January 19, 2021

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Edited Transcript of BNTX.OQ earnings conference call or presentation 31-Mar-20 12:00pm GMT

Apr 8, 2020 (Thomson StreetEvents) — Edited Transcript of BioNTech SE earnings conference call or presentation Tuesday, March 31, 2020 at 12:00:00pm GMT

BioNTech SE – Chief Business Officer, Chief Commercial Officer & Member of Management Board

UBS Investment Bank, Research Division – Equity Research Analyst of Specialty Pharmaceuticals and Large Cap Pharmaceutic

Joh. Berenberg, Gossler & Co. KG, Research Division – Analyst

Ladies and gentlemen, thank you for standing by, and welcome to the BioNTech fourth quarter and full year operational progress and financial results call. (Operator Instructions) I must advise you this call is being recorded today, Tuesday, the 31st of March, 2020.

And I would now like to hand the call over to the Vice President, Investor Relations and Business Strategy, Sylke Maas. Please go ahead.

Thank you for joining us today for BioNTech’s Fourth Quarter and Full Year 2019 Update Call. Before we start, we encourage you to view the slides for this webcast as well as the financial results press release issued this morning, both of which are accessible on our website in the Investors section. Slides 2 and 3 provides legal disclosures related to the pending acquisition of Neon Therapeutics.

As shown on Slide 4, during today’s presentation, we will be making several forward-looking statements. These forward-looking statements include, but are not limited to, the timing for enrollment and completion and reporting of data from our clinical trials and preclinical programs, the potentially registrational nature of certain of our clinical trials, expectations regarding the timing for completion and potential benefits of the Neon acquisition, the impact of the COVID pandemic on our business and our financial outlook. Actual results could differ from those we currently anticipate. You are, therefore, cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this conference call and webcast.

Speaking and available for questions today will be Ugur Sahin, Chief Executive Officer; Özlem Türeci, our Chief Medical Officer, Sean Marett, Chief Business and Commercial Officer; Ryan Richardson, Chief Strategy Officer; and Sierk Poetting, Chief Financial and Operating Officer.

I now hand the call over to Ugur Sahin, BioNTech’s CEO.

Thank you, Sylke. It’s a pleasure to welcome you all to our fourth quarter and full year 2019 conference call. I will start with a few introductory remarks followed by an update of our significant efforts to address the COVID-19 pandemic that is having a severe impact around the globe. I will invite Ryan Richardson to provide a brief update on the pending Neon Therapeutics acquisition announced in January of this year. And Özlem Türeci will provide some pipeline updates. Sierk Poetting will then review our financial results. I will then make a few closing remarks on the outlook for 2020 before opening up the call for questions.

To start on Slide 5. Over the past year, we have taken a number of important steps towards our vision of building a global, next-generation immunotherapy company. We have built a broad suite of novel therapeutic platform to explore the full potential of the immune system. We are advancing along with our pharmaceutical collaborator a broad pipeline of first-in-class immunotherapies for the treatment of cancer.

We have built a growing number of programs targeting infectious disease. Most importantly, one of the programs is our recently announced mRNA vaccine program aimed at preventing COVID-19, which we initiated earlier this year as part of our Project Lightspeed in response to the global coronavirus pandemic. Our COVID-19 vaccine program based on our deep experience in the cancer vaccine field and growing footprint in infectious diseases. To address this epidemic, we are applying the full spectrum of our capabilities, our broad mRNA vaccine platform, our integrated GMP manufacturing infrastructure and our broad base of global world-class collaborators. I will come back to the COVID-19 in a few minutes and provide an update on the status of our program.

Turning to Slide 6. Our accomplishments in 2019 and so far in 2020 demonstrate our ability to execute on our vision. 2019 was a transformational year for BioNTech. We have continued the strong momentum in this year against a challenging market backdrop. I want to quickly highlight a few of these key achievements.

Consistent with our stated objectives, we have increased the number of product candidates in clinical testing from 7 to 10 since the completion of our IPO in October last year and have announced our intention to initiate multiple late-stage studies over the next 12 months.

We have also increased our pharma partnerships through the recent expansion of our Pfizer collaboration and the announcement of our first Asian partnership, a strategic alliance with Fosun Pharma. Early in January, this year, we announced the signing of a merger agreement and our offer to acquire Neon Therapeutics, which, if Neon shareholders vote in favor of the merger and the other conditions to closing are met, we expect to bring us some exciting new pipeline candidates in cell therapy space. This complementary technology and our — and the U.S. R&D hub will support the growing number of studies we are conducting in the U.S. And we completed 2 successful financings, our Series B round and, of course, the Nasdaq IPO, which together brought in gross proceeds, $374 million to the company.

Lastly, we made good progress in our multiyear investment program to expand our in-house messenger RNA and cell therapy manufacturing capacity. Manufacturing remains a key strategic priority for us as we advance our pipeline of product candidates towards the market.

I will now turn to Slide 7 and discuss COVID-19. The growing global health threat that has dominated the world’s attention over the past weeks. Earlier this month, we announced that we are developing a vaccine, which aims to induce immunity and prevent COVID-19. We initiated the Project Lightspeed because we feel we have the duty to fully utilize our technology and immunotherapy expertise to help to address this pandemic emergency created by the global spread of the dangerous pathogen.

For our COVID-19 program, we are leveraging our proprietary messenger RNA platform for infectious diseases, our fully owned GMP manufacturing infrastructure for mRNA vaccine production and our global clinical development capabilities. We have partnered with Pfizer for worldwide development of the vaccine and have also established a strategic alliance with Fosun to develop the vaccine in China. We have been in close contact with regulatory and scientific authorities around the world and in ongoing discussions with research organizations. We anticipate initiating clinical testing in late April, subject to regulatory approval. We expect to conduct a global development program spanning Europe, United States and China.

Our mRNA vaccine for COVID-19 exploits a highly potent lipid nanoparticle, or LNP, messenger RNA vaccine product. We believe that mRNA vaccines are ideally suited for this challenge. mRNA vaccines have been shown to be highly immunogenic and induce neutralizing antibodies as well as T cell responses. mRNA is a naturally occurring molecule with well-characterized safety properties. Furthermore, mRNA vaccines are well-defined biopharmaceuticals with high purity and are animal-material free. We believe mRNA vaccines may offer several advantage over traditional vaccine approaches, including an ability to precisely design and manufacture them rapidly in a large quantity.

Sean, do you want to say a few words about our recently announced collaborations for our COVID-19 vaccine?

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Sean Marett, BioNTech SE – Chief Business Officer, Chief Commercial Officer & Member of Management Board [4]

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Thanks, Ugur. For COVID-19, we are collaborating with one of the world’s largest pharmaceutical companies, Pfizer; and one of the leading health care groups in China, Fosun Pharma. Just a few weeks ago, we signed a letter of intent with Pfizer regarding development of BNT162 outside of China and expect to provide more details of the financial terms behind our collaboration soon. As we already have a successful collaboration with Pfizer for infectious diseases aimed at developing influenza vaccines, we have been able to immediately start work to rapidly advance BNT162 towards clinical testing for the prevention of COVID-19. We are currently utilizing multiple research and development sites from both BioNTech and Pfizer and look forward to providing further updates on this fast-moving collaboration in the future.

We also recently announced our strategic alliance with Fosun Pharma, our first strategic collaboration in Asia, to jointly develop BNT162 in China. Together with Fosun Pharma, we intend to conduct clinical trials in China, leveraging our mRNA vaccine technology and manufacturing and Fosun’s extensive clinical development, regulatory and commercial capabilities in the country. Under the agreement, both companies will collaborate to conduct clinical trials in China.

Fosun Pharma has the rights to commercialize the vaccine in China and will pay BioNTech up to USD 135 million, that’s EUR 120 million, in upfront and potential future investment and milestone payments. The 2 companies will share future gross profits from the sale of the vaccine in China.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [5]

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Thanks, Sean. Before I move on, I would like to note that we are currently monitoring the situation in regards to the potential impact of COVID-19 on our operations. Özlem and Sierk will provide additional detail later in the call. But there has been impact to some of our previously communicated prior time lines, in particular, to planned study starts for 2020. We will continue to monitor the situation and provide updates as appropriate.

I will now ask Ryan to provide a brief update on our announced offer to acquire Neon Therapeutics. First, however, I wanted to highlight Ryan’s appointment as Chief Strategy Officer. He has significantly contributed to multiple key corporate development initiatives, including the acquisition of Neon. And he was instrumental in successfully taking BioNTech public in a challenging market environment. I want to thank him for his accomplishments so far and look forward to his continued efforts in helping to execute our global growth strategy. Ryan?

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Ryan Richardson, BioNTech SE – Chief Strategy Officer, MD & Member of Management Board [6]

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Thank you, Ugur. Turning to Slide 8. In January, we announced entry into a definitive merger agreement under which BioNTech would acquire Neon in an all-stock transaction. The transaction remains subject to a vote of Neon’s shareholders, which we expect to take place during the second quarter. For those unfamiliar with Neon, it’s a biotechnology company based in Cambridge, Massachusetts, developing novel neoantigen-based T cell therapies.

From a strategic standpoint, this acquisition is a strong fit on multiple levels. For one, it will bring us some exciting preclinical programs, including NEO-PTC-01, a personalized neoantigen-targeted T cell therapy candidate, consisting of multiple T cell populations that target the most therapeutically relevant neoantigens from each patient’s tumor. It also brings NEO-STC-01, a T cell therapy candidate targeting shared RAS neoantigens.

In addition, Neon has assembled libraries of high-quality TCRs against various shared neoantigens across common HLAs, which we believe will complement our own technology toolkit. Neon’s pipeline is underpinned by several complementary platform technologies, including RECON, its machine learning bioinformatics platform and also NEO-STIM, its proprietary process to directly prime, activate and expand neoantigen-targeting T cells ex vivo. The acquisition will enable us to significantly expand our presence and capabilities in the United States, which remains a strategic priority for us.

Under the terms of the agreement, Neon would become a wholly owned subsidiary of BioNTech upon closing. As previously indicated, subject to a favorable vote of Neon shareholders, we expect the transaction to close during the second quarter of 2020. We look forward to closing the acquisition and beginning the integration process.

I will now hand over to Özlem to discuss key updates in our development programs.

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [7]

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Thank you, Ryan. Today, I’m going to provide key updates for our pipeline since our last call in November. I’ll start with some detail on the effects of the coronavirus pandemic on the timing of our clinical trials. The short message is that we do expect some impact to the time lines we have previously communicated. As shown on Slide 9, while our review of the impact is ongoing, we are developing and implementing the 3-point plan to manage the still evolving disruptions that the pandemic is creating.

First, we still intend to initiate Phase II trials for BNT111, BNT113 and the iNeST program as originally planned. We assume that the anticipated start date of end-of-year 2020 provides time for stabilization of the clinical trial environment. We believe that the trial of BNT111 and BNT113, these are our FixVac products for melanoma and for HPV-positive cancers, have the potential to be registrational studies. Therefore, continuing this — the activities to progress towards initiation of these trials is a key priority for the company.

Second, we will manage for ongoing Phase I exploratory and dose escalation trials to support timely completion. We have seen evidence of slowed enrollment in our trials, given restrictions at clinical sites and travel restrictions for patients. We expect BNT111 and 114, the TNBC and melanoma FixVac trials to be less affected given that these trials are near completion of enrollment. The recently initiated programs, such as BNT112, which is prostate cancer FixVac, are more likely to be affected by these delays.

Third, we expect that there will be delays to some of our first-in-human studies planed to commence this year. For now, we maintain timing guidance for our CARVac program, BNT211. Delayed start of first-in-human Phase I studies may occur for our RiboMabs program, BNT141 and 42; our RiboCytokine program, BNT151, 52 and 53; and our TLR7 agonist program, BNT411. And also for our Influenza program and our Rare Disease program. At this time, we estimate the delay for these trials at approximately 3 to 6 months. Overall, as coronavirus situation remains dynamic, we will continue to monitor the situation as it evolves. We will update investors as appropriate.

Now I’ll discuss key updates to our clinical pipeline, as shown on the next slide, where we have 10 products in 11 ongoing trials. First, an update on BNT111, our FixVac candidate for the treatment of advanced melanoma. Data from our Phase I trial in advanced melanoma is on track to be published soon. Further regulatory discussions have occurred regarding next steps, and I will provide more details later.

BNT112 is our FixVac candidate for the treatment of prostate cancer. Dosing of patients in a Phase I/IIa study has been initiated. Eligible patients for dose titration have metastatic castration-resistant prostate cancer. In the expansion part, also patients with newly diagnosed, high-risk, localized prostate cancers are eligible and will be treated with BNT112.

BNT114 is a program that evaluates a range of novel antigens for the treatment of TNBC for immunogenicity in a Phase I/II trial. The data was previously expected to be presented at CIMT annual meeting, scheduled for May. Given the postponement of the conference due to the COVID pandemic, BioNTech is evaluating the appropriate opportunity to present the data later this year.

Moving on to our individualized neoantigen-specific immune therapy or iNeST program. Earlier this year, at our JPMorgan presentation, we provided some additional clinical data from the Phase I trial for BNT121, the precursor to RO7198457 or BNT122. This data update demonstrated stable disease in melanoma patients for up to 60 months post vaccination.

For BNT122, we disclosed with Genentech that 2 additional Phase II clinical trials in the adjuvant setting are planned for initiation in 2020. The first adjuvant Phase II study will evaluate the efficacy, safety, pharmacokinetics, immunogenicity and biomarkers of BNT122 plus atezolizumab compared with atezolizumab alone in patients with Stage 2-3 non-small cell lung cancer, who are positive for circulating, tumor DNA following surgical resection and have received standard-of-care adjuvant platinum-doublet chemotherapy. The second indication has not been yet disclosed.

Regarding the iNeST Phase II trial in first-line melanoma, we still plan to provide detailed interim data in 2021 and an enrollment update in H2 2020. We expect the interim data in 2021 to include top line efficacy and safety data as of the interim date.

Now turning to our intratumoral immunotherapy program, partnered with Sanofi. The data update from the ongoing Phase I/II trial of BNT131 in solid tumors remains on track for later this year. I’m also pleased to report that our next-generation checkpoint immunomodulatory program, partnered with Genmab is moving rapidly. Top line data from the Phase I/II trial, BNT311, in multiple solid tumors is now expected in the second half of this year, ahead of our previous expectation for a data readout in the first half of 2021.

And finally, progress has been made in our clinical program for BNT321. The first patient has been dosed in the reduced Phase I/II study, evaluating the safety and recommended Phase II dose of BNT321 in patients with pancreatic and other CA19-9 positive malignancy.

I will now move to Slide 11 and provide some quick updates on our preclinical pipeline. First, for our FixVac portfolio, BNT116 has been added to our product portfolio and is currently in preclinical development for non-small cell lung cancer. As I mentioned earlier, BNT211, our CAR-T program targeting solid tumors is on track to go in the clinic in summer this year. This program combines our CAR-T therapeutic approach with our mRNA vaccination and uses our proprietary tumor selective target Claudin 6. For our TLR7 agonist, BNT411, the IND was allowed in Q4 2019. We expect Phase I initiation later this year. And lastly, Project Lightspeed. As Ugur mentioned earlier, we expect to dose the first patient in our clinical program, testing BNT162, our COVID-19 vaccine candidate, in April of this year.

Now on Slide 12, I want to give some additional detail on 2 of our most advanced immuno-oncology programs, BNT111 and BNT122. For BNT111, our melanoma FixVac, we expect data from our Phase I trial in advanced melanoma to be published in a medical journal in late H1 2020. As I mentioned earlier, we have had further discussions with regulatory authorities regarding next steps and the design of a registrational trial. Based on those discussions, we believe, there may be potential to conduct a registrational Phase II trial instead of a Phase III trial. We are not providing full trial design details at this time, but we can say that we expect the arms to include BNT111 in combination with a checkpoint inhibitor and controls. The study population will be patients who are checkpoint inhibitor experienced. We expect to provide a further update on the expected trial design in Q3 2020.

For BNT122, a data update for the Phase I/II trials in multiple solid tumors was planned at the AACR annual meeting, which due to the COVID-19 pandemic, has been rescheduled for August 2020. Our data is embargoed until to that presentation date. We are very pleased that iNeST was included during the recent Genentech Research and Early Development or gRED event. For those that may have missed the presentation, Genentech highlighted iNeST’s potential to provide a personalized cancer vaccine for a broad range of cancer patients.

I will now hand the call over to Sierk to discuss our current financial results for the fourth quarter and full year 2019.

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Sierk Poetting, BioNTech SE – CFO, COO & Member of Management Board [8]

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Thank you, Özlem. Before presenting the financial results, I would like to provide you information on our measures that we put in place in order to mitigate the potential impact of the coronavirus pandemic on our operations.

In response to the coronavirus outbreak, we continue to monitor the potential impact to our supply chain and manufacturing operations, which includes mRNA manufacturing for FixVac and iNeST platform products as well as our CAR-T manufacturing site. So far, our manufacturing operations are unaffected and still running at full capacity. In terms of our personnel, we have instituted measures to ensure their safety for precautionary reasons. We are closely monitoring any employee that has potentially been in contact with affected individuals or in affected areas, and we are limiting access to BioNTech facilities as appropriate.

Now I would like to summarize our financial results that are shown on Slide 13. Cash and cash equivalents as of December 31, 2019, were EUR 519.1 million. As we indicated earlier in the year, we expect net cash used in operating activities and other investments to total approximately EUR 300 million for the full year of 2020. At this time, we are maintaining that guidance.

Total revenue consisting primarily of revenue from collaborative agreements was EUR 28 million for the fourth quarter of 2019 compared to EUR 63.8 million from the prior year period. This decrease was primarily due to decreased revenues from our collaboration with Sanofi. Total revenue consisting primarily of revenue from collaborated agreements was EUR 108.6 million for the full year of 2019 compared to EUR 127.6 million for the prior year. The decrease was primarily due to decreased revenues from our collaboration with Sanofi. The decrease in revenue from Sanofi is primarily driven by revenue of EUR 33.2 million for a onetime reimbursement of certain sublicensing costs that was fully recognized in the year 2018.

Research and development expenses were EUR 65.4 million for the fourth quarter of 2019 compared to EUR 51.8 million for the prior year period. The increase was primarily due to an increase in headcount and higher expenses regarding our collaboration projects. Research and development expenses were EUR 226.5 million for the full year of 2019 compared to EUR 143 million for the prior year. The increase was primarily due to an increase in headcount, the full year impact of our ESOP program and higher spending for purchased services and laboratory supplies for the projects.

General and administrative expenses were EUR 11.1 million for the fourth quarter of 2019 compared to EUR 10.1 million for the prior year period. General and administrative expenses were EUR 45.5 million for the full year of 2019 compared to EUR 26.3 million for the prior year. The increase was primarily due to an increase in headcount, the full year impact of our ESOP program and a charge in connection with certain withholding tax payments for intellectual property licenses that was recorded in the year 2019.

Net loss was EUR 58.2 million for the fourth quarter of 2019 compared to a net loss of EUR 1.5 million for the prior year period. Net loss was EUR 179.2 million for the full year of 2019 compared to net loss of EUR 48.3 million for the prior year. Shares outstanding as of December 31, 2019, were approximately 226.8 million.

With that, I will return the call back to Ugur for concluding remarks.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [9]

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Thank you, Sierk. Following a strong and productive 2019, there are several important milestones ahead of us in 2020, as shown on Slide 14. This includes 6 trial updates, including publishing BNT111, FixVac melanoma Phase I data in a peer-reviewed journal. We look forward to the initiation of a trial for our BNT111 FixVac melanoma candidate, which we believe has registrational potential. We also expect the initiation of 2 additional iNeST trials in adjuvant stage cancer this year.

By the end of next month, we expect the initiation of the clinical testing of our COVID-19 vaccine candidate, BNT162. I would like to point out that we expect to start a Phase I/II trial using CARVac BNT211 in Claudin 6-positive solid tumors. And we want to start a Phase I trial of our TLR7 program, BNT411, in solid tumors.

Lastly, we will work to integrate our U.S. hub in Cambridge, Massachusetts, following the expected closing of the Neon acquisition in the second quarter 2020. We look forward to updating investors and other stakeholders throughout 2020. We thank our shareholders for their trust and support. We will now take any questions you may have. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) The first question we have today comes from the line of Cory Kasimov from JPMorgan.

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Cory William Kasimov, JP Morgan Chase & Co, Research Division – Senior Biotechnology Analyst [2]

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A couple of them for you. I guess, to start, your COVID-19 program, BNT162, is — what are the gating factors to getting this product into the clinic? And can you maybe discuss at a high level, how your vaccine approach might be differentiated?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [3]

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Yes. Thanks for the question. So the development of our COVID vaccine is based on our in-house platforms. We have 3 messenger RNA platforms, which are currently exploited for development of COVID vaccines, exploiting different epitopes. So it’s the modified messenger RNA platform; then the uridine mRNA-based platform, which we are using currently in — for treatment of cancer patients and the self-amplifying RNA platform. The sequence of development events is based on preclinical evaluation of signals and on GMP manufacturing of the material, GLP toxicology and discussions about the clinical trial design with the regulatory authorities in Germany, China, and with the FDA and the related ethics committees. We are on track in the development of our vaccine approach and expect a timely start of the first clinical trial in Germany in the second half of 2020. The differentiation factors of our vaccine platform is one intention is — that we get — develop a vaccine, which is not only safe, but it enables immune responses, neutralizing antibodies with the lowest possible dose.

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Cory William Kasimov, JP Morgan Chase & Co, Research Division – Senior Biotechnology Analyst [4]

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Okay. And then from a time line point of view, would you expect this to follow a similar path to other vaccines that have been publicly commented on?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [5]

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To which type of vaccines do you refer?

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Cory William Kasimov, JP Morgan Chase & Co, Research Division – Senior Biotechnology Analyst [6]

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Well, to other COVID-19 vaccines that we’ve heard about from other companies that have been commented, they’ve talked about, and they’ve talked about time lines and talked about things like 12 to 18 months in a situation like this, potentially get it from start to finish. Do you think that’s a kind of a realistic expectation for your program as well?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [7]

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So maybe Özlem can answer…

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [8]

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Yes, I can take this one. These are plausible sounding time lines. At the end of the day, this will — the time lines will depend on positions of regulatory authorities and based on which type of data such a vaccine would be made available to a larger population. So this will need to be really worked out in the ongoing discussions we, and also the other companies you are referring to, have with the regulators and the data which we can all present from our trials.

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Cory William Kasimov, JP Morgan Chase & Co, Research Division – Senior Biotechnology Analyst [9]

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Okay. Makes sense. And then one non-COVID-19 question, if I may. Can you just give us a sense of where you are in terms of dose escalation for BNT311? And how much data we should maybe expect in the second half of this year?

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [10]

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That’s the DuoBody.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [11]

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Yes, yes.

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [12]

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The DuoBody. We are — you refer to the PD-L1/4-1BB DuoBody, which we are developing in cooperation with our partner, Genmab. We are pretty advanced in our dose escalation so have cleared a number of dose levels which were planned and the data disclosure or presentation would definitely include data referring to safety of the different doses, probably also the Phase II dose.

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Operator [13]

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The next question today comes from the line of Tazeen Ahmad from Bank of America.

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Tazeen Ahmad, BofA Merrill Lynch, Research Division – VP [14]

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With regards to your publication that you mentioned in your prepared remarks, as expected, in the second half of the year of Phase I data for melanoma, can you give us an idea of what level of detail you expect to have in that article? And as it relates to a potential for registrational study, what in your discussions with FDA gives you confidence that you would be able to potentially use the next study as registrational versus having to do a full Phase III?

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [15]

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So the first question, referring to our publication. Here, the data we will publish is data that comes from our Lipo-MERIT trial of a dose escalation, dose expansion trial with our melanoma FixVac in heterogeneous population of patients with advanced melanoma. And what we will publish, the focus here is primarily on the mode of action of the vaccine, which we show for the first time in humans, in particular, also the immune responses, their magnitude, their type and their kinetics, but also some safety and activity data.

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Tazeen Ahmad, BofA Merrill Lynch, Research Division – VP [16]

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Okay. And as it relates to your discussions with FDA on the potential for a registrational study.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [17]

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Yes. So the discussion with the FDA was, of course, based on the design of the clinical trial, the statistical parameters required for showing the end points of the clinical trial and the treatment and control arms. And based on this discussion — and we will further provide updates, specific updates about different arms and the size of the arms later on. Based on the discussion with the FDA, we are confident that if we can deliver the request of the study — of the desired study design, then the FDA would be in agreement with the registrational nature of the trial.

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Tazeen Ahmad, BofA Merrill Lynch, Research Division – VP [18]

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And would that require an in-person meeting once you deliver the study design?

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [19]

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Sorry, can you repeat?

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Tazeen Ahmad, BofA Merrill Lynch, Research Division – VP [20]

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Sure. Once you deliver the study design to the agency, would you then need to have an in-person meeting with the agency to determine if this can be registrational?

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [21]

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In general, the agency also enables non-in-person meeting, also phone conferences. So that would be also in this case, be sufficient.

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Operator [22]

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The next question today comes from the line of Shanshan Xu from Berenberg.

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Shanshan Xu, Joh. Berenberg, Gossler & Co. KG, Research Division – Analyst [23]

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Regarding BNT162, that’s the COVID-19 vaccine, among S, M, E, N proteins, what could be your target? And are you thinking about receptor binding domains? And you also mentioned that you saw neutralizing antibodies generated in the BNT162 preclinical study. Can you share with us, which epitopes you observed for these neutralizing antibodies? And do you think titer of neutralizing antibodies can serve as surrogate clinical efficacy end point in COVID-19 vaccine development? And I have one follow-up.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [24]

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Thank you, Shanshan, for the interesting questions. So yes, we are evaluating different epitopes, including the full-length spike protein, but also subdomain. We will provide details of our subdomain vaccines in the coming weeks and immune responses that we observe against the full-length protein and the subdomain parts. We have established a number of assays studying immune responses in mice, including antibody responses, T cell responses, neutralizing antibody responses using pseudotype and virus-based neutralization assays. And based on the assays, we are confident to reduce the spectrum of candidate to a meaningful number to be tested in the clinical trial.

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Shanshan Xu, Joh. Berenberg, Gossler & Co. KG, Research Division – Analyst [25]

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Okay. And another question regarding the RNA format and also the delivery formulation. So mod RNA, that’s the modified RNA, that is the mRNA format you used in your Zika vaccine. To us, it is not highly immunogenic. Can you tell us what is the scientific rationale of using it in infectious disease vaccine? And also for your delivery formulation, the lipid nano particle, LNP, you saw that with this delivery technique, it was modified to shift the immune response more towards Th2 cells, not Th1 cells. Can you share us — with us what modifications have been done on this LNP formulation to increase Th2 activation?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [26]

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Yes. So actually, we have a set of mechanistic data that the different platforms, which we are using, all produce different levels of Th1 responses. So it is also the modified on a platform together with the novel formulation, has strong T follicular helper immune responses. And most importantly, induces highly neutralizing antibody responses, which are in our working hypothesis, are the most important immune response parameters required to control COVID-19. We used the unmodified mRNA platform since it comes with TLR7 co-stimulatory activity to evaluate if the additional TLR7 agonistic activity can further reduce the dose. And we are using a self-amplifying RNA-based approach to further elaborate whether due to the self-replication based on the vaccine amplification after delivery, we can further reduce the dose. There is evidence in the preclinical settings, we have published data showing that this is the case for HIV and this is the case for influenza vaccine. And therefore, also based on preclinical data that we have seen for COVID-19, which are encouraging, we decided also to evaluate this platform in a clinical trial.

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Operator [27]

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The next question today comes from Navin Jacob from UBS.

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Navin Cyriac Jacob, UBS Investment Bank, Research Division – Equity Research Analyst of Specialty Pharmaceuticals and Large Cap Pharmaceutic [28]

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Navin from UBS. So a couple of questions. Just as it relates to targeting this spike protein, can you give us any kind of color on how you’re thinking about whether mutations around the spike protein could create selective pressure? And then separate — and then with regards to that, how you’re thinking about time lines? What exact — what data you need to see to ensure that, that is not going to be — that won’t be an issue? And then separately or along the same sort of lines, how are you thinking about antibody-dependent enhancement?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [29]

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Yes. Thanks for the interesting question. So first of all, there are now emerging publications showing the genetic profile of different — of COVID sequencing data, and the positive conclusion from the studies is that COVID-19 genome is relatively stable. We have also done a deeper look, particularly to the epitopes that we are targeting. And we see minimal differences in different — in COVID variance isolated in different regions of the planet. So that we are confident that escape of the spike protein is not an issue.

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Operator [30]

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The next question today comes from the line of Daina Graybosch from SVB Leerink.

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Daina Michelle Graybosch, SVB Leerink LLC, Research Division – MD & Senior Research Analyst [31]

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First, a couple on COVID-19, and I want to ask one about your oncology work. We’ve heard some people speculate that coronaviruses may need a T cell immunogenistic response in addition to an antibody, and you’ve talked mostly about antibody response. And I wonder if you can talk about a cellular response. And how important that is in your preclinical work? And the second question is, there’s a lot of speculation how durable immune responses are to coronaviruses, broadly and COVID-19 specifically. And can you help us understand how you’re thinking about durability of protection with your vaccine and your hypothesis on necessary boost schedules?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [32]

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Yes. Yes. So first of all, all of our formats induced, in the combination with the formulation which we are using, powerful CD4 as well as CD8 T cell responses. So that’s not an issue. The second is durability of the immune response induced by the virus infection itself is something different than the durability of the immune response induced by a vaccine. So we are using here a vaccine with an inherent adjuvant effect. And we see with this type of vaccine, regardless of the epitopes that we are using, long-lasting immune responses. We have shown that for our — for all of our platforms that we observe long-lasting neutralizing antibody responses for more than 1 year with the different platforms and T cell responses — long-lasting T cell response. So we are not concerned with regard to the durability of the immune responses that we are generating by the vaccine. With regard to the durability of immune responses that are generated by the COVID-19 infection, we have just to see because the data are emerging and long-term observational data are needed.

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Daina Michelle Graybosch, SVB Leerink LLC, Research Division – MD & Senior Research Analyst [33]

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Great. And then on oncology, you’ve talked a lot about delays. But we’ve heard reports of other challenges in conducting trials that are already enrolled, say, protocol violations like missed scans. And I think that’s so important for your early Phase I trials. And I wonder how you’re monitoring that? And if you’re taking any mitigating action to make sure the data you get is what you need or at least we understand problems in the data.

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [34]

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Sure. Sure. You’re perfectly right. That indeed is one of the major activities, namely monitoring the situation, understanding the specific impact on what is happening at the clinical sites, how regulatory authorities see, for example, potential deviation. And how to mitigate those deviations we identify as potentially emerging patterns under the current situation is one of the major actions taken here in our company. And you may have heard that some regulatory authorities give guidance in particular for deviations, how to document them, for example, in order to ensure that they can then be addressed by regulators appropriately, given the situation the entire clinical trial landscape is in. But fully agree, this is one of the major aspects, which are implemented into the way we are dealing now in this — for emerging situation with the way we conduct our clinical trials and decide upon how the individual trials should be adapted or further conducted.

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Operator [35]

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The next question today comes from the line of Akash Tewari with Wolfe Research.

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Akash Tewari, Wolfe Research, LLC – Director of Equity Research & Senior Research Analyst [36]

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I have a few questions. So Roche made some comments that there’s tweaks and optimizations that can be made to the iNeST program. Any color on what those tweaks are? And I think more broadly, where is the ideal setting for a personalized cancer vaccine? And would it be in the late-stage, more bulky, solid tumors or perhaps in earlier settings?

Next, on your COVID vaccine, can you talk about your self-amplifying mRNA platform in the context of your vaccine? And given your current manufacturing capacity, what’s the largest dose you think is commercially feasible to serve a broader population?

And then finally, there’s been a lot of work recently that’s shown the growing role of B cells and tertiary lymphoid structures in the role of IO responses. What’s your opinion on some of this emerging research in context of your cancer vaccine platform and also your PD-L1/4-1BB bispecific.

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [37]

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Many questions.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [38]

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Okay. Many questions. So starting with our personalized vaccine approach. So we have, of course, ongoing trials with our actually third-generation messenger RNA platforms running with — in collaboration with Genentech. And of course, we are further developing the platform and continuously evaluating improvements, like, for example, improvements in antigen design, improvements in formulation, optimization, improvement in the number of epitopes that we are delivering and improvement in the extent of TLR stimulation, which is included with our vaccine. And we are — in the next 12 months, we are going to publish a number of collaborative studies with Genentech showing how next-generation vaccines could look like.

With regard to the positioning of personalized cancer vaccine, we and Genentech believe that particularly tumors with a lower tumor load and particularly tumors with an adjuvant stage could be ideally suited for the vaccine in combination or even without checkpoint blockade. For diseases, which are more in the advanced and later stage, there might be necessary to add additional combinations of IO drugs, for example, cytokines to further improve the activity of a vaccine in this prior settings.

So what was the last question? sa-RNA. So with regard to the sa-RNA, so we have published a number of preclinical studies. And one of the interesting insights in using sa-RNA is that sa-RNA can reduce the dose, which is required to induce a strong antibody and T cell response, can reduce the dose up to 60- to 80-fold as compared to a nonamplified vaccine. And this is, of course, an exciting opportunity to elaborate and to test in a setting where the manufacturing of the sufficient scale of vaccine could be a challenge. We are currently continuously increasing our manufacturing scale. We will update about the target scale for manufacturing in the coming weeks and months. But it is clearly our vision to have sufficient capacity to deliver to hundreds of million individuals doses of vaccine in a reasonable time period.

Yes, there was another question that’s related to the B cell infiltration in human tumors. Yes, I think, this — there is a series of publications showing the different type of infiltrates, including infiltrates with dendritic cells and B cells are associated with the improved prognosis and responds to a checkpoint blockade. And of course, we are aware of these studies. We — for example, for all of our iNeST studies, we are evaluating with some [focus with] tumors, yes, and evaluating and are able to see which type of infiltrate is associated with type of immune response. And based on this type of information, we can, of course, exploit different type of immunomodulatory treatments.

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Operator [39]

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That question comes from the line of Arlinda Lee from CG.

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Arlinda Anna Lee, Canaccord Genuity Corp., Research Division – Analyst [40]

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First on the COVID vaccine. You mentioned that you were working with the German, Chinese and U.S. governments. Wondering if you could provide some color on your conversations and maybe your strategy on potentially manufacturing at risk. Secondly, on — we had the chance to see sample cancer care changes during COVID. And I was wondering if you could comment on modifications to your clinical trials or enrollment criteria. And also, you’re doing a lot of biomarker studies. I’m wondering if some of these assays can be done on archival samples and how that might be affected.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [41]

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So we are talking to regulatory authorities in China, Germany and the U.S. and part of the dialogue is, of course, harmonization of the clinical trial designs in these different countries. And not only harmonization, but also having complementary trial designs, which allow to maximize the amount of information that can be generated. And interestingly, the situation, where Europe and U.S. now became the hotspot of the infection and the infection rate in China is cooling down, so giving us different opportunities in different regions affected with different frequency of infections. And this is also a good-to-have situation. Of course, based on the situation, we can generate safety and activity, efficacy and effectivity data in different regions of the world.

With regard to the biomarker strategy, of course, we need to evaluate antibody responses before vaccination and after vaccination. And this is a straight-forward approach. There is established — there is an established industry for collecting samples or analyzing examples. We have already identified CROs supporting us here. So this will not be a challenge.

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Ryan Richardson, BioNTech SE – Chief Strategy Officer, MD & Member of Management Board [42]

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Yes. And maybe just to add to that, Arlinda. In terms of the manufacturing at risk part of your question, and I think, it was our strategy from the beginning to try to get a global consortium in place. And we leveraged our partnerships, both existing and also new to do that. And so we are continuing to evaluate how best to scale up the manufacturing effort and fund it through our — through those relationships with existing partners and also potential new sources of capital.

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Arlinda Anna Lee, Canaccord Genuity Corp., Research Division – Analyst [43]

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Great. And maybe just following up on your oncology pipeline. Just — can you — since biopsy volumes are down, I’m just curious if the enrollment criteria that you have in place enables use of archival tissue. And how you’re collecting biomarker data for your oncology trials, collecting and processing? And then maybe lastly, can you talk about your strategy for your cytokine pipeline?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [44]

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Okay. Okay. So the archival tissues for development of oncology trial, yes. Özlem, would you like to answer it? Yes.

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Özlem Türeci, BioNTech SE – Chief Medical Officer & Member of Management Board [45]

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I will take that one. So it depends on really the drug we are investigating in those trials. In trials, in which we want to see and collect biospecimen in order to see the effect of the drug and need a baseline and undertreatment sort of biopsy or blood sample, there is no flexibility to work with archival tissues or samples because this is really about seeing the impact of the drug. In studies, we are — we — for someone to test whether the patient has a certain marker, which is stable, we work, in fact, with archival tissue from this patient. So it really depends on which question needs to be answered. And we have a mixture of both fresh tissues and materials and archival materials.

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [46]

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And if your question refers to the enrollment of patients into iNeST studies, yes, we can here use and we are using archival material, which is paraffin fixed so that means there is no essential need to do fresh biopsies.

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Operator [47]

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Thank you very much. Would you like to make some closing remarks?

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Ugur Sahin, BioNTech SE – Co-Founder, CEO & Member of Management Board [48]

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So thank you. Thank you for today’s call, and we look forward for meeting you in near future. Thank you.

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Operator [49]

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Thank you very much. That does conclude the conference for today. Thank you for participating. You may all disconnect.

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