from the line of Tazeen Ahmad from Bank of America Securities.

[Tazeen Ahmad, analyst]

I appreciate your time. I wanted to ask you about one of the data catalysts that you mentioned that's upcoming in 2025. Perhaps we'll talk about this more in detail next week but for 323, specifically, I believe you've got data coming for endometrial cancer. Can you talk about the level of data you expect to show next year for that program and what you're looking for in order to move forward?

[Özlem Türeci, executive]

Katin, thank you for this question. The question was about our mitral cancer data with BNT323. And what I can tell you about that is that in 2025, we expect to share data from our single-arm trial in second-line endometrial cancer, we will be able to show efficacy data and safety data across different HR positivity, populations, and this will be presented at one-off of major cancer conferences.

[Tazeen Ahmad, analyst]

And also what would be positive data in your mind for that program?

[Özlem Türeci, executive]

Can you repeat?

[Tazeen Ahmad, analyst]

What would be positive data for that study in your mind data?

[Özlem Türeci, executive]

What would justify to continue with the compound is a strong clinical activity profile and a favorable safety. And this is also what we see in the data, and we see this across different HER2 expression levels. .

[Operator]

Thank you. We will now take the next question from the line of Daina Graybosch from Leerink Partners.

[Daina Graybosch, analyst]

I have one on the VEGF PD-L1, BNT327. I think we're all aware of a similar bispecific that has a PD-1 side, whereas you have a PD-L1 side and in small trials in similar indications like triple-negative breast cancer, the two bispecifics look to have similar outcomes, was that expected? And what does that tell you about the mechanism? And do you believe BNT327 could be differentiated in any indications?

[Ugur Sahin, executive]

In, thanks for the question. Yes, this is a good question. And at the end of the day, both by specific link these activities of notarizing VEGF and authorizing PD-1, PD-L1 interaction, they have this in common. The biggest distance is that BNT327 is directed against PD-1, which comes with the potential advantage of being further enriched in the tumor micro environment by binding to PD-L1 or vice versa enabling or adding to the binding of VEGF and [indiscernible]. The data that we have so far, these are -- there are some overlapping clinical trial. As you as we mentioned, look similar. And they have to see whether this potential mechanistic difference could translate into better response rate and better durability, particularly in PD-L1 positive tumors. So we have to see that there is a slight trend in this direction, but it's too early to, yes, to validate it.

[Operator]

We will now take the next question from the line of Akash Tewari from Jefferies.

[Unknown Analyst]

This is Kathy on for Akash. So for your VEGF PD-L1 bispecific BNT327, when do the AEs and reductions in dose for hypertension proteinuria job in comparison to what we've seen historically for VEGF PD-L1 when co-administrated as two separate drugs. And additionally, weren't you going forward with it to first-line NSCLC in all-comers population? And what's the rationale for going as a biomarker selected population..

[Ugur Sahin, executive]

Okay. I take both parts of the question. So the first question was the comparison with the historical starting to safety profile, particularly with bevacizumab. Yes. So yes, now more than 700 patients treated either as mono-compound or in combination. And the comparison to historical to the historical safety profile clearly shows reduced side effect profile with regard to the key concern in side effects of bevacizumab bleeding hypertension of the formation of fistulas. We have not seen any significant increase of bleeding cases in this cohort, which goes beyond what is observed in this population, for example, for PD-1 antibody and hypotension rate is significantly lower than the historical [indiscernible] of [indiscernible]. The mechanism for this can only be speculated and that by linking the entire body with the VEGF part to PD-1 and the anti-VEGF interaction is more targeted to the tumor site and that's less active in PD-L1 negative areas. And this is, of course, encouraging and provides an additional argument beyond increased so far increased clinical activity for this compound class. So this was the first part.

And the second part is why we prefer to go into outcome population. The response to that is that our bispecific has shown a clinical activity, not only in PD-L1 positive and we have run low population, but also in populations, which do not express PD-L1 or CPS. I would refer to our data set that we generate in TNBC where the objective response rate in the TNBC or current population with extremely intelligent. We see something similar with a clear indication of clinical activity in the PD-L1 negative population in the second 9 months announced small cell lung cancer and [indiscernible] positive population.

So the working hypothesis that we have is that this bispecific antibody, fully comes -- overcomes the limitation, the rotation of pure clinical activity in PD-L1 positive tumors and opens up the potential to bring check point blockade plus VEGF activity into tumors that are also PDL negative. So the clinical trial in non-small cell lung cancer is an [indiscernible] trial, but we are documenting and collecting standards for TD evaluation, and we are stratifying patients accordingly the [indiscernible] positivity.

[Operator]

We will now take the next question from the line of Suzanne van Voorthuizen from VLK. .

[Suzanne van Voorthuizen, analyst]

This is Suzanne. Maybe I missed it, but can you clarify what the exact amount is that you have taken as a provision for contractual disputes this year? Is this it? Or will there be more and can you indicate what this relates to, if this is the ongoing patent dispute with other mRNA players on the COVID vaccine? Or if there are other contractual disagreements you are dealing with?

[Jens Holstein, executive]

Yes. Happy, Susanne, to take the question. So as you stated, the other operating result is reflecting these provisions that we have taken care of for contractual disputes with licenses and collaborators. We -- at this point in time, given the legal situation that we're in, cannot give precise messaging and for what this is. There are a couple of disputes that are related, as I stated with some of the players and collaborators that we're working with. In total, we have accrued around about EUR 600 million year-to-date for this, and this is the amount that we feel is accurate at this point in time.

[Operator]

We will now take the next question coming from the line of Terence Flynn from Morgan Stanley. .

[Terence Flynn, analyst]

I was just wondering if you can tell us what you think the relevant benchmark is for survival for the upcoming BNT327-TNBC data that we're going to see at the San Antonio conference in December?

Were you able to hear my question?

[Ryan Richardson, executive]

Can you just repeat that? Sorry.

[Terence Flynn, analyst]

Survival benchmarks for the upcoming BNT327-TNBC data at the San Antonio conference in December. And then the second part of the question is, is it reasonable to expect some interim data from your global Phase II lung cancer trial next year?

[Ugur Sahin, executive]

Okay. I can take the question. The trial will be an against chemotherapy standard of care. And the private sales is powered for PFS and OS -- the PFS is in this indication in the range of 4 to 5 months as I can't recall at the moment.

[Ryan Richardson, executive]

Right. I think we're going to have updates plant to provide an update at the 15 and 18-month OS mark in terms of percentage of patients read. And that's starting to get into a relevant one, Terence, when you look at the what pembro has achieved in a similar indication, which is basically in the 15 to 23 -- up to 23-month median OS, depending on the patient, CPS patient model.

[Ugur Sahin, executive]

Absolutely. And we have recently reported PFS data in the single region, reaching now about 13 months and still ongoing.

[Operator]

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

[Yaron Werber, analyst]

Great. Maybe just a follow-on Terence's question. on TNBC is the starting Phase IIIs to go for CPS less than 10 specifically in that cohort? Or would you go across all CPS levels in Phase III. And then secondly, on small cell, is the primary going to be head-to-head against chemo to centric or is it going to be against chemo alone? Thank you so much.

[Ugur Sahin, executive]

So the first trial is intended in the patient population below 10% and will be against chemotherapy alone. But we plan also further or we are in the evaluation of additional cars going to the above 10% population.

[Ryan Richardson, executive]

And can you just repeat the second part of your question?

[Yaron Werber, analyst]

Yes. And just switching to small cell lung cancer is the Phase III going to be head-to-head against chemo or against chemo to centric. Thank you in small cell lung cancer.

[Ryan Richardson, executive]

Chemo to centric.

[Operator]

Thank you. We will now take the next question. from the line of Jessica Fye from JPMorgan Chase.

[Jessica Fye, analyst]

Two first on guidance of the various assumptions factoring into your guidance what changed to lead you to guide the low end of the range, even though Pfizer, I believe, maintained its community guidance last week? And then on the pipeline for BNT327, the VEGF PD-L1 bispecific, what do you see as the fastest to market indications? And what's the right way to think about R&D spend as the company expands trials for this product?

[Jens Holstein, executive]

Yes, Jessica, let me take the first part of the question. So we've guided at the beginning of the year, EUR 2.5 billion to EUR 3.1 billion based on, of course, certain scenarios. Year-to-date, Q3 has been very, very good. And Q3 so far or the year-to-date figures so far have been generated dominantly by revenues that we generated in high-income countries. We have seen, though, low demand and also low pricing in some of the low and middle income countries within the Pfizer territory, and therefore, we specified our guidance to the low end for this year.

[Unknown Executive]

And then second question?

[Ryan Richardson, executive]

I think your second question was speed to market. What we think would be the fastest to market for 327 is that correct?

[Jessica Fye, analyst]

Yes.

[Ryan Richardson, executive]

So I think we're going to provide more details at our innovation series week in terms of the paths to market. But I think what we can see is that we do think that small cell lung cancer to be one of the leading indications that we're looking at very closely. We initiated a Phase II trial and believe that we can start a Phase III trial. It's a Phase II/III effectively, so Phase III portion of that trial in the coming months. by first of next year. So that could represent one fast path to market. But of course, we're looking at others as well.

[Operator]

We will now take the next question from the line of Cory Kasimov from Evercore ISI. .

[Cory Kasimov, analyst]

So your Trop-2 ADC BT looks like an important part of your emerging combination strategy with 327, looking at the clinical trial posting shows that you're evaluating a variety of different dosing combinations. So wondering if you can add some color on the dosing strategies in your content level. that all three mechanisms together will not compromise safety?

[Ugur Sahin, executive]

Yes. The current exploration of combination is exactly also directed to explore the safety of the molecule in combination -- so 325 that to ADC comes with a safety profile that is characterized by stomatitis. And one of the questions that we want to ask is what is the combination with built, what he have an additive toxicity effect, that is something that we would like to understand. We do not expect any other overlapping toxicity since the BNT327 a table the safety profile. We will start with lower doses and then escalate to higher doses and assess and safe those identity space dose profile in explore cohort for also determining the contribution of efficacy PERC. .

[Operator]

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

[Unknown Analyst]

This is Kevin on for Chris. Just wanted to ask another one on the PD-L1 VEGF 327. So you touched on potential mechanistic differences with bevacizumab earlier, if we can assume that the clinical profiles remain relatively similar, do you believe this is a story more about clinical execution? And if so, how can you differentiate there?

[Ryan Richardson, executive]

Yes. Thank you for the question, Kevin. I'll start and then to add to it. So I think that -- we do think that there's sufficient -- actually, there's significant room for differentiation in clinical strategy. And that's actually one of the main drivers that we're evaluating now because we do see applicability across many different tumor types, and as Ugur also alluded across different patient segments within tumor types. And I think one of the unique features of our portfolio in oncology is the combination agents that we could bring to bear with 327. So I think we've talked about chemo combinations being likely the fastest path to market initially. And we've guided to a couple of early indications, but we're definitely thinking broader than that. We're thinking about BDC, 327 combinations to follow shortly thereafter. Our current thoughts would be to initiate those trials already in 2025. The first combination potentially in 2025 rather than waiting to do those in sequence. And we're also going to be evaluating other combinations as well. down the road. So I do think that, that's a differentiation angle that we can -- we're well positioned to exploit. So it really comes down to a combination of combination strategy and also clinical execution indeed as potential differentiators for this large opportunity that we see.

[Operator]

Thank you. We will now take the next question. from the line of Etzer Darout from BMO Capital Markets. .

[Unknown Analyst]

This is Luke [indiscernible] on for Etzer. So what are you learning about a survival cause brand leases that you're looking at? I mean what's your level of confidence that you can beat standard of care given the importance of that endpoint to regulators?

[Ryan Richardson, executive]

So I think we had a little bit of a buzz in the question. I think you were asking about the importance of overall survival. Is that correct? .

[Unknown Analyst]

Yes. So like when we are for overall survival across breast and money and like what level of confidence you have given the importance of that endpoint to regulators?

[Ugur Sahin, executive]

Yes. Yes. So we completely understand the rational of this creating particularly based on disappointing [indiscernible] coming within many indications at an improved PRS, but did not translate into an OS. And there are, of course, of course, collecting our own in-house data. And and we clearly see that this maturing OS data, unpublished [indiscernible] data, we are getting more and more encouraged and that improved PFS is translating also into an OS. I would like to remind you that PFS improvement that we are seeing, for example, in TNDC is more than substantial, okay? So it's not the pan and that is usually observed with usually bevacizumab added 2 to 3 months additional PFS and then the drop in was steep this following the pattern that is observed with chemotherapy alone. We are not seeing this pattern we are seeing that particularly in locations where there the combined BNT327 this chemotherapy that there is a sustained PFS and the PFS does not drop in the term like a steep curve that goes slowly down. And this is the best -- this is the best thing that we have so far for that we can translate to OS. And I think we can definitely answer the question in the next 3 months for the first indications in which we are TNBC, small cell lung cancer and second months of the lung company. .

[Operator]

Thank you. We will now take the next question. from the line of Ellie Merle from UBS.

[Eliana Merle, analyst]

So the flu COVID combo program, I guess, what's the latest on this program after the Phase III missed d1 of the endpoints? And what's your latest thinking around the time lines for the second-gen program with the trivalent mRNA flu vaccine just given Moderna expects to launch its combo next year, curious dilutes on your strategy with your combination?

[Ryan Richardson, executive]

Yes, Ellie, thanks for the question. So we're working with Pfizer now on our next-generation flu covid vaccine combination a combination vaccine program. And I think it's a little too early to give you a precise road map, but we're hoping to give you -- and planning to give you updates over the course of 2025. I think needless to say, I think it is a program that has or the full weight of Pfizer and biotech R&D teams behind it. And we do think that some of the problems that have been -- we're seeing in an initial trial that those can be addressed through further optimization of the construct. And we have early evidence that supports that. But I think before we give you a definitive road map, I think we'd like to generate a little more data and hopefully come out with that next year.

[Operator]

Thank you. SP1 We will now take the next question from the line of Yifeng Liu from HSBC Bank plc.

[Yifeng Liu, analyst]

I have one on your oncology portfolio. Just wondered for the other assets, apart from BNT327, 325 especially on the IO space. In the next 12, what are we going to hear your update on specifically things like 312 or 314, those early stage -- early mid-stage assets. So I think.

[Ryan Richardson, executive]

At 312, of course, is the CD44BB program with [ Genmab ], and that's an ongoing trials right now. I think our intention is to bring data forward upon that trial's completion. We don't yet have dates for that, but it's likely going to be next year. And I think the other programs, generally speaking, our intention is to bring data out when we think we have something relevant to share. We tend to do that in our preferred mode of data disclosure is in medical meetings. And so of course, that requires that you've got data in hand that it's clean and been analyzed and is accepted by public auction. So we can't always give precise guidance on when every program will read out. But I think those other programs are progressing, and I think we plan to update our pipeline disclosure schedule going into early next year.

[Operator]

Thank you. We will now take the next question from the line of Simon Baker from Redburn Atlantic.

[Simon Baker, analyst]

Another one on BMT327. And going back to Terence's question. I just wanted to double check that the comments you made with respect to trial design were related to triple-negative breast rather than the planned non-small cell lung cancer study. If that is indeed because is there anything you can shed on the design of the upcoming first-line study in terms of geography comparator arm, I think you mentioned stratification and interim results, but any detail would be much appreciated.

[Özlem Türeci, executive]

Simon, I would like to refer you to our Innovation Day next week, where we will disclose in more detail a couple of study designs and benchmarks we are comparing against also contextualized to our entire trial were also questions around BNT327 pivotal trials we are planning will be disclosed. .

[Operator]

Thank you. We will now take the next question from the line of Manos Mastorakis from Deutsche Bank. .

[Manos Mastorakis, analyst]

Since my question was stolen. Basically, I just wanted to ask on your ongoing confidence on your TROP-2 program, but also your nest meal program as well? Thank you very much.

[Özlem Türeci, executive]

So first question was about ADC. I get that right. So we -- as you know, our TROP2 ADC 327 is at an early stage of testing. And in particular, we see potential in combination with BNT327, which we see as we have already dust as a platform to combine with different ADCs and the combination trial. We just have started to explore first of all, safe combination doses is going into this direction and is exploring TNBC on small cell lung cancer and ovarian cancer and cervical cancer cohorts up for TROP2 and the ADC and combination. .

The second question was about our Nestor individualized platform. We are continuing to expand into the adjuvant space. As you might know, we have adjuvant -- we have trials running in adjuvant colorectal cancer with an upcoming interim analysis end of next year. We have started with our partner Genentech a trial in the actual setting of pancreatic cancer, motivated and informed by small Phase I trial with however, exciting data. And we just have started a third trial in this in the adjuvant setting with muscle invasive urothelial cancer or also a randomized, potentially pivotal trial. So these are the ongoing trials. And we are reading out our trial in first-line melanoma, and we'll be able to disclose more about that in our upcoming innovation day next week.

[Ryan Richardson, executive]

And I would just add to that, that in summary that we continue to believe that INS has disruptive potential in particular in those adjuvant settings that [indiscernible] mentioned, and we're investing accordingly in the program. .

[Operator]

Thank you. We will now take the last question from the line of Jay Olson from Oppenheimer. .

[Jay Olson, analyst]

Congrats on the progress, and thank you for providing this update. Can you comment on the approximate level of R&D spending increase you expect in the next few years considering how rapidly you're expanding the number of Phase III programs in oncology? And is there an ideal number of Phase III trials that would optimize your organizational and financial resources?

[Jens Holstein, executive]

Yes, thanks for the question. I mean it's a bit early for any guidances that we are not intending to give now in November. I think we feel comfortable with the 2.4%, 2.6% that we currently have running. And on one hand, we want to control costs, on the other hand, of course, we want to invest wisely. If we talk about 37 and the potential, of course, it would be not very clever to not invest in that compound to just use this example, specifically. So -- but be assured that we control our costs going forward, being at SG&A expenses will be in an R&D expenses.

[Ryan Richardson, executive]

Yes. And with regard to the target pipeline, I think it's a very good question. I would just note that with the current level of R&D spend that Jens has just alluded to, and we currently have 10 ongoing Phase II or III trials. Some of those are with partners. Some of those are fully bio-type self-funded. But I think it already shows you that we've already reached at this current R&D level pretty significant scale in the mid- and late-stage pipeline.

[Operator]

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