BioNTech Q3 2024 Earnings Call Transcript

Quartr
Provided by Quartr
November 4, 2024

There are 19 speakers on the call.

Operator

Welcome to BioNTech's Third Quarter 20 24 Earnings Call. I would like to hand the call over to Michael Horowitz, Director, Investor Relations. Please go ahead.

Speaker 1

Thank you. Good morning and good afternoon. Thank you for joining BioNTech's Q3 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.

Speaker 1

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 this conference call. We undertake no obligation to update or revise any of these statements.

Speaker 1

On Slide 3, you can find the agenda for today's call. Today, I am joined by the following members of BioNTech's management team: Ugur Zahin, Chief Executive Officer and Co Founder Ozlem Tureci, 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 Uwe.

Speaker 2

Thank you, Michael. Welcome to all those joining us today. I will be keeping my introduction as I will be today. We made significant achievements during the Q3, including advancements across our oncology pipeline and a strong start to the season for our COVID-nineteen vaccine franchise. Our progress in this quarter is on what has already been an impactful year.

Speaker 2

I would like to highlight achievements in 3 areas. 1st, with regard to our COVID-nineteen vaccine leadership, we have successfully launched updated vaccines targeting the latest variant, distribution now underway in multiple regions globally. In oncology, we have presented our progress in 2 strategic priority areas, namely our bispecific immunomodulator BNT327 partnered with BioPhales and our mRNA cancer vaccine portfolio. As part of our pipeline progress, we shared numerous clinical updates across our oncology pipeline at the ESMO Congress. We and our partner, Biophayus, have kicked off the broad global development of BNT-three twenty seven, our bispecific antibody targeting PD L1 and VGFA.

Speaker 2

The data sets presented at ESMO and at conferences earlier this year support the pan cancer potential of this priority asset and support our clinical development plans that we will touch on today and discuss in greater detail at our innovation series next week. We took significant steps forward in the execution of our clinical development plan this quarter and dosed the first patients in 2 optimization studies in small cell lung cancer and triple negative breast cancer to inform the pivotal studies planned in both indications. With regard to our mRNA vaccine portfolio, we announced earlier in the quarter that our off the shelf 6 vac mRNA cancer vaccine candidate BNT-one hundred and eleven met the primary endpoint in the ongoing randomized 2 trial evaluating BNT-one hundred and eleven in combination with Regeneron's anti PD-one agent cemiplimab in patients with Stage 3 and Stage 4 cutaneous melanoma. This preliminary result underscores our belief in the transformative potential of our proprietary mRNA vaccine technology, which is a key pillar of our oncology strategy. Moreover, we have taken another step to broaden our personalized mRNA cancer vaccine development program.

Speaker 2

We and our partner Genentes have initiated a new randomized controlled Phase II clinical trial, evaluating our personalized cancer vaccine candidate in patients with bladder cancer in the adjuvant setting in combination with immune checkpoint inhibition. Our personalized vaccine program now includes 4 ongoing Phase II clinical trials. In addition, during Q3, we had our inaugural AI Day, where we highlighted our in house AI company, InstaDeep, and provided an overview of BioNTech's collective AI capabilities. This was an exciting event where we showcased our commitment to building state of the art AI. Before turning over to Estan for more detailed coverage of these achievements, let me remind you our overarching strategy for oncology.

Speaker 2

BioNTech was established with the ambition to revolutionize cancer treatment through the development of mRNA based immunotherapies, particularly to personalized cancer vaccines. This approach remains at the forefront of our efforts to PIONEER next wave of cancer treatment, aiming to tailor therapies to the individual genetic makeup of each patient's tumor. Building on this foundation, we have systematically assessed next generation immune modulator with a focus on bispecific molecules that can engage more than one target. BNT327, our bispecific antibody targeting PDL-one and VGFA, has emerged as a key molecule in our pipeline. We believe that BNT-three twenty seven has the potential to serve as a foundational component in the treatment regimens from multiple cancer types, enhancing the effectiveness of our therapeutic mRNA cancer vaccines and other therapies through its dual targeting mechanism.

Speaker 2

Complementing these mechanisms of action, we have recently expanded our portfolio to include targets immunotherapies, such as antibody drug conjugates and CAR T cell therapies. These modalities offer precise mechanisms for attacking cancers, providing new avenues for combination therapies, particularly for fighting large metastatic tumors. Our integrated long term approach will combine these synergistic therapeutic platforms to optimize cancer treatment. Our strategy aims not only to address the existing challenges in cancer care, but also to significantly improve long term survival rates, even in patients with advanced disease states. By continually evaluating the effectiveness of individual compounds and innovative combinations, we can better identify the most promising treatment strategies for specific patient populations.

Speaker 2

Today, Erfan will discuss in more detail our progress on BNT-three twenty seven and our expanding efforts on our therapeutic mRNA cancer vaccine front, 2 proprietary key pillars of our strategy. Before handing over, I would like to thank you all for your ongoing support as we enter this truly exciting period for BioNTech and progress towards our founding vision. Thank you.

Speaker 3

Thank you, Uker. Glad to be speaking with everyone today. I will begin with our COVID-nineteen franchise. Ahead of this vaccination season, regulatory and public health authorities advise vaccine manufacturers to revise the antigen composition for the authorized COVID-nineteen vaccines in line with the latest epidemiologic data. The continuous evolution of SARS CoV-two and the emergence of variants have led to regionally different recommendations for this year's vaccine strain selection.

Speaker 3

We have been able to rapidly meet these different requirements due to the flexibility of our mRNA technology, which enables us to adapt our construct on relatively short notice. In Europe, less than 3 weeks after the regulatory authority recommended the use of a JN1 spike antigen in the COVID-nineteen vaccine for

Operator

the 2024, 2025 season, we were able to submit our application to a

Speaker 3

European regulator, and we began rolling out our updated vaccine shortly after approval in early July. Anticipating the regional differences, we followed up with the development and submission for a KP2 adapted vaccine. In the UK, the regulator approved our JN1 adapted COVID-nineteen vaccine in July and our KP2 adapted COVID-nineteen vaccine in early October. In the United States and Canada, regulatory authorities recommended the use of KP2 as the preferred lineage for the present season. Less than 2 weeks after recommendation, we initiated our rolling submission with the U.

Speaker 3

S. FDA and received approval of our KP2 adapted vaccine in August. In Japan, we received our JF-one approval in early August. These early strain recommendations and approvals have allowed for the timely delivery and early availability of vaccines for the fall vaccination campaigns. Execution at such speed was enabled by our continued surveillance and analysis of areas of concern by the strength of our mRNA technology, which allows for scalable rapid production and due to our expertise at navigating the regulatory landscape on a global scale.

Speaker 3

We will continue to monitor the evolving epidemiology of COVID-nineteen and remain prepared to develop vaccines with adapted antigenic compositions in line with regulatory recommendations. COVID-nineteen transitions to an endemic infection pattern. Data on weekly new hospital admissions due to infections caused by RASCO2 and by influenza show different patterns of seasonality. This past season, like in the prior year, COVID-nineteen disease related hospitalization had 2 prominent peaks, 1 in winter and an additional one in summer. In contrast, for influenza, we predominantly see increases in hospitalizations in the winter.

Speaker 3

The emergence of new variants, coupled with the waning of both vaccine and infection induced immunity, indicates that susceptibility to COVID-nineteen infection remains a concern after the winter vaccination season. These different patterns of seasonality of influenza and COVID-nineteen may have an impact on regulatory guidelines to facilitate protection throughout the year. Recently, U. S. Authorities recommended older and immunocompromised individuals

Operator

receive

Speaker 3

an additional COVID-nineteen vaccine dose, administration of additional doses later in this season could contribute to improved vaccine coverage over time, mitigating the risks associated with evolving COVID-nineteen variants. Given our current understanding of COVID-nineteen seasonality and its burden on health care systems, we are proud that our vaccine can contribute to mitigate severe infections and protect people around the world from COVID-nineteen related hospitalized patients and deaths. Turning now to our oncology pipeline. Our multi platform immune oncology clinical pipeline is continuing to advance, and it is a rich source for the strategically planned novel novel combinations that we consider a key pillar of our vision for oncology. As you can see, 2 of our modalities, namely mRNA and immune neuromodulator IOs, are dominantly represented in our pipeline and particularly so in the advanced clinical stages.

Speaker 3

This is a testament to our drive towards mid to late stage trials as part of our ambition to achieve multiple product launches in oncology by 2,030. As Luca pointed out, we have a special focus on our mRNA cancer vaccine portfolio and our BNT-three twenty seven center clinical development program with the latter becoming our platform for unique combinations with several of our other assets, in particular, our ADC. BNT-three twenty seven is a bispecific antibody candidate that targets both PD L1 and VEGF A, thus combining 2 complementary functions. The binding of PNT-three twenty seven to PD L1 in tumors restores effector T cell killing of tumor cells and enriches VEGF neutralization within the tumor microenvironment to create a cycle of vascular normalization, improved blood flow and reduced hypoxia within tumors. BNT-three twenty seven also reverses the negative effect of the EGFA signaling on infiltration and activation of immune cells in the tumor microenvironment.

Speaker 3

By co localizing the blockade of PD L1 and VEGF A signaling to the tumor, BNT-three twenty seven is designed to deliver superior anti tumor effects compared to individual targeting of PD L1 and VEGF A with the potential to minimize adverse events associated with systemic anti VEGF A therapy. With the anti PD L1 and VEGF A antagonistic mechanisms being validated across numerous tumor types and in some cases in combination, we have a roadmap for the development of PN-three twenty seven. We and our partner partner, Biophias, have treated over 700 patients in clinical trials across a wide range of clinical indications with PNT-three twenty seven, either as monotherapy or in combination with various standard of care treatments. In these early studies, BNT-three twenty seven demonstrated encouraging activity as mono and combo therapy with a favorable safety profile that was shown to be generally well manageable and in line with adverse events and inhumane related adverse events observed with other therapies targeting PD L1. The data also indicates robust single agent activity for BNT-three twenty seven and in combination with standard of care chemotherapy across tumor types and treatment plan.

Speaker 3

This extensive data collection provides us with a solid foundation for making data driven decisions on potential indications and patient cohorts for future potentially registrational study. One of the indications we have selected for further development is triple negative breast cancer or TNBC, the type of breast cancer with the poorest outcomes. In first line metastatic TNBC, we have observed a high objective response rate with encouraging responses and long progression free survival for BNT-three twenty seven in combination with an upcycled taxyl. As noted here, we presented updated efficacy and safety findings from the ongoing Phase III study in this indication. Approximately 10 to 3 population of 42 patients, we observed a confirmed objective response rate of 74%.

Speaker 3

Importantly, responses were shown to be clinically meaningful irrespective of PD L1 status. In patients with PD L1 combined positive scores of TPS, smaller than 1 confirmed objective response rate, the rate was 76.9%. In patients with PD L1 TPS between 1 10, the confirmed objective response was 56%. And in patients with PD L1 CPS higher than 10, the confirmed objective response rate was 100%. We also observed record tumor shrinkage with a median time to response of 1.9 months and an encouraging median duration of response of 11.7 months in the intent to treat population.

Speaker 3

Treatment related adverse events of Grade 3 or above occurred in 57% of patients leading to treatment discontinuation in 4.8 percent of patients. In summary, we are encouraged by the potential of BNT-three twenty seven in combination with chemotherapy to offer clinically meaningful anti tumor activity regardless of PD L1 status and by its manageable toxicity. We have prioritized the planning of global trials in TNBC where unmatched need remains high, particularly for those with PD L1 negative tumors as they are not eligible for current anti CD1 treatment. We will be presenting additional data in first line TNBC at the San Antonio Breast Cancer Conference next month. We believe that BNT-three twenty seven and this drug class at large are showing an increasingly validated mechanism of action.

Speaker 3

The dose optimization trials in the U. S. Initiated recently allow us to create a robust scientific data package to inform the global development of this asset and tick off 3 waves of focused development. We plan to execute quickly and move broadly into three ways. First, we are investigating the NT-three twenty seven combination with standard of care chemotherapies as an intended path to market approach.

Speaker 3

The data generated by our partner, BioPhiast, have driven our decision to prioritize the planning of registrational trials in small cell lung cancer, TNBC and non small cell lung cancer due to start in the next few months. 2nd, we plan to evaluate BNT-three twenty seven with our ADCs in some of these tumor types and additional key indications. The first exploratory trial evaluating novel BNT-three twenty seven combination was started earlier this year with our proprietary TROP-two eighty six, BNT-three twenty five. These novel combinations may open up new areas of activity for BNT-three twenty seven. We plan to initiate additional trials evaluating novel proprietary combinations of BNT-three twenty seven with ADCs before year end and over the next 12 months.

Speaker 3

Lastly, we aim to expand with standard of care chemotherapy and novel combinations beyond ADCs across further indications and treatment settings. It is a strategic goal for us to explore VNT free 27 as part of novel novel combination. Given our experienced clinical development team, which has an increasingly global footprint, our strong financial position and unique pipeline, we are confident that we are well positioned to efficiently execute on this comprehensive clinical development strategy. Now to the other cornerstone of our oncology portfolio, our mRNA cancer vaccine platform, Inez and Sigvecs. Inez targets neoantigens derived from somatic mutations in cancer cells that are unique to an individual's tumor.

Speaker 3

Inez vaccines are investigational vaccines that are being co developed with our partner Genentech and are manufactured on demand and personalized to the individual patients. Thick sex vaccines target multiple non mutated tumor antigens shared by a majority of patients with a given tumor type and are also shared cancer vaccine candidates. The computational approaches to discovering and selecting these 2 different types of target antigens are one of our core competencies. IMS and FICC both use the same vaccine and delivery technology, namely our proprietary mRNA LKX platform. Today, we have ongoing trials in multiple disease settings and indications across both vaccine platforms.

Speaker 3

We have reported translation and clinical data over the last couple of years and future data updates from multiple trials shown on this slide, our plan. Aggregate data that we have reported in the past across IMS and FICC FACT trials indicate that urogin mRNA Lpx based vaccines have a manageable and largely mild safety profile as single agent in combination with anti PD-one PD L1 compound and in combination with chemotherapy. Our data also indicates that our uridine mRNA alphase based vaccine platform is highly proficient in inducing and expanding high magnitude functional and long lived T cell responses in the majority of patients, which is a prerequisite for clinical activity. Furthermore, our data from small sample size patient cohorts indicates clinical activity alone and in combination with anti PD-onePD L1 treatment. In our fixed set program, I would like to highlight 2 vaccine candidates for which we had important updates during the quarter.

Speaker 3

For BNT-one hundred and thirteen, our mRNA vaccine candidate against HCV16 positive cancer, we presented data from 2 trials at the ESMO conference. One data set was from the safety run-in cohort of our potentially deregistration Phase II randomized trial ahead MERIT. This trial evaluates PNTR-one hundred and thirteen in combination with pembrolitumab versus pembro alone in first line HPV-sixteen positive, PD L1 positive head and neck squamous cell carcinoma. The data supports the tolerability of PNT-one hundred and thirteen and clinical activity in combination with pembro and the induction of high magnitude de novo T cell responses against HPV-sixteen antigen encoded in this vaccine. In summary, we are encouraged by the data of the safety cohort.

Speaker 3

The 2nd data set from investigator initiated Phase III trials exploring BNT-one hundred and thirteen as single agent in patients with localized metastatic animal head and neck cervical and other HBV-sixteen driven carcinoma further confirmed positive safety and immunogenicity findings. We have reported top line findings for BNT-one hundred and eleven, which is being investigated in patients with anti PD-one relapsed or refractory melanoma. BNT-one hundred and eleven encodes 4 melanoma associated antigens, which collectively cover more than 90% of melanoma patients and are highly immunogenic. In the randomized Phase II clinical trial conducted in collaboration with Regeneron. PNT-one hundred and eleven is being evaluated in combination with their anti PD-one compounds iniplimab.

Speaker 3

The trial enrolled 184 patients with PD L1 refractory unresectable stage 3 or 4 melanoma and comprises 3 arms of which one evaluates the combination and the other to measure the activity of BNP-one hundred and eleven alone or semipramer alone. The trial set its primary endpoint achieving a statistically significant improvement in ORR and objective response rate in the BNT-one hundred and eleven semiplimab combination arm as compared to a historical control of anti PD-one monotherapy in a relaxed respiratory patient based on multiple late stage clinical trials that established the expected ORR for monotherapy checkpoint inhibitors in the setting for the patient population. The results we saw in the Phase II study are consistent with results seen in the preceding Phase III trial in patients with advanced melanoma who had exhausted treatment options. BNT-one hundred and eleven alone, all in combination with an anti PD-one compound, induced 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. We plan to present the full data from the primary analysis at a medical conference.

Speaker 3

The various HICC data updates provided in Q3 are a proof of concept in 3 dimensions. Firstly, for our mRNA cancer vaccine technology that uses uridine mRNA chemistry, a non coding backbone that is engineered for optimal translation performance and our proprietary LIGO PEG formulation for systemic delivery, which we are using in both iNEXT and fixed VEG vaccine secondly, for our computational approaches for selecting suitable tumor antigens and targets for our indication specific fixed VEG program candidate. Lastly, a proof of concept for our strategy to combine synergistic modalities in the case of BNT-one hundred and eleven and BNT-one hundred and thirteen with established immune checkpoint inhibitor treatment. Moving to autogenzilunarum, also known as BNT-one hundred and twenty two, our individualized mRNA cancer vaccine candidate based on our INS platform in development with our partner Genentech. We consider individualized cancer vaccines as a potential medical breakthrough in addressing the high unmet medical need of reductable cancers and in adjuvant or minimal residual disease treatment settings.

Speaker 3

We have demonstrated that our individualized vaccine candidate 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 when vaccine induced immune responses was reduced over a 3 year follow-up period. We have 2 active randomized Phase II trials evaluating our individualized cancer vaccine in the echelon setting, mainly in pancreatic ductal adenocarcinoma or PEDAP and in colorectal cancer. The 5 year survival rate in PDAB after resection is 10% and up to 75% of patients with PDAB relapsed even though they appear tumor free within 5 years after adjuvant treatment. For high risk colorectal cancer, about 35% of patients relapse within 5 years after resection and adjuvant therapy. So to summarize, we aim to bring individualized cancer vaccines into the adjuvant treatment setting in tumor types where the unmet medical need is high.

Speaker 3

As such, we have expanded into a new indication with the start of a Phase II trial evaluating our individualized cancer vaccine candidate in the adjuvant treatment of muscle invasive urothelial carcinoma, which has started screening patients. The current treatment includes neoadjuvant chemotherapy followed by cystectomy and for eligible patients, this is followed by adjuvant treatment with an immune checkpoint inhibitor. The high teen survival among patients with metastatic bladder cancer is about 8%. Adjuvant treatment of muscle invasive disease is an important opportunity to potentially avoid recurrent metastasis and improve overall survival. The randomized double blind multisite Phase 2 clinical trial aims to evaluate autogen selunarang as an adjuvant treatment with the immune checkpoint inhibitor and dolomab in patients with high risk disease.

Speaker 3

The trial is expected to enroll about 360 patients to evaluate the efficacy of PNT-one hundred and twenty two in combination with nivo compared to nivo alone, a standard of care for this indication in the U. S. The primary endpoint for this study is investigator assessed disease survival. Secondary objectives include overall survival and safety. Lastly, as a final note, I would like to invite you to our upcoming Innovation Series Day next week, where we will share additional details on these and other programs of our improved PRP pipeline.

Speaker 3

With that, I will now pass the presentation to our CFO, Jens Holstein.

Speaker 4

Thank you, Aslem, and a warm welcome to everyone who has dialed in today's call. Let me start by reviewing our financial results for the 3 months ended September 30, 2024. The total revenues reported for the period were approximately EUR 1,245,000,000 mostly recorded in September, compared to approximately EUR 895,000,000 for the Q3 of 2023. The increase compared to the same period last year can be largely attributed to earlier approvals of our variant adapted COVID-nineteen vaccines this year versus last year. Moving to cost of sales.

Speaker 4

Cost of sales amounted to approximately €179,000,000 for the Q3 of 2024 compared to approximately €162,000,000 for the comparative prior year period. Research and development expenses were approximately €550,000,000 for the Q3 of 2024 compared to approximately €498,000,000 for the comparative prior year period. These expenses were mainly influenced by progressing clinical trials for our late stage oncology pipeline candidates. Sales, general and administrative expenses amounted to approximately €151,000,000 for the Q3 of 2024 compared to about €154,000,000 for the comparative prior year period. SG and A expenses were primarily driven by personnel expenses.

Speaker 4

The company's other operating results amounted to approximately negative €355,000,000 in the Q3 of 2024 compared to negative €9,000,000 for the comparative prior year period. The other operating result was primarily influenced by accruals for contractual disputes. Income taxes were realized with an amount of about €39,000,000 in the Q3 of 2024 compared to approximately €67,000,000 of accrued tax expenses for the comparative prior year period. For the Q3 of 2024, we reported a net income of approximately €198,000,000 compared to about €161,000,000 for the comparative prior year period. Our diluted earnings per share for the Q3 of 2024 amounted to €0.81 compared to €0.66 for the comparative prior year period.

Speaker 4

As of September 30, 2024, our cash and cash equivalents plus security investments reached approximately €17,800,000,000 Our strong balance sheet allows us to invest in future value creation. Consequently, we will continue to invest in maintaining a leading cash generative COVID-nineteen vaccine business in the development of our indolized therapies and in our core capabilities to support additional late stage trials and potential commercialization of our most encouraging oncology assets. We will continue to assume a rigorous gono go decision making across all development stages as part of our portfolio prioritization strategy. This allows us to maintain our focus on materializing the value in our pipeline. Turning to the next slide, where you see our financial guidance for the full year of 2024.

Speaker 4

We saw a strong quarter in terms of revenues, which included certain revenues that we previously anticipated in the last quarter of 2024. With this, we expect full 2024 financial year revenues to be at the low end of the guidance range provided in our outlook. Our guidance reflects some risk of write downs and other charges by our collaboration partner Pfizer, which we estimate to be approximately 10% of company revenues. We will continue to monitor the risk of potential write downs to determine the full scope of charges related to the 2024, 2025 vaccination season. In line with our disclosure earlier in the year, we expect to report a loss for the 2024 financial year as we continue to invest in our most differentiating assets and technologies.

Speaker 4

We are committed to responsible and sustainable growth. And with this, updating our full 2024 financial year expenses guidance to indicate a decrease in estimated SG and A expenses and capital expenditures. Reflecting our focus on continued investment in our pipeline, we're maintaining our R and D expense guidance. We have lowered the initial full 2024 financial year SG and A expense guidance by €100,000,000 from €700,000,000 to €800,000,000 to €600,000,000 to €700,000,000 We also reduced our capital expenditures guidance by €100,000,000 from the initial 2024 guidance range of between €400,000,000 500,000,000 to between €300,000,000 €400,000,000 Please note that these guidance updates for SG and A expenses and CapEx do not reflect any M and A collaboration or licensing transaction that we may enter into in the future, nor any potential payments resulting from the outcomes of ongoing and or future legal disputes or related activities, such as judgments or settlements or other extraordinary items, all of which may have a material effect on our results of operations and or cash flows. In summary, we remain focused on executing the company's strategy highlighted by the progress across our pipeline.

Speaker 4

We have advanced and started new dose optimization and potentially registrational trials and have shared encouraging data that demonstrates the potential of our product candidates. In our oncology portfolio, our focus remains on investing in our innovative technologies that we believe can have the greatest impact on medical practice while progressing our late stage programs efficiently towards potential approvals. Our cash position and financial discipline allows us to continue to invest in those assets with the highest disruptive potential 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 our strategic outlook and concluding remarks. Thank you.

Speaker 5

Thank you, Jens. Starting with COVID-nineteen, we continue to execute on our successful launch of this season's JN1 and KP2 variant adapted vaccines in more than 40 countries and regions around the world. In September, we began distribution of our KP2 variant adapted vaccine in Europe following the initial rollout of JN1 vaccines in July. We expect additional markets, including the UK that received initial shipments of JN1 vaccine to transition to KP2 deliveries in November. In the United States, we continue to expect vaccination rates this year that are generally comparable to last year, with potential for slightly higher volumes due in part to the earlier approval and rollout of vaccines and supported by ACIP's recommendation in October for a second dose of COVID-nineteen vaccine for individuals who are 65 or older or immunocompromised.

Speaker 5

Internationally, we have seen the opening up of several private markets in countries like the UK, Japan, Switzerland, Australia, South Korea, Singapore and Brazil. This year, we have also increased our supply of prefilled syringes in a number of international markets. The epidemiology of COVID-nineteen over the last two years and the associated global demand for vaccination continue to support our view that COVID-nineteen vaccines will be a sustainable market for the foreseeable future. We expect to maintain or even gain market share in a number of key markets this year versus last year and believe that we are likely to enter a period with improved visibility into vaccine demand. One of the unique features of our COVID-nineteen vaccine business is its lean cost structure.

Speaker 5

Our partnership with Pfizer allows us to leverage its manufacturing infrastructure and global commercial capabilities, which we expect will continue to enable us to limit the OpEx flowing through our P and L. These features create the potential for us to generate significant cash flow from our COVID-nineteen business, a feature we expect to benefit from in the future. Turning to the next slide. We are entering a catalyst rich period for our company, in particular for our oncology portfolio. Today, we have more than 10 Phase II and III trials ongoing across multiple tumor types.

Speaker 5

In the next 18 months, we expect multiple clinical data updates from these trials and we'll initiate several additional trials with registrational potential. Data is expected in 2025 from both our mRNA cancer vaccine platforms, FixVac and INAST. We also expect data updates for BNT-three twenty seven, our anti PD L1 VEGF bispecific antibody and BNT-three twenty three, our HER2 ABC. Before we conclude our planned remarks, I would like to invite everyone to watch our annual innovation series event on November 14. This event will include a deeper dive into our oncology strategy, including plans for BNT-three twenty seven and our mRNA cancer vaccine candidates.

Speaker 5

We look forward to engaging with you later this month to share more on our plans to create value for patients, society and shareholders. With that, we would like to open the floor for questions. Thank

Operator

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

Speaker 6

Thank you. Good morning and appreciate your time. I wanted to ask you about one of the data catalysts that you mentioned that's upcoming in 2025. Perhaps you'll talk about this more in detail next week. But for 3/23 specifically, I believe you've got data coming for endometrial cancer.

Speaker 6

Can you talk about the level of data you expect to show next year for that program and what you're looking for in order to move

Speaker 3

forward? Thanks. Tazeen, thank you for this question. The question was about our endometrial cancer data with BNP-three twenty three. And

Speaker 2

what

Speaker 3

I can tell you about that is that in 2025, we expect to share data from our single arm trial in second line endometrial cancer. We will be able to show efficacy data and safety data across different HER2 positivity populations, and this will be presented at one of the major cancer conferences.

Speaker 6

And also what would be positive data in your mind for that program?

Speaker 3

Can you repeat?

Speaker 6

What would be positive data for that study in your mind?

Speaker 3

Positive data?

Speaker 6

Yes. What would justify

Speaker 3

to continue with the compound is a strong activity clinical activity profile and a favorable safety. And this is also what we see in the data, and we see this across different HER2 expression levels.

Operator

Thank you. We will now take the next question from the line of Daina Graybosch from Leerink Partners. Please go ahead.

Speaker 6

Hi. Thank you for the question. I have one on the VEGF PD L1 BNT327. I think we're all aware of a similar bispecific that has a PD-one side, whereas you have a PD L1 side. And in small trials, in similar indications like triple negative breast cancer, the 2 bispecifics look to have similar outcomes.

Speaker 6

Was that expected? And what does that tell you about the mechanism? And do you believe BNT-three twenty seven could be differentiated in any indications? Thank you.

Speaker 2

Hi, Dana. Thanks for the question. Yes, this is a good question. And at the end of today, both bus specific link these activities of notarizing VQF and notarizing PD-onePD L1 interaction, they have this in common. The biggest difference is that BNT-three twenty seven is directed against PD L1, which comes with the potential advantage of being further enriched in the tumor microenvironment by binding to PTR-one or vice versa, enabling or adding to the binding of VGF and the tumor microenvironment.

Speaker 2

The data that we have so far, yes, these are there are some overlapping clinical trial, as you mentioned, looks similar. And they have to see whether this potential mechanistic difference could translate into a better response rate and better durability, particularly in PD L1 positive tumors. So we have to see that there is a slight trend in this direction, but it's too early to yes, to validate that.

Operator

Thank you. We will now take the next question from the line of Akash Tewari from Jefferies. Please go ahead.

Speaker 7

Hi, this is Kathy on for Akash. So for your VEGF PD L1 bispecific BNT-three twenty seven, when do the AEs and reductions in dose for hypertension and proteinuria show up in comparison to what we've seen historically for VEGF PD L1 when coadministrated as 2 separate drugs? And additionally, weren't you going forward with it to first line NSCLC in all commerce population? And what's the rationale for going as a biomarker selected population?

Speaker 2

Okay. I'll take both parts of the question. So the first question was the comparison with the historical safety profile, particularly with bivacitumab. So we have now more than 700 patients treated either as mono compound or in combination. And the comparison to historical safety profile clearly shows reduced side effect profile with regard to the key concerning side effects of vivacizumab, bleeding, hypertension or the formation of fistulas.

Speaker 2

We have not seen any significant increase of bleeding cases in this cohort, which goes beyond what is observed in this population, for example, for PD-one antibody. And hypertension rate is significantly lower than the historical comparison with lebacizumab. The mechanism for this can only be speculated and that by linking the antibody with the VGF part to PD L1 And anti VGF interaction is more targeted to the tumor sites and less active in PD L1 negative areas. And this is, of course, encouraging and provides an additional argument beyond the increased so far increased clinical activity for this compound class. So this was the first part.

Speaker 2

And the second part is why we prefer to go into an allokammer population. The response to that is that our bispecific has shown a clinical activity not only in PD L1 positive and PD L1 low populations, but also in populations which do not express PD L1 or CPS. So I would refer to our data sets that we generate in PNVC where the objective response rate in the TNBC oral count population is extremely encouraging. We see something similar

Speaker 8

with a

Speaker 2

clear indication of the clinical activity in the PD L1 negative population in the 2nd line non small cell lung cancer and the AGA positive population. So the working hypothesis that we have, yes, is that this bispecific antibody totally comes overcomes the limitation of pure clinical activity in PD L1 positive tumors and opens up the potential to bring checkpoint blockade plus VGF activity into tumors that are also PD L1 negative. So the clinical trial in non small cell lung cancer is an all comer trial, but we are documenting, yes, and collecting samples for PD L1 evaluation, and we are stratifying patients according PD L1 possibility.

Operator

Thank you. Thank you. We will now take the next question from the line of Susanne Van Voorheesen from VLK. Please go ahead.

Speaker 9

Hi, team. This is Suzanne. Thanks for taking my question. Maybe I missed it, but can you clarify what the exact amount is that you have taken as a provision for contractual disputes this year? Is this it?

Speaker 9

Or will there be more? And can you indicate what this relates to if this is the ongoing patent dispute with other mRNA payers on the COVID vaccine? Or if there are other contractual disagreements you are dealing with? Thank you.

Speaker 8

Yes. Happy, Susan, to take the question. So as you stated, the other operating result is reflecting these provisions that we have taken care of for contractual disputes with licensers and collaborators. We at this point in time, given the legal situation that we're in, cannot give precise messaging on what and for what this is. There are a couple of disputes that are related, as I stated, with some of the players and collaborators that we're working with.

Speaker 8

In total, we have accrued round about €600,000,000 year to date for this, and this is the amount that we feel is accurate at this point in time.

Speaker 3

Thanks.

Operator

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

Speaker 10

Great. Thanks so much for taking the question. I was just wondering if you can tell us what you think the relevant benchmark is for survival for the upcoming BNT-three twenty seven TNBC data that we're going to see at the San Antonio Conference in December. Thank you. Hi, were you able to hear my question?

Speaker 11

Yes. Can you just repeat that? Sorry.

Speaker 10

Survival benchmark is for the upcoming BNT327 TNBC data at the San Antonio Conference in December. And then the second part of the question is, is it reasonable to expect some interim data from your global Phase II lung cancer trial next year? Thank

Speaker 2

you. Yes. Okay. I can take the question. The trial will be randomized against chemotherapy standard of care.

Speaker 2

And the pilot itself is powered for PFS and OS. The PFS is in this indication in the range of 4 to 5 months OS. I can't recall at the moment. With the ratio of 0.7.

Speaker 11

Right. I think we're going to have updates, we plan to provide an update at the 15 18 month OS mark in terms of percentage of patients reach. And that's starting to get into a relevant zone, Terrence, when you look at the what pembro has achieved in a similar indication, which is basically in the 15 to 23 up to 23 month median OS depending on

Speaker 2

the patient, the MCPS patient. Absolutely. And we have recently reported PFS data in the single arm trial, reaching now above 13 months and still ongoing.

Operator

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

Speaker 12

Great. Maybe just a follow on on Terence's question. In TNBC, is the thought in Phase III is to go for CPS less than 10 specifically in that cohort? Or would you go across all CPS levels in Phase III? And then secondly, on small cell, is the primary going to be head to head against chemo to centric or is it going to be against chemo alone?

Speaker 12

Thank you so much.

Speaker 2

So the first trial is intended in the patient population below 10%, and will be against chemotherapy alone. But we plan also further we are in the evaluation of additional trials going to the above 10% population. And can you just repeat the second part of your question?

Speaker 12

Yes. Hey, Ryan. And just switching to small cell lung cancer, is the Phase 3 going to be head to head against chemo or against chemopecentriq? Thank you, in small cell lung cancer.

Speaker 2

Chemo prostacentriq.

Operator

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

Speaker 7

Hey, guys. Good morning. Thanks for taking my questions. 2, first on guidance, of the various assumptions factoring into your guidance, what changed to lead you to guide to the low end of the range even though Pfizer, I believe, maintained its Comirnaty guidance last week? And then on the pipeline for BNT-three twenty seven, the VEGF PD L1 bispecific, what do you see as the fastest to market indications?

Speaker 7

And what's the right way to think about R and D spend as the company expands trials for this product? Thank you.

Speaker 8

Yes, Jessica, let me take the first part of the question. So we've guided at the beginning of the year €2,500,000,000 to €3,100,000,000 based on, of course, certain scenarios. Year to date, Q3 has been very, very good. And Q3 so far or the year to date figures so far have been generated dominantly by revenues that we generated in high income countries. We have seen though low and low demand and also low pricing in some of the low and middle income countries within the Pfizer territory.

Speaker 8

And therefore, we specified our guidance to the low end for this year.

Speaker 2

And then second question?

Speaker 11

I think your second question was speed to market. What would we think would be the fastest to market for 327, is that correct?

Speaker 2

Yes.

Speaker 11

So I think we're going to provide more details at our innovation series event next week in terms of the paths to market. But I think what we can say now is that, we do think that small cell lung cancer could be one of the leading indications that we're looking at very closely. We initiated a Phase II trial and believe that we can start a Phase III trial. It's a Phase II, III effectively. So Phase III portion of that trial in the coming months by first half next year.

Speaker 11

So that could represent one fast path to market, but of course we're looking at others as well.

Operator

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

Speaker 13

Hi. Thanks for taking the question. So your TROP-two ADC BNT-three twenty five looks like an important part of your merging combination strategy with 3/27. Looking at the clin trial posting shows that you're evaluating a variety of different dosing combinations. So wondering if you can add some color on the dosing strategies and your confidence level that all three mechanisms together will not compromise safety.

Speaker 13

Thank you.

Speaker 2

Yes. The current exploration of combination is exactly also directed to explore the safety of the molecule in combination. So 20, 3 to 5 as a top 2 ADC comes with a safety profile that is characterized by a tumor target. And one of the questions that we want to ask is whether the combination with BLT-three to 7 would have an additive toxicity effect. That is something that we would like to understand.

Speaker 2

We do not expect any other overlapping toxicity since the NTPD7 has a very stable safety profile and start with lower doses and then escalate to higher doses and assess then safe dose identify that safe dose profile in an exploratory cohort for also determining the contributions of efficacy part.

Operator

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

Speaker 14

Hi, this is Kevin on for Chris. Thanks for taking our question. Just wanted to ask another one on the PD L1 VEGF-three twenty seven. So you touched on potential mechanistic differences with Ibanezumab earlier. If we can assume that the clinical profiles remain relatively similar, do you believe this is a story more about clinical execution?

Speaker 14

And if so, how can you differentiate there? Thanks.

Speaker 11

Yes. Thank you for the question, Kevin. I'll start and then also add to it. So I think that we do think that there's sufficient actually there's significant room for differentiation in clinical strategy. And that's actually one of the main drivers that we're evaluating now because we do see applicability across many different tumor types and as Uwe also alluded across different patient segments within tumor types.

Speaker 11

And I think one of the unique features of our portfolio in oncology is the combination agents that we could bring to bear with 327. So I think we've talked about chemo combinations being likely the fastest path to market initially. And we've guided to a couple of early indications, but we're definitely thinking broader than that. We're thinking about ADC-three twenty seven combinations to follow shortly thereafter. Our current thoughts would be to initiate those trials already in 2025, the first combinations potentially in 2025, rather than waiting to do those in sequence.

Speaker 11

And we're also going to be evaluating other combinations as well, down the road. So I do think that that's a differentiation angle that we can we're well positioned to exploit. So it really comes down to a combination of combination strategy and also clinical execution indeed as potential differentiators for this large opportunity that we see.

Speaker 14

Great. Thank you.

Operator

Thank you. We will now take the next question from the line of Edsir Darutz

Speaker 2

from

Operator

BMO Capital Markets. Please go ahead.

Speaker 15

Hi, this is Luke Shumway on for Etzer. Thanks for taking my question. So, what are you learning about overall survival of cost for us and lung cancer indications that you're looking at? And what's your level of confidence that you can beat standard of care given the importance of that endpoint to regulators?

Speaker 11

So I think we had a little bit of a buzz in the question. I think you were asking about the importance of overall survival. Is that correct?

Speaker 15

Yes. So like what have you learned for overall survival across breast and lung? And like what level of confidence you have given the importance of that endpoint to regulators? Yes.

Speaker 2

So we completely understand the rationale of this question, particularly based on disappointing results coming with vivacitumab, which in many indications had an improved PFS, but did not translate into an OS. And we are, of course, collecting our own in house data, and we clearly see that this maturing OS data, unpublished OS data, we are getting more and more encouraged that improved PFS is indeed translating also into an OS. I would like to remind you that PFS improvement that we are seeing, for example, in TNDC is more than substantial. So it's not the pattern that is usually observed with bevacizumab. Usually, bevacizumab added 2 to 3 months additional PFS, yes?

Speaker 2

And then the drop in PFS was steep. This following and the pattern that is observed with chemotherapy alone. We are not seeing this pattern. We are seeing that particularly in indications where we combine BNT-three twenty seven with chemotherapy that there is a sustained PFS and the PFS does not drop in the pattern like a steep curve, but goes slowly down. And this is the best thing that we have so far for that this can translate to OS.

Speaker 2

And I think we can definitely answer the question in the next 1st month for the first indications in which we are TNBC, small cell lung cancer. And second 9 months, second 9 months, small cell lung cancer.

Operator

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

Speaker 16

Hey, guys. Thanks for taking the question. For the flu COVID combo program, I guess, what's the latest on this program after the Phase 3 missed one of the endpoints? And what's your latest thinking around the timelines for the 2nd gen program with the trivalent mRNA flu vaccine, just given Moderna expects to launch its combo next year? Curious to the latest on your strategy with your combination?

Speaker 16

Thanks.

Speaker 11

Yes, Ali, thanks for the question. So we're working with Pfizer now on our next generation flu COVID vaccine combination a combination vaccine program. And I think it's a little too early to give you a precise roadmap, but we're hoping to give you and planning to give you updates over the course of 2025. I think needless to say, this is a program that has our full weight of Pfizer and BioNTech R and D teams behind it. And we do think that some of the problems that have been we're seeing in that initial trial that those can be addressed through further optimization of the construct.

Speaker 11

And we have early evidence that supports that. But I think before we can give you a definitive roadmap, I think we'd like to generate a little more data and hopefully come out with that next year.

Speaker 16

Great. Thanks.

Operator

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

Speaker 17

Hello. Good morning. Thanks for taking my question. I have one on your oncology portfolio. Just wondered for the other assets apart from BNT327, BNT325, especially on the IO space, in the next 12 months, when we what we're going to hear your update on specifically things like 312 or 314 those early stage early mid stage assets?

Speaker 17

Thanks.

Speaker 11

So I think that 312, of course, is the CD44 and VB program with Genmab and that's an ongoing, it's an ongoing trials right now. I think our intention is to bring data forward upon that trial's completion. We don't yet have dates for that, but it's likely going to be next year. And I think the other programs, generally speaking, our intention is to bring data out when we think we have something relevant to share. We tend to do that in our preferred mode of data disclosure is in medical meetings.

Speaker 11

And so of course that requires that you've got data in hand that it's clean and been analyzed and is accepted by publication. So we can't always give precise guidance on when every program will read out. But I think those other programs are progressing and I think we'll plan to update our pipeline disclosure schedule going into early next year.

Speaker 17

Thanks a lot.

Operator

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

Speaker 18

Thank you for taking my question. Another one on BMT-three twenty seven. I'm going back to Tanja's question. I just wanted to double check that the comments you made with respect to trial design were related to triple negative breast rather than the planned non small cell lung cancer study. If that is indeed the case, is there anything you can shed on the design of that upcoming first line study in terms of geography comparative arm?

Speaker 18

I think you mentioned stratification already and interim results, but any detail would be much appreciated. Thank you.

Speaker 3

Simon, I would like to refer you to our Innovation Day next week, where we will disclose in more detail a couple of study designs and benchmarks we are comparing against also contextualized to our entire trial, where also questions around BMG-three twenty seven pivotal trials we are planning will be disclosed.

Speaker 18

Thank you very much.

Operator

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

Speaker 17

Hello, thank you very much since my question was stolen. Basically, just wanted to ask on your ongoing confidence on your TROP-two program, but also your Inest melanoma program as well. Thank you very much.

Speaker 3

So the first question was about TROP 2 ADC, did I get that right? So we as you know, our TROP 2 ADC, BNT-three twenty seven is at an early stage of testing. And in particular, we see a potential in combination with BNT-three twenty seven, which we see as we have already discussed as a platform to combine with different ADCs. And the combination trial, we just had started to explore, 1st of all, safe combination doses is going into this direction and is exploring TNBC non small cell lung cancer and ovarian cancer and cervical cancer cohorts up to for our top 2 and the AADC and our BNP3-two ninety seven combination. The second question was about our I NIST, our individualized vaccine platform.

Speaker 3

We are continuing to expand into the adjuvant space. As you might know, we have adjuvant colorect we have trials running in adjuvant colorectal cancer with an upcoming interim analysis end of next year. We have started with our partner Genentech a trial in the adjuvant setting of pancreatic cancer motivated and informed by small Phase I trial with however exciting data. And we just have started a 3rd trial in this in the adjuvant setting with muscle invasive urothelial cancer, also a randomized potentially pivotal trial. So these are the ongoing trials.

Speaker 3

And we are reading out our trial in first line melanoma, and we'll be able to disclose more about that in our upcoming Innovation Day next week.

Speaker 11

And I would just add to that, that in summary that we continue to believe that INS has disruptive potential in particular in those adjuvant settings that also mentioned and we're investing accordingly in the program. Thank you.

Operator

Thank you. We will now take the last question from the line of Jay Olson from Oppenheimer. Please go ahead.

Speaker 13

Congrats on the progress and thank you for providing this update. Can you comment on the approximate level of R and D spending increase you expect in the next few years considering how rapidly you're expanding the number of Phase 3 programs in oncology? And is there an ideal number of Phase 3 trials that would optimize your organizational and financial resources? Thank you.

Speaker 8

Yes. Thanks for the question. I mean, it's a bit early for any guidances that we are not intending to give now in November. I think we feel comfortable with the 2.4, 2.6 that we currently have running. And on one hand, now we want to control costs.

Speaker 8

On the other hand, of course, we want to invest wisely. If we talk about V27 and the potential, of course, it will be not very clever to not invest in that compound to just use this example specifically. So but be assured that we control our costs going forward being at SG and A expenses will be at R and D expenses.

Speaker 11

Yes. And with regard to the target pipeline, I think it's a very good question. I would just note that with the current level of R and D spend that Jens has just alluded to, and we currently have 10 ongoing Phase 2 or 3 trials. Some of those are with partners, some of those are fully BioNTech self funded. But I think it already shows you that we've already reached at this current R and D level pretty significant scale in the mid and late stage pipeline.

Speaker 13

Great. Thank you.

Operator

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

Remove Ads
Powered by Quartr
Earnings Conference Call
BioNTech Q3 2024
00:00 / 00:00
Remove Ads