BioNTech SE

Good morning and good afternoon. Thank you for joining BioNTech's first quarter 2024 earnings call. As a reminder, the slides we will be using on this call and the corresponding press release we issued this morning can be found in the investor relations section of our website. On the next slide, you will see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings with the US 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 three, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team. Ugo Sahin, Chief Executive Officer and Co-Founder, Aslim 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.

Thank you, Victoria. A warm welcome to all those joining us today. We believe that we are entering a transformational period for BioNTech. We have founded BioNTech with the vision to discover and develop scientific breakthroughs that harness the immune system to fight diseases and bring new medicines to patients. In the years following our establishment, We developed various therapeutic platforms, demonstrate the safety and clinical effectiveness of various drug candidates in early clinical trials. The period from now to 2030 is about progressing this candidate into late-stage development and registration trials to become a multi-product company with the first product to be delivered by our late-stage oncology pipelines. We are continuing to execute this vision and our strategic priorities with intense focus. In the first quarter, we progress our latest stage oncology pattern on multiple fronts. We dose the first patient in the pre-votal phase three clinical trial, evaluating our HER2-ADC BNT3-2-3 in HR-positive HER2-low metastatic breast cancer. At the AACR annual meeting, We presented three-year follow-up data from a clinical trial evaluating our endodontic mRNA cancer vaccine, autogen-seme-vumaran in pancreatic cancer. This data showed encouraging relatively survival in certain patients with immunogenic response to the vaccine, demonstrating the promise of our vaccine platform to induce persisting de novo neoantigen-specific T-cell responses that correlate with improvements in survival. We have also taken significant steps for our first launches in oncology. Annemarie Harnekamp, an accomplished leader with a remarkable track record, is joining our team in July to drive and execute our global commercialization strategy. We appointed a general manager in the U.S. who has commands building out our commercial operations in the U.S., and we appointed further expertise in our global commercial team. For our COVID-19 vaccine franchise, we initiated preparations to be on track to introduce a new variant-adapted COVID-19 vaccine for the upcoming season. We have received preliminary strain selection recommendations from the World Health Organization and European Medicines Agency and plan to submit for regulatory approval later this month. Today, Özlem and I will focus on our oncology strategy while Jens and Ryan will provide updates on our financial and corporate progress. Slide six. Our oncology portfolio strategy is driven by understanding the key challenges in cancer. Cancer is genetically diverse and heterogeneous disease driven by the sequential acquisition of mutations. One consequence of this is that many treatments have an initial effect but are not associated with long-term remission or cure. Our aim is to provide solutions across the continuum of cancer disease and establishing new treatment paradigms. We believe our cancer vaccine candidates are particularly suited for early intervention, while thoughtfully designed combination treatments are intended for advanced and high-volume tumors. We want to bring our therapies to as many patients as possible, and we want to use the potential power of our platforms alone and in combination. Slide eight, our therapeutic strategy. brings together synergistic mechanisms of action across three key categories. The first are novel immune modulators, or IO, which are designed to engage the immune system, overcome cancer-mediated immunosuppression, and amplify immune responses. Second, targeted therapies, which include CAR T-cell therapies and antibody drug communicates, that can dramatically reduce the tumor burden. The third category are mRNA vaccines, which are the centerpiece of our oncology strategy. Our mRNA cancer vaccines are designed to target multiple cancer antigens in parallel and can be individualized for each patient. BioNTech was built from the very beginning as a technology agnostic company. We do not limit ourselves to any one technology. We are interested in addressing unmet medical needs with the best possible solutions. Having a diversity of assets in our pipeline, we are positioned to pursue combination approaches that are proprietary and unique. This strategic advantage allows us to evaluate the activity of each individual compound and enables us to determine those patient populations for which monotherapy or synergistic combinations are best suited. The potential for synergy in this combination is significant. enabling us to design treatment regimens that could lead to improved patient outcomes and broaden the scope of therapeutic options. We believe that our strategy has the potential to address fundamental challenges of cancer and to drive meaningful improvements in the long-term survival rates for patients. Slide nine. To reiterate, we are entering a transformative period for BioNTech, specifically in the development of our oncology pipeline and the formation of our oncology business which will continue to evolve over the next few years. In 2024, we are aiming to increase the number of potential pivotal trials across our lead programs to 10 or more by year end. These trials will focus on areas of unmet medical needs, clinical indications in which we may achieve an expeditious path to market, and there, after the first approval in the initial indication, there's a high potential for expanding the market opportunity to additional indications. Starting in 2025 and continuing into the following years, we expect to enter a period rich with pivotal data that, if positive, could support regulatory submissions for marketing authorization across our pipeline. We have begun building a fully integrated oncology organization to support our transition into a global multi-product company. This process will be accelerated this year as we bring our new chief commercial office on board. Ultimately, we are building our organization to support multiple oncology launches beginning in 2026. With that, I would like to thank you all for your ongoing support. I will now turn the call over to Özlem.

Thank you, Ugo. Glad to be speaking with everyone today. As Uwe highlighted, we will focus in the next few years on increasing the number of potentially pivotal clinical trials to fuel our transition towards becoming a multi-product company by 2030. In oncology, we have already started to execute against this goal. This is why you can see that the late stage part of our pipeline on this slide is enriched and populated with multiple trials that feature our priority assets, such as our mRNA vaccines, and also our most advanced ADCs and IOs, including those which we consider as attractive backbones of unique combination treatments. To highlight recent additions to our pipeline, one is a phase three trial in collaboration with Duality Bio, evaluating BNT323 in patients with hormone receptor positive and her to low metastatic breast cancer that have progressed on hormone therapy and or cyclin-dependent kinase for six blockers. With BNT323, we are also planning to start a confirmatory phase three trial this year in patients with metastatic endometrial cancer that will complement our ongoing single arm trials in this indication. In our early-stage pipeline, we have started a Phase 1-2 trial in collaboration with GENMAP, evaluating BNT314, a bispecific antibody product candidate was outcome-dependent for 1Bb agonistic activity in multiple solid tumors. Our aim is to continue to progress our oncology pipeline towards pivotal data readouts and submissions for regulatory approvals in the next 18 months. Before highlighting some of the programs, and platforms that we consider priority assets to contribute to clinical progress, let me say a couple of words to execution. The coming years will be about late-stage clinical trial execution. Enrolling the patients to participate in clinical trials requires deep coordination across multiple functions within our company and with our partners and collaborators who are integral part of our global trial execution approach. As we and our partners have increased the number of ongoing late-stage trials, we have also drastically increased the number of patients that participate in trials generating data for our fully owned and partnered product candidates. Comparing the average quarterly number of patients enrolled across the last few years here on this slide, On quarterly average in 2022, through the first quarter of 2024, we have increased the number of patients enrolled by over 400%. On the back of this significant increase in enrollment and thus progress in clinical trial execution, we expect our clinical development pipeline to generate the corresponding increase in the number of data sets in the coming years. Our ultimate goal at BioNTech is to bring our data-backed scientific breakthroughs to patients in need. Moving to our priority assets, let me start with BNT327 or PMH002, a bispecific antibody consisting of an anti-VGFA SC silence IgG fused to a humanized anti-PD-L1 BHH binder being developed in collaboration with our partner, Biofears. BNT327 combines two validated mechanisms of action. VGFA binding inhibits the VGFA-VGFR axis, blocks tumor angiogenesis, which leads to reduced tumor cell proliferation and survival. VGFA inhibition also counteracts formation of the immune-suppressive tumor microenvironment as does the PD-L1 arm of this specific antibody by reverting PD-L1, PD-1 excess mediated T-cell exhaustion. The PD-L1 arm also anchors this antibody to the tumor bed for efficient and localized scavenging of VGFA, which may contribute to mitigate of tumor on target side effects. Data from ongoing Phase 1-2 clinical trials across several indications in over 600 patients executed by our partner biofears have shown a favorable safety profile. Our partner biofears presented selected examples of this compound's performance in 2023, showing strong single compound activity and high response rates in combination with chemotherapy in triple negative breast cancer and small cell lung cancer. In first-line TNBC in combination with NAP-paclitaxel, almost 80% objective response rate as shown on this slide. At ESCO now, there will be more data disclosures in cervical in ovarian cancer, and in non-small cell lung cancer. An investigational new drug application has been accepted by the FDA for further studies in the United States, and we plan to start global trials in several indications this year. One area that will see increased development activity in the coming years will be our mRNA cancer vaccine candidates. mRNA cancer vaccines are a centerpiece of our pipeline and are pivotal to our goal of developing breakthroughs for cancer patients. The aim is to develop this technology as monotherapy in combination with standard of care and in combination with candidates from our proprietary pipeline. Our six vaccines use sets of multiple antigens shared by patients across one tumor type. iNest, our individualized vaccine program, partnered with Genentech, identifies neoantigens derived from cancer mutations that are unique to an individual's tumor. While iNest and FixVac target different types of cancer cell antigens, they are based on the same mRNA and delivery technology, namely our Uridin mRNA LipoPax platform. Its distinct mechanism of action is that the delivered antigen is presented by professional antigen-presenting cells in lymphoid compartments body-wide in close proximity to T cells to be induced, and that it comes with intrinsic adjuvanticity. These features, by design, promote the induction of high in the magnitude T cell immune responses that we have been detecting in all our clinical trials across tumor types and for various types of targeted cancer cell antigens, as shown on the right-hand side of this slide. On the next slide, you can see exemplary data from different trials in different treatment settings and tumor types in which we are evaluating our neoantigen-based individualized cancer vaccines, including several years of follow-up. Our mRNA-based neoantigen vaccine has demonstrated the ability to induce the novel neoantigen-specific functional, polyspecific, and persistent T cell responses at substantial magnitudes in high proportions of treated patients. Frequently, against tumor antigens that were overlooked by the patient's immune system, so-called de novo immune responses. We have shown that our vaccine-induced T cells persist over years and build immunological memory. And the two papers quoted on this slide, we have shown that vaccination with neoantigen encoding mRNA is associated with reduction of recurrences in patients. The favorite setting for developing our individualized vaccines are patients that have minimal residual disease or require adjuvant treatment to reduce the probability of recurrence. Today, we have iNest and FIXVAC trials in multiple disease settings and indications, and data releases from several of the trials shown on this slide are planned. In our FIXVAC program, we are evaluating four vaccine candidates, which each target tumor-associated antigens specific to melanoma, HPV16-positive head and neck cancer, prostate cancer, and non-small lung cancer, as monotherapy and in several combinations. We shared early data for all fixer candidates in the past years and plan to present additional data this and next year. Further, we plan to start an additional trial with INEST in the adjuvant setting with our collaborator Genentech. I would like to highlight three of these programs that are on our priority list. two programs using our individualized cancer vaccine and cancer types that have a low tumor mutational burden and are resistant to immune therapy, namely colorectal cancer and PDAC, and our NSCLC FixVac program. Starting with CRC, with colorectal cancer, the majority of patients with early-stage localized and resectable CRC undergo surgery followed by adjuvant chemotherapy. Standard of care in stage two high risk and stage three disease after adjuvant treatment is watchful waiting. 20 to 35% of patients experience recurrences of their disease. CTDNA is a marker for minimal residual disease and identifies patients with high risk of such recurrence. We are running a phase two trial with our individualized vaccine in stage 2 high risk and stage 3 rejected CRC patients that are CTDNA positive post-surgery. After adjuvant chemotherapy, patients are randomized to either receive autogen, sevumaran, or individualized vaccine, or observation. We expect the first readout of this trial in the second half of 2025. Secondly, a randomized phase two clinical trial evaluating our individualized vaccine in combination with the anti-PD-L1 agent, atesolizumab, followed by standard of care chemotherapy in patients with resected pancreatic cancer, PDAC, compared to chemotherapy alone, was started in collaboration with Genentech in 2023 and is recruiting patients. PDAC is a high medical need tumor expected to become the second leading cause in cancer-related death. Up to 85% of patients with localized pancreatic cancer that undergo surgical resection and adjuvant chemotherapy do experience recurrence of disease. This trial was initiated based on data from an investigator-initiated trial that were published last year and updated at AACR a few weeks ago. That phase one trial showed that with our individualized vaccine combined with adesolizumab and standard of care adjuvant chemotherapy, half of the 16 treated patients develop high magnitude vaccine-induced immune responses and that these patients have a much lower risk of tumor recurrence at 1.5 years of median follow-up and continue to do so after a three-year follow-up period. Moving to our off-the-shelf tumor-associated antigen-based mRNA cancer vaccine candidate, BNT116. BNT116 is an RNA-like complex cancer vaccine candidate comprising six mRNAs, each encoding a tumor-associated antigen, mageA3, Claudine 6, KKLC1, frame mageA4, mageC1. We have selected these tumor-associated antigens by an in silico approach developed for design of six vaccines for different tumor types and based on low or lack of expression in toxicity-relevant organs, expression in a substantial fraction of lung tumors of various histologies, immunogenicity, and tumor biological role. About 85% of And SCLC specimens express at least one of the six selected tumor-associated antigens, and more than 60% express at least two of them. BNT116 is currently being evaluated with our partner Regeneron in two clinical trials that cover various non-small cell lung cancer patient populations. One is a phase one trial investigating BNT116 in adjuvant first-line and second-line plus settings, and various treatment regimens listed on the left side of this slide. We plan to introduce novel unique combination cohorts into this multi-cohort Phase I trial. The second trial is a randomized Phase II evaluating BNG116 in combination with Simiprimab in first-line treatment of patients with PD-L1 high-expressing non-small cell lung cancer shown on the right side of the slide. At AACR, we presented preliminary results from cohort three of the LukaMerit phase one trial, evaluating BNT116 in combination with docetaxel in patients with advanced, unresectable, or metastatic non-small cell lung cancer that progressed on PD-1, PD-L1 inhibitor and platinum-based chemotherapy. Combination treatment with BNT116 and docetaxel was active, with an overall response rate of 30%, a disease control rate of 85%, medium progression-free survival of 4.4 months. Comparable to other six FAC candidates, BNT116 presents a manageable safety profile alone and in combination. We expect further data from these cohorts in the next 12 months, and that will inform further development of PNT116 in Lancaster. The ESCO annual meeting is right around the corner. At ESCO, we and our partners will present new clinical data for several of our programs, data that is of relevance for making informed decisions about the direction of those projects' development. Firstly, we at GENMAP plan to present data for BNT311 from our Phase II in post-IO non-small cell lung cancer patients. BNT311 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4,1-BB co-stimulatory activation. Second, as already mentioned, monotherapy data from Phase II trials are planned to be presented for BNT327 the biospecific anti-VEGF-A, anti-PD-L1 antibody we are developing in collaboration with Biofeas. Third, we and our partner MediLink plan to present first in human data for our free targeting ADC. Then we will also present epidemiologic data, including post-operative ctDNA prevalence and prognostic value from a non-interventional observational study in patients with resected high-risk stage 2, stage 3 colorectal cancer that supports and informs the development of our individualized vaccine in this patient population. And lastly, for BNT211, our CAR T-cell product candidate, we plan to initiate a potentially registrational trial in patients with germ cell tumors. At ESCO, we will present real-world evidence of overall survival and treatment patterns of this patient population in the U.S. that will inform the trial design for our Phase II trial. With that, I will now pass the presentation to our CFO, Jens Holzstein.