Great. Good afternoon. Welcome, everyone. My name's Jess Fye. I'm a biotech analyst at J.P. Morgan, and we're continuing our 44th annual healthcare conference today with BioNTech. First, you're going to hear a presentation from the company, and then we're going to go into some Q&A. So if you have a question in the room, just raise your hand, and someone will bring you a microphone. Or alternatively, you can submit it online, and I'll read it off the iPad up here. So with that out of the way, please to introduce BioNTech's CEO, Ugur Sahin.
Hello, everyone. It's a pleasure to be here. I would like to welcome everyone here and online. These are the typical disclaimers. And I would like to start with the status quo that we have here. While BioNTech has grown and evolved, our vision has remained the same, namely translating science into survival. From the current situation, from today's perspective, we have so far delivered, together with our partner Pfizer, five billion doses of vaccines worldwide. We have engaged with our mRNA technology in global health programs. We have six programs here running. Most importantly, we pivoted back to oncology, have currently 25 clinical trials ongoing and 16 clinical programs.
We have also integrated AI and advanced GMP manufacturing capabilities, providing us the opportunity to rapidly translate science into clinical trials. Our key achievements in 2025, it was a strong, eventful year. We maintained the COVID market leadership and launched our variant vaccine. We advanced our oncology programs with, in the meantime, 25 phase II and III clinical trials running with more than 10 novel combination therapies. We executed strategic deals. The most important, the partnership with BMS, which gave us the opportunity to strengthen the execution, but also de-risk our program. We acquired Biotheus, which helped us to get the full rights for our key molecule, Prometimic, and we acquired CureVac, thereby strengthening our position in the mRNA field. Moreover, we increased the 2025 revenue guidance and ended the year with a strong financial position with more than $17 billion in cash and cash equivalents and securities.
A little bit more into the details. In 2025, we have delivered, in the meantime, our fifth variant adapted vaccine. This is getting to become routine. We maintained our leadership and distributed our vaccine in more than 180 countries. What is really important and what I would like to emphasize here, the evidence for the clinical benefit for our vaccines is overwhelming. There are hundreds of studies about this. Recently, there is a study published which is really worth mentioning. It's a study performed in France. It's a real-world study in about 27 million adults, 22 million who received the vaccine, 5 million who did not receive the vaccine. We see that COVID vaccines are really saving lives, even in the population of 18-50 year-old individuals. The overall mortality was reduced.
The COVID-associated mortality was reduced more than 70%, which is really impressive and shows that we can translate our mRNA science into survival. With regard to clinical execution, we advanced our late-stage programs. We have now 25 late-stage programs running. More than 4,000 patients have been enrolled in our clinical trials, and the result of this is that we are expecting now 15 phase III readouts in the years of 2026 and 2027, so we continued also to run the company with financial discipline. We continue to use the revenues from our COVID vaccines to finance our oncology programs. We strengthen our P&L through the partnership and cost sharing with BMS. We have a very strong cash balance helping us in the oncology execution, and we maintain disciplined resource allocation with an active portfolio management focusing on late-stage programs that really provide a clear value increase.
So 2026, what are the key objectives in 2026? We have three priority goals. First, accelerate late-stage development of our first wave of oncology assets. Second, build momentum by engaging into multiple combination strategies. And third, shift our approach from a platform-centric to a tumor-centric clinical development approach. So I will show you in a few minutes what this all includes. This is just a view on our current pipeline. We have the ambition to become a multi-product oncology company. Today, we have more than 17 late-stage and pivotal trials across multiple high-prevalence solid tumors. This includes, of course, areas of unmet medical need where we believe we can make a meaningful difference for patients. In parallel to these developments, we are pursuing multiple combination trials, and we are building commercial capabilities in selected tumor types where we anticipate our first launches.
We are executing for our oncology portfolio a synergy-driven development strategy across three modalities. These are next-generation immunomodulators, targeted therapies with a key focus on ADCs, and mRNA cancer immunotherapies covering fixed combinations as well as personalized mRNA vaccines. The core of this strategy is the rationale that combination across these modalities can help to prevent or overcome resistance and create conditions for more durable responses, ideally translating into better outcomes for patients. The additional advantage of the strategy is that execution risk is mitigated through diversification across assets, indications, modalities, and partnerships, reducing the dependence on any single agent. This is the pipeline that we built. It's a differentiated oncology pipeline. We have, for our immune modulators, two late-stage assets, Prometimic, PD-L1 VEGF bispecific antibody partnered with BMS, and gotistobart, a CTLA-4 targeting Treg depleting molecule partnered with OncoC4.
Both molecules are designed as next-generation immuno-oncology backbones. We have a growing ADC portfolio, including programs directed against HER2, HER3, B7-H3, TROP2, and other targets, allowing us to execute an ADC-based pan-tumor strategy. Finally, our mRNA immunotope programs include individualized vaccines that are currently tested in three indications: CRC, pancreatic cancer, and bladder cancer, and FixVac approaches where we focus currently on lung cancer. Today, I'm going to walk you through three programs which are visible on the slide: Prometimic, Gotistobart, and BNT324, DB-1311. So starting with Prometimic, it's a PD-L1 VEGF bispecific antibody, which we believe has the potential to become the next-generation IO standard across multiple cancer indications. The molecule is an Fc-silenced bispecific antibody, which is engineered to deliver dual blockade of VEGF and PD-L1 as a single molecule.
Our preclinical work supports a differentiated mechanism, which includes complex formation by the bispecific molecule that increases the internalization of PD-L1, a mechanism that cannot be done by the combination of the two antibodies. Clinically, Prometimic has been studied broadly and has shown impressive efficacy signals across indications regardless of PD-L1 expression. Our development momentum is strong. With BMS, we anticipate eight pivotal studies will be ongoing by the year-end 2026, along with a broad portfolio of combination therapies. This is just one example of efficacy data which we have recently announced in a global phase II study where we have observed 85% objective response rate in first-line small cell lung cancer and 70% objective response rate in triple-negative breast cancer, with activities reported irrespective of the PD-L1 level. These response rates offer best-in-class potential for this difficult-to-treat patient population.
To fully realize Prometimic's potential, we are executing a staggered three-wave development strategy. Wave 1 establishes chemotherapy combinations in priority indications such as SCLC, NSCLC, and TNBC. Wave 2 is expanding into more than 10 additional indications, mostly in combination with chemo. Wave 3 will explore novel combinations to further deepen and broaden the activity across tumor types. Our goal is to meaningfully expand the number of patients who can benefit from effective cancer immunotherapy. We believe that Prometimic has the potential to both replace first-generation immuno-oncology drugs in multiple indications and, second, expand the reach of IO into new settings. In both settings, there is a substantial unmet medical need driven by different high-incidence cancers. Coming now to Gotistobart. While Prometimic is intended to improve on checkpoint blockade, Gotistobart is an antibody which goes beyond checkpoint blockade. It's an antibody partnered with OncoC4.
It has a differentiated mode of action by selective killing of regulatory T cells in the tumor microenvironment. And I would like to clearly state this is not just another CTLA-4 blockade. This is a mechanism of killing of regulatory T cells that allows to address multiple mechanisms because regulatory T cells not only use CTLA-4, but they act as an IL-2 trap. They have inhibition by cell-cell contact. So by eliminating regulatory T cells, we accomplish a much more potent mechanism. Together with our partner, OncoC4, we have generated data in more than 1,000 patients so far. The program is now in pivotal phase development in second-line squamous non-small cell lung cancer and has received recently from the FDA orphan drug designation. In parallel, we are evaluating Gotistobart in proof-of-concept combinations, including radioligand therapies, mRNA immunotherapies, and ADCs.
These are data from an unblinded stage 1 analysis of our phase III study in squamous non-small cell lung cancer, where Gotistobart was evaluated in a randomized fashion against docetaxel, which is the standard of care. It showed a 54% reduction of the risk of death versus chemotherapy, which represents a clinically meaningful benefit in a population with very limited treatment options. The first interim data for efficacy readout is expected in 2026, so these data are extremely relevant in the setting of a major unmet need. Patients with squamous non-small cell lung cancer who progress after prior checkpoint therapy have limited options, and multiple phase III programs in this population have failed in the recent years. Standard of care is typically chemotherapy with response rates generally below 20% and overall survival of around 10 months.
So if the phase III results from part 1 are confirmed, we believe Gotistobart could offer a transformation chemotherapy-free treatment option for this patient population. The third molecule that I would like to introduce here is our B7-H3 ADC partnered with Duality that has shown pan-tumor activity and favorable safety profile. B7-H3 is a target expressed across multiple solid tumors. It is one of the most interesting ADC targets. This includes tumors like prostate cancer, lung cancer, small cell lung cancer, GI cancer, gynecologic tumors, making the tumor interesting as a pan-tumor target. In partnership with Duality, we are evaluating currently BNT324 in more than 10 cancer indications. While several B7-H3 ADCs are in development, we believe that BNT324 is differentiated based on its emerging safety and efficacy profile.
Across the studies today, we have observed encouraging clinical activity in multiple tumor types with low single-digit rates of grade 3 for treatment-related adverse events and low rates of ILD pneumonitis. What is important is that patients with sustained clinical benefit have been treated now for up to a year and longer, supporting the potential of this molecule as a longer-term targeted therapy across multiple cancer indications. In terms of efficacy, we have seen encouraging clinical activity across multiple tumor types, and combination studies with Prometimic are ongoing. One area of particular interest is metastatic castration-resistant prostate cancer, where we have observed strong activity in heavily pretreated patients. With our goal moving into earlier lines of treatment, we have designed a phase III clinical trial in first-line MCRPC. The IND for this phase III trial has been cleared, and we expect the recruitment to start in the coming months.
Here again, this is an important indication within the prostate cancer spectrum. Metastatic castration-resistant prostate cancer remains one of the highest unmet medical needs. The treatment paradigm is currently shifting towards more intensive therapies earlier. For example, docetaxel is increasingly used in the first-line setting for appropriate patients. At the same time, many patients are not eligible for chemotherapy or prefer to avoid it. We believe BNT324 is well-positioned to address the need for an easily accessible, well-tolerated treatment option with the potential for more durable responses. We view this single-agent development as an important first step to establish clinical value and build market presence. Over time, we expect combination regimens to unlock the additional benefit to therapeutic synergy and support broader adoption.
As our oncology strategy is built on synergy-driven combination approach, we are systematically testing each modality in combination with each other's, which means we combine ADCs with IO, mRNA with IO, or mRNA with ADCs. This is here a table showing our matrix approach across priority tumor indications, including lung, breast, genitourinary, gastrointestinal, and gynecologic cancers, where we paired our ADC candidates with Prometimic. Our goal is to identify the ADC combinations and dose levels that deliver the best balance of efficacy and tolerability in combination with Prometimic. We establish a strong preclinical validation of this combination approach and anticipate multiple phase I/II readouts in 2025, and this data will help us guiding the decision and inform phase III trial decisions. In addition to ADCs, we believe that mRNA cancer vaccines are ideal combination partners for Prometimic and our ADCs, driving robust tumor-specific immunity that enhances checkpoint inhibition.
Our individualized therapy, autogene cevumeran, induced both neoantigen-specific T cell responses across multiple tumor types. And furthermore, we have shown that combination of our BNT116 lung cancer vaccine with anti-PD1 demonstrated encouraging survival in patients with first-line and second-line non-small cell lung cancer indications, which usually have OS, second-line non-small cell lung cancer with OS in the range of 12 months. So these combination strategies will become the foundation of our tumor-focused approach. We have built tumor area strategies which are centered around high-incidence cancers like lung cancer, breast cancer, and other tumors. And we are developing now a strategy where we address several lines of treatment with different combinations. Let me illustrate that with an example in lung cancer. Lung cancer is a heterogeneous disease and remains the leading cause of cancer-related mortality.
Many patients are diagnosed with late-stage disease, and long-term outcomes remain poor despite advances from checkpoint inhibitors and targeted therapies. We are building here a durable position in this indication. Across lung cancer indications, we use Prometimic, Gotistobart, our ADC portfolio, and BNT116, either as monotherapies in combination with chemotherapy or as combination partners in different settings. Our first registration studies for Prometimic are in combination with chemotherapy. In parallel, we are advancing this molecule with ADC combinations in second- and third-line to increase the optionality for patients, so let me turn to what we expect to deliver in 2026. 2026 is packed with value-creating catalysts in late-stage readouts. We have five late-stage readouts, including our HER2 ADC TPAM, our anti-CTLA-4 Gotistobart, our HPV vaccine for head and neck cancer, BNT113, Prometimic from data from a Chinese study in TNBC, and our personalized vaccine for treatment of high-risk colorectal cancer.
This late-stage trial readouts will be complemented with early-stage combination therapies, including Prometimic plus different types of ADC trial readouts. In total, we anticipate 15+ data readouts here. This should result in a steady news flow throughout the year, which will support us in rapid decision-making and meaningful value creation. Our ambition is to build a fully integrated multi-product oncology company, and 2026 is just the beginning of our roadmap. As of today, we expect 17 late-stage and pivotal trial readouts across different tumor types. We are entering a phase of sustained clinical data output from 2026 to 2029, and we will provide regular updates on execution and progress. This pipeline supports multiple approval opportunities, and we are building launch readiness now, developing indication-specific expertise and advancing market access capabilities in the tumor types where we anticipate first launches. Summing up, 2025 provided the foundation for our strategy.
We advanced our pipeline and R&D. We progressed key programs into pivotal stage, established partnerships with BMS, increased our balance sheet, and to fund our pipeline. 2026 and 2029 will be in the focus of driving our execution at scale and speed here with advancing combination therapies, accelerating pivotal trials, and building indication-specific oncology portfolios. For 2030, we expect that BioNTech will be a diversified multi-product technology company here, and we will use this data-based approach to ensure that we can fully leverage our pipeline and generate the data required for registration. Thank you for your attention.
Great. And as a reminder, if you have a question in the room, just raise your hand, someone will bring you a camera. You can come sit. Okay. Great. So I guess maybe starting with Prometimic, in what settings thus far do you see Prometimic's data as most differentiated?
Is that working?
Yeah, it's working.
Okay. I think we have generated data now in multiple cancer indications. And what we see is what impresses us most is really the activity of the compound in cancer indications and patient populations, which have a rather low PD-L1 expression. So what is really impressive is, for example, the clinical readout in the TNBC patient population below 10%, where we have seen from China readouts that we have a PFS of 13 months. OS is going more into the direction of 20+ months. And we have been recently able to reproduce the data in a global trial. And we see this pattern now occurring in different indications.
Overall, what also impresses me is that in more than 10 clinical indications where we combined Prometimic with chemotherapy, we have almost clinical benefit rates in the range of 80%-100%, which really shows that this molecule provides an opportunity even for aggressive tumors to provide stable disease and strong objective responses.
Maybe, Jessica, if you allow me, we would move one step forward. I'm Ramos Zapata. I'm the CFO of BioNTech since mid last year. The other thing that I believe is very exciting is, of course, not just about the asset, but the approach that we are taking in the combination strategy that we have. I think, of course, there are other companies that now they have PD-L1s or PD-1s, but nobody has the breadth and depth of the ADC and the assets where we can combine novel approaches with Prometimic, as well as the strength that the collaboration with BMS gives us in terms to go in the more efficient way after the development approaches in this late-stage program, clinical studies, as well as the conviction to go commercially very deep and wide with the asset.
What about relative to ivonescimab? How much of a read-through do you see from the data for that product to Prometimic's potential? Where do you see the products differentiating so far?
The general rules seem to be class-specific, so the rules are improved disease control rate, improved objective responses, improved PFS in multiple indications, and I would say a clear trend for improved overall survival, and this is something that we are also seeing. Of course, we are not doing any head-to-head studies. Therefore, it's difficult given the heterogeneity of the patient population to draw conclusions, but the mechanism of action of our compound provides a mechanistic advantage because our compound is not only an immune modulator, but also a targeted therapy. It is directed against PD-L1. PD-L1 is highly expressed in tumors. It's highly expressed on tumor-associated macrophages, so we are targeting with this molecule the tumor microenvironment directly and have the opportunity to bring in VEGF inhibition and all the related immune suppression blockade into the tumor microenvironment.
We believe that this actually could translate to a prolonged control, but this is just a hypothesis, and we have to see.
So kind of sticking with that, what metric would we look to kind of see that differentiation play out?
I think we will not see in the next five years head-to-head studies of one bi-specific against the other bi-specific. So this would be the most fundamental metric doing it. But at the end of the day, I believe there are three ways of differentiation. It's the engineering of the molecule with the mode of action. Then the breadth of development in different indications. We will have, at the end of this year, we will have eight pivotal studies in multiple indications. And it, of course, counts in how many indications you are positioning the molecule. And the third, and this might be the most important, is the combination approach. So we are using an unprecedented combination therapy assessment approach with multiple ADCs, with our mRNA vaccines, and with other molecules.
And the partnership with BMS allows us really to fully exploit our portfolio of compounds and the BMS portfolio of compounds. And we are completely open also to consider other compounds. So I believe at the end of the day, while entering with chemotherapy combinations into and providing clinical benefit early on with chemotherapy combinations, the overall trend will be combination with this type of molecules. And this is something that will go on at least the next five to eight years because we really believe that we have, for the first time in oncology, the opportunity to get durable control in patients in first line, but also open up clinical benefit for patients who are not responding to checkpoint blockade. So this is a huge opportunity. And there is, in my view, enough room for several players in the field.
Just maybe turning to the ADCs. So with multiple ADCs in development, can you talk about how you're prioritizing which to move forward as monotherapy and which to study in combination with Prometimic?
Yes, sure. So we have generated ADC data in more than 1,200 patients so far. We are systematically analyzing multiple cancer indications, different doses. We very well understand the safety efficacy profile of these molecules in different indications. Our strategy is if we really see that a compound has a differentiated mono single-agent activity in an indication with high unmet medical need, we are ready to go with the compound alone. So this is an example with prostate cancer, where we have seen that even in late-stage patients, we see significant objective responses, excellent PFS trend. So this was the decision to go into these indications. We have other indications where we see similar signals in advanced cancers, where we might come up with additional mono activities. For combining with Prometimic, we are actually doing really the side-by-side studies.
We are evaluating, for example, our HER3 with Prometimic, and we are evaluating B7-H3 with Prometimic. One of the learnings of this bispecific antibody is that actually preclinical work is not always able to predict what is going to happen in the clinic. Having an experimental approach and comparing the data head-to-head in different indications is the best way so that we not just jump on TROP2 ADCs, which are at the moment used for combination therapies, but also consider other options.
So you laid out a bunch of upcoming milestones. But with respect to your ADC pipeline, just over the next 12-24 months, what are the highlights that you would orient investors to really look forward to in terms of data readouts?
The combination data. So we will have combination data with Prometimic mid to end of this year. And we will present this data on conferences. And this will be, of course, exciting because with Prometimic, we have a next-generation immune modulator. We believe that some of our ADCs are also very much differentiated. So combining those and excelling to the next level of disease control is the most exciting thing.
I would add what is the word as well in the next 12 months.
It was an ADC question.
Okay.
Yes, but you are right. I'm also excited about Gotistobart.
Gotistobart combination, that's what I was thinking.
So maybe to pull you in, Ramón. So the company's got a large cash balance. What are your plans for it?
Yeah. So I think at least until we have more line of sight on where the actual revenues of TPAM, Gotistobart, Prometimic, and all of these combinations are coming, which they should be, of course, TPAM and Gotistobart a little bit earlier, but then with Prometimic more towards the end of this decade, beginning of the next, I think the first and utmost priority would be to keep developing the internal pipeline that we have, grow organically. And then I would say the second priority is if there are any inorganic acquisitions or collaborations that we can do, that would be then the second place where we will be deploying these resources. And then as we get more certainty on how and when we are going to be launching and the size of opportunity, maybe we can start discussing other types of utilization of this cash.
I think we're just out of time, so we'll stop there. But thank you.
Thank you.
Thank.