BioNTech - Earnings Call - Q2 2025

Transcript

Speaker 9

Welcome to BioNTech's second quarter 2025 earnings call. I would like to hand the call over to Douglas Maffei, Vice President of Strategy and Investor Relations. Please go ahead.

Speaker 6

Thank you, operator. Good morning and good afternoon. Thank you for joining BioNTech's second quarter 2025 earnings call. As a reminder, the slides we will use during this call and the corresponding press release can be found in the Investor Relations section of our website. On the next slide, you will see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings with the U.S. Securities and Exchange Commission, or SEC. 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.

I'm joined by the following members of BioNTech's management team: Ugur Sahin, Chief Executive Officer and Co-Founder, Özlem Türeci, Chief Medical Officer and Co-Founder, Ramón Zapata, Chief Financial Officer, and Ryan Richardson, Chief Strategy Officer. With this, I'll hand the call over to Ugur.

Speaker 0

Thank you, Doug. A warm welcome to you all as you join us today. Doug joined BioNTech recently as our new Head of Investor Relations, and I would like to welcome him to the company. As previously announced, Ramón Zapata joined last month as our new Chief Financial Officer and will be speaking on the call today. Ramón is a seasoned financial leader with a wealth of international pharmaceutical experience from companies including Novartis and Zendo. With over 25 years of experience, Ramón has a deep understanding of market and business dynamics, resource optimization, and high-performing teams. We are delighted to have Ramón on board and look forward to working together in the coming months and years. Our long-serving Chief Strategy Officer, Ryan Richardson, will depart BioNTech in September.

I would like to thank Ryan for his many contributions and commitment as we develop BioNTech from a private clinical stage biotech into a Nasdaq-listed, fully integrated biotechnology company. The management board and I wish Ryan all the best as he embarks on the next chapter of his career. I will now continue with our overarching vision and strategy. As BioNTech has grown and evolved significantly over the years, our vision has remained unchanged: to translate science into survival by building an immunotherapy powerhouse and becoming a fully integrated biopharmaceutical company with multiple approved therapies. We believe that the future of cancer treatment and the ability to improve cure rates will be driven by combination therapies that combine compounds with synergistic mechanisms of action.

Aligned to our vision, we are working to address the full continuum of cancer across different stages, from resected cancers which are in the adjuvant stage and at risk of recurrence to early-stage metastatic cancers, as well as the late-stage cancers which are refractory to multiple treatments. We have built a robust pipeline with compounds from different drug classes that are well-suited to achieve this across a broad range of cancers, allowing for a novel combination of next-generation immunomodulators with targeted therapies and mRNA cancer immunotherapies. With a clear focus, we will continue to invest in our technologies and drug candidates that have the potential to improve outcomes for patients across a wide range of tumor types. We are focused on two priority pan-tumor programs: our mRNA cancer immunotherapies, including CYXEC and INEST, and our bispecific antibody BNT327 that targets PD-L1 and VEGF-A.

Both approaches have disruptive potential and align to our vision. We believe these programs could establish new standards of care, enhancing patient outcomes in multiple cancer indications globally. We are investing significantly in the clinical development of these programs across various cancer types and stages. At the same time, we are building commercial infrastructure to enable future launches in key markets and enhancing manufacturing capabilities to support both clinical trials and commercial supply. Moving now to our key achievements from this quarter related to our outlined strategy and vision. We believe BNT327 has the potential to become a standard of care treatment across a broad range of tumor types, including those currently treated with checkpoint inhibitors and those where checkpoint inhibitors have previously not shown benefit. Core to our strategy is developing combinations of BNT327 with a broad range of potentially synergistic therapeutics.

With such combinations, we may be able to improve the safety and efficacy profile, thereby unlocking better clinical outcomes for as many patients as possible in areas of high unmet medical need. Earlier this year, we closed the acquisition of Biofuse, and with that, fully integrated BNT327 into our pipeline. In order to significantly accelerate and broaden its clinical development, we entered into a global 50/50 co-development and co-commercialization collaboration with BMS in June. Since the announcement, our teams have collaborated closely to shape joint development plans to unlock BNT327's full potential. We believe BNT327 has both potential to be a next-generation IO backbone. We will continue to drive its clinical development with the goal to establish a new standard of care for cancer patients across multiple tumor types.

In the quarter, we also launched the first patient in a new cohort, evaluating our NSCLC CYXEC BNT116 in combination with our B7H3 antibody drug conjugate BNT324. This is another important first for the company in terms of novel combinations, combining an mRNA cancer immunotherapy with an ADC. We see great potential to combine targeted therapies such as ADCs with mRNA cancer immunotherapy. ADCs can debug metastatic tumors and alter the tumor microenvironment, and mRNA cancer immunotherapies may be more effective in creating polyfunctional and durable tumor-associated antigen-specific T-cell responses once the primary tumor is partially degraded. Also in the quarter, we took steps to strengthen mRNA as one of our platform technologies. We announced a strategic transaction to acquire CureVac in a public exchange offer. This planned transaction aims at complementing BioNTech's capabilities and proprietary technologies in mRNA design, delivery formulations, and mRNA manufacturing.

With regard to our COVID-19 vaccine franchise, which is partnered with Pfizer, we are preparing for the global commercial rollout of our new variant-adapted COVID-19 vaccine for the upcoming season, pending regulatory approvals. Data recently presented and shared with regulators globally indicated that LP8.1 strain-adapted COVID-19 vaccines confer improved immune response against currently dominant and emerging sub-lineages compared to vaccine formulations used in the 2024-2025 vaccination campaign. Lastly, we expanded our partnership with the UK government to broaden our regional R&D activities for innovative medicines, with plans to invest up to £1 billion over the coming decade. The agreement builds on our existing multi-year collaboration aimed at accelerating clinical trials for personalized mRNA immunotherapies and focuses on establishing two new R&D centers and a London-based UK headquarters. We were able to achieve all this while maintaining a strong financial position.

Leveraging our COVID-19 vaccine business and our fortress balance sheet, we will continue to invest significantly in the clinical development of our priority oncology programs across key tumor indications. Now, coming to our recent landmark collaboration with BMS. We aim to establish BNT327 broadly as a new standard of care across multiple tumor types. We are currently advancing BNT327 across more than 10 indications, including two global registration trials with more planned. Our early conviction around this modality and BNT327 has put us in a strong position, and if approved, we aim to be the first or second to launch in a number of indications to help patients in need. Our collaboration with BMS aims to strengthen both companies' positions in oncology. Our decision to partner reflects our belief in the transformative potential of BNT327.

In recent years, we have built out our capabilities to support the development and planned commercialization of our growing oncology pipeline. To support this growth, we have established a global clinical development organization, international clinical manufacturing capabilities, and have begun to establish a commercial organization. Today, we are closer to the goal of becoming a multi-product global oncology company and see this partnership as supporting that ambition. With Bristol Myers Squibb's deep immuno-oncology expertise, market presence, commercial capabilities, and global reach, they are the ideal partner for us and this asset. We also see commonality in their science-led approach and focus on shaping the oncology market through novel modalities and combinations. We have a clear shared vision in this regard, and I look forward to our companies working closely together. I will now turn the call over to Sierk Pötting to provide more details on select clinical programs.

Speaker 13

Thank you, Ugur. I'm glad to be speaking with everyone today. Let me start by highlighting where we stand with the programs that are spearheading our pipeline. With our PD-L1/VEGF-A bispecific antibody BNT327, we have initiated two global pivotal clinical trials in first-line small cell and non-small cell lung cancer and expect to start a third phase 3 in first-line triple-negative breast cancer later this year. We aim to further accelerate and expand BNT327 development with a strategic partnership with Bristol Myers Squibb. For our mRNA cancer immunotherapies, including CYXEC and INEST, we anticipate sharing clinical updates in late 2025 and early 2026. As we look towards becoming a commercial oncology company, we are advancing toward our first oncology BLA submission with BNT323, our HER2 ABC in HER2-expressing second-line endometrial cancer. BNT327 localizes the blockade of PD-L1 and VEGF-A signaling to the tumor.

This bispecific is designed to deliver superior anti-tumor immune modulatory and anti-angiogenic effects compared to the combination of the two individual antibodies and with the potential to minimize adverse events associated with systemic anti-VEGF-A therapy. We now have data from over 1,200 patients which show signals of single-agent and combination anti-tumor activity across tumor types where checkpoint inhibitors are and are not effective. Additionally, we have observed a manageable safety and tolerability profile at multiple dose levels with low rates of high-grade treatment-related adverse events. We have also seen low rates of high-grade adverse events typically observed with VEGF-A targeted therapies. In totality, the clinical data generated to date further strengthen our conviction on this asset and allow us to make informed and robust decisions for our clinical development strategy.

With this clinical database for BNT327 and with the anti-PD-L1 and anti-VEGF-A mechanism having been evaluated and validated across numerous tumor types and in some cases in combination with each other, we have a clear roadmap for development. We aim to develop BNT327 in tumor types where checkpoint inhibitors have been successful for only a group of patients and also in tumor types where checkpoint inhibitors have not yet been successful in improving patient outcomes. We are pursuing a three-way development strategy that we refer to as Establish, Combine, Broaden. We believe that this approach positions us to expand the therapeutic impact across a broader oncology landscape and realize the full potential of this asset. In the last quarter, we have continued to progress in executing this strategy.

With our first wave of development, we aim to establish BNT327 combined with chemotherapy as a new standard of care for three key priority indications: small cell lung cancer, non-small cell lung cancer, and triple-negative breast cancer. This first wave leverages clinical data from multiple phase 1 and phase 2 clinical trials generated and published in the last 12 months. These data have encouraged us to start multiple registration studies in these indications. Our two global pivotal studies for BNT327 are progressing. The first was Saturlung-01, evaluating BNT327 in combination with chemotherapy versus atezolizumab in combination with chemotherapy as a first-line treatment of patients with extensive stage small cell lung cancer. The second was Saturlung-02, evaluating BNT327 in combination with chemotherapy versus pembrolizumab in combination with chemotherapy as a first-line treatment of patients with squamous or non-squamous non-small cell lung cancer, regardless of PD-L1 status.

We also plan to start a phase 3 trial for ZetaBreast01 in first-line triple-negative breast cancer later this year. The high medical need in these three indications and the clinical data we have seen so far in these tumor types are the reason for choosing these first indications. Extensive stage small cell lung cancer is an immunologically cold tumor for which high unmet need remains. Today, these patients are treated with a combination of atezolizumab and chemotherapy and experience a median overall survival of 12.3 months as observed in the IMpower133 phase 3 clinical trial. Based on our emerging data, we believe that BNT327 has the potential to improve clinical outcomes for patients with small cell lung cancer.

Earlier this year, at the European Lung Cancer Congress, we disclosed interim data from a phase 2 clinical trial evaluating BNT327 in combination with chemotherapy as a first-line treatment for patients with extensive stage small cell lung cancer. Beyond the encouraging response rate and median progression-free survival observed, the ELCC data also included for the first time median overall survival data with a median overall survival of 16.8 months. While these data are still immature, we are encouraged by the findings. These data support our decision to evaluate BNT327 in combination with chemotherapy in the ongoing global randomized phase 3 clinical trial for Saturlung-01.

In the last quarter, we completed enrollment in the global phase 2 dose optimization trial evaluating BNT327 in combination with chemotherapy in patients with untreated extensive stage small cell lung cancer and in patients with small cell lung cancer that progressed after first or second-line treatment and will provide a data update from this clinical trial later this year. Another priority indication is non-small cell lung cancer as it's one of the most prevalent cancers globally. Long-term outcomes depend on PD-L1 status and histology, but overall remain poor despite improvements in care by checkpoint inhibitors. At the ASCO NUM meeting last year, we presented data from the phase 1 trial evaluating BNT327 as a monotherapy first-line treatment in metastatic PD-L1 positive non-small cell lung cancer. BNT327 monotherapy indicated encouraging anti-tumor activity across PD-L1 low and high tumors and manageable safety in this patient population.

These data support our decision to start with Saturlung-02 for our global phase 3 trial that evaluates BNT327 in combination with chemotherapy to improve on survival outcomes when compared to the standard of care pembrolizumab in combination with chemotherapy as a first-line therapy for non-small cell lung cancer patients without actionable genomic alteration. Today, we are enrolling patients in the phase 2 part and expect to progress to the phase 3 part later this year. Triple-negative breast cancer is also a priority indication for BNT327 based on the unmet need we see for patients and based on the clinical profile observed to date. Currently, stage 4 patients, depending on their PD-L1 status, are either treated with checkpoint inhibitor in combination with chemotherapy or with chemotherapy alone.

PD-L1 positive patients have a median overall survival of 23 months, while PD-L1 negative patients have a median overall survival of 15.2 months as observed in the KEYNOTE 355 study. Data from a study in first-line metastatic triple-negative breast cancer showed that BNT327 in combination with chemotherapy has an encouragingly high objective response rate irrespective of PD-L1 status. We also observed in the trial encouraging landmark overall survival rates such as 69.7% at 18 months for BNT327 in this setting, suggesting that effective control of disease can translate into improved overall survival. Based on these data, we plan to start a phase 3 trial later this year in the first-line setting. We have also continued enrollment in our global phase 2 dose optimization trial evaluating BNT327 in combination with chemotherapy in the first and second-line treatment of patients with locally advanced or metastatic triple-negative breast cancer.

We plan to share data also from the phase 2 trial at a medical meeting later this year. Our second wave of development with BNT327 reflects that IO plus ABC combos are an emerging treatment paradigm in oncology. We have started exploring combinations of BNT327 with our ABCs directed against PROC2, NER2, and B7H3 from our partnership with Duality, informed by a robust database of single-agent data for these ABCs. In the second quarter, we dosed the first patients in two new BNT327 ABC combination studies. The first is a phase 1/2 clinical trial that is evaluating BNT327 in combination with BNT323, our two targeted ABCs in HR positive and negative HER2 low and ultra-low metastatic breast cancer patients.

The second is a phase 2 clinical trial that is evaluating BNT327 in combination with BNT324, our B7H3 ABC in multiple types of lung cancer, including non-small cell and small cell lung cancer patients, patients with known actionable genomic alterations and across treatment lines. In July, we also dosed the first patient in another phase 2 trial that is evaluating BNT327 in combination with our B7H3 ABC in additional tumor types, including hepatocellular carcinoma, cervical cancer, melanoma, and head and neck squamous cell carcinoma. Later this year, we plan to initiate our first clinical trial evaluating BNT327 in combination with BNT326, our HER3 targeted ABCs. The first BNT327 ABC combination trial evaluating BNT327 in combination with BNT325, our PROC2 ABC in multiple tumor types, was initiated a few months ago and we are starting to get initial data.

At the AACR annual meeting earlier this year, we demonstrated that when dosed in combination, BNT327 and our PROC2 ABC demonstrated superior anti-tumor effects preclinically compared to each drug alone. Our preliminary clinical data and a small sample size suggest that BNT327 plus BNT325 had a manageable safety profile with few overlapping toxicities and clinically meaningful activity. These data provide the first sturdy support for our ambition to combine BNT327 and antibody-drug conjugates with the aim of replacing the chemotherapy in some treatment regimens. We believe that combination regimens in which traditional chemotherapy is replaced by targeted chemotherapy in the form of antibody-drug conjugates may be more tolerable and potentially more efficacious, especially when those regimens are combining two synergistic approaches.

Over the coming 12 to 18 months, we will gather preliminary clinical data from these signals seeking BNT327 antibody-drug conjugate combination clinical trials to help us define which antibody-drug conjugate combinations and which indications to prioritize for late-stage development. The last wave of our three-way strategy aims at further broadening our global clinical development program with BNT327 through additional novel combinations and across additional tumor types. We anticipate that some of the early studies evaluating novel combinations or evaluating new tumor types will begin this year. One clinical trial which we anticipate will begin soon is a phase 1/2 clinical trial evaluating BNT327 in combination with a bispecific antibody we are developing with our partner Genmab that targets both FOLR1 and 4-1BB in metastatic colorectal cancer patients. FOLR1 is highly expressed in colorectal cancers. The other arm of the molecule is a potent 4-1BB agonist.

When activated, 4-1BB signaling promotes T-cell activity and survival. We are excited to bring this and other novel combinations into the clinic soon, and we look forward to updating you on these trials and their rationale as we move forward. As demonstrated in these three waves, we have broad ambitions for BNT327 development that we continue to pursue with focus. Along with our partner Bristol Myers Squibb (BMS), we feel uniquely positioned to fully leverage the complete breadth of potential of this molecule. We will work expeditiously to execute the next global registration trials and accelerate bringing BNT327 to market in multiple areas. Moving now to our mRNA cancer immunotherapy platform, which is the other cornerstone of our oncology strategy and includes INEST and CYXEC. Autogene cevumeran, also known as BNT122, developed in partnership with Genentech, is based on the INEST platform.

INEST targets neoantigens, which are unique tumor-specific mutations, and is manufactured on demand for each individual patient. We believe this approach to be best suited for the early stage, including adjuvant setting. CYXEC, in contrast, targets shared non-mutated tumor antigens and is an off-the-shelf approach in combination with checkpoint immunotherapy. We believe that these programs have pan-tumor potential and could be combined with different modalities to address large patient populations with high unmet medical needs. While our robust clinical development program continues for our whole mRNA cancer immunotherapy pipeline, we look forward to providing data updates from our trials later in late 2025 and 2026. While we are evaluating our mRNA cancer immunotherapy with approved checkpoint inhibitors or chemotherapy, we consider our mRNA cancer immunotherapies as ideal for novel combinations and partners for both our immune modulators and our targeted therapy.

We are excited to have recently dosed the first patient in an exploratory cohort evaluating our non-small cell lung cancer CYXEC, BNT116, and our B7H3 targeted ABCs, and anticipate dosing the first patient in the exploratory cohort with our HER3 targeted ABCs soon. Given they are available off-the-shelf, we believe that our CYXEC candidates are uniquely positioned as combination partners in the metastatic setting when patients do not have time to wait for fully personalized approaches. Turning to the 2025 data update, earlier this year, we announced that we received data from a phase 2 trial evaluating our individualized RNA immunotherapy Autogen Sivoruran, in combination with pembrolizumab versus pembrolizumab alone, as a first-line treatment for patients with metastatic or advanced melanoma. The trial did not meet its primary endpoint of a statistically significant improvement in progression-free survival in this advanced patient population.

However, we did observe a numerical trend favoring the combination arm in overall survival. We will be presenting the top-line data from this trial at the upcoming ESMO Congress in October. We believe that these data support our view that our fully individualized mRNA cancer immunotherapies are best positioned in earlier settings, such as adjuvant treatment regimens. In early settings, tumor mass is low, resistance and immune suppression mechanisms have not been established, and the immune system is much healthier. This is where all three of our current phase 2 clinical trials are positioned. Last year, we announced that our CYXEC candidate for melanoma, BNT111, met the primary endpoint in a randomized phase 2 trial evaluating BNT111 in combination with cimiclimab and also assessing both antibodies alone in patients with anti-PD-1 resistant or refractory melanoma.

We will also be presenting these data at the upcoming ESMO Congress and will discuss the path forward for this program around then. Next, a data update from a cohort evaluating our non-small cell lung cancer CYXEC, BNT116, in combination with cimiclimab as treatment for patients with unresectable stage 3 non-small cell lung cancer after receiving concurrent chemoradiotherapy, will be provided at the 2025 World Conference on Lung Cancer in September. We continue to generate clinical data for BNT116 in multiple non-small cell lung cancer treatment settings, demonstrating the broad potential of our CYXEC approach. To conclude, we remain as strongly convinced as ever that our combination-based approach offers the potential to positively impact the future outcomes for patients in key indications such as in breast and lung cancer. With that, I will now pass the presentation to our CFO, Ramón Zapata.

Speaker 6

Thank you, Ramón. It's an honor to be here today for my first earnings call as BioNTech's Chief Financial Officer. Since joining, I've had the opportunity to meet many of our talented teams. I look forward to working with them and the Management Board to accelerate our common vision, which Ugur and Ramón just walked us through. As BioNTech navigates its transition towards becoming a multi-product oncology leader, I will focus on driving sustainable organizational excellence and global execution in financial reporting, accounting, tax, treasury, and purchasing with the aim of furthering cost-effective value generation. As part of my responsibilities, I'm also looking forward to collaborating with Doug, our new Head of Investor Relations. Together, we are serving as your primary points of contact, and I hope to meet many of you in the coming weeks.

With that, I will now cover our financial results for the second quarter of 2025. For the three months ended June 30, 2025, our total revenues reached approximately €261 million, compared to €129 million for the second quarter of 2024. The increase compared to the second quarter of 2024 is mainly driven by higher revenues derived from our COVID-19 vaccine collaboration. In addition, parts of our total revenues were also derived from a pandemic preparedness agreement with the German government and from a one-time effect associated with Pfizer's opt-out from the development of our shingles program. Research and development expenses were approximately €509 million for the second quarter of 2025, compared to approximately €585 million for the comparative prior year period. The decrease was mainly driven by the reprioritization of clinical trials towards focused programs.

SG&A amounted to approximately €138 million in the second quarter of 2025, compared to €184 million in the comparative prior year period. The decrease was primarily driven by a reduction in external services. For the second quarter of 2025, we reported a net loss of €387 million, compared to a net loss of €808 million for the comparative prior year period. Our basic and diluted loss per share for the second quarter of 2025 was €1.60, compared to a basic and diluted loss per share of €3.36 for the comparative prior year period. During the quarter, we maintained our strong financial position with €16 billion in cash plus security investments. This strategic cash reserve and robust financial position provide us the flexibility to fully pursue our long-term strategy in the coming years.

As part of that strategy, we will continue to invest in the development of our immunomodulator and individualized therapies and in the build-out of the manufacturing capacities and capabilities to support additional late-stage trials and commercialization of our growing oncology portfolio. To create long-term value, we aim to advance our clinical programs fast, responsibly, and cost-efficiently towards potential registration. With that goal in mind, I would like to guide you through what we anticipate to be the financial effects of the collaboration with BMS. As Ugur highlighted in the key strategic drivers of this partnership, it is a landmark deal that will allow us to broaden the potential clinical utility and global access to BNT327, a key piece of our diversification into oncology.

I will now focus on the anticipated financial implications of this deal, which we believe will significantly strengthen our cash position and P&L for the years to come. As part of the agreement, we expect to receive $1.5 billion in an upfront cash payment this year. This payment is to be reflected in our cash position as of Q3 2025. We also expect to receive $2 billion in total non-contingent anniversary cash payments through 2028. The upfront and non-contingent cash payments amounting to $3.5 billion are expected to be recognized as revenues over the development phase of BNT327. In addition, we will be eligible to receive up to $7.6 billion in development, regulatory, and commercial milestones. The majority of milestone payments are expected to be triggered upon approvals and during commercialization. All milestone payments are anticipated to be recognized as revenues following milestone achievement.

Also, as part of the agreement, we will share joint BNT327 development and manufacturing costs on a 50/50 basis with BMS, subject to certain exceptions. Upon commercialization, global profits and losses will be equally shared between BMS and ourselves. Turning to the next slide, we are reaffirming the company's financial guidance for the 2025 financial year, with revenue expected to be in the range of €1.7 to €2.2 billion. Research and development expenses expected to be in the range of €2.6 to €2.8 billion. SG&A expenses expected to be in the range of €650 million to €750 million, and capital expenditures expected to be in the range of €250 million to €350 million. We anticipate a revenue phasing weighted towards the last three to four months of the year, driving the full-year revenue figure.

Given the COVID-19 vaccine market dynamics and shifting policy, specifically in the U.S., we assume lower COVID-19 vaccination rates than the prior year. However, we continue to expect similar market share and pricing as compared to 2024. We continue to monitor current and potential further developments in law, public policy, international trade, and public sentiment as they continue to evolve and could further impact our anticipated COVID-19 vaccine revenues and expenses. In addition, regarding our revenue outlook, we estimate some inventory write-downs and other charges in the range of roughly 15% of BioNTech's share of gross profit from COVID-19 vaccine sales in Pfizer's territory. Beyond our COVID-19 vaccine business, we also expect revenues from a pandemic preparedness contract with the German government, as well as revenues from our collaborations, now including BMS, and our service businesses to contribute to our overall group revenues.

To conclude, and looking ahead, we continue to diligently invest in our growth strategy while maintaining financial discipline. We remain focused on achieving long-term sustainable growth and generating value for patients and shareholders. With that, I would like to turn the call over to Ryan for concluding remarks. Thank you. Thank you, Ramón. I will close our prepared remarks with a brief summary of our 2025 strategic priorities. As Ugur mentioned, we continue to focus on executing against two pan-tumor product opportunities, BNT327 and our mRNA cancer immunotherapies, CYXEC and INEST. We currently have multiple ongoing phase 2 and 3 trials across these programs, reflecting our strategy to bring novel combinations to patients. We expect to generate additional meaningful data for these programs throughout this and early next year.

We also continue to build out our commercial capabilities in oncology to support our goal of becoming a fully integrated biopharmaceutical company. These include a broad global commercial leadership team to drive our transition to the commercial stage in oncology, beginning with the potential approval and launch of BNT327 as early as 2026. In infectious diseases, we have continued to invest to maintain our and Pfizer's global leadership position in the COVID-19 vaccine market while advancing next-generation and combination vaccines in the clinic. On the next slide, I would like to highlight some important investor events we'll be holding this year. Our second AI Day will take place on October 1. We also plan to hold our Innovation Series event on November 11, and we'll share more details on both events later in the year. Finally, I would like to conclude on a personal note.

As Ugur mentioned, I will step down from my executive role at BioNTech at the end of September. As this is my last earnings call as Chief Strategy Officer, I would like to extend my deepest gratitude to those in the investment and analyst community who have been long-term supporters of our efforts to positively impact patients' lives. I would also like to thank my colleagues on the Supervisory and Management Boards, as well as my teams, for their dedication and collaboration during these crucial and fruitful years. It has been a true privilege to support BioNTech's transformation into one of the most exciting disruptors in our industry, and I'm very excited to follow the company's continued growth in the years to come. With that, we would like to open the floor for questions.

Speaker 12

Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. Please limit yourself to one question and speak loud and clearly into your mic. To withdraw your question, please press star one and one again. Please stand by while we compile the Q&A roster. We will now go to the first question. Your first question today comes from the line of Tazeen Ahmad from Bank of America. Please go ahead.

Can you hear me now? I think I was muted. Good morning. Thanks for taking my question. First of all, Ryan, thanks for all of your help from the IPO onward, and you'll be missed. Can I just ask for a little bit of clarity about how you're thinking about vaccine development on a go-forward basis? You've talked about continuing to invest in the infectious disease segment of the business. You've talked about combination therapies. Just based on where you're seeing vaccination rates now, let's focus on the U.S. What do you think are going to be the products that are going to motivate people to perhaps increase their rate of vaccinations for ones that, for example, need annual or maybe biannual rates of vaccination, just because it does seem like stats indicate that those rates are tending to flow lower?

Why does it make sense to continue investing in that? Thanks.

Speaker 6

Thank you, Tazeen. I'll start off and appreciate the kind words. In terms of vaccine development, of course, our COVID-19 vaccine business is going to continue to be a priority for the company, along with building out oncology and entering the commercial stage. I think, in terms of the rates of vaccination, we've seen lower rates of vaccination for COVID-19 over the past couple of years, and we've guided to a range that we think reflects a similar ballpark this year. We've noted that that's still subject to certain policy dynamics, and we're continuing to track that. We feel overall pretty good about the overall value proposition of the COVID-19 vaccine franchise. We've seen rates of about 20% over the last couple of years. Obviously, we're going to track that going in here to the second half of the year, which is the main part of the season.

We think we're on track overall to be ready to meet market demand. We do think that even in a market that's focused on the high-risk population, that's still a substantial number of people, approximately 100 million in the United States. This is also going to continue to be a global business. I think, overall, we're going to be prepared with Pfizer to continue market leadership in COVID-19. I think as it relates to your question about what's driving demand, ultimately it's going to continue to be based on the value proposition of these vaccines. We're going to continue to work on next-generation concepts, including exploring combination vaccines that we think could add additional value for patients in the coming years. Beyond COVID-19, too, we have a number of vaccine programs that are in either preclinical or phase 1 development.

Our strategy as it relates to vaccines, aside from COVID, will remain focused on leveraging partnerships to bring those forward.

Speaker 7

Thank you, Ryan. Thank you, Tazeen, for the question. I also believe that we expect the combination vaccines will gradually complement rather than replace standalone COVID-19 vaccines. There are several factors that may sustain the monoclonal vaccine beyond convenience considerations, such as immunocompromised patients, overwhelming preference of 60+ population to receive high-dose flu plus a mono COVID vaccine, and some asynchronous vaccination schedules where patients need COVID-19 boosters. I think, as Ryan is mentioning, we still hold a very high market share, more than 50% worldwide, with Pfizer. We are prepared as well to keep developing our combination and keep leading in these markets.

Speaker 12

Thank you. We will now go to the next question. Your next question comes from a line of Terence Flynn from Morgan Stanley. Please go ahead.

Great. Thanks for taking my question and best of luck, Ryan, in next steps. I was just wondering, on the 327 trial Rosetta Lung-02, if you can tell us the doses that you're exploring in the phase 2 portion. Can you just confirm again that you'd plan to release any top-line data here from the phase 2 portion before year end? We didn't see that on the slides. We just wanted to confirm the timing of that data release. Thank you.

Speaker 6

Thank you, Terence. I think the question is around doses for the phase 2 portion and top-line data. Özlem, do you want to take that?

Speaker 5

Yes, I can take that. We will talk to doses actually for both trials, our Lung-01 in small cell lung cancer and Lung-02 in non-small cell lung cancer later this year. For the small cell lung cancer study, part one, you will hear already more in September on the WCLC.

Speaker 12

Thank you. Your next question comes from the line of Daina Graybosch from Leerink Partners. Please go ahead.

Hi. I wonder if you can talk more about BNT327 in front-line TNBC and how you're thinking about the success of the TROPE2 ADC, both in combo with PD-1 and without, and PD-L1 high and low, if you could still do a study without a TROPE2 ADC in front-line in your control arm or in your active arm. Thank you.

Speaker 2

Hi, Daina. I can take this question. Yeah, that's right. TNBC provides for BNT327 several opportunities. We have generated data in TNBC with chemotherapy in combo, reaching a PFS between 13 to 14 months and highly encouraging OS data. Of course, the combination with TROPE2 or other ADCs, we have also her free ADC, could provide the opportunity to further increase the therapeutic efficacy. These are, as you might remember, one of the combo studies that we are doing at the moment is BNT327 and BNT325, our TROPE2 ADC. Based on the data, we might decide also to go for a combo in this indication.

Speaker 12

Thank you. Your next question comes from the line of Cory Kasimov from Evercore. Please go ahead.

Hey, guys. First of all, Ryan, been great interacting with you over all these years and best of luck with what's coming up next. I guess I'll go with my first ever question for Ramón. In thinking about the model, how do you see R&D spend now evolving over the intermediate to long-term post your deal with Bristol Myers Squibb? This collaboration should clearly offset a significant amount of future expenses, but is the plan to reallocate the majority of those to other programs or is still somewhat TBD there? Thank you.

Speaker 7

Thank you, Cory, for the question. I think increasing investments into our priority late-stage program, of course, BNT327 that now are going to be with collaboration, but also in mRNA cancer immunotherapies and ADCs would be some of the key drivers. Having said that, we will be very consistent with our portfolio prioritization strategy, and we also expect to decrease our R&D spending outside of these priority areas. We expect R&D to increase in the second half of this year. As we see the starting phases of the work in phase 3 BNT327 in TNBC and BNT323 in EC, as Özlem was alluding to, and as we see how these programs are progressing as well in CYXEC and INEST, we will be, of course, updating you accordingly on how we see this spending going more towards the two to three-year period.

Great. Thank you.

Speaker 12

Thank you. Your next question comes from the line of Asad Haider from Goldman Sachs. Please go ahead.

Speaker 6

Great, thanks. Congratulations on all the progress and best of luck, Ryan. Just one quick question back to the COVID question, just your assumption on lower vaccination rates relative to last year. You are keeping revenue guidance the same, recognizing it is a wide range, but any quantification in terms of the pushes and pulls with respect to vaccination uptake would be helpful. In the context of the deal with Bristol Myers Squibb, maybe just double-click a little bit more on the acceleration strategy, specifically with respect to any new phase 3 trials that have been planned since the announcement of the collaboration. Also, just on the development costs, given that they'll be 50/50, how should we be thinking about the cadence of R&D spend going forward?

If I can just squeeze one last one on the CYXEC melanoma trial, if you could just double-click on what you're planning to present at ESMO and the overall plans for that program going forward. Thank you.

Speaker 9

Great. I think, Ramón, maybe you want to take the first two questions, and then Özlem can take the ESMO question.

Speaker 7

Thank you, Asad. On the revenue guidance for the COVID-19 market, as I was saying, we anticipate that this revenue is going to be phased over the last three or four months of the year. Given the COVID-19 vaccine market dynamics and shifting policy, we assume that we will have lower COVID-19 vaccination rates than the previous year. We also need to take this into consideration with the fact that the vaccination rates in the U.S. are already low at around 20%. This is going to be maybe a couple of points lower, but we are still believing that the pricing and our market share assumptions are going to be broadly in line with the previous year. That is what I would say on COVID. On the MSA3 trials, the collaboration, I think it's clear.

It is going to be a 50/50 development cost around these spends, and as these programs progress through the different phases, we will have transparency on these amounts.

Speaker 9

Of course, on the BMS collaboration, new trials are being considered and evaluated right now, and those decisions will be communicated once made.

Speaker 5

Yes. There was, I think, a question for 111, our melanoma CYXEC, which I can answer, namely what we are going to present at ESMO. This year, we will present the efficacy data. This trial has an objective response rate and duration of objective response rate primary endpoint. This data will be matured until later this year and will be presented. We will also speak to secondary endpoints like PFS and OS and safety data. There will be also some translational data characterization of the immune responses.

Speaker 12

Thank you. Your next question comes from the line of Akash Tewari from Jefferies. Please go ahead.

Hey, thanks so much. Ryan, it was really a pleasure working with you. I'll keep it a little more general. Under the new FDA regime, has the BioNTech team seen any shift in the FDA's willingness to accept Chinese data for your VEGF-A specific for the ADCs? For BNT327, for NSCLC, small cell, and then TNBC, can you tell us whether, you know, when you'd be able to satisfy Project Optimist regulatory requirements and proceed with the go-forward phase 3 dose for these three indications? Thank you.

Speaker 9

Great. Thank you, Akash. Ugur, Özlem, do you want to take that?

Speaker 5

Yes. We are discussing and finalizing these discussions currently for all three indications in which we are in phase 3 trials. The discussions are very positive because, as you know, we are producing on top of the China data, which we have in early parts of our phase 2 freeze or independent global studies, also some dose data and dose optimization data in the Western population. We think that within the next couple of weeks, we will be able to move ahead in all those three indications.

Speaker 12

Thank you. Your next question comes from the line of Jessica Fye from JPMorgan. Please go ahead.

Hey, guys. Good morning. Thanks for taking my question. Ryan, similarly, it's been great working with you over the years. I have a few on the pipeline. With the upcoming global phase 2 readouts for BNT327, can you remind us when you say, for example, the small cell data and non-small cell data is expected this year, will we see that data? If so, what endpoints will we see and what are the relevant benchmarks in those settings? For the registrational HER2 positive endometrial cohort, did that slip a bit? I think we were previously expecting a file by year end 2025, and now it sounds like data at a conference in 2026. I just want to confirm whether we'll hear top-line data this year or what the timeline is.

Lastly, for the INEST randomized phase 2 in ctDNA positive adjuvant colon cancer, can you just share your latest expectation for timing there? Thank you.

Speaker 6

Yeah, yeah. Thank you, Jess. I think maybe just on the last one, I can briefly comment and then hand over to Özlem to speak to the benchmark to the small cell lung cancer and non-small cell. On adjuvant CRC, we're maintaining our prior guidance that we're expecting data late 2025 or early 2026, and we think we're on track to meet that in terms of the adjuvant CRC data for INEST. Özlem, do you want to address the 327 question?

Speaker 5

Yeah. The 327 question, the question was a small cell lung cancer trial and our non-small cell lung cancer trial, the benchmarks, right? Did I get that right? For the small cell lung cancer trial, actually, for both trials, our aim is to achieve clinically meaningful and statistically significant improvement over the standard of care. For the small cell lung cancer trial, Rosetta 01, our primary endpoint is OS. For the non-small cell lung cancer trial, we have a dual endpoint, PFS and OS. When I say standard of care, the benchmark trials or the benchmarks we are comparing against for small cell lung cancer is IMpower133 with median OS outcomes there. For non-small cell lung cancer, we have both non-squamous and squamous histologies covered in our phase 3 trial. Here we refer to the KEYNOTE-189 and the KEYNOTE-407 studies as benchmarks.

I think there was a question regarding 323, right? When we will show data from that study, the plan is to share data from our single-arm second-line endometrial cancer study, which will also be the data package for BLA submission later this year. This data will be shared in early 2026. We want to make sure that the data further matures and that the data which will be shared with the community is in sync with the data we are planning to submit to FDA.

Speaker 12

Thank you. We will now take our final question for today. The final question comes from the line of Yaron Werber from TD Cowen. Please go ahead.

Good morning. On for you, Yaron. Congrats on your quarter and thanks for taking our question. On competition for BNT327, Pfizer said that their asset binds to VEGF-A, it increases the estimated PD-L1 by 100-fold. Is this kind of cooperative binding also true for BNT327? Are there any other points of differentiation you might note between yours and Pfizer's molecule besides the obvious PD-L1 versus PD-L1? Thanks so much.

Speaker 6

Ugur, do you want to take the question on whether or not BNT327 has a cooperative binding effect and other different points of differentiation?

Speaker 2

Yes. I can take this question. I think the mechanism is more complicated than this. We will present the mechanism probably mid-next year in a conference. We are evaluating the mechanism for BNT327. As you know, it's a binder which binds in the tumor microenvironment PD-L1, and thereby provides the opportunity to bind also in the tumor microenvironment to VEGF-A. The combination of both has synergistic activities, but it's not simple. The increase of the affinity is more complicated.

Speaker 12

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