BioNTech - Earnings Call - Q3 2025

Transcript

Speaker 0

Welcome to BioNTech's third quarter 2025 earnings call. I will now hand the call over to Doug Maffei, Vice President, Strategy and Investor Relations. Please go ahead.

Speaker 2

Thank you, Operator. Good morning and good afternoon, everybody. Thank you for joining BioNTech's third quarter 2025 earnings call. As a reminder, the slides we'll use during the call and the corresponding press release can be found in the investor section of our website. On the next slide, you will see our forward-looking statement disclaimer. Additional information about these statements and other risks are described in our filings with the U.S. Securities and Exchange Commission, or SEC. Forward-looking statements on this call are subject to significant risks and uncertainties and speak only as of the date of this conference call. We undertake no obligation to update or revise any of these statements. On slide three, you can find the agenda for today's call. I'm 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, and Ramón Zapata, Chief Financial Officer. With this, I'll hand the call over to Ugur.

Speaker 1

Thank you, Doug, and warm welcome to you all as you join us today. As BioNTech has grown, our vision has remained constant, namely translating science into survival. We are building a global immunotherapy powerhouse, a fully integrated biopharmaceutical company with the science, scale, capabilities, and the aim to deliver multiple approved therapies and reach patients in need. Cancer remains a systems problem, heterogeneous across patients and variable within individual tumors. We believe the future lies in rationally defined combinations pairing potent and precise mechanisms of action that create biological synergies. To this aim, we have purpose-built a diversified clinical pipeline spanning mRNA immunotherapies, next-generation immunomodulators, ADCs, and other targeted agents that enable the development of potent, personalized precision medicines and novel novel combinations across solid tumors.

Our goal is to address the full continuum of cancer, from resected high-risk tumors in the adjuvant setting to advanced and metastatic disease to treatment-resistant and refractory cancer. Our strategy concentrates capital on two priority pan-tumor programs that are designed to anchor various combinations. One is pomitamic, formerly BNT327, a PD-L1 VEGF-A bispecific that unites checkpoint inhibition with vascular normalization in one molecule. We believe pomitamic is particularly suited as a next-generation IO backbone to combine with chemo, ADC, and other immunomodulators. The other is mRNA cancer immunotherapy that is designed to activate and educate the immune system with precision. Our mRNA cancer immunotherapies have advanced in randomized late-stage trials with focus on the adjuvant setting. Both approaches have disruptive potential and align with our vision. We believe these programs could establish new standards of care and improve survival outcomes.

Together, these programs provide breadth, optionality, and scalable registration paths across solid tumors. We are investing deliberately, scaling clinical development, building manufacturing that ranges from personalized to large-scale production, and preparing for commercialization in key markets to reach patients in need. Now, turning to how our achievements in the quarter relate to our vision and strategy. We see pomitamic as a potential standard of care across diverse tumor types, spanning settings already treated with checkpoint inhibitors and those where checkpoint inhibitors have not demonstrated benefit. With our partner BMS, we are executing a broad registration program. This quarter, we made significant progress in advancing pomitamic, taking concrete steps toward our registration plan. In Q3, we progressed enrollment in two global registration trials in lung cancer and remained on track to initiate a TNDC phase 3 this year.

This keeps us aligned with our target of first potential launches before the end of the decade. Across the portfolio, more than a dozen signal-seeking studies progressed, either with chemo backbones to expand into additional indications or as novel novel combinations with BioNTech proprietary assets. Importantly, we advanced clinical monoagent profiling of potential combination partners, helping to de-risk those schedule and safety assumptions for future registration designs. These steps, including phase three recruitment momentum, initiation of new combination cohorts, and deeper combination partner characterization, are all about informing your next wave of registration trials planned with BMS from now onwards. Turning to our mRNA cancer immunotherapy platform, in October, we presented phase two trial updates for BNT111, our fixed-cell candidate in anti-PD-1 resistant refractory melanoma, and for autogene cevumeran, our fully personalized mRNA cancer immunotherapy in first-line treatment of metastatic melanoma.

Our data reinforces our view that adjuvant settings where tumor burden is low and immune control is most effective represent where mRNA immunotherapy can deliver the most significant benefit to patients. I'll send you shared details on how. Reads out sharpening our development focus. This quarter, we hosted our second AI day. It underscored that we are not only pioneers in new pharmaceutical technologies but a fully integrated AI tech bio company with AI tools that enable discovery and development of innovative medicines. We showcased AI-based approaches designed to convert complex dimensions of data diversity into personalized therapy development. We demonstrated two distinct strengths of our AI capabilities, addressing interpatient heterogeneity and intratumor variability and driving precision and potency in our treatment approaches. With regard to our COVID-19 vaccine franchise, which is partnered with Pfizer, we successfully launched our variant-adapted vaccine for the current season following regulatory approval.

With this launch in major markets and with a strong balance sheet over EUR 16 billion in total cash equivalents and securities, we have the resources and the flexibility to fund the oncology transition while maintaining a disciplined P&L. Simply put, we are transforming scientific advances into late-stage progress in our priority oncology program. Across indications. In parallel, we are building the capabilities and the financial strength to translate positive data rapidly into market opportunities and, most importantly, into patient benefit. With that. I will hand over to Özlem to discuss our clinical execution and near-term data readouts.

Speaker 0

Thank you, Ugur. I'm glad to be speaking with everyone today. I'll start with a top-line status of the programs that are heading our pipeline before moving to specifics. Firstly, with our PD-L1 VEGF-A bispecific antibody pomitamic, we are executing a broad registration program in partnership with Bristol-Myers Squibb. Second, for our mRNA cancer immunotherapies, we have recently provided two phase 2 updates that support and inform our current development strategy. Third, for trastuzumab-pamirtekan, or TPEM, our HER2-targeted ADC, known previously as BNT323, that we developed with our partner Duality, we continue to progress towards first BLA submission now planned for 2026, subject to regulatory feedback. We are evaluating TPEM as a monotherapy into randomized phase 3 trials, one in metastatic endometrial cancer and one in breast cancer. For both studies, we expect data in 2026.

We have also initiated a signal-seeking trial evaluating the novel combination of TPEM with pomitamic. For pomitamic, let me recap the clinical development framework. Our refined three-wave plan that we are pursuing with our partner BMS. Wave one aims to establish pomitamic in three foundational first-line indications: small cell lung cancer, non-small cell lung cancer, and triple-negative breast cancer through global registrational phase 3 trials. Wave two and three aim to expand the opportunity of pomitamic by amplifying its differentiation. We do this in two dimensions. First, through signal-seeking studies in combination with standard of care across tumors that inform our indication strategy and prioritization. Second, through novel combinations, notably with our ADCs that enhance efficacy. We have delivered tangible progress on all these three waves in Q3.

Regarding wave one, in small cell lung cancer, the global phase 3 is recruiting and the phase 3 dose is locked based on the dose optimization data set with a safety profile consistent with known PD-L1 VEGF chemo experience. In non-small cell lung cancer, the phase 2 part of the seamless phase 2-3 trial achieved full enrollment and the phase 3 portion is recruiting. In TNBC, we remain on track to initiate the global phase 3 this year, targeting the PD-L1 low segment where unmet need is highest. This slide shows additional studies. These are supportive studies for dose finding, setting refinement, and regional programs that contribute to the body of evidence supporting our three foundational global phase 3s. Wave two serves as our expansion engine. We now have more than a dozen chemo-based signal-seeking studies across tumor types and lines of therapy.

In Q3, we opened new cohorts and continued to mature data sets that will feed into our pivotal planning. This helps to ensure that the next registrational wave is evidence-led and prioritized by benefit-risk profiles, patient population size, well-informed study design, and commercial opportunity, alongside other key factors in our decision matrix. Spearheading this next round of pivotal trials, we are initiating two trials in partnership with BMS with registrational intent for pomitamic in combination with chemotherapy in first-line microsatellite stable colorectal cancer and first-line gastric cancer. Wave three elevates the potential of pomitamic through novel combinations to maximize its clinical impact, reinforce class differentiation, and set up a multi-year pathway to sustain the value and the longevity of the drug into the new decade. Here, several combo cohorts of pomitamic with our ADCs or other novel compounds are already enrolling and have gained momentum in Q3.

Initial data over the next year will inform decision-making for our first pivotal combinational regimens. In parallel, we are continuing monoagent profiling of potential combination partners to set clear baselines for dose, safety, and sequence. Taken together, Q3 was a quarter of strong clinical execution that strengthened our registrational core, widened our expansion engine, and advanced the novel combinational rationale that we believe will further distinguish and elevate pomitamic over time. Let me now highlight two Q3 focal points. First, our first-line small cell lung cancer registrational program and why the recent updates are catalytic. Second, our advances in monoagent profiling for refining our combination strategy. Small cell lung cancer remains a challenging immunologically cold disease in which responses to immune checkpoint therapy tend to be short-lived, resulting in modest gains over chemotherapy alone and low long-term survival.

Over the last 18 months, we have built a cohesive evidence base across multiple phase two studies in first and second-line small cell lung cancer, initially in China and now globally, showing encouraging activity and a manageable safety profile. This quarter, at WCIC, we reported the first global data from our phase two dose optimization study in untreated extensive stage small cell lung cancer, evaluating two dose levels of pomitamic plus chemotherapy. All patients, irrespective of dose, had disease control. At 20 mcg per kg, we observed a confirmed objective response rate of 85% and a median progression-free survival of 6.3 months. 30 mcg per kg yielded a confirmed objective response rate of 66% and a median PFS of seven months. Median overall survival data were not yet mature.

Safety remained consistent and manageable with low discontinuation and no new signals beyond those typically seen with chemo and PD-L1 VEGF agents. Two points are worth emphasizing. First, dose clarity, which is a critical de-risking step for any registrational program. The global dose optimization readout allowed us to lock the phase three regimen at 20 mcg per kg every three weeks. Second, consistent performance across regions. Earlier China data sets in first-line extensive stage small cell lung cancer showed robust activity and manageable safety. The global Q3 data are consistent with those findings, which further strengthens our confidence in pomitamic's benefit across patient populations and practice patterns. Together, these results support our ongoing global phase three Rosetta-Lung-01 trial, which compares pomitamic plus chemotherapy against atezolizumab plus chemotherapy in untreated small cell lung cancer.

In parallel, in China, we continue with second-line randomized phase three trial of pomitamic plus chemo versus chemo alone. This quarter, we expanded our pomitamic small cell lung cancer program to include novel testing, and we launched signal-seeking studies of pomitamic plus our B7H3 ADC, BNT324, in both first and second-line small cell lung cancer. As phase 3 readouts and phase 1-2 ADC combination data sets mature, we will be increasingly well positioned to select and advance additional regimens designed to establish long-standing presence in small cell lung cancer. This brings me to our strategy for advancing combinations of pomitamic with other novel agents, one of our key differentiation approaches. The cornerstone is establishing monoagent evidence of activity, durability, and safety before we decide to pair with pomitamic. For our B7H3 ADC, BNT324, our monoagent database has expanded significantly over the last 12 months.

B7H3's broad expression profile aligns well with pomitamic's pan-tumor opportunity. In small cell lung cancer, BNT324, as monotherapy, achieved an objective response rate of 56% with deep tumor shrinkage across the waterfall, an unusually strong single-agent signal in this setting. In non-small cell lung cancer, activity was observed in both squamous and non-squamous disease, including an EGFR mutant subset with an objective response rate of 21%. In heavily pretreated metastatic castration-resistant prostate cancer, we observed meaningful tumor shrinkage with BNT324 and a durable radiographic progression-free survival with a manageable safety profile. Recently, at ESMO, we reported data for our TROP2 ADC, BNT325, in second-line plus TNBC, with an objective response rate around 35%, disease control rate of roughly 81%, and median progression-free survival of about 5.5 months.

Also, in Q3, for our HER2 ADC TPEM, we saw a substantial expansion of the monotherapy database by the Dynasty Breast O2 phase 3 trial, our partner Duality Biologics conducts in China, that met its primary endpoint of PFS improvement versus trastuzumab and Tamsin in pretreated patients with HER2-positive, unresectable, or metastatic breast cancer. TPEM is another promising combination partner with the potential to expand pomitamic's therapeutic reach into the HER2-expressing tumor spectrum. Taken together, these data provide a clear monotherapy baseline and help us set the bar for add-on benefit from pomitamic plus ADC combinations. Across these programs, the mechanistic rationale is consistent. VEGF-A blockade can normalize vasculature to improve ADC delivery, while PD-L1 inhibition can convert ADC-mediated cytotoxicity and antigen release into a broader, durable immune response, aiming for deeper debulking plus immune control. These represent complementary mechanisms that single agents cannot engage simultaneously.

Operationally, we made two key advances in Q3: continued monoagent profiling to refine dose and sequence and codification of our add-on benefit threshold, and expansion of pomitamic plus ADC cohorts across prioritized settings. Of note, our go-no-go decision-making process is driven by a holistic evaluation that goes beyond efficacy signals and safety profiles. We strategically assess market opportunity, unmet needs, competitive dynamics, and weigh other key factors to ensure every decision aligns with our mission to deliver transformative benefit for patients. Moving now to our second oncology cornerstone, mRNA cancer immunotherapy. INEST is individually manufactured per patient to target personal neoantigens. The biology and our clinical experience point to greatest relevance in earlier disease settings where lower tumor burden allows the immune system to consolidate control. Our ongoing randomized phase 2 trials are designed to test that premise in a rigorous way.

Off-the-shelf Sixfac that includes BNT111 for melanoma, BNT113 for HPV16 positive head and neck cancer, and BNT116 for non-small cell lung cancer targets shared antigens and is intended to pair with checkpoint inhibitors and increasingly our next-gen backbones. We continue to advance execution and evidence generation across multiple tumor settings while keeping optionality around where and how Sixfac is best positioned longer term. This quarter, at WCIC, we presented results for BNT116 plus Simiplimab as consolidation treatment in unresectable stage 3 non-small cell lung cancer. We also presented data at ESMO from two randomized phase 2 trials in melanoma, one with BNT111 Sixfac and the other for autogene cevumeran INEST. I will briefly walk you through the melanoma readouts and their implications, starting with BNT111 Sixfac in the high medical need population of patients who had relapsed or not responded to PD-1 treatment.

The phase 2 study evaluated BNT111 plus Simiplimab against a historical control objective response rate of 10% reported for anti-PD-1 treatment in this setting. The study included two calibrator monotherapy cohorts to characterize the safety of each agent and its activity on objective response rate. The objective of this design was signal characterization, not cross-arm efficacy claims. In the monotherapy cohorts, on-progression addition of the second agent was permitted. More than half of the patients in each arm opted for this addition after a median duration of either monotherapy treatment of around four months. The study met its pre-specified primary endpoint by rejecting the null hypothesis of an ORR of 10% with statistical significance. The ORR of the combination was 18%, including deep and durable responses. Notably, two-thirds of the responses were complete responses, supporting the depth of activity. Follow-up showed a positive impact on long-term survival.

37% of patients were still alive after 24 months. 21% were free of tumor progression. Safety was manageable, driven largely by expected mostly grade 1, 2 cytokine-related events consistent with the mRNA platform. BNT111 monotherapy also demonstrated objective responses and a consistent safety profile. Taken together, these results support that BNT111 is active in this difficult post-IO setting and provide us useful footing to guide setting selection and optimal combinations going forward. Turning to INEST, the data presented at ESMO come from our randomized phase 2 trial evaluating autogene cevumeran in combination with pembrolizumab versus pembrolizumab alone in first-line metastatic advanced melanoma. As previously disclosed, the trial did not meet the primary endpoint of a statistically significant improvement in progression-free survival. That said, we observed a numerical trend favoring the combination in overall survival.

In the combination arm, 12-month overall survival was 88%, and 24-month overall survival was 74% compared to 71% and 63% in the pembrolizumab arm, respectively. Of note, crossover was allowed, and patients randomized to pembrolizumab received the combination at progression. For the overall survival analysis, those patients remain in their originally assigned arm, which can dilute the observed treatment effect over time. We observed robust neoantigen-specific T-cell responses in the majority of evaluable patients with multi-epitope breadth and persistence of T-cell clones well beyond induction, indicating that the mRNA therapy is mediating the intended biological activity that we want to achieve. The translational readouts give us three actionable insights. First, T-cell response breadth correlates with activity.

Within the combination arm, patients who mounted a broader neoantigen-specific T-cell response experienced longer progression-free survival, supporting our ongoing efforts to maximize antigen breadth and to target early and low tumor burden disease with still proficient immune cell priming capacity. Second, immune cell PD-L1 matters. We saw a trend of improved overall survival for the combination in tumors where immune cell PD-L1 was high, while tumor cell PD-L1 did not discriminate overall survival in this data set, supporting that low tumor cell PD-L1 should not exclude tumor types from vaccine PD-1 strategies. Third, signal in IO in sensitive biology. There was a trend of improved overall survival with the combination in tumor mutational burden low patients, precisely the population that typically gains less from IO.

This is consistent with the concept that the vaccine can supply immunogenic targets when endogenous mutation load is limited and further encourages development in settings such as pancreatic cancer and MSS colorectal cancer with low tumor mutational burden and unresponsiveness to IO. Altogether, these mechanistic insights support our ongoing randomized phase 2 trials, both the specific indications we have chosen, which is colorectal, pancreatic, and bladder cancer, as well as our focus on the adjuvant setting, where tumor burden and heterogeneity is lowest and T-cell proficiency is still high. Now, looking ahead, what comes next? We will continue to generate and present new clinical data across our oncology pipeline, data that directly steer late-stage decisions. For pomitamic, we will share early data from our TNBC program in December, including from our dose optimization cohorts, which are central to defining the phase 3 regimen.

From our ADC platform, we expect additional monotherapy updates from BNT324 in cervical cancer and platinum-resistant ovarian cancer, from BNT325 in TNBC, and from BNT326 in HER2 null and low hormone receptor-positive breast cancer. These studies explore indications, define dose, and sequence guardrails, and set the add-on benefit bar for pomitamic's novel-novel combinations. For the randomized phase 2 trial evaluating autogene cevumeran monotherapy treatment versus watchful waiting in adjuvant circulating tumor DNA positive stage 2 high-risk or stage 3 colorectal cancer, we expect an interim update in early 2026. The efficacy evaluation of the primary endpoint of disease-free survival is projected for the end of 2026, when the data set will have reached the intended maturity.

Later this year, we plan to present data together with our partner Ongsifor from the non-registrational first part of the ongoing global phase 3 trial evaluating our anti-CTLA-4 antibody gotyslobat versus chemotherapy as a second-line treatment for squamous non-small cell lung cancer. Overall, these upcoming data points advance the same theme: evidence-led prioritization by establishing dose finding and mono ADC baselines to further refine pomitamic registrational paths and leverage randomized setting-specific readouts to position our mRNA immune therapies where they are most likely to succeed. With that, I will now turn the presentation over to our CFO, Ramón Zapata, for the financial update. Thank you, Özlem. A warm welcome to everyone who has joined today's call. I will begin by reviewing our financial results for the three months ended September 30, 2025. Note that all figures are in EUR unless otherwise specified.

The total revenues reported for the period were EUR 1,519 million, an increase from the same quarter in 2024, which was EUR 1,245 million. This increase was mainly driven by the recognition of $700 million as part of the BMS collaboration in the third quarter of 2025. For context, in total, we expect to receive $3.5 billion in upfront and non-contingent cash payments from BMS between 2025 and 2028. We expect to recognize this as revenue in increments annually over the development phase of pomitamic. For the third quarter 2025, we reflected $700 million in our revenues. Moving to cost of sales, these amounted to approximately EUR 148 million for the third quarter of 2025, compared to approximately EUR 179 million for the same period last year, driven by lower inventory write-downs.

Research and development expenses were approximately EUR 565 million for the third quarter of 2025, compared to approximately EUR 550 million for the same period last year. R&D expenses were mainly driven by the initiation of late-stage trials for our immunomodulators and ADC programs, and partially offset by cost savings resulting from active portfolio management towards our priority programs. SG&A expenses amounted to approximately EUR 148 million in the third quarter of 2025, compared to EUR 150 million for the same period last year. The decrease was mainly driven by lower external costs, partially compensated by our ongoing commercial build-out. Our other operating result amounted to approximately negative EUR 705 million in the third quarter of 2025, compared to approximately negative EUR 355 million for the same period last year. Our other operating result for the third quarter of 2025 was primarily influenced by the settlement of a contractual dispute.

For the third quarter of 2025, we reported a net loss of EUR 29 million, compared to a net income of EUR 198 million for the comparative prior year period. This was mainly driven by the effect of settlement disputes. Our basic and diluted loss per share for the third quarter of 2025 was EUR 0.12, compared to basic earnings per share of EUR 0.82 and diluted earnings per share of EUR 0.81 for the comparative prior year period. At the end of the third quarter of 2025, our cash, cash equivalents, and security investments totaled EUR 16.7 billion, including the $1.5 billion upfront payment received from BMS. Our strong financial position empowers continued investment in our late-stage priority programs and preparations for commercialization of our diversified oncology portfolio. Turning to the next slide, we are updating the company's financial guidance for the 2025 financial year.

Our previously issued revenue guidance range for 2025 was EUR 1.7 billion-EUR 2.2 billion. Today, we are increasing it to EUR 2.6 billion-EUR 2.8 billion. This is mainly driven by the recognition of $700 million from our BMS collaboration. Other guidance considerations, such as those related to our COVID-19 vaccine business, including inventory write-downs from COVID-19 vaccine sales in Pfizer's territories, as well as expected revenues from the pandemic preparedness contract with the German government and revenues from our service businesses, remain unchanged. Turning to expenses, we are lowering our prior 2025 financial year R&D expense guidance by EUR 600 million to a new range of EUR 2 billion-EUR 2.2 billion. This updated guidance reflects our active portfolio management that has enabled significant R&D efficiencies. As part of that, we follow a rigorous go-no-go decision-making across all development stages as part of these prioritization efforts.

This allows us to focus on the programs in our portfolio, which we believe represent the largest opportunities. Consistent with our commitment to discipline and sustainable growth, we are also improving our full-year guidance for SG&A and capital expenditure for operating activities. We are reducing our full-year SG&A expense guidance by EUR 100 million to a range of EUR 550 million-EUR 650 million as a result of ongoing cost optimization initiatives. We are also reducing our full-year guidance for capital expenditures for operating activities to a range of EUR 200 million-EUR 250 million to better reflect our targeted investment in manufacturing. Aligned with our disclosures earlier in the year, we expect to report a loss for the 2025 financial year as we continue to invest in our transition to become a fully integrated commercial oncology company.

As Ugur outlined, we continue to focus on executing our strategy around two pan-tumor product opportunities: pomitamic and our mRNA cancer immunotherapies. We currently have multiple ongoing phase two and three trials across these programs, reflecting our strategy to bring novel combinations to patients. We expect to generate additional meaningful data for these programs in the months ahead. As we advance, we will continue to maintain rigorous financial discipline and remain focused on achieving long-term sustainable growth. Before concluding, I would like to invite you to watch our annual Innovation Series R&D Day event on November 11. During the R&D Day, we plan to provide a deeper dive into our oncology strategy, including plans for pomitamic and our mRNA immunotherapy candidates. Thank you for your ongoing support and interest as we continue to create value for cancer patients, society, and shareholders.

With that, we would like to open the floor for questions. Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. We kindly ask you to limit yourselves to one question per person and ask you to speak loudly and clearly into your microphone. We will now take our first question. From the line of Tazeen Ahmad from Bank of America Securities, please go ahead. Hi, guys. Good morning. Thank you for taking my question. I wanted to get a sense about how you're thinking about the market opportunity for MSS-CRC and first-line gastric cancer. Can you just talk about how your product can be particularly differentiated from what's currently used? Thanks. Hi, Tazeen. Thank you for the question. We lost your audio there a little bit.

Could you just—sorry, could you just repeat that question? Just want to make sure we get it correct. Yeah, sorry about that. I wanted to ask a question about the market opportunity for MSS-CRC and for first-line gastric. I wanted to get a sense of how you think about the opportunity. Relative to the competition. Thanks. Thank you, Tazeen. We got it that time. That was a question about how we think about the CRC first-line opportunity in gastric. And how it compares to the competitive field. Oslem, would you like to take that question? Yes, I can take that question. Both indications, MSS-CRC and gastric first-line, are still high medical need indications. We think that the combination of VEGF-A and PD-L1 blocking from a biology point of view has a rationale for development and has the potential of improving the clinical benefit for these patient populations. Thank you.

We will now take the next question. From the line of Terence Flynn from Morgan Stanley. Please go ahead. Hi. Thanks for taking the question. I had one question and one just clarification. For BNT323, I was just wondering if you could share any more color on the delay in the BLA filing in terms of the gating factor here. On the new R&D guidance, just want to clarify that that reflects the assumption of some of the 327 expenses by Bristol-Myers and that that was the driver of the change here, if there's other prioritizations that fed into this. Thank you so much. Yep. Okay. Thank you, Terence. Two clarifications in there. If we do the R&D guidance first, I'll direct that one to Ramón. Oslem, I'll direct the 323 BLA progress question to you after that. Thank you for the question, Terence.

I would say that the lower guidance on R&D is not about reducing spending on 327. We are updating this guidance to reflect the lower R&D expenses for the year. The reduction is mainly driven by the phasing of certain programs and a deliberate focus on our key strategic priorities, meaning 327, as you rightly mentioned. This demonstrates disciplined portfolio management, but I would say it's too early to say whether this represents a structural shift. Depending on the pace of our late-stage programs, including the expanded efforts on pomitamic, R&D spending could remain at similar levels or increase again next year. I think what really matters is that we continue to allocate resources with focus and flexibility to maximize long-term value and support our key strategic priorities and programs. Özlem, would you like to take— Please, Tahsin. Take the second question, Terence.

The reason why we— Originally, we guided towards end of 2025 for 323 BLA submission. This moves now into 2026 because we have continued discussions and conversations with the FDA to further understand additional data needs and are generating this information. The plan is still to submit in 2026. And in 2026, we will also get for this program data from our ongoing breast cancer study. Thank you. We will now take the next question from the line of Daina Graybosch from Leerink Partners. Please go ahead. Hi, guys. Thank you for the question. I have a question on the overall strategy with pomitamic of establish and elevate as two steps.

And why you're taking that approach versus, in some indications, doing them simultaneously, let's say in multi-arm phase 3 studies with ADC combos and pomitamic on top of traditional standard of care chemo to leapfrog, particularly where you have some early data with the ADC and indication, and the competition is fierce. Thank you. Thank you. Thank you, Daina, for that question. That's a question about our strategy for pomitamic and the various stages, the various steps to our strategy with establish and elevate. I'll direct that question to Özlem. Sure. Thank you, Daina, for this question. You are actually right. We have this three-wave strategy: establish, expand, elevate. Even though we call it three-wave, these are activities which are going on in parallel. We have a certain focus on the chemo combinations, so combinations with standard of care, because these studies can be simply started much faster.

We have a focus on speed to be really first to market in certain indications. However, there is data generation in combination studies ongoing in these indications with our ADCs, for example, and will come very soon also following this establish wave. Thank you. We will now take the next question from the line of Assad Haider from Goldman Sachs. Please go ahead. Hi, thanks. This is Nate Jennings on for Assad and the Goldman team. Given that the BNT327 phase 3 trial in triple-negative breast cancer is initiating this year, could you provide any insight as to what we can expect to see in the phase 2 details coming up at SABCS? And is there any new information we can expect that provides additional confidence in the phase 3 success? Thanks. Thank you, Nate, for that question. It's a good one.

Just to recap that for pomitamic, the phase three triple-negative breast cancer, which is initiating. Özlem, the specific question is whether we can provide any additional details on the phase two results that we will be presenting at SABCS. We will present somewhat efficacy data, safety data, and also dose data. Thank you. We will now take the next question from the line of Akash Tewari from Jefferies. Please go ahead. Hey, this is Manoj for others. Just one question. We recently saw Harmony III trial in first-line NSCLC making some changes to look at primary PFS and OS statistical analysis separately for squamous and non-squamous populations. Considering these changes, do you still think Rosetta 02 trial in BNT327 plus chemo is sufficiently powered for PFS and OS endpoints in the phase three portion? Will there be any trial design changes based on this new information? Yeah.

Thank you for that question. It's a little hard to hear some of the details on that, but I heard you talking about Harmony III and whether that may have any read-through or effect on the way that we're conducting our trials for pomitamic. I'll direct that question to Özlem. Yes, we are constantly, with upcoming new data, re-evaluating our statistical analysis spend for ongoing trials, and we'll also look into this specific trial. Thank you. Thank you. We will now take the next question from the line of Yaron Werber from TD Cowen. Please go ahead. Great. Thank you so much. I had a quick follow-up for Özlem on 323. Just that need to generate more data to support filing. Can you be maybe a little bit more explicit?

Do you need to generate—it sounds like you're going to have more data, as you noted, in breast cancer next year. Is the thought to then file for breast cancer next year? What was the feedback for endometrial cancer? Do you still plan to file for that, or maybe just give us better clarity? Thank you. Yes, maybe I was misleading. The endometrial cancer discussions with FDA have nothing to do with ongoing breast cancer study. It's not about generating new data. It's about follow-up data and further analysis. That pushes the timelines a bit into 2026, but does not change our submission strategy and our plans for 323 overall. Okay. That's for breast cancer. What about endometrial cancer? What's the plan there? Thank you. No, no, no. Endometrial cancer is our first submission. This is what we said all along. Originally, it was planned for 2025.

This is pushed out to 2026 because, as I said, we are in discussions with—in pre-BLA discussions with the FDA and providing further data. The breast cancer study, phase three study, is ongoing. We'll read out later in 2026. Thank you. We will now take the next question. From the line of Mohit Bansal from Wells Fargo. Please go ahead. Great. Thank you very much for taking my question. So. Again, question on VEGF PD-1. One key comment we get from KOLs or experts is that. With these bispecifics, it does look like that they are better VEGF inhibitors, but it does not look like that the PD-1 component is better. So, I mean, how do you think about that?

And in the context of this bispecific showing an OS benefit in lung cancer trials, how important it is for PD-1 to be better at this point, given that we are seeing good PFS benefit, but OS is kind of on borderline? So we would love to get your thoughts on that. Thank you. Okay. Thank you, Mohit. So question generally around how much confidence we or others have in the bispecific class. And you mentioned that VEGF binding is maybe better, but PD-1, you are saying maybe not as good in bispecifics and specifically the OS benefit in lung. So. Direct that question to Özlem? I can start, and Özlem can take a second. First of all, I think. Is it okay I start? Yeah, sure. Please go ahead. Yeah. Let's start with our confidence. Our confidence is increasing into this class.

And the confidence is not based on better VEGF or better PD-1, but what the antibody really does. The bispecific molecule. And we are seeing now that this is getting more and more clinical data, that this is not only on PFS, but also have an impact in OS. Maybe, Özlem, if you would like to add mechanistic understanding. That could also be helpful. Yes. Mechanistically, in principle, our preclinical data, and that was also part of preclinical development and selection process for this antibody, shows that blocking of the PD-1, PD-1 pathway, as well as the VEGF-A blocking in the respective preclinical settings, is robust and is not inferior to what you would see with the individual antibodies.

Having said that, we also think that the fact that we have a PD-1, not a PD-1 arm here, adds an additional element to the mode of action, namely targeting of this molecule into the tumor microenvironment. And this, again, is a very good condition to amplify both on the PD-1, PD-1 side, but also on the VEGF receptor signaling side, all the effects on canonical and non-canonical effects of these two targets. So this is the preclinical piece and mode of action piece, but the clinical data has to tell the truth. From the data we have across tumor indications. This is not yet phase three data. We are very confident that the activity has PFS effect in certain indications and also duration of progression-free survival starts to look good. Thank you. Thank you. We will now take the next question. From the line of Herbert Desta from BMO.

Please go ahead. Hi. This is actually Mark Moffinon for Evan from BMO. Appreciate you taking our question. Thinking about the guidance range for this quarter, could you quantify how much of this reflects the relatively stronger quarter for COVID versus just general updates for the BMS collaboration and U.K. government agreements? I know you mentioned most of this was tied to the collaboration, but was curious if there were any minor changes on the COVID front. Would be helpful to think about the relative contributions here. Appreciate it. Thank you, Malcolm. Let us talk a little bit about the revenues. I will refer to your COMIRNATY question, but I also think it would be helpful for the audience to understand a little bit of the BMS revenue. So for COMIRNATY, we continue to see a stable position with a strong market share and stable pricing. U.S.

vaccination rates are roughly 20%, which is in line with what we had anticipated. We have always assumed lower volumes versus last year. Overall, the business is performing within expectations for the year. While the broader market remains uncertain, we continue to lean on our strengths, like strong brand recognition, reliable supply, and rapid adaptation. We do expect to close the year in line with our outlook. Now, if we talk about the BMS revenues, the updated revenue guidance mainly reflects the collaboration with BMS, as you rightly point out. On this agreement, we will receive a total of $3.5 billion in upfront and continued cash payment between 2025 and 2028. While the timing of cash inflows and revenue recognition differ, revenues will be recognized in broadly equal amounts over the next three years, with the remaining balance recognized together with the final payment in 2028.

This will provide a clear and predictable contribution over the next several years. Thank you. We will now take the next question from the line of Joshua Tassaro from Evercore ISI. Please go ahead. Hi. This is Josh on for Cory Kasimov. Thanks for taking our question. On your and your partner's decision to push pomitamic into gastric cancer, did you see compelling clinical data? Not sure if this was presented or not. Or is this push into this new indication based off your understanding of the mechanism of action? Thank you. Yeah. Thanks, Josh, for that question. It was a question about pomitamic and our announced decision to move into gastric cancer. What was that based on? Have we seen any data that we can speak to that supports that decision? Luca, would you like to take that question? Yes. We have emerging data for pomitamic in gastric cancer.

It's an indication for which checkpoint blockade is approved. It's an indication where we have seen responses in combination with chemotherapy. It's an indication where we see, based on the data that we got in other GI indications, a clear room for improving over standard of care. Also, the mechanistic rationale that anti-angiogenic and PD-1 targeting approaches. Are validated approaches in gastric. Thank you. We will now take the final question from the line of Jay Olson from Oppenheimer. Please go ahead. Oh, hey. Thanks so much for taking our question. We're curious about your collaboration with Bristol-Myers Squibb. And can you talk about the governance structure and which party makes the decisions for new trials and who leads the new clinical trials when you initiate them? Thank you. Yeah. Okay. Thank you, Jay. Thanks for that question. It's an interesting one about how our collaboration with BMS works mechanically.

I can't say that word. So, Özlem, I'll pass that over to you. Who makes decisions? Ugur. Who makes decisions on clinical development? Yeah. So. It's a classical approach with multiple collaborative arms. We have a JSC where we discuss all the indications. So far, all decisions that are made are based on interoperable partners, but both partners have the opportunity to do combination trials with their products, regardless of whether the other partner is interested to join directly or not. We have a lot of flexibility in this collaboration, aiming really to do all kinds of studies and to exploit the pipeline of the other partners as exhaustive as possible. Great. Thank you. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.