BioNTech SE

Good morning and afternoon. Thank you for joining us today for BioNTech's second quarter 2023 earnings call. As a brief reminder, the slides to accompany this call and the second quarter 2023 press release that was issued this morning can be found in the investor section of our website. As outlined on slide two, you can see our forward-looking statements disclaimer. Additional information about these statements and other risks are described in our filings made with the U.S. Securities and Exchange Commission. Forward-looking statements on the call are subject to substantial risks and uncertainties. Speak only as of the call's original date, and 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'm joined by the following members of BioNTech's management team. Our CEO and co-founder, Ugr Zahin, Erzlem Tureci, our chief medical officer and co-founder, Jens Holstein, our chief financial officer, and Ryan Richardson, our Chief Strategy Officer. I would like to turn the call over to Ugur Zahin.

Thank you, Victoria. A warm welcome to all the call participants. We appreciate your continued support. Today, I will summarize our second quarter 2023 highlights and priorities before I pass the call over to my team to provide some further details. Slide five. Let me start reiterating our 2023 strategic priorities that we set at the beginning of the year and highlight our recent progress executing against them. We pursue our priority to expand and sustain our COVID-19 leadership with Pfizer by advancing our next generation and combination vaccine candidates and by advancing key Cominati features. During this quarter, we received recommendations from regulatory authorities and the World Health Organization on the composition of the adapted COVID-19 vaccine for the 2023-2024 fall season. Based on these recommendations, we together with our partner Pfizer have submitted regulatory packages for the Omicron XBB1.5-adapted monovalent COVID-19 vaccine to the U.S., FDA, EMA, and other regulatory agencies. They have also kicked off commercial launch activities for the Omicron XBB1.5-adapted monovalent COVID-19 vaccine. Our second 2023 strategic priority is to accelerate our oncology pipeline and initiate multiple trials with registrational potential. Our new collaborations with Duality Bio and OncoC4 complement our pipeline with multiple mid- to late-stage clinical programs that will help us to achieve this goal in the near term. In the second quarter at ASCO annual meeting, we and our respective collaboration partners presented three new clinical data sets that Erslan will cover later. Further, jointly with our partner Oncosee4, we began a pivotal phase three trial evaluating the next generation CTLF4 antibody candidate, BNT316, gotistobar as a second line treatment for patients with non-small cell lung cancer. Our first strategic goal is to initiate and accelerate clinical programs with high medical need in infectious diseases. We are expecting multiple data readouts for our mRNA-based vaccine candidates in the second half of this year. In summary, we continued our focus execution against strategic priorities in the second quarter and look forward to additional progress in all three of these areas in the remainder of this year. Slide six, starting with COVID-19. While variants of concern have emerged in all seasons in the past few years, we expect that in the fall and winter, in line with other common respiratory diseases, such as influenza and RSV, hospitalization will increase. Slide seven, in 2023, four years after the start of the COVID-19 pandemic, There's a high zero prevalence in the global population as a result of vaccination and or infection. Profiles of immune responses against SARS-CoV-2 are highly heterogeneous as individuals have been infected with different variants and or vaccinated using a variety of vaccine platforms. The substantial genetic and antigenic evolution of SARS-CoV-2 and its spike protein continues with divergence of the evolutionary trajectory from the original wild-type virus. Despite increasing gaps in the genomic surveillance globally, the available sequencing data indicates that the original virus and other early variants such as alpha, beta, gamma, delta are no longer detected in humans. As of July 2023, the XBV1 descendant lineages predominate globally and they have further antigenic distance from previous variants. Clinical data have shown that currently approved COVID-19 vaccines provide a level of protection against this new variant. However, with the antigenic breadth of current variants of concern, signs of waning protection have been observed starting two to four months after boosters with last season's B4, B5 adapted vaccine, including against severe COVID-19. Due to the greater antigenic distance of this variance of concern and the further immune escape, absolute vaccine effectiveness against hospitalization due to COVID-19 is reduced as time passes between vaccination and subsequent infection. In summary, this data supports a rollout of a COVID-19 vaccine adapted to the most recent variance of concern this fall. We plan to launch an Omicron XBB 1.5 adapted monovalent COVID-19 vaccine this fall, subject to approval by regulatory authorities. Our goal is to maintain protection against severe COVID-19 disease, hospitalization, and death by providing a vaccine that is better matched to the time it's circulating strains and that is designed to be more closely aligned to the newer evolving lineages. Slide 8. Let me remind you of the core principles of our overarching strategy. We pursue a multi-technology-driven approach rooted in deep fundamental understanding of biology and immunobiology. We leverage the power of computational science and AI. Our acquisition of InstaDeep has expanded our capabilities in that regard. Together, we aim to become the global leader in applying cutting-edge artificial intelligence and machine learning technology and research to discover, design, and develop next-generation immunotherapies at scale. We build novel platforms with the ability to produce multiple product candidates for our clinical pipeline, including approaches that enable and accelerate individualization of treatment. To leverage synergistic mode of action we explore opportunities for combining modalities, both developed internally and accessed via collaboration partnerships. Last quarter, we announced that we initiated a collaboration with Duality Biologics to access two of their next generation antibody drug conjugates. This quarter, we and Duality shared clinical data from one of these programs and expanded our collaboration to a third encouraging program from Duality Biologics pipeline. Slide 9. ADCs consist of three main components, antibody, linker, payload. Each of these components has an impact on ADCs pharmacological and clinical properties. ADCs are precision medicines allowing for targeted drug delivery, particularly to tumor cells with high specificity and potently induced cell death with the benefit of reduced off-target events. When the monoclonal antibody binds to the target expressed in the tumor cell, the ADC is internalized, allowing for the release of the cytotoxins, which leads to cell death. We continue to broaden our access to ADCs because we believe this technology has the potential to replace highly toxic chemotherapy regimens to become a new combination backbone for cancer immunotherapy. Advancements in this technology have resulted in its extended use for the treatment of solid tumors. ADCs can also synergize with various immunotherapy modalities, including those in our current immunotherapy pipeline. Our growing ADC pipeline now includes ADCs directed against three distinct targets and is of interest for a broad range of cancer types. In the future, we plan to combine these ADCs with our proprietary pipeline programs to maximize the patient impact of this exciting modality. With that, I would like to thank you all for your confidence in our success and your continued support. I will now turn the call over to Özlem.

Thank you, Ugo. I am delighted to speak with everyone today and to provide our pipeline update. Slide 11, starting with our COVID-19 vaccine. We expect that as SARS-CoV-2 continues to evolve and the risk of severe COVID-19 disease and death continues, there will be persisting demand for vaccine boosting and vaccinations, especially for at-risk and immunocompromised groups. The Omicron XBB sublineages currently account for the majority of COVID-19 cases globally and are antigenically distant from prior circulating SARS-CoV-2 lineages, including Omicron BA45 and the original SARS-CoV-2 strain. Although Omicron BA45-adapted bivalent vaccines provide some protection against a range of outcomes from XBB-related COVID-19, evidence suggests that vaccines better matched to currently circulating sublineages can help further improve protection against symptomatic disease and severe COVID-19. XBB lineage viruses have reduced neutralization in comparison to earlier Omicron lineages, but have similar neutralization profiles to each other. The spike sequence of XBB1.5 and XBB1.16 differ in only two mutations highlighted here. In May, the EMA and other health authorities provided guidance highlighting that updated vaccines targeting Omicron XBB1 sublineages may help to maintain protection against COVID-19 during the upcoming fall and winter season. Then COVID-19 case rates and hospitalizations are expected to increase. Also, the FDA's Vaccines and Related Biological Products Advisory Committee, the VRBAC, issued guidance recommending manufacture of an Omicron XBB1.5-adapted monovalent COVID-19 vaccine for the 2023 and 2024 fall and winter seasons. We and Pfizer submitted regulatory applications to the EMA and to the FDA for our Omicron XBB 1.5 adapted monovalent COVID-19 vaccine for individuals six months of age and older. Following guidance from regulatory authorities on the requirements for strain changes, the applications include data suggesting that Omicron XBB 1.5 adapted monovalent COVID-19 vaccine may generate improved responses against circulating XBB sublineages compared to the current Omicron BA45-adapted bivalent COVID-19 vaccine. Moving to slide 12. We and our partner Pfizer tested the potential effectiveness of an Omicron XBB 1.5-adapted monovalent vaccine as a primary series and booster in mice. Here you see the neutralizing antibody response in mice immunized with Omicron BA.4.5 adapted bivalent vaccine as booster after two doses of the original vaccine. One group of mice, again, received the BA.4.5 adapted bivalent COVID-19 vaccine as a fourth dose, and the other group received the new XBB1.5 adapted monovalent COVID-19 vaccine as a fourth dose. you can see a four to five-fold increase of neutralization of several XBB-related variants when dose four is the XBB 1.5 adapted monovalent vaccine as compared to last season's bivalent vaccine, indicating that XBB 1.5 variant adapted monovalent vaccine in the pre-vaccinated setting has the potential to induce broad cross-neutralizing antibody titers against multiple XBB sublineages. We made significant progress toward a monovalent COVID-19 vaccine against Omicron XBB1.5 with regulatory submissions to the U.S. FDA, EMA, and other regulatory authorities, and we are well prepared to launch an adapted COVID-19 vaccine if approved in early fall this year. Moving to our oncology pipeline, let me put our second quarter pipeline advancements into the broader context of our clinical stage pipeline, which is depicted on slide 13. In the second quarter, the initiation of our pivotal phase three trial in non-small cell lung cancer marks the first landmark in our strategic collaboration with OncoC4. The randomized phase III trial is evaluating BNT316, a pH-sensitive anti-CTLA-4 antibody with distinctive mode of action and is expected to enroll approximately 600 patients with metastatic immunotherapy-resistant non-small cell lung cancer. The trial initiation follows the FDA fast-track designation granted in 2022 and is based on Phase I-II safety and efficacy data for the monofurope in metastatic immune checkpoint inhibitor-resistant non-small cell lung cancer. Further, we expanded our collaboration with Duality and added a third ADC to our oncology pipeline. DB1305 is currently in a Phase I-II clinical trial for solid tumors. Then I have news from BNT116, our lung cancer antigen-based FIXVAC candidate. A second trial with BNT116 has dosed its first patient end of July. Together with our partner Regeneron, we will evaluate BNT116 in combination with simiplimab versus simiplimab monotherapy alone in treatment-naive patients with stage IIIb, stage IIIc, or stage IV squamous or non-squamous non-small cell lung cancer patients with at least 50% PD-L1 expression in a randomized multicenter open-label phase II study. A phase I clinical trial is ongoing with BNT116 to evaluate the safety tolerability and preliminary efficacy of BNT1-16 alone and in combination with Simiplimax in patients who have progressed on prior PD-1 inhibitor treatment or are not eligible for chemotherapy and in combination with Docetaxel in patients who have received prior PD-1 inhibitor therapy and platinum-based chemotherapy. We are planning to start several trials with our partners imminently. Building on compelling Phase I data in patients with resectable PDAC in the adjuvant setting that we recently reported in Nature, a Phase II trial with autogen-sevoumarin BNT122, our individualized cancer vaccine candidate, is planned with our partner Genentech, evaluating the efficacy and safety of autogen sevomirin in combination with atezolizumab and modified folferinox compared to modified folferinox as standard of care alone. Second, another trial is planned to start with our second ADC developed by Duality Bio. BNT324 is a humanized antibody conjugated to a novel DNA topoisomerase 1 inhibitor via a cleavable linker. The phase one part of the study will evaluate the safety in all comas and determine the recommended phase two dose. In the phase two dose expansion part, we aim to evaluate safety and efficacy in small cell and non-small cell lung cancer, esophageal cancer, prostate cancer, melanoma, and other solid tumors. On the next couple of slides, I want to summarize the recently presented data from three of our programs at the ESCO annual meeting. On site 14, starting with BNT316, ONC392. Antibody targeting of CTLA-4 works primarily by depleting regulatory T cells and thus their suppression of tumor-specific immunity. Physiologically, CTLA-4 recycles continuously between the cell surface and the endosomes. Interruption of this process by a binding antibody is associated with the development of autoimmunity. Autoimmunity and immune-related adverse events are a major limitation of approved anti-CTLA-4 antibodies that disrupt CTLA-4 recycling by promoting lysosomal degradation of this important immune checkpoint molecule. BNT316, in contrast, dissociates from the CTLA-4 molecule in the endosome, allows normal recycling of both the antibody and the CTLA-4 molecule, and thus is designed for stronger cancer therapeutic effects and less immune-related adverse effects. Preliminary data showed that BNT316 is well-tolerated with no dose-limiting toxicities. The single-agent recommended phase 2 dose was determined to be 10 mcg per kick, without MTD being reached. Severe immune-related grade 3 adverse event rate in the combo dose escalation with pembrolizumab was 23%, which is considered lower than what was reported for comparable IO-IO combinations. The recommended phase 2 dose for combination is 6 mcg per kick. Overall, BNT316 dosed as monotherapy, and in combination was well-tolerated, and the safety profile appears to allow higher dosing for a longer duration of treatment as compared, for example, to ipilimumab. Early efficacy data as monotherapy in platinum-resistant ovarian cancer patients and in combination with pembrolizumab in multiple solid tumors were promising. Slide 15, with our colleagues from Oncocifor, We presented data from the Phase 1-2 study investigating BNT316 in 35 non-small cell lung cancer patients with metastatic lesions that progressed on immune checkpoint inhibition in previous lines. The majority of patients had an ECOG status of 1. The objective response rate was about 30%, and disease control rate was 70%. Patients that responded to BNT316 had previously failed multiple lines of treatment, including several immune checkpoint inhibitors. In this cohort, BNT316 has shown manageable safety and tolerability when dosed at 10 mg per kick twice and followed with 6 mg per kick every three weeks. Immune-related adverse events of grade 3, 4 were observed in 34% of patients, and included immune-mediated colitis, ALT-AST increase, and immune hepatitis. Our findings support the further development of BNT316 in non-small cell lung cancer in the Phase III study Preserve-OO3. Slide 16. Our second presentation at ESCO was together with our colleagues from Duality Bio and about our first clinical data for BNT323, our next generation HER2-targeting ADC. BNT323 is comprised of a HER2-targeting antibody covalently linked to the proprietary DNA topoisomerase I inhibitor via a cleavable linker. Approved ADCs have shown anti-tumor activity and clinical benefits in multiple types of cancer, and we believe that midterm ADCs as a modality will become a broadly used backbone for combos in oncology. More efficacious and safer anti-HER2 ADCs, for example, regarding potential lung toxicity, may add further clinical benefit. Preclinical data for BNT323 described a significantly improved therapeutic window as compared to DS8201A or TDM1 analogs to the approved HER2-ADC trastuzumab deoxycan and trastuzumab emtazine, respectively. BNT323 has a high drug-to-antibody ratio, and when incubated with RET, monkey and human plasma demonstrated outstanding plasma stability. In HER2-positive and HER2-negative mixed cell cultures, BNT3-23 inhibited the proliferation of both cell types, demonstrating its bystander effect. Pharmacokinetic and pharmacodynamic analysis of BNT3-23 in xenograft mouse models showed targeted delivery of the toxin into tumor tissue. in vivo studies in monkeys showed a superior stability of BNT323 and rapid systemic clearance of the toxin. Altogether, these properties result in maintenance of efficacy and reduction of systemic toxicity in animal models. Slide 17. The program has received fast track designation from the FDA and is being evaluated in a Phase I-II clinical trial. The study is enrolling pretreated patients with advanced or metastatic HER2-targetable solid tumors. HER2 status is identified via IHC or ISH for expression level, via NGS for HER2 amplification, or HER2 mutation. the majority of patients had the HER2 expression by IHC of 2 plus or 3 plus. We showed preliminary antitumor activity in heavily pretreated HER2-expressing patients with a median of seven prior systemic treatment signs, including other anti-HER2 ADCs, anti-HER2 antibody therapy, or anti-HER2 TKI therapy. In HER2-positive breast cancer patients objective response rate is 50%, the disease control rate is 96%. In HER2-low breast cancer patients, objective response rate is 38%, the disease control rate is 84%. Anti-tumor activity of BNT323 was also observed in non-breast cancer tumor types, such as colorectal cancer, ovarian cancer, and endometrial cancer. Responses were observed in patients treated with different dose levels and HER2 expression status. BNT323 was well tolerated, and all adverse events were manageable so far. Interstitial lung disease of grade 1 occurred in two patients out of 85 patients. Expansion cohorts are ongoing in selected tumor patients treated at recombinant phase 2 dose And we expect further data this year. Slide 18. Finally, we presented data on our Self-ERP product, candidate BNT211. We developed a highly sensitive second generation car targeting Chlorine 6 with high specificity. The carcinoembryonic antigen Chlorine 6 is an ideal target for Self-ERP as it is absent in healthy tissues, but highly expressed in many high medical need cancers. To improve CAR-T cell engraftment and persistence, we co-developed a CAR-T cell amplifying RNA vaccine, or CARVAC for short. The goal is to keep CAR-T cells at therapeutically relevant levels. In animal studies, we have shown that the persistence and effector function of CAR-T cells can be further enhanced by repeated administration of CARVAC. a nanoparticulate RNA vaccine that encodes CLA-D6. Kavak is based on our uridine nucleoside mRNA lipopax vaccine technology and mediates body-wide RNA delivery to lymphoid compartment resident antigen-presenting cells. In multiple preclinical models, the display of a translated natively folded CAR-target protein on antigen-presenting cells mediated in vivo stimulation and controlled expansion of CAR T-cells, induced a memory T-cell phenotype along with higher target sensitivity, and enabled tumor control even if sub-therapeutic CAR T-cell doses were administered. We are testing the safety, tolerability, and activity of a combination of Chlorine 6 CAR T-cells and CAVAG in a bifurcated dose escalation study with increasing dose levels of CAR T-cells and a fixed CARB-X schedule in patients with various cancer types that are Claudine 6 positive, defined as more than 50% of tumor cells with 2 to 3 plus intensity. A dose escalation has been completed for CAR T-cells derived from a manual manufacturing process, and we have presented data with highly encouraging signs of clinical activity and manageable safety at various conferences in the past. Slide 19, a subsequent cohort of 19 patients have been treated with a CAR-T product manufactured with a scalable automated version of the process. No DLTs have been observed so far, and Claudine's six CAR-T cells, as well as CARBEC, were well tolerated reflecting the safety profile detected in the first dose escalation level. The objective response rate was 41% for all 17 available patients and 75% for eight patients treated at dose level two, namely one times 10 to the eighth CAR T-cells. Next to germ cell tumors, which dominated the first dose escalation, we observed ovarian cancer patients responding. We are expecting an additional data readout later this year. Once we have determined the recommended phase 2 dose for BNT211, we plan to initiate a pivotal trial in germ cell tumors, which has already received prime designation by the EMA. Advancing our pipeline remains a key strategic priority for the year. This and next year, we plan to transform our pipeline as we advance multiple programs towards the pivotal stage. I will now pass the presentation to our CFO, Jens Holzstein.