BioNTech SE

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. Ugo Shaheen, chief executive officer and co-founder, Ozlem Tureci, Chief Medical Officer and Co-Founder, Ramon Zapata, Chief Financial Officer, and Ryan Richardson, Chief Strategy Officer. With this, I'll hand the call over to Ugar.

Thank you, Dax, and a warm welcome to you all as you join us today. Dax joined BioNTech recently as our new Head of Investor Relations, and I would like to welcome him to the company. As previously announced, Ramon Zapata joined last month as our new chief financial officer and will be speaking on the call today. Ramon is a seasoned financial leader with a wealth of international pharmaceutical experience from companies including Novartis and Zando. With over 25 years of experience, Ramon has a deep understanding of market and business dynamics, resource optimization, and high-performing teams. We are delighted to have Ramon 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 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 actual 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 novel-novel combination of next-generation immunomodulators with targeted therapies and mRNA cancer immunotherapy. 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 6-Vac and iNest, and our bispecific antibody BNT327 that targets PD-L1 and VGFA. 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 this program 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 outline 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 Bioceus, 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 dosed the first patient in a new cohort, evaluating our NSCRC fixed-vec 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 target 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 partners 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 sublineages compared to vaccine formulations used in the 2024-2025 vaccination campaigns. 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 pounds 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 BNT food to seven both as a new standard of care across multiple tumor types. We are currently advancing BNT food to seven across more than 10 indications, including two global registrations 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' position 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 development and planned commercialization of our ongoing oncology pipeline. To support this goal, 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 multiproduct global oncology company and see this partnership as supporting that transition. With BMS deep immunooncology 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 for novel modalities and combinations. We have a clear shared vision in this regard, and I look forward for our companies working closely together. I will now turn the call over to Esben to provide more details on select clinical programs.

Thank you, Ugo. 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 BGFA 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 III in first-line triple-negative breast cancer later this year. We aim to further accelerate and expand BND327 development with a strategic partnership with Bristol-Myers Squibb. For our mRNA cancer in Europe, including SIGSEQ and iNES, 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 DLA submission with BNT3-23, our HER2-ADC, in HER2-expressing second-line endometrial cancer. BNT3-27 localizes the blockade of PD-L1 and VEGFA signaling to the tumor. This bispecific is designed to deliver superior anti-tumor, immunomodulatory, and antiangiogenic effects compared to the combination of the two individual antibodies and with the potential to minimize adverse events associated with systemic anti-BGF8 therapy. We now have data from over 1,200 patients which show sickness 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 VEGFA-targeted therapies. In totality, the clinical data generated to date further strengthen our conviction in this effort 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-VEGFA mechanisms 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 BMT327 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 established combined broadens. 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 free 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 one and phase two 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, Rosetta Lung O1, is 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, Rosetta Lung O2, is 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 three trial for Zeta Breast O1 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 Empower One 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 two 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 medium 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 III clinical trials for Zeta-Lung O1. In the last quarter, we completed enrollment in the global phase II 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 we'll provide a data update from the clinical trials 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 ESCO annual meeting last year, we presented data from the Phase I trials 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 Zeta-Lung O2 our Global Phase III trial that evaluates BNT327 in combination with chemotherapy to improve on survival outcomes when compared to standard-of-care pembrolizumab in combination with chemotherapy as a first-line therapy for non-small cell lung cancer patients without actionable genomic alterations. Today, we are enrolling patients in the Phase II part and expect to progress to the phase three 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 four 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 state. We also observed in the trial encouraging landmark overall survival rates, such as 69.7% at 18 months for BND327 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 three trial later this year in the first-line setting. We have also continued enrollment in our global phase two 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 two trial at a medical meeting later this year. Our second wave of development with BNT327 reflects that IO plus ADC combos are an emerging treatment paradigm in oncology. We have started exploring combinations of BNT327 with our ADCs directed against DROC2, SIRT2, and B7H3 from our partnerships with Duality, informed by a robust database of single-agent data for these ADCs. In the second quarter, we dosed the first patients in two new BNT327-ADC combination studies. The first is a phase one to clinical trial that is evaluating BNT327 in combination with BNT323. However, two targeted ADCs in HR positive and negative for low and ultra-low metastatic breast cancer patients. The second is a phase two clinical trial that is evaluating BNT327 in combination with BNT324 or B7H3ADC in multiple types of lung cancer, including non-small cell and small cell lung cancer patients, patients with non-actionable genomic alteration and across treatment lines. In July, we also dosed the first patient in another phase two trial that is evaluating BNT327 in combination with our B7H3 ADC 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 aid. The first BNT327-ADC combination trial evaluating BNT327 in combination with BNT325, our TROC2 ADC 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 dose in combination BNT327 and our drug to ADC demonstrated superior anti-tumor effects preclinically compared to each drug alone. Our preliminary clinical data in this small sample size suggests that BNT327 plus BNT325 had a manageable safety profile with few overlapping toxicities and clinically meaningful activities. These data provide the first early support for our ambition to combine BNT327 and ADCs 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 ADCs 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 signal-seeking BNT327 ADC combination clinical trials to help us define which ADC combinations and which indications to prioritize for late-stage development. The last wave of our pre-wave 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 I-II clinical trial evaluating BNT327 in combination with the bispecific we are developing with our partner, GenMed. that targets both EPCOM and 4-1-BB in metastatic colorectal cancer patients. EPCOM is highly expressed in colorectal cancers. The other arm of the molecule is a potent 4-1-BB agent. When activated, 4-1-BB signaling promotes T cell activity and . 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 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 of trials and accelerate bringing BNT327 to market in multiple areas. Moving now to our mRNA Cancer Immune Therapy platform, which is the other cornerstone of our oncology strategy and includes INES and FIXVEX. Autogen Sivuliran, also known as BND122, developed in partnership with Genentech, is based on the INES platform. INES 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 settings. Fixed-back 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 pen 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 immunotherapies, with approved checkpoint inhibitors or chemotherapy, we consider our mRNA cancer immunotherapies as ideal for novel-novel combinations and partners for both our immunomodulators and our targeted therapies. We are excited to have recently dosed the first patient in an exploratory cohort evaluating our non-small cell lung cancer PIC-seq, BNT116. and our B7H3-targeted ADC, and anticipate dosing the first patient in the exploratory cohort with our HIR-3-targeted ADC soon. Given they are available off the shelf, we believe that our PICSVAC 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 two trial evaluating our individualized RNA immunotherapy autogen 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 immunotherapy are best positioned in earlier settings such as adjuvant treatment regimen. In early settings, tumor mass is low, resistance and immunosuppression mechanisms have not been established, and the immune system is much healthier. And this is where all three of our current Phase II clinical trials are positioned. Last year, we announced that our fixer candidate for melanoma, BNT111, met the primary endpoint in a randomized Phase II trial evaluating BNT1-11 in combination with semiprimus, and also assessing both antibodies alone in patients with anti-PD-1 relapse or refractory melanoma. We will also be presenting these data at the upcoming ESMO Congress, and we'll discuss the PAIRS orbit for this program around that. Next, a data update from a cohort evaluating our non-small cell lung cancer fix-facts, BNT1-16, in combination with Cygnetimab as treatment for patients with unresectable stage III 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 BNT1-16 in multiple non-small cell lung cancer treatment settings, demonstrating the broad potential of our feedback 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, Ramon Zapata.