BioNTech SE

Thank you for joining BioNTech's second quarter 2024 earnings call. As a reminder, the slides we will be using during this call and the corresponding press release we issued this morning can be found in 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 the 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. Ugar Zahin, Chief Executive Officer and Co-Founder. Özlem Türeci, 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 Ugo.

Thank you, Victoria. A warm welcome to all those joining us today. I will start with an overview of the quarter's highlights with a focus on community and our late-stage oncology portfolio. First, we'll talk about some of our recent oncology pipeline advancement in more detail. Jens and Ryan will then provide updates on our financial and corporate progress and the outlook for the remainder of the year. Slide five. The second quarter of 2024 was marked by a significant execution across our oncology pipeline and our leading COVID-19 franchise. Our progress in the quarter will set up for an impactful end of 2024 as we continue to progress towards our long-term vision. I would like to highlight achievements in three areas. First, with regard to our COVID-19 vaccine leadership. On the back of the first regional approvals, we have initiated the launch of our new variant-adapted vaccine and expect additional approvals in the coming weeks and months. Second, in oncology, we shared numerous updates at major medical meetings that highlighted our clinical execution and pipeline progress and provided data on several of our assets across modalities. Usman will discuss some of these updates in more detail, but I would like to highlight two of those specifically. Last week, we announced that our off-the-shelf Tic-Tac mRNA cancer vaccine for melanoma BNT1-11 met the primary endpoint in the ongoing randomized phase 2 trial, evaluating BNT1-11 in combination with Simiprimab in patients with stage 3 and stage 4 cutaneous melanoma. This preliminary result is a significant milestone for our company and underscores our belief in the transformative potential of this new class of medicine and of our mRNA vaccine technology which is a key pillar of our oncology strategy. We have exciting news also with regard to another key pillar of our oncology strategy, namely the development of novel IO-ADC combinations. This quarter, we started the first of several preparatory trials for our combination therapy strategy. The trial evaluates the combination of our anti-PD-L1 VGS bispecific antibody, BNC327, and our top two ADC BNTC25. We look forward to the initiating additional tribes every year to novel IO-ADC combinations over the next 12 months. The third area in which we made progress is our mission towards the creation of sustainable and resilient end-to-end vaccine ecosystem in Africa by expanding our partnership with CPI. CPI is committed up to 145 million U.S. dollars to support us to accept the mRNA vaccine clinical and commercial scale manufacturing capabilities at our facility in Kigali, Rwanda. These capabilities will contribute to better prepare for potential future epidemic and pandemic press in Africa in alignment with our corporate purpose of ensuring equitable access to our medicines. starting with our COVID-19 franchise. The continuous circulation of SARS-CoV-2 leads to the ongoing evolution and emergence of novel variants of the virus, which we continue to monitor and evaluate for the immune evasive potential and . In September 2022, the X3B lineage gradually emerged, dominated globally throughout 2023 with multiple sub-images and was successfully addressed by XBB1-class variant-adapted COVID-19 vaccine, including our own. This year, JN1 lineage, including KP2, became the predominant variant globally, leading to the current surge in infections in many regions in the northern hemisphere. Shown on the right graph, we observed effectiveness data demonstrate that the antigenic shift and the distance of JN1 lineages from XBB15 has impacted the vaccine effectiveness of the XBB15 adapted vaccine against the now prevalent JN1 lineages. Slide seven. Based on this and additional data, regulatory and public health authorities consequently advised vaccine manufacturers to revise the formulation for their authorized COVID-19 vaccine. The WHO and the EMA recommended the use of JN1 lineage antigen in a monovalent COVID-19 vaccine for the season 2024-2025. And 17 days later, we were able to submit our application to the European regulator. Based on this recommendation and the conference and EMA approval on July 3rd, we have begun rolling out our updated Cominati JN1 vaccine in Europe. In the United States, the FDA further recommended the use of KP2 as the preferred J1 lineage antigen for the 2024-2025 COVID-19 mRNA vaccine on June 13th. Less than two weeks later, we initiated our rolling submission with the US FDA. We and our partner Pfizer are working hard to enable early availability of variant-adapted vaccines for people around the world with the aim of reducing or preventing severe disease, hospitalization, and COVID-19-related deaths. We expect the FDA approval of our KP2 adaptive vaccine by mid-September, and we aim to deliver the first vaccine doses to the people in the United States shortly thereafter. Slide eight. The other area I'm highly excited about is the focus on our oncology pipeline. Before I hand over to Özdem to deep dive into the recent achievement, let me remind you of our overarching oncology strategy. mRNA cancer immunotherapies were our starting point when we founded BioNTech, and they remain the centerpiece. Ever since, we have been pursuing a technology-agnostic approach by not limiting ourselves to any one technology. Over the past two years, we added platforms to complement the mRNA centerpiece. Today, we have an oncology toolkit featuring multiple modalities, including targeted therapies such as ADCs and immunomodulators, IOs, that open up new combination opportunities to synergistic mechanisms of action. Having this diversity of assets in our pipeline enable us to pursue combination approaches that are proprietary and unique. This strategic advantage allows us to evaluate the activity of each individual compound and to determine those patient populations for which monotherapy or zoonogistic combinations are best suited. We believe that our strategy has the potential to address fundamental challenges of cancer and to drive meaningful improvements in a long-term survival race for patients. And as you will hear from us, the last quarter has been about executing towards this vision. Before I hand over, I would like to thank you all for your ongoing support as we enter this truly exciting period for BioNTech and our progress towards our founding vision. Thank you.

Thank you, Ugo. Glad to be speaking with everyone today. Our multi-platform immunology clinical pipeline is continuing to grow and to progress, and it is a rich source for the rationally planned novel-novel combinations that we consider a key pillar of our strategy. As you can see, two of our modalities, namely mRNA and immunomodulator IOs, are dominantly represented in our pipeline, and particularly so in the advanced clinical stages. Today, I want to focus on priority assets within these modalities, which have our special attention, our mRNA vaccines and one of our I.O. compounds, BNT327. Before I cover these assets, let me just mention that a rich clinical pipeline and ambitious plans require execution capability, which we are continuously building. As you can see on the slide, we are accelerating the pace of pipeline-wide patient accrual compared to last quarter. Compared to 2022, we and our network of partners are now recruiting six times as many patients per quarter to support enrollment into the clinical trials you saw on the previous slide. This increase is a testament of our drive towards more and larger mid- to late-stage trials as part of our ambition to achieve multiple product launches in oncology by the year 2030. It also underlines the success of our partnership strategy, which not only gives us access to compounds that complement our own pipeline, but enables us to leverage additional clinical trial execution capacity and know-how and geographic reach. Now to a centerpiece of our oncology portfolio, our mRNA cancer vaccine platforms, iNest and FixVac, which differ in the type of tumor antigen they target. iNest targets new antigens derived from somatic mutations in cancer cells that are unique to an individual's tumor. iNest vaccines are manufactured on demand and personalized to each individual patient. FixVac vaccines target multiple non-mutated antigens shared by a majority of patients with a given tumor type and are off the shelf. The computational approaches to discover and select these two different types of target antigens are one of our core competencies. INUS and FixVac both use the same technology, namely our proprietary mRNA LPX platform. Today, we have ongoing trials in multiple disease settings and indications across both vaccine platforms. We have reported translational and clinical data over the last couple of years, and future data updates from multiple trials shown on this slide are planned. Aggregate data that we have reported in the past across INS and SIGSEQ trials indicate that uridine mRNA LPX-based vaccines have a manageable and largely mild safety profile as single agents in combination with anti-PD-1, PD-L1 compounds, and in combination with chemotherapy. Our data also indicates that our uridine mRNA LPX-based vaccines are proficient in inducing and expanding high-magnitude functional and long-lived T cell responses in the majority of patients, which is a prerequisite for clinical activity. Furthermore, our data from small sample size patient cohorts indicates clinical activity alone and in combination with anti-PD-1, PD-L1 treatment. Several of the now ongoing trials shown on this slide aim to answer the material question of whether our mRNA vaccines are superior to the respective standard of care. In our FICSAC program here on the right, I would like to highlight three vaccine candidates currently being evaluated in multiple trials in both the metastatic and adjuvant settings. First, BNT113, being well underway in first-line HPV16-positive, PD-L1-positive head, neck, squamous cell carcinoma in a potentially registrational phase 2 randomized trial. Second, BNT116, being investigated in two trials as single agent and in various combinations in different non-small cell lung cancer patient populations and treatment lines. And last but not least, BNT1-11 being investigated in anti-PD-1 relapsed or refractory melanoma, about which I would like to talk a bit more. BNT1-11 is a uridine mRNA LPX-based vaccine that encodes four melanoma-associated antigens that collectively cover more than 90% of melanoma patients and are highly immunogenic. In the randomized three-arm phase two clinical trial conducted in collaboration with our partner, Regeneron, we are evaluating BNT1-11 in combination with Regeneron's anti-PD-1 compound, Simiplimab, and we measure activity of BNT1-11 alone or Simiplimab alone in a total of 184 enrolled patients with PD-L1 refractory unresectable stage three or stage four melanoma. As Ugo noted earlier, we very recently announced that the trial met its primary endpoint, achieving a statistically significant improvement of overall response rate in the BND1-11-Siniplimab combination arm as compared to historical control of anti-PD-1 monotherapy in relapsed refractory patients. The historic control was based on multiple late-stage clinical trials that established the expected objective response rate for monotherapy checkpoint inhibitors in this setting for this patient population. While the data are further maturing, we do see a trend towards improved overall survival. The BNT11001 trial is based on the earlier lipomeric phase 1-2 trial in patients with advanced melanoma who had exhausted treatment options. The trial established the dose and provided initial safety, efficacy, and immunogenicity data on BNT1-11 as single agent and with checkpoint inhibitors approved in this patient population. In that proof-of-concept study, we observed that treatment with BNT1-11 alone or in combination with anti-PD-1 could induce strong high-magnitude T cell responses against at least one targeted tumor-associated antigen in all analyzed patients, most of which were not detectable prior to using the vaccine. As shown here, objective responses by BND111 were durable, with some patients followed up for several years. The safety profile was generally mild and in line with expectations for those patients who were co-treated with checkpoint inhibitors. The results we are seeing in the Phase 2 BND11101 study are consistent with these prior results. We plan to present the full data from the primary analysis at the medical conference in 2025 and are entering into discussions with regulatory authorities regarding our data and the clinical path forward for this program. Cutaneous melanoma carries a high and continuously increasing incidence and mortality burden. The introduction of checkpoint inhibitor-directed therapies was a breakthrough for patients that led to significant improvements in survival. Nonetheless, in advanced disease stages, only a third of patients achieve a long-term response and long-term survival. After failure of checkpoint inhibitors, there is no established standard of care with only limited and short-lived responses to salvage therapy. While a new adoptive self-therapy has recently become available for this patient population, we do not expect that all patients will be eligible, leaving a significant unmet medical need unaddressed. In this context, our BNT111 may be of interest to potentially help treat this high medical need population. Moreover, the BNT111 data is a proof of concept in three dimensions. Firstly, a proof of concept for our decade-long improved mRNA cancer vaccine technology that uses uridine mRNA chemistry, a non-coding backbone that is engineered for optimal translational performance, and our proprietary lipoplex formulation for systemic delivery. Second, this is a proof of concept for our computational approaches for selecting suitable tumor antigens and targets for our cancer indication-specific SIGSEC program candidates. And lastly, it's a proof of concept for our strategy to combine synergistic modalities, in this case BNT111, with an established immune checkpoint inhibitor treatment. All three of these also apply to BNT122, our individualized mRNA cancer immunotherapy based on our iNest platform and the same delivery technology. We consider individualized cancer vaccines as a medical breakthrough in addressing the high unmet medical need of resectable cancer and in adjuvant or minimal residual disease treatment settings. Here, I want to highlight ongoing randomized phase two trials with our individualized vaccine in pancreatic ductal adenocarcinoma and in colorectal cancer. The five-year survival rate in pancreatic ductal adenocarcinoma after resection alone is 10% and up to 75% of patients with pancreatic ductal carcinoma relapse even though they appear tumor-free within five years after adjuvant treatment. As for high-risk stage 2 or stage 3 colorectal cancer, about 35% of patients relapse within five years after resection and adjuvant therapy. As discussed in the last earnings call, we demonstrated that our individualized vaccine used in patients with adjuvant pancreatic cancer can induce de novo T-cell responses that are specific to the individual mutant tumor neoantigens, and that the risk of recurrence of cancer for patients with vaccine-induced immune responses was reduced even after a three-year follow-up period. At the recent ESMO GI conference, we disclosed findings from the biomarker sub-study of our ongoing Phase II INUS trial, BNT12201, involving patients with stage 2 high-risk or stage 3 colorectal cancer who remain ctDNA positive following the surgical excision of their localized cancer. Upon completion of standard-of-care adjuvant chemotherapy, these patients received BNT122, our individualized vaccine, in contrast to the conventional wait-and-watch approach. In the subset of 12 patients who were accessible for immunogenicity analysis, a high-magnitude de novo T cell response against at least one vaccine-encoded neoantigen was observed in all patients. These T cell responses were amplified with successive vaccination cycles. Notably, in several patients, the T cell responses were sustained even after two years of follow-up. All 12 patients involved in the immunogenicity analysis remain disease-free at the time of data cutoff. Enrollment for the main part of the colorectal cancer study is underway to establish the safety and efficacy of BND122 in patients with ctDNA-positive stage 2, stage 3 colorectal cancer, as opposed to the standard wait-and-watch strategy. We anticipate presenting the results from this randomized phase 2 study by late 2025 or early 2026. As multiple phase 2 trials are ongoing and our clinical data on mRNA immunotherapy continues to mature, we are scaling up our manufacturing capabilities and capacities for bulk mRNA drug supply, for off-the-shelf fixed vaccines, and also for our individualized vaccine programs. To build out our manufacturing capacity for personalized mRNA, we are currently building a pilot facility in Mainz, Germany to support our ongoing late-stage trials and potentially in the future commercialization. We also continue to leverage InstaD, our wholly owned AI subsidiary company, to work with our teams in improving both the up- and downstream processes in personalized mRNA. mRNA manufacturing. From our mRNA cancer vaccines, I'm now moving to our immunomodulatory IO compounds, specifically BNT327, which we consider as a key immunomodulatory concept and compelling backbone for novel combinations. BNT327 combines two validated mechanisms of action. VEGFA binding inhibits the VEGFA-VEGFR axis, blocks tumor angiogenesis, which leads to reduced tumor cell proliferation and survival. VEGFA inhibition also counteracts formation of the immunosuppressive tumor microenvironment, as does the PD-L1 arm of a bispecific antibody by reworking PD-L1-PD1 axis-mediated The PD-L1 arm also anchors this bispecific antibody to the tumor bed for efficient and localized scavenging of VEGFA, which may contribute to mitigate of tumor-on-target side effects. Given that both the anti-VEGFA and the anti-PD-1 mechanisms are validated across many tumor types and in some cases as a combination, we have a clear roadmap ahead of us where to develop BNT327. Beyond these initial indications in which we may combine with standard of care chemotherapy, we plan to evaluate novel BNT327 combinations, the first of which were started recently. These novel BNT327 combinations may open up new areas of activity for our anti-VEGFA and anti-PD-L1 molecules. We and our partner, Biofeus, have treated over 600 patients across a wide range of clinical indications with BNT327, either as monotherapy or in combination with various standard of care protocols. This extensive data collection effort provides a solid foundation for making informed, data-driven decisions on potential indications and patient cohorts for future registration studies. Notably, the data demonstrates robust single-agent activity of BNT327 in previously untreated advanced non-small-cell lung cancer and high response rates in combination with standard of chemotherapy in triple-negative breast cancer and small-cell lung cancer. Specifically, in first-line triple-negative breast cancer, we observed an objective response rate approaching 80% with durable responses then combined with NAP-paclitaxel. The safety profile in these indications was generally well-managed and in line with adverse events observed with other therapies targeting PD-L1 and appears to be more favorable than those seen with anti-VEGFA agents. These data have driven our strategic decision to initiate registration trials in small cell lung cancer, non-small cell lung cancer, and in triple negative breast cancer this year and next year. In small cell lung cancer, therapeutic options for the treatment of metastatic disease remain limited, with few innovative approaches beyond frontline anti-PD-1 checkpoint inhibitors, which only achieve response rates of around 20%. TNBC patients, particularly those with PDI-1 negative tumors, have few treatment options as they are not eligible for current anti-PD-1 therapy. In metastatic non-smother lung cancer, while anti-PD-1 inhibitors have significantly changed the treatment landscape, nearly half of these patients still do not respond to frontline therapy in combination with chemotherapy. We will soon start two global phase 2 dose optimization studies to enable selection of a registrational dose for global registrational trials in these particular indications. At ESCO, we presented updated preliminary efficacy and safety data from an ongoing phase 1-2 study in cohorts of advanced cervical cancer, platinum-resistant relapsed ovarian cancer, and advanced relapsed non-small cell lung cancer. we will be presenting signal finding data from additional tumor indications at upcoming conferences. This will add to our extensive database and is the basis of our plans for further development in key indications. Most importantly, as Ugo also noted, it is a strategic goal for us to explore BNT327 as part of novel-novel combinations in particular with our ADC assets and mRNA therapies. We have started to implement this strategy by investigating BNT327 in combination with our top two ADC, BNT325. Further combinations will be announced in the coming months. We are very excited to advance these combination trials with our partners. On my final slide now, I would like to provide an outlook on upcoming Congress presentation in September with updates on some of our priority assets. Congress in Barcelona. Here, we will present an update on our two trials evaluating BND113 . The first update will include patients with anal head and neck, cervical, and other HPV16-driven carcinomas. And we report mainly safety and immunogenicity findings from the Phase I-II trials. The second update from a safety run-in cohort of our ongoing Phase II trials evaluating BNT1-13, dosed in combination with pembrolizumab versus pembrolizumab alone, will include patients with HPV16-positive head neck squamous cell carcinoma. This update will focus on the safety, immunogenicity, and preliminaries activity findings of the cohort. We will also present the updated results on BNT327 in patients with TNBC, with EGFR-mutated non-small cell lung cancer, and with kidney cancer, together with our partner, BioFeels. These updates will contain either initial or follow-up data on safety and efficacy of BNT327 as immunotherapy, And there's a combination with different chemotherapeutic regimens. And finally, we will be presenting updated results from our ongoing phase one trial evaluating safety and efficacy of our Claudine 6 CAR T cells in combination with Claudine 6 encoding mRNA vaccine in patients with relapsed refractory Claudine 6 solid tumors. These data will be a follow-up from what was presented at last year's ESMO Congress and will include updated safety and efficacy data, as well as data on CAR-T self-assistance. We will share additional details on these and further Congress publications in the near future. With that, I will now pass the presentation to our CFO, Jens Holzstein.