BioNTech - Q2 2024

Transcript

Operator (participant)

Welcome to BioNTech's second quarter 2024 earnings call. I would like to hand the call over to Dr. Victoria Meissner, Vice President of Strategy and Investor Relations. Please go ahead.

Victoria Meissner (Head of Investor Relations and Corporate Strategy)

Thank you. Good morning and good afternoon. 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 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. 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: Ugur Sahin, 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 Ugur.

Ugur Sahin (Co-Founder and CEO)

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 Comirnaty and our late-stage oncology portfolio. Özlem will talk about some of our recent oncology pipeline advancements 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 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. Özlem 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 FixVac mRNA cancer vaccine for melanoma, BNT111, met the primary endpoint in the ongoing randomized phase II trial evaluating BNT111 in combination with cemiplimab in patients with stage III and stage IV 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 VEGF bispecific antibody BNT327 and our TROP2 ADC BNT325. We look forward to initiating additional trials evaluating novel IO-ADC combinations over the next 12 months. The third area in which we made progress is our mission towards the creation of a sustainable and resilient end-to-end vaccine ecosystem in Africa by expanding our partnership with CEPI.

CEPI is committed up to $145 million to support us to establish 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 threats 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 their immune evasive potential and virulence. In September 2022, the XBB lineage gradually emerged, dominated globally throughout 2023 with multiple sub-lineages and was successfully addressed by XBB.1.5 variant-adapted COVID-19 vaccines, including our own. This year, JN.1 lineage, including KP.2, became the predominant variant globally, leading to the current surge in infections in many regions in the northern hemisphere.

Shown on the right graph, real-world effectiveness data demonstrates that the antigenic shift and the distance of JN.1 lineages from XBB.1.5 has impacted the vaccine effectiveness of the XBB.1.5-adapted vaccine against the now prevalent JN.1 lineages. Slide 7. Based on this and additional data, regulatory and public health authorities consequently advised vaccine manufacturers to revise the formulation for their authorized COVID-19 vaccines. The WHO and the EMA recommended the use of JN.1 lineage antigen in a monovalent COVID-19 vaccine for the season 2024-2025, and 70 days later, we were able to submit our application to the European regulator. Based on this recommendation and the consequent EMA approval on July 3rd, we have begun rolling out our updated Comirnaty JN.1 vaccine in Europe.

In the United States, the FDA further recommended the use of KP.2 as the preferred JN.1 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 U.S. 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 KP.2-adapted 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 progress on our oncology pipeline. Before I hand over to Özlem to deep dive into the recent achievements, 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 through synergistic mechanisms of action. Having this diversity of assets in our pipeline enables 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 synergistic combinations are best suited. 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.

As you will hear from Özlem, 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 the truly exciting period for BioNTech and our progress towards our founding vision. Thank you.

Özlem Türeci (Co-Founder and CMO)

Thank you, Ugur. 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 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 IO 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 to 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 neoantigens 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. iNeST 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 the slide are planned. Aggregate data that we have reported in the past across iNeST and FixVac 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-sized 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 FixVac 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 HPV-16 positive, PD-L1 positive head and neck squamous cell carcinoma in a potentially registrational phase II 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, BNT111, being investigated in anti-PD-1 relapsed or refractory melanoma, about which I would like to talk a bit more. BNT111 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 II clinical trial conducted in collaboration with our partner Regeneron, we are evaluating BNT111 in combination with Regeneron's anti-PD-1 compound, cemiplimab, and we measure activity of BNT111 alone or cemiplimab alone in a total of 184 enrolled patients with PD-L1 refractory, unresectable, stage III or stage IV melanoma.

As Ugur noted earlier, we very recently announced that the trial met its primary endpoint, achieving a statistically significant improvement of overall response rate in the BNT111 cemiplimab combination arm as compared to a 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 BNT111-01 trial is based on the earlier Lipoplex phase I/II 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 BNT111 as single agent and with checkpoint inhibitors approved in this patient population.

In that proof of concept study, we observed that treatment with BNT111 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 BNT111 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 II BNT111-01 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 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 FixVac program candidates. 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 cancers and in adjuvant or minimal residual disease treatment settings.

Here, I want to highlight ongoing randomized phase II trials with our individualized vaccine in pancreatic ductal adenocarcinoma and in colorectal cancer. The 5-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 5 years after adjuvant treatment. As for high-risk stage II or stage III colorectal cancer, about 35% of patients relapse within 5 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 3-year follow-up period.

At the recent ESMO GI Conference, we disclosed findings from the biomarker sub-study of our ongoing phase II iNeST trial, BNT122-01, involving patients with stage II high-risk or stage III colorectal cancer who remained 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 remained 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 BNT122 in patients with ctDNA positive stage II, stage III colorectal cancer as opposed to the standard wait-and-watch strategy. We anticipate presenting the results from this randomized phase II study by late 2025 or early 2026. As multiple phase II trials are ongoing and our clinical data on mRNA immunotherapies continues to mature, we are scaling up our manufacturing capabilities and capacities for bulk mRNA drug supply for off-the-shelf FixVac 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 InstaDeep, our wholly-owned AI subsidiary company, to work with our teams in improving both the up- and downstream processes in personalized 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. VEGF-A binding inhibits the VEGF-A-VEGF-R axis, blocks tumor angiogenesis, which leads to reduced tumor cell proliferation and survival. VEGF-A inhibition also counteracts formation of the immunosuppressive tumor microenvironment, as does the PD-L1 arm of this bispecific antibody by reverting PD-L1-PD-1 axis-mediated T-cell exhaustion. The PD-L1 arm also anchors this bispecific antibody to the tumor bed for efficient and localized scavenging of VEGF-A, which may contribute to mitigation of tumor-on-target side effects.

Given that both the anti-VEGF-A 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-VEGF-A and anti-PD-L1 molecules. We and our partner, Biotheus, 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 demonstrate robust single-agent activity of BNT327 in previously untreated advanced non-small cell lung cancer and high response rates in combination with standard of care 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 when combined with nab-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-VEGF-A 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 PD-L1-negative tumors, have few treatment options as they are not eligible for current anti-PD-1 therapy. In metastatic non-small cell 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 II dose optimization studies to enable selection of a registrational dose for global registrational trials in these particular indications. At ESMO, we presented updated preliminary efficacy and safety data from an ongoing phase I-II 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 Ugur 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 TROP2 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 presentations in September with updates on some of our priority assets. At the annual ESMO Congress in Barcelona, here we will present an update on our two trials evaluating BNT113 FixVac.

The first update will include patients with anal, head, and neck, cervical, and other HPV16-driven carcinomas and will report mainly safety and immunogenicity findings from the phase I-II trial. The second update, from a safety run-in cohort of our ongoing phase II trial evaluating BNT113, 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 preliminary 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, Biotheus. These updates will contain either initial or follow-up data on safety and efficacy of BNT327 as a monotherapy and as a combination with different chemotherapeutic regimens.

Finally, we will be presenting updated results from our ongoing phase I trial evaluating safety and efficacy of our Claudin-6 CAR T-cell in combination with a Claudin-6 encoding mRNA vaccine in patients with relapsed refractory Claudin-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-cell persistence. 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 Holstein.

Jens Holstein (CFO)

Thank you, Özlem, and a warm welcome to everyone who has dialed in today's call. Let me start by reviewing our financial results for the three months ended June 30, 2024.

Our total revenues reported for the second quarter of 2024 reached approximately EUR 129 million, compared with approximately EUR 168 million for the second quarter of 2023. Our second quarter revenues reflect the current demand of a seasonal endemic COVID-19 vaccine market, and are expected to be the low point in this year's COVID-19 vaccine uptake. Parts of our total revenues are derived from a pandemic preparedness agreement with the German government, which is expected to run until early 2027. Moving to cost of sales. Cost of sales amounted to approximately EUR 60 million for the second quarter of 2024, compared to approximately EUR 163 million for the comparative prior year period. Research and development expenses were approximately EUR 585 million for the second quarter of 2024, compared to approximately EUR 373 million for the comparative prior year period.

Of the total R&D spend in the second quarter, we invested approximately 90% in our non-COVID business, mainly by initiating larger clinical studies for our late-stage oncology candidates and by investing in additional personnel in our R&D departments to run those clinical trials. Sales, general, and administrative expenses amounted to approximately EUR 184 million in the second quarter of 2024, compared to about EUR 138 million in the comparative prior year period. The increase in SG&A was mainly due to the increased expenses for our IT environment, as well as an increase in headcount to support the scaling of our business. Regarding the company's other operating results during the second quarter of 2024, this amounted to approximately EUR 267 million in negative operating result, compared to about EUR 57 million in negative operating result for the comparative prior year period.

This change was primarily due to the recording of a provision related to a contractual dispute. Income taxes were accrued with an amount of EUR 2 million of tax expenses for the second quarter of 2024, compared to approximately EUR 222 million of realized tax income for the comparative prior year period. The effective income tax rate for the first half of 2024 was approximately 1.3%. For the second quarter of 2024, we reported a net loss of approximately EUR 808 million, compared to a net loss of about EUR 190 million for the comparative prior year period. Our loss per share for the second quarter of 2024 amounted to EUR 3.36, compared to a loss per share of EUR 0.79 for the comparative prior year period. As of June 30, 2024, our cash and cash equivalents and security investments reached approximately EUR 18.5 billion.

Our strong balance sheet provides us with a strategic flexibility to invest in our long-term growth strategy. As part of that strategy, we will continue to invest in the development of our individualized therapies and in the build-out of the manufacturing capacities and capabilities to support additional late-stage trials and commercialization. To create long-term value, we aim to advance our clinical programs quickly, yet cost-efficiently towards potential registration. Turning to the next slide. Today, we are reiterating the company's financial guidance for the current financial year. Consistent with the expectations of approval of our variant-adapted COVID-19 vaccine in the United States in mid-September, we expect to recognize the vast majority of our full-year revenues, mostly in Q4.

Independent of the timing of the revenue generation, and as communicated earlier in the year, we expect to report a loss for the 2024 financial year while we continue to invest in our proprietary assets and technologies. As such, we also reiterate our R&D and SG&A guidance with EUR 2.4 billion-EUR 2.6 billion for R&D and EUR 700 million-EUR 800 million for SG&A expenses. Those expenses are expected to increase in the second half compared to the first half of 2024. Please note that this guidance does not include any M&A transactions, payment for collaboration agreements, or licensing deals not yet disclosed, nor any potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activities, such as judgments or settlements, which may have a material effect on our results of operations and/or cash flows.

In summary, our focus so far has been on executing the company's strategy highlighted by the progress in our pipeline. We've advanced and started new potentially registrational trials and have shared encouraging data that demonstrates the potential of our pipeline. Our focus in oncology remains on investing in our innovative technologies that we believe can make a difference while progressing our late-stage programs towards potential market authorizations. Supported by our strong cash position and demonstrated financial discipline, we will continue to invest in our pipeline and focus on generating value for patients and our shareholders. With that, I would like to turn the call over to our Chief Strategy Officer, Ryan Richardson, for an update on our strategic outlook and concluding remarks. Thank you.

Ryan Richardson (Chief Strategy Officer)

Thank you, Jens. Our efforts over the last few months have put us in a strong position to execute our COVID-19 vaccine launches this fall season.

In June, the European Medicines Agency recommended marketing authorization for our JN.1 adapted COVID-19 vaccine, followed by European Commission approval on July 3. We started distributing vaccine doses to EU member states shortly thereafter. We expect the earlier launch of our updated COVID-19 vaccine in Europe relative to last year will allow vaccination campaigns this year to be more closely aligned with seasonal influenza vaccination campaigns. In the United States, the FDA has recommended the use of KP.2 as the preferred strain for the 2024-2025 season. We and our partner, Pfizer, have initiated a rolling submission with the FDA for our KP.2 adapted COVID-19 vaccine and expect to be in a position to begin vaccine distribution in the U.S. following regulatory approval, with first shipments expected in September. COVID-19 vaccine demand continues to be globally distributed.

We and our partner, Pfizer, are preparing to launch our variant-adapted COVID-19 vaccine in over 40 countries and regions worldwide. We expect approximately two-thirds of demand potential to reside outside the United States. While some regions outside the U.S. continue to be served by government contracts, we anticipate several newly established private markets to open up in regions like the U.K. and Japan. This could enable broader access to COVID-19 vaccines for individuals who may not qualify under local immunization recommendations, which tend to focus on the higher-risk population segments. In addition, we have increased our supply of prefilled syringes, but we'll continue to offer a mix of prefilled syringes, single-dose vials, and multi-dose vials across regions. We believe the Comirnaty franchise is well-positioned to maintain its leading position globally in the continued fight against COVID-19. Moving to oncology on the next slide.

We will continue to invest in our mRNA cancer vaccine platforms based on our belief that personalized mRNA cancer vaccines have potential to establish a new paradigm in cancer treatment. These vaccines employ cutting-edge mRNA technology, which aims to address the root cause of cancer, genomic mutations or neoantigens that are largely specific to each individual's tumor. Neoantigens selection for each patient is today driven by AI algorithms and a fully in silico process. We believe this is fundamentally distinct from other pharmaceutical products in that it will allow for iterative improvement over time, powered by data assets. In addition to their ability to be combined with other therapies with complementary mechanisms of action, we believe these therapies have potential to extend beyond the product lifecycle of a traditional off-the-shelf pharmaceutical product.

The next slide highlights the key pipeline milestones to focus on as we look ahead to 2024 and 2025. We are entering a catalyst-rich period over the next 18 months, with data updates and regulatory submissions expected from multiple product candidates. This includes, but is not limited to, phase III COVID flu combination vaccine top-line data expected this year and data expected in 2025 from both our mRNA cancer vaccine platforms, FixVac and iNeST. We also expect data updates for BNT327, our anti-PD-L1 VEGF bispecific antibody, and BNT323, our HER2 ADC, in a variety of solid tumor indications. Finally, we plan to initiate multiple combination trials in solid tumor indications over the next 12 months, consistent with our strategy to develop novel combinations which leverage complementary mechanisms of action.

Turning to the next slide, we continue to focus on our late-stage oncology portfolio in line with our near-term goal to have 10 potentially registrational trials active by the end of the year. While still in the early stages, we are making progress in attracting talented professionals to join our commercial organization to support our first wave of anticipated oncology product launches. We believe that focusing execution on our diverse late-stage pipeline will bring significant potential for mid and long-term value creation. On the next slide, I would like to remind everyone that we plan to hold our first artificial intelligence innovation series event via webcast on October 1st, followed by our annual innovation series event on November 14. Further details will be released soon. We welcome you to join these events for a deeper look at the exciting developments taking place at BioNTech.

With that, I would like to open the floor for questions.

Operator (participant)

Thank you. To ask a question, please press star one one on your telephone and wait for your name to be announced. To whisper your question, please press star one one again. We kindly ask participants to limit themselves to one question per person. We will now take the first question from the line of Daina Graybosch from Leerink Partners. Please go ahead.

Daina Graybosch (Senior Research Analyst)

Hi. Thank you, guys, and thanks for the question. This one is on the launch as early as 2026. I wonder if you could talk about what specific programs and settings trials you think are most likely to be able to launch in 2026, and if that's dependent on accelerated approval, what gives you confidence in accelerated approvals by that date? I guess I'm specifically referencing whether any of those are your phase II vaccine trials. Thank you.

Ryan Richardson (Chief Strategy Officer)

Yeah. Thank you, Daina. I'll start briefly, and my colleagues can jump in. So I think for 2026, we have a couple of different programs that potentially could launch in that timeframe, and the first of which is BNT323, our HER2 ADC. And we've highlighted the potential for, we think, for an accelerated approval in second- and third-line endometrial cancer. So that would be one asset where we're expecting data next year. And if that timeline is confirmed with further FDA discussions, we think that that could be a 2026 launch opportunity. In addition, we've highlighted the potential for an accelerated pathway with our BNT122, iNeST, and adjuvant colorectal cancer.

I think we still have further discussions to take place with the FDA, but based on the current study design and the pace of enrollment, we do think that there's the potential, if the data is strong, also for data to be for submission and potentially a launch in that sort of timeframe, most likely towards the end of the year or early 2027, but it could fall in 2026.

Operator (participant)

Thank you. We will now take the next question from the line of Yaron Werber from TD Cowen. Please go ahead.

Yaron Werber (Managing Director and Senior Biotechnology Analyst)

Yeah. Hi. Thanks for taking my question. Maybe just a quick question.

I know you probably can't say a lot, but BNT111, FixVac, when you're looking at historical controls and you're looking at sort of the overall survival sort of trend, can you give us a sense which historical control do you think are most appropriate just to kind of help gauge what the efficacy could be? Thank you.

Özlem Türeci (Co-Founder and CMO)

Yes. You know this is a very dire indication, CPI refractory resistant melanoma, and the controls against which we compare anti-PD-1, PD-L1 treatments which have been tested in this indication, or chemotherapies which have been tested in this indication. And as compared to those, we see clinically meaningful benefit with regard to objective response rate. There is a trend for overall survival, but it is too early to be more specific about PFS and OS.

Now the data will mature, and at the time when we present the data next year, we will be able to be more specific.

Operator (participant)

Thank you. We will now take the next question from the line of Tazeen Ahmad from Bank of America Securities. Please go ahead.

Tazeen Ahmad (Analyst)

Hi. Good morning. Thanks for taking my question. Regarding the upcoming phase III COVID flu combo data later this year, can you frame for us what would be good data and how would you think that would impact the demand for the regular COVID vaccine going forward? And then also related to that, how long before you think that this product, the combo product, would be able to launch? Thanks.

Ugur Sahin (Co-Founder and CEO)

Hi. It's Ugur. Yeah. Thanks for your question. So we are expecting that timeframe with safety immunogenicity data and efficacy data end of this year.

And based on the results, we have to see whether the data qualify for submission and potential approval for the season 2025-2026.

Tazeen Ahmad (Analyst)

What would you consider good data, though, Ugur, to be an improvement over the regular COVID vaccine?

Ugur Sahin (Co-Founder and CEO)

Can you repeat your question? I didn't get that.

Tazeen Ahmad (Analyst)

What would you consider to be good data relative to the COVID-only vaccine in order to justify?

Ugur Sahin (Co-Founder and CEO)

Yeah. I think the data is very clear. It's an efficacy trial. Yeah. It's about compatibility with the COVID-19 plus efficacy in the flu arm and additional immunogenicity data supporting the mode of action of the vaccine.

Operator (participant)

Thank you. We will now take the next question from the line of Etzer Darout from BMO Capital Markets. Please go ahead.

Etzer Darout (Managing Director and Senior Biotechnology Analyst)

Hi. Thanks for taking the question.

Just wondering sort of in the wake of the acasunlimab update and your maintenance of R&D guidance, is there a specific internal oncology program that potentially benefits here? In other words, maybe potential of acceleration of investments or broadening out of the program? Just so curious your thoughts around who maybe what programs may benefit from this internally.

Ryan Richardson (Chief Strategy Officer)

Yeah. Yeah. Thank you for that question. I mean, ultimately, this does come down to portfolio strategy, as I think your question alludes to. And the fact is that we have multiple programs that we think could have potential in non-small cell lung cancer. We've already started the phase III for BNT116. We've just brought out data at ASCO for BNT327, which, albeit early, we do think is quite promising. And we also have a FixVac program that's also in SCLC.

So we've got already critical mass in our portfolio in the non-small cell lung cancer indication, and we are planning a multi-pronged strategy to execute against. So while we found the data encouraging for acasunlimab, we decided to prioritize other programs, frankly, over this in the next phase. I think the important takeaway here, though, of course, is that as Genmab now takes this program forward into phase III, we will still retain an economic stake in the program and a stake in the future success of the program, but we won't fund phase III. And we think that that's the right balance given the many shots on goal and exciting data that we're seeing from the portfolio.

Etzer Darout (Managing Director and Senior Biotechnology Analyst)

All right. Thank you.

Operator (participant)

Thank you. We will now take the next question from the line of Yifeng Liu from HSBC Bank PLC. Please go ahead.

Yifeng Liu (Pharma and Biotech Equity Research Analyst)

Hello. Thank you for taking my question. I've got a question on margin progression. So just how should we think about as your oncology pipeline progresses and also, in the meantime, you've scaling out manufacturing and potentially investment in R&D and then SG&A, how should we think about that margin progression, especially as you're launching your oncology products in the future? Thanks.

Ryan Richardson (Chief Strategy Officer)

Yeah. Yeah. We couldn't hear you very well there, but just want to make sure we get the question right. So your question is about how do we see margin progression over the next couple of years, specifically as it relates to oncology? Is that right?

Yifeng Liu (Pharma and Biotech Equity Research Analyst)

Yes. Because yeah, I think the launches predominantly we see sort of in oncology space. And yeah, just the question on margin progression. Thank you.

Ryan Richardson (Chief Strategy Officer)

Maybe I'll start. It's awfully difficult, actually, to understand you. You're fading away somewhat.

But I mean, we've seen that, of course, the margin that we have in our partnership with Pfizer is extremely good. I mean, we're close to 100% given the gross margin share structure that we have with Pfizer. So that's outstanding and certainly not normal. In terms of oncology going forward, we would expect that we see similar sort of margins as you see with other companies. I think in looking forward in terms of individualized medicine, I think we got to wait a little bit on how we can when we can make some statements in terms of the margin. But we're working very hard. I can assure you we're working very hard to bring the costs down for individualized medicine candidates. Yeah. And I would just add one point to that.

So in addition to what you just said about oncology, I think we're still expecting, of course, that our COVID business is going to still be, for the next couple of years, still a driver of our overall margins. And I think there we've got, as we've pointed out in the past, a very attractive economic model, vis-à-vis our partner, Pfizer, that we think will allow us to keep our overall operating profile quite attractive.

Yifeng Liu (Pharma and Biotech Equity Research Analyst)

All right. Thank you.

Operator (participant)

Thank you. We will now take the next question from Michael Yee from Jefferies. Please go ahead.

Akash Tewari (Global Head of Biopharmaceutical Research)

Hi. This is actually Akash. So you recently toplined data from your 111 trial in cutaneous melanoma. Our analysis suggests that combo arm would have a 24% delta versus roughly the 11% historical control rate for ipi/PD-1. Is that the ballpark way to think about the ORR delta in this study?

What would you have to see on PFS and OS to justify moving this forward into a phase III? And maybe just stepping back, what does this trial teach the BioNTech team about the ideal place for cancer vaccines? I feel like one of the lessons from your early iNeST data was that cancer vaccines were perhaps not well-suited for patients with metastatic late-stage disease, and yet these patients were PD-1 refractory. So how should we interpret that? Thank you.

Ugur Sahin (Co-Founder and CEO)

Okay. Thank you. It's a great question. So the personalized cancer vaccines have a manufacturing turnaround time in the range of 6-8 weeks. And therefore, in the metastatic setting, this type of vaccines are difficult to provide a clinical benefit since these patients rapidly progress. So the statement refers to the personalized vaccines. With regard to FixVac, we have seen that FixVac has two activities.

It's on the one side, the direct activity due to the adjuvant function. We are seeing a type I interferon response, yeah, and have seen now in a number of indications, not only in melanoma but also in lung cancer, objective responses in patients with advanced cancers. And we expect that a combination, particularly with a treatment that is able to control the disease for a certain time. And we are particularly interested here in our ADC mRNA vaccine combinations. We will see a number of trials coming up in 2025 for this. It would be an exciting opportunity for our FixVac approach. And maybe for the other part, I give to Özlem.

Özlem Türeci (Co-Founder and CMO)

Yes. Your question regarding BNT111 was about the clinical benefit, which we would like to see as compared to standard of care. I cannot preempt our disclosures, which will come when we have mature data.

But what I can say is, as you know, standard of care, objective response rates for this patient population is around 10%-ish. What we would like to see is something well above that. This is also what our data shows us. We also want to see duration of response. This looks clinically meaningful in the current dataset which we have. Then it's obviously also about safety. What we see is that BNT111, as a FixVac based on RNA lipoplex technology, has a very manageable safety profile. In combination with cemiplimab, we don't see anything which is surprising. There is no additive toxicity or so, which for us means that the clinical profile looks very promising for this patient population.

Operator (participant)

Thank you. We will now take the next question from the line of Jessica Fye from JPMorgan Chase. Please go ahead.

Jessica Fye (Managing Director and Equity Research Analyst)

Hey, guys. Good morning. Thanks for taking my question. It looks like the BioNTech top-line guidance reflects a different expectation for 2024 Comirnaty sales than what Pfizer's guidance would imply. What gives you confidence in achieving this result? And to the extent that part of the delta is driven by German pandemic preparedness contract, which I believe falls outside the collaboration, can you quantify what that is contributing to the guidance? Thank you.

Jens Holstein (CFO)

Yeah. Let me start. And maybe Ryan wants to jump in. So I think we are very much aligned with Pfizer in terms of our combined expectations. We should keep in mind that Pfizer has iterated its guidance. We did the same today. You should be aware that, and take into account that we have a contract together with the European Union. We have approval in the U.K.

So I think for Europe, this gives us some comfort in terms of how the full year should look like. Of course, there's always some insecurity in that respect. But in that sense, we feel good about it. And in terms of the pandemic preparedness contract, we have confidentiality with the German government. So we're a bit limited in really stating here some numbers. But you should expect that there is a significant amount of money being part of what we have reported in the first half. So we have reported outside of Comirnaty, if you look into the documents, EUR 120 million. So a big chunk of that in the first half comes from that pandemic preparedness contract.

Jessica Fye (Managing Director and Equity Research Analyst)

Thank you.

Operator (participant)

Thank you. We will now take the next question from the line of Cory Kasimov from Evercore ISI. Please go ahead.

Cory Kasimov (Senior Managing Director and Fundamental Research Analyst)

Hi. Thanks for taking the question.

Regarding the upcoming data at ESMO for BNT327 and EGFR-mutated non-small cell lung cancer, there's obviously been a lot of attention of late on the competitive PD-1 VEGF bispecific that's out there. I'm curious, kind of based on what you know about that compound and the data presented to date, how similar or different do you expect your approach to be? And how confident are you in having competitive data in this population? Thank you.

Ugur Sahin (Co-Founder and CEO)

Yeah. Thank you for the question. I can keep it short. I think the data that we are going to present will be competitive. And as you know, the asset that BNT327 is now a molecule that is currently in evaluation multiple indications at BioNTech and our collaboration partner, Biotheus. And we will see additional studies to be announced end of this year, beginning next year.

Cory Kasimov (Senior Managing Director and Fundamental Research Analyst)

Okay. Thank you.

Operator (participant)

Thank you. We will now take the next question from the line of Chris Shibutani from Goldman Sachs. Please go ahead.

Chris Shibutani (Managing Director and Senior Equity Research Analyst)

Yes. Thank you. If I could just follow up on the BNT327. Noting from slide 10, it appears, from the change in your pipeline plans, there are some additional trials there, which seem to signal that BioNTech is quite enthusiastic in that regard. I think it would be helpful. The investor community was certainly attentive during ASCO, to understand how your approach may differ from that of a competitor, Summit Therapeutics. And in particular, can I ask you, are you looking to do any head-to-head trials involving Keytruda? How are you thinking about sort of clinical development strategy that we can understand to be differentiated? Thank you.

Özlem Türeci (Co-Founder and CMO)

Thank you for this question, Chris. We can not comment on the strategy of others.

But what we can say is that we think that BNT327 and this concept is highly compelling and qualifies as an IO backbone for various combinations. And our approach here is to be broad with regard to the indications, which we will pursue also in potentially registrational trials. We are well poised for that because our partner, Biotheus, has already brought a multi-indication program ongoing with a number of signal-seeking cohorts in various indications with various standard of care regimens so that we have a wealth of data already and can pick the indications and expand that as they mature. And another dimension of diversification is that we see BNT327 as a backbone for many of our pipeline assets, our wholly owned ones, but also those we have partnered because it has such permissive synergistic prone mode of action.

Ugur Sahin (Co-Founder and CEO)

Yeah. Regarding pembrolizumab, so we are seeing, of course, data from now, a number of indications coming in and continue to mature. We have seen data for which, for example, historical benchmark data are available, for example, in triple-negative breast cancer. The extent of clinical benefit that we are observing with BNT327 is really encouraging. For any indication in which pembrolizumab is approved as a backbone, our plan would be, of course, to compare ORR of BNT327 plus X against the counterpart standard of care. If it's pembrolizumab, we would compare against pembrolizumab.

Chris Shibutani (Managing Director and Senior Equity Research Analyst)

Thank you.

Operator (participant)

Thank you. We will now take the next question from the line of Terence Flynn from Morgan Stanley. Please go ahead.

Chris Ahn (Analyst)

Hi. Thanks for taking our questions. This is Chris Ahn for Terence. We have a two-part question on BNT122 in colorectal cancer.

Updated data by the end of 2025 or early 2026. But is there a potential for an interim analysis that would allow you to look at the data earlier? And then second, what will you and your partner, Roche, need to see in this trial in order to advance it into phase 3? Thank you.

Ugur Sahin (Co-Founder and CEO)

Yeah. We have hinted to a potential analysis in end of 2025. As you know, the study's endpoint is disease-free survival in this indication. And the general principle that we expect from individualized cancer vaccines is that metastatic tumor cells, which are present after surgery, could be removed by inducing a T-cell response. The indication that we have chosen is a ctDNA-positive indication.

That means based on the published data, we know that this patient population who are ctDNA-positive after surgery with a stage II, stage III colorectal cancer have a PFS in the range of 10-12 months. And after chemotherapy, the PFS is more around median PFS is around more 6-8 months. So that means at that time point, we would expect that at least part of the data would be matured. And then based on the results, yeah, it will depend how the results are and whether additional studies would be required at that time point or whether the data would be sufficient to continue and request potential regulatory steps.

Chris Ahn (Analyst)

Great. Thank you.

Operator (participant)

Thank you. We will now take the next question from the line of Simon Baker from Redburn Atlantic. Please go ahead.

Simon Baker (Partner and Head of Global Biopharma Research)

Thank you for taking my question. It's a question on iNeST capacity.

I wonder if you can give us an idea of the capacity that Mainz facility will give you in 2027. And also, you mentioned the ability to reduce the bottlenecks in vein-to-vein time. I wonder if you could give us an idea of where they stand and where this could currently go to. And just related to this, based on your comments on 122, is it right to assume that completion of that facility is rather 122 approval is not contingent on completion of that facility? Thanks so much.

Ugur Sahin (Co-Founder and CEO)

Yeah. So at the moment, we can't comment on the capacity of the facility that is being built because we are still in further process improvements, increasing the overall capacity. So reliable numbers will be available end of 2025 for the capacity.

But the facility has been built, has been built with the idea that it could act as a pilot facility if one of the personalized vaccine products is approved at that time point. So this is ongoing work. And parallel for building this facility, which is intended to act as a potential pilot facility, we are expanding currently our clinical trial capacity to ensure that we can start additional trials in 2025 and later on.

Ryan Richardson (Chief Strategy Officer)

And then I think there's Simon, you asked about bottlenecks in terms of vein-to-vein time?

Simon Baker (Partner and Head of Global Biopharma Research)

Yes, please.

Ugur Sahin (Co-Founder and CEO)

Bottlenecks. Yeah. So this is, of course, a completely new process, manufacturing a vaccine in real time. And you can imagine that every step must be validated. So this is we have established personalized manufacturing of mRNA vaccines for the first time in 2014. Since then, we have been through two additional innovation cycles.

We have recently implemented an additional change in the manufacturing, further reducing the turnaround time. But still, manufacturing release of such a vaccine comes with multiple release tests for the individual batches. So we are working on making the steps more robust, reducing the cost. And this will become more or less also the value driver of this approach, being able to reduce the cost substantially and thereby allowing that this is an affordable approach broadly available for a large population of patients.

Simon Baker (Partner and Head of Global Biopharma Research)

Thanks so much.

Operator (participant)

Thank you. We will now take the next question from the line of Eliana Merle from UBS. Please go ahead.

Eliana Merle (Analyst)

Hi, guys. Thanks so much for taking the question. Your slides mentioned starting the first novel combo trials in oncology this year. I guess just a strategic question in terms of your oncology combination strategy, given the breadth of your portfolio. I guess, what are the programs that you are most excited about or prioritizing for combinations? Thanks.

Özlem Türeci (Co-Founder and CMO)

Thank you for the question, Eliana. We are, in principle, very excited about the IO-ADC combination concept because we expect and also our preclinical data supports this, that this is highly synergistic. And as you pointed out, we have started our first trial, which is the first of a series you will see where we use BNT327 as the IO backbone, which in the first trial is combined with our TROP2 ADC from our partnership with Duality in multiple solid cancers. And this will be extended to additional ADCs from our pipeline to be combined with BNT327.

We are also very excited about a combination which is ongoing for quite some time, namely one of our priority assets, BNT211, which is our Claudin-6 CAR T-cell in combination with our vaccine, which is designed in this case in a way that it specifically acts on the adoptively transferred CAR T-cells. Our data, which shows that the vaccine, in fact, adds to the persistence and duration of adoptively transferred CAR T-cells is getting stronger and stronger with data maturing.

Eliana Merle (Analyst)

Great. Thank you.

Operator (participant)

Thank you. We will now take the next question from the line of John Newman from Canaccord Genuity. Please go ahead.

John Newman (Managing Director and Biotechnology Analyst)

Hi there. Thanks very much for taking my question. You're obviously in the midst of very active development for BNT327. I'm wondering specifically for the trials where you're combining with BNT325, your TROP2 ADC. Do you see the potential down the road for accelerated approval in some of those indications? Thank you.

Ugur Sahin (Co-Founder and CEO)

Thank you. This is too early to say.

John Newman (Managing Director and Biotechnology Analyst)

Okay. Thanks.

Operator (participant)

Thank you. We will now take the next question from the line of Manos Mastorakis from Deutsche Bank. Please go ahead.

Manos Mastorakis (Research Analyst)

Hello. Thank you for taking my question. Again, on BNT327, just wanting to understand how you're thinking about the clinical trial design. Are you hoping or aiming to study mainly PD-L1 positive populations, or are you keen to keep that open and see what the data looks like after the fact? Thank you.

Ugur Sahin (Co-Founder and CEO)

Yeah. This is a great question. Let me share our view. So the introduction of anti-PD-1 treatments led to the division of patient population in PD-L1 high, PD-L1 low, and PD-L1 negative populations.

The exciting observation that we made now in two indications is that the combination of chemotherapy plus BNT327 appears to be effective in a highly clinically meaningful manner also in the PD-L1 negative population. This really provides the great opportunity. We believe that BNT327 is not only something which could be better than existing PD-1 treatments, but we see the chance that we overcome the current classification of the patients into PD-L1 negative and PD-L1 positive patient populations. This is exciting. By this, of course, the patient populations would dramatically increase, and clinical trials could be done in a much easier way, and standard of care could become easier manageable based on treatment combinations that are independent of PD-L1 staining.

Manos Mastorakis (Research Analyst)

Thank you.

Operator (participant)

Thank you. This is all the time we have for questions today. I would like to hand back over to the speakers.

Ryan Richardson (Chief Strategy Officer)

Yes. Thank you very much for joining us today.

Operator (participant)

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