Biontech SE (BNTX) 2020 Q4 法說會逐字稿

Good day, and thank you for standing by.

Welcome to BioNTech's Corporate Update and Financial Results Fourth Quarter and Full Year 2020 Conference Call.

(Operator Instructions) Please be advised today's conference is being recorded.

(Operator Instructions)

Now I'd like to hand the conference over to your first speaker today, Sylke Maas, Vice President, Investor Relations and Strategy.

Please go ahead.

Thank you.

Good morning and good afternoon.

Thank you for joining us today to review BioNTech's fourth quarter and full year 2020 operational progress and financial results.

Before we start, we encourage you to view the slides for this webcast as well as the operational and financial results press release issued this morning, both of which are accessible on our website in the Investors section.

As shown on Slide 2, during today's presentation, we will be making several forward-looking statements.

These forward-looking statements include but are not limited to our current estimate of COVID vaccine revenues based on current contracted supply orders, expenses, expenditures and tax rate for 2021; our target vaccine production capacity for 2021; our COVID-19 vaccine revenues which are subject to numerous estimates as more fully described in our annual report on Form 20-F; the ability of BioNTech to supply our COVID-19 vaccine; the planned next steps in BioNTech's pipeline program; the timing for enrollment, initiation, completion and reporting of data from our clinical trials; other risks described in our filings made with the U.S. Securities and Exchange Commission, including our most recent annual report on Form 20-F.

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 today, shared today during this conference call and webcast.

Also, please note that Slide 3 provides details and important safety information regarding our recently launched COVID-19 vaccine.

On the call from BioNTech management today will be Ugur Sahin, our Chief Executive Officer and Co-founder; Özlem Türeci, our Chief Medical Officer and Co-Founder; Sean Marett, our Chief Business and Commercial Officer; Sierk Poetting, our Chief Financial and Operating Officer; and Ryan Richardson, our Chief Strategy Officer.

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

Good morning and good afternoon, and thank you to everyone joining the call today.

I'm delighted to be here to discuss the progress that we made in 2020, and I would like to introduce the important milestones we have planned in 2021 and beyond.

Slide 5. 1 year ago, when the whole world was witnessing the rapid spike of the SARS-CoV-2 virus, at BioNTech, we made an early decision in January last year to tackle the virus head on.

We utilized the powerful mRNA vaccine platform and our deep immunoengineering competencies we have been developing for over a decade.

This early decision and the enormous amount of work and energy that followed it resulted in a highly effective vaccine in less than a year.

Now 1 year later, we are already seeing the first signs of the positive impact the vaccines are having in reducing infections, hospitalizations and mortality.

Our work against COVID-19 is not finished.

In today's presentation, I will summarize what we are currently doing and what will come next.

Turning to Slide 6. 2020 has literally transformed BioNTech.

Our COVID-19 vaccine has now been authorized for use in more than 65 countries, with more than 200 million doses having been supplied as of March 23.

During the fourth quarter of 2020, we recognized our first commercial product sales.

This is a major milestone given the considerable investment in research and development which we have made over the past 13 years.

We are now a fully integrated biopharmaceutic company.

We have built a sales force in Germany, and we have built global commercial-scale manufacturing capacity.

We expect to be able to produce up to 1 billion doses of our vaccine in 2021 in BioNTech's own manufacturing network.

Our Marburg facility has made remarkable progress since we acquired it and will be ramping up production in the second quarter.

Despite COVID-19 being the spotlight last year, we made progress in advancing our oncology pipelines.

We now have 13 oncology product candidates in 14 ongoing trials across 4 different drug classes.

Many of these products demonstrate promising activity in Phase I clinical trials, and we plan to initiate multiple Phase II trials this year.

We recently started first-in-human trials for our CARVac product BNT211 and for our RiboCytokine product BNT151.

Further, we are advancing our first wave of product opportunities toward the market.

We expect up to 3 product candidates, including our mRNA cancer vaccines and our lead bispecific antibody, will be entering into randomized Phase II trials by the end of this year.

Ultimately, the core of our success is our employees.

We have built a global footprint with establishment of our U.S. research and development hub, and we have increased our workforce to over 1,900 employees worldwide.

I want again to thank our employees for their tremendous efforts during a; challenging and exciting year.

Moving to Slide 7. I want to highlight some key takeaways for us as we reflect on 2020.

First, it became clear that our mRNA pharmaceuticals have a great potential to address major health challenges.

While the first generation of our mRNA vaccine technology has already proven to be powerful, we are working on rapid iterations to further improve this new class of products.

Our mRNA approach is not based on a simple technology.

Our way of developing our technologies is not based on the idea of a single-trick pony.

Rather, our goal from the very beginning was to build a novel industrial approach for precision pharmaceuticals that can address medical need in multiple disease areas.

We did more than a decade-long research to develop a broad toolbox of mRNA technology platforms.

Each of this technology platforms is tailored and optimized for potency and immunological precision to enable the development of best-in-class product candidates for various disease areas.

Second, we believe that mRNA will revolutionize the field of immunology, and BioNTech is well placed to continue to lead the revolution given our broad technology base, robust IP portfolio and deep know-how in the field.

We intend to increase further our investment in the space given the tremendous opportunity we see.

In addition, we learned from our COVID-19 experience that product development can be faster.

We intend to apply the capabilities and learnings we developed during the Project Lightspeed to rapidly advance our pipeline products toward the market.

And finally, we learned that our collaboration model works.

Our focus on innovation and our strategic partnership with powerful collaborators like Pfizer has helped us not only develop product in record time but establish an early market-leading position.

We intend to continue to leverage our strategic partnerships by building our own capabilities in long term.

As depicted on Slide 8, we see a great opportunity ahead.

We will accelerate the development of our innovative pipeline and expand the number of product candidates and indications we pursue.

Our goal is to launch several additional products in oncology and infectious disease fields over the next 5 years, and long term -- our long-term goal remains to build a 21st century global immunotherapy powerhouse developing products for multiple disease areas.

Later in our prepared remarks, Ryan will provide some more detail into the steps we are taking to realize this vision.

Moving to Slide 9. mRNA vaccines are now established as a powerful new drug class.

On the back of this validation, we intend to rapidly industrialize our mRNA technology.

We believe mRNA vaccines are poised in the near term to displace or complement traditional modalities in a range of infective diseases and in the field of immuno-oncology.

The proceeds from our COVID-19 vaccines will allow us to accelerate our pipeline development in these core areas.

Longer term, we see applications for the technology in the field of autoimmune diseases, allergy, inflammatory diseases and even regenerative medicine.

We have established early research program at BioNTech in this research area, and we plan to significantly ramp up the effort in the coming years.

Finally, it is important to point out that our ability to industrialize mRNA technology is linked to the deep expertise and know-how we have built over the course of more than a decade.

It is also underpinned by our broad IP portfolio covering our platforms, product candidates and often the target and formulations we use.

Now moving to Slide 11.

The strong clinical results observed for our vaccine on our global Phase III trial were a clear highlight in the fourth quarter.

The study results demonstrated that our vaccine can prevent symptomatic COVID-19 with a well-tolerated safety profile.

BNT162b2 demonstrated 95% efficacy in a trial with approximately 44,000 participants, including 94% efficacy in participants older than 65 years.

The safety profile was favorable with a low frequency of grade 3 adverse events and mostly typical vaccine-related side effects.

Key characteristics of our vaccine are broad immunogenicity profile that is polyepitopic and multifactor.

The vaccine induces high titers of neutralizing antibodies, Th1 type CD4 T cell responses and robust CD8 T cell responses.

We believe all of these factors contribute to the protection conferred by our vaccine.

Turning to Slide 12.

We recently announced first real-world evidence data supporting the clinical profile of our vaccine.

This exciting news comes from an observational analysis conducted by the Israeli ministry of health between January 17 and March 6, 2021.

During this time, our COVID-19 vaccine was the only vaccine available in the country.

Specifically, the data from Israel shows that 2 weeks after the second dose vaccine effectiveness was at least 97% in preventing symptomatic disease, severe and critical disease, hospitalization and death.

The analysis also showed a vaccine effectiveness of 94% against asymptomatic SARS-CoV-2 infections.

At the time of the Israel study, the U.K. variant B.1.1.7.

was the dominant strain in the country, indicating the likely effectiveness of our vaccines against COVID-19 caused by this variant.

In this context, it is important to point out that in vitro data also supports our COVID-19 vaccine's efficacy against several variants.

We have public data in the New England Journal from in vitro studies of our vaccine's neutralization activity against 3 different variants.

In these studies, we have neutralized all the virus that is tested and showed no significant reduction in activity against B.1.1.7.

and P1 spike viruses.

The neutralization of the South African variant, B1351, spike virus was lower but it was still robust.

In addition to this in vitro testing, we are continuing to monitor real-world efficacy against several emerging variants.

As outlined on Slide 13, we anticipate that COVID-19 may become an endemic disease over the next few years.

We already see evidence that immune responses in vaccinated individuals wanes over time.

This is not surprising, indicating that re-boosting may be required.

In addition, there is a growing body of evidence showing that new variants with antibody-escape mutations are driving new infections in many regions.

As a result, we believe that there is likely a future need for additional vaccine boosters and potentially also variant-specific vaccines.

Due to their ability to be rapidly designed, customized and rapidly produced at scale, we believe that mRNA vaccines are well suited to play an important role in addressing the next stage of the disease.

Expanding broad access to BNT162b2 remains a key focus for us, as shown on Slide 14.

We highlight here 6 key levers to expand BNT162b2 reach.

The first is supply.

We have increased our supply target for 2021 to 2.5 billion doses.

This will require further process improvements and further expansion of our supplier and CCM own network, but we believe we are on track to achieve this.

Continuing to broaden our vaccine's label is also a key priority.

We have extended our clinical program to additional vulnerable populations such as pregnant women.

In February, first participants were dosed in global Phase II trial in healthy pregnant women.

The study will recruit 4,000 healthy pregnant women 18 years of age or older during the 24 and 34 weeks of gestation.

Another important pillar is our pediatric trials.

We plan to submit the safety and efficacy data in 2,000 children 12 to 15 years of age from the Phase III trial to the regulatory authorities in the second quarter.

Another study in healthy children 6 months to 11 years of age has started.

We are also planning further studies in individuals with compromised immune system.

Another key lever is geographic expansion.

Our vaccine has now been approved for emergency or temporary use or granted conditional marketing authorization in more than 65 countries, and we are moving in additional regions.

In Japan, a Phase I clinical trial started in October to evaluate our vaccine's activity in adults of 20 to 85 years of age.

In February, Japan's health minister approved BNT162b2 under the exceptional approval scheme.

Last November, a Phase II clinical trial of our vaccine started in China to evaluate BNT162b2 in healthy individuals of up to 85 years of age.

We now have initiated the regulatory submission process in Mainland China and hope to be able to provide an update soon.

We are working to broaden access and enable more centralized approach to vaccine provision.

While BNT162b2 is available in the U.S. under emergency use authorization, we are preparing BLA filing in the second quarter for full regulatory approval.

Further regulatory submissions in other regions are also expected.

Stability of formulation testing and optimization work remains another key focus.

Over the past few weeks, the U.S. FDA and EMA approved the update that undiluted frozen vials of our vaccine may be transported and stored at minus 25 degrees Celsius to minus 15 degrees Celsius for a period up to 2 weeks.

We expect additional stability profile updates over the next few months.

We are also developing ready-to-use and lyophilized formulation with improved thermal stability profiles.

We are fast-tracking development of the ready-to-use formulation and do not currently expect additional clinical studies to be required for this formulation.

For the lyophilized formulation, we announced today that we will start a trial to evaluate the safety, tolerability and immunogenicity of this formulation.

We expect data from this trial in Q3 or Q4 2021.

Antibody responses wane over time.

To address the waning of immune responses, we are evaluating the safety and immunogenicity of a third dose of our vaccine.

The aim of this trial is to understand the effect of a booster to prolong immunity against COVID-19, caused by the circulating and potentially newly emergent SARS-CoV-2 variants.

As mentioned, today, there's no evidence that an adaptation of our current vaccine against key identified emerging variants is necessary.

Despite this, we have developed a comprehensive strategy to address these variants should the need arise in the future.

In March 2021, the FDA approved an additional amendment to the study protocol of the global Phase I/II/III trial to include for a third dose of BNT162b2 or a third dose of a modified version of the vaccine carrying the spike protein segment of so-called South African variant in order to further describe duration of protection and protection against potential emerging variants of concern.

An additional group of BNT162b2-naive participants will be enrolled and receive 2 doses of the South African variant vaccine version to describe protection against the emerging variant of concern against the reference strain.

The part of this trial with the variant is expected to start by end of March.

I will now turn the call over to Sean to provide an update on our COVID-19 manufacturing and commercial supply status.

Thank you, Ugur.

Slide 15 shows the flexible manufacturing process of our COVID-19 vaccines.

We can go from DNA template production to sterile filtration and filling in as few as 9 to 13 days.

Although 50,000 steps are required from manufacturing the mRNA to the bulk drug substance, the overall manufacturing from DNA template to fill and finish can be done in less than 2 weeks.

Following production, quality control and release can take another 4 to 5 weeks, and then, we are ready to deliver the vaccine.

One of the advantages of our mRNA technology is that it allows a rapid adoption of the vaccine to variants.

Unlike traditional vaccine production, we can adapt our manufacturing to encode a new variant, if needed, simply by providing a DNA template that encodes protein sequence of the new variant.

This can be done within a couple of weeks and without the need for new scale up of the overall process and pending regulatory approval.

Another advantage I would like to point out, we can increase or decrease manufacturing quantities with a short lead time.

Thus, our manufacturing technology provides us with the flexibility to respond to market demand.

Moving on to Slide 16.

We have firm orders of 1.4 billion doses to date.

Recently, we announced that the United States had exercised its option for an additional 100 million doses, bringing the total to 300 million doses.

We also announced that the EU will be supplied with an additional 200 million doses with an option for an additional 100 million further doses.

This brings the total number of doses to be delivered to the EU member states by the end of 2021 to 500 million, with the potential to increase further up to 600 million doses.

Discussions for additional commitments worldwide are ongoing.

BioNTech and Pfizer's initial goal was to manufacture up to 1.3 billion doses in 2021, but we've been able to increase our target capacity to up to 2.5 billion doses for the year.

The increase was driven by a number of factors, including the increase from 5 to 6 doses per vial, additional suppliers and CMOs, continued success in process optimization and initiation of production at our Marburg facility.

On March 26, we announced that the EMA approved the manufacturing of the COVID-19 vaccine drug product at the facility in Marburg.

The approval has made BioNTech's Marburg manufacturing site one of the largest mRNA vaccine manufacturing sites worldwide with an annual production capacity of up to 1 billion doses of our COVID-19 vaccines once fully operational.

Due to optimized operational efficiencies, which were initiated last year, we were able to increase the expected annual manufacturing capacity by 250 million doses.

The first batches that are being manufactured at the Marburg site are expected to be delivered in the second half of April.

We plan to produce up to 250 million doses of BNT162b2 in the first half of 2021.

Lastly, we have taken our first step in executing our commercial strategy for our COVID-19 vaccine in Germany and Turkey while Pfizer is responsible for the rest of the world outside of China.

This is the first time that BioNTech has commercialized a product from its pipeline.

I will now turn the call over to Özlem to provide an update on our oncology pipeline.

Thank you, Sean, and hello, everyone.

As usual and in the interest of time, I'm going to provide updates on selected programs.

For further details on the stages of our other oncology programs, please refer to our annual report, which is being filed with the U.S. Securities Exchange Commission today.

As to be expected, we have continued to see some ongoing impact from the COVID-19 pandemic on our clinical operations.

Specifically, there has been a slowdown in the enrollment in some of our ongoing studies.

Despite these constraints, we expect to present several data sets and initiate multiple new trials this year.

Slide 18 outlines our immuno-oncology strategy.

Our strategy is based on several first-in-class therapeutic approaches to target cancer and to modulate the immune response.

The programs address a broad range of cancers in different disease stages.

Our 6 technology platforms have all reached clinical stage by now with 13 clinical-stage product candidates.

We see multiple blockbuster opportunities and the potential for synergistic combination.

Our later-stage programs are shown on Slide 19.

Starting with BNT111, our FixVac product candidate for the treatment of advanced melanoma.

We expect to start randomized Phase II trials in the U.S. and EU in the first half of 2021.

The trial will evaluate BNT111 in combination with Regeneron's Libtayo versus both BNT111 and Libtayo monotherapy in patients with advanced melanoma progressing during or after prior therapy with a PD-1 inhibitor.

In February, we received permission from FDA to move forward with the trial.

The next FixVac product candidate is BNT113, our mRNA vaccine encoding E6 and E7 proteins of human papillomavirus 16.

We expect to start a Phase II trial evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma expressing PD-L1 in the first half of 2021 in the U.S. and EU.

BNT113 has not been combined with anti-PD-1 before, and the Phase II trial will start with a run-in portion designed to demonstrate the safety of the combination of BNT113 and pembrolizumab.

These data are required to address the partial clinical hold on the subsequent randomized part of the Phase II trial.

Moving to our individualized neoantigen-specific immunotherapy or iNeST platform, which is partnered with Roche/Genentech.

Our iNeST product candidate BNT122 has been given the international nonproprietary name autogene cevumeran.

The Phase II trial in first-line melanoma in the Phase I basket trial in solid tumors remain ongoing.

Data updates are not expected for these trials this year.

We, along with Genentech, have made the strategic decision to discontinue the previously planned Phase II trial in patients with high-risk resected early-stage non-small cell lung cancer given challenging accrual time lines in the context of the COVID pandemic and the evolving landscape of treatment options.

We and our partner Genentech are evaluating other options for treating early-disease cancer patients with iNeST.

One of these early disease development options in the adjuvant setting is colorectal cancer.

We expect to dose the first patient in the first half of the year in a randomized Phase II trial evaluating BNT122 in circulating tumor DNA-positive surgically resected stage 2 high-risk phosphate-free colorectal cancer.

We strongly believe that iNeST could be best positioned in the earlier stage or adjuvant setting and minimal residual disease setting.

Moving to our next-generation checkpoint immunomodulators program, which is partnered with Genmab.

We expect to present a data update in the second half of 2021 for the first-in-human Phase I/II trial of BNT311, also called GEN1046.

BNT311 conditionally targets PD-L1 and 4-1BB and has the potential to be first in class.

Given the unmatched need for improved checkpoint immunotherapies, we remain very encouraged by the results presented at last year's SITC conference and seen to date and believe the product has significant potential across multiple oncology indications.

We look forward to moving this program forward with Genmab.

For BNT312, which conditionally targets CD40 and 4-1BB, we plan to present data from the ongoing Phase I/II trial in the second half of 2021.

In addition, an abstract highlighting preclinical data for BNT312 has been accepted for presentation at the upcoming AACR meeting.

The abstract describes the mechanism of action of conditional CD4 and 4-1BB activity to induce dendritic cell maturation and enhancement of T cell activation and effector function.

Slide 20 provides an overview of programs across 4 different technologies that have the potential to advance innovation beyond current boundaries.

We are pleased to announce that from our CAR-T technology, our first CARVac product candidate has entered clinical testing.

We dosed the first patient in a first-in-human trial in February for BNT211.

I'll discuss this program in detail shortly.

In the first half of 2021, we also expect to dose our first patient with BNT221, the first product from our NEO-STIM T cell therapy program, which features adoptive transfer of individualized neoantigen-specific autologous T cells.

This Phase I dose escalation trial will evaluate the safety, immunogenicity and efficacy of BNT221 in patients with checkpoint inhibitor refractory and responsive metastatic melanoma.

I'm also pleased to report that the first patient was dosed in a Phase I trial in solid tumors in February for BNT151, our first RiboCytokine to enter clinical testing.

I'll also discuss this program in greater detail shortly.

For BNT152 and BNT153 in combination, our second RiboCytokine program, a Phase I trial in multiple solid tumors is expected to start in the first half of 2021.

The BNT152 plus BNT153 IND for the Phase I trial in the U.S. was approved by the FDA end of February.

As our RiboCytokines, also our RiboMabs, BNT141 and BNT142 are intravenously administered immunotherapies with RNA encoded proteins expressed in the liver and deployed into the vascular compartment to reach therapeutically active serum concentration.

Phase I trial of our first RiboMab in multiple solid tumors are expected to start in the second half of 2021.

The FDA recently allowed our BNT141 IND.

Starting with Slide 21, more details to BNT211, the first clinical-stage product candidate from our engineered T cell program, which is expected to overcome CAR-T cell therapeutic areas that restrict the efficacy and widespread use of CAR-T cell therapies, particularly in patients with solid tumors.

BNT211 consists of 2 components.

One is a novel chimeric antigen receptor functionalized with an antibody-derived Claudin 6 binding domain with exclusive specificity and high sensitivity for Claudin 6. Claudin 6 is an ideal candidate for CAR-T cell therapy due to its absence in healthy adult tissue while high medical need cancers frequently show expression of this tumor antigen.

The second-generation CAR scaffold also includes a costimulatory domain 4-1BB, which we believe mediates prolonged survival and very positive killing ability of engineered CAR-T cells.

In preclinical studies, BNT211 demonstrated strong recognition and lysis of Claudin 6-positive target cells.

As shown on Slide 22, the second component of BNT211 is a CAR-T cell amplifying RNA vaccine, named CARVac.

We use our proprietary RNA lipoplex technology known from FixVac studies to encode full-length Claudin 6, namely the CAR-T target.

Following intravenous administration of RNA lipoplexes, the mRNA is specifically delivered to antigen-presenting cells residing in secondary lymphoid organs.

This mediates expression of Claudin 6 on the surface of those specialized cells.

Thus, Claudin 6 is recognized by adoptively transferred CAR-T cells in the lymphoid compartment that provides an ideal context for strong stimulation of these engineered T cells.

Repetitive administration of CARVac allows for controlled in vivo expansion to keep the frequency of CAR-T cells on therapeutic levels.

That expansion also results in increased persistence and superior functionality of CAR-T cells, which require a memory phenotype in preclinical models.

We are optimistic that our CARVac products allows to overcome key challenges related to CAR-T cell therapy, which includes severe toxicities, restricted trafficking to and activation within tumors as well as suboptimal persistence in vivo.

This is an excellent example for the potential of our therapeutic modalities for synergistic combinations.

Slide 23 shows the trial design for BNT211.

The Phase I trial will recruit patients with Claudin 6-positive relapsed or refractory advanced solid tumor.

Part 1 of the trial is the dose escalation of Claudin 6 CAR-T cells as monotherapy while part 2 of the trial displays the combination of Claudin 6 CAR-T cells with Claudin 6 CARVac.

Once the maximum tolerated dose or recommended Phase II dose is determined, dose expansion cohorts will follow in ovarian, testicular, endometrial, non-small cell lung and gastric cancers.

Initial Phase I data from this trial is expected in the second half of this year.

The clinical material for this trial is manufactured at our GMP-certified IMFS facility in Idar-Oberstein, Germany, which has extensive cell and gene therapy manufacturing capabilities.

Our RiboCytokines on Slide 24 are another example of another class of RNA-based therapeutics from our immuno-oncology pipeline designed to address the limitations of current therapeutic approaches.

Major challenges associated with the therapeutic use of cytokines relate to their short-term half-life and low bioavailability.

This impedes therapeutic efficacy and necessitates high and frequent dosing, which often results in dose-limiting toxicities.

Encoding cytokines by mRNA and producing them in the patient addresses these shortcomings.

The right side of the slide describes our first RiboCytokine candidate, BNT151, which has entered clinical testing.

BNT151 is a nucleoside-modified mRNA that encodes an optimized interleukin-2 fusion protein.

IL-2 is a key cytokine in T cell immunity, supporting differentiation, proliferation, survival and effector functions.

The drug design is optimized to improve pharmacokinetic properties with an increased tolerability and activity of IL-2.

Importantly, BNT151 has been designed to stimulate antitumor T cells without triggering T reg cells.

As shown on Slide 25, the ongoing Phase I trial in solid tumors with no available standard therapy features monotherapy and combination therapy dose escalation.

BNT151 will be combined with anti-PD-1 or other standard of care in cancer types such as squamous cell carcinoma of the head and neck, hepatocarcinoma, renal cancer, TNBC and non-small cell lung cancer.

While the products I just featured, CARVac, RiboCytokines and RiboMabs, are mRNA-based approaches, they quite obviously differ from one another and from the version of our mRNA technology used for creating the first COVID-19 vaccine, again demonstrating the high diversification of our mRNA platform and the many years of know-how development that went into it.

I will now hand the call over to Sierk to provide an update on our financials.

Thank you, Özlem.

I will summarize our financial results for the fourth quarter and the full year 2020, as shown on Slide 27.

I'll start with the total revenues, which were estimated to be EUR 345.4 million for the fourth quarter of 2020 compared to EUR 28.0 million for the fourth quarter of 2019.

For the full year of 2020, total revenues were estimated to be EUR 482.3 million compared to EUR 108.6 million for the full year of 2019.

Total revenues increased due to the recognition of revenues under our new collaboration agreement signed with Pfizer and Fosun Pharma as part of our vaccine program against COVID-19.

Newly generated COVID-19 vaccine commercial revenues significantly drove our total revenues.

As a reminder, under the Pfizer collaboration, territories have been allocated between the companies based on marketing and distribution rights.

A breakdown of our commercial revenues is shown on Slide 28.

Our 2020 commercial revenues comprise an estimated amount of EUR 188.5 million share of gross profit from COVID-19 vaccine sales in the Pfizer territory.

Please note this is a net figure.

Additionally, as it will be detailed in our annual report filed with the SEC, this figure is only estimated based on preliminary data shared between Pfizer and us and may be subject to adjustments as we receive final data on input parameters like sales and transfer prices.

Changes in our share of the collaboration partner's gross profit will be recognized prospectively.

Our COVID-19 vaccine commercial revenues also include EUR 61.4 million sales to our collaboration partner of product manufactured by us and EUR 20.6 million of direct COVID-19 vaccine sales to customers in our territory, Germany.

Now returning to Slide 27 and moving to cost of sales, which were estimated to be EUR 41.0 million for the fourth quarter of 2020 compared to EUR 4.4 million for the fourth quarter of 2019.

For the full year of 2020, cost of sales were estimated to be at EUR 59.3 million compared to EUR 17.4 million for the prior year.

The increase was driven by estimated EUR 35.6 million cost of sales which were recognized for the first time with respect to our COVID-19 vaccine sales and include Pfizer's share of gross profit earned by us.

Note that cost of sales do not include costs related to the production of prelaunch products since those were expensed as R&D expenses in the period incurred.

R&D expenses were EUR 257.0 million for the fourth quarter of 2020 compared to EUR 65.4 million for the comparable period in 2019.

For the full year of 2020, R&D expenses were EUR 645.0 million compared to EUR 226.5 million for the full year 2019.

The increase was primarily due to an increase in R&D expenses related to our BNT162 program.

R&D expenses include our share of expenses under the terms of the Pfizer collaboration agreement.

As a reminder, development costs are equally shared between the 2 companies.

Higher expenses for purchased laboratory supplies as well as an increase in head count leading to higher wages, benefits and social security expenses contributed to the increase.

And in addition, from the date of acquisition, our U.S.-based subsidiary, BioNTech US, Inc., also contributed to our R&D expenses.

G&A expenses were EUR 36.1 million for the fourth quarter of 2020 compared to EUR 11.1 million for the comparable period in 2019.

For the full year of 2020, G&A expenses were EUR 94.0 million compared to EUR 45.5 million for the prior year period.

The increase was mainly due to higher expenses for professional services and increase in head count leading to higher wages, benefits and social security expenses and higher insurance premiums.

In addition, from the date of acquisition, our U.S.-based subsidiary, BioNTech US, Inc., also contributed to our G&A expenses.

Following the authorization of approval of our COVID-19 vaccine for emergency or temporary use or having been granted conditional marketing authorization, the recognition of deferred tax assets was reevaluated.

As of December 31, 2020, net deferred tax assets with respect to the accumulated tax losses and temporary differences of the German tax group were recognized with a EUR 161.0 million income tax effect.

For the fourth quarter of 2020, we showed a net profit of EUR 366.9 million.

This compared to a EUR 58.2 million net loss for the fourth quarter of 2019.

For the full year of 2020, we were also profitable, showing a net profit of EUR 15.2 million compared to EUR 179.2 million net loss in the prior year period.

We ended 2020 with cash and cash equivalents of EUR 1.2 billion as a result of successful financing transactions in 2020, which strengthened our position for the execution of our strategy which will be accelerated by 2021 growth.

Now moving to Slide 29 that outlines our 2021 financial outlook.

Based on the current contracted supply orders of approximately 1.4 billion doses, we are providing estimated COVID-19 vaccine revenues to BioNTech of approximately EUR 9.8 billion.

This estimate reflects expected revenues from direct COVID-19 vaccine sales to customers in our territories, expected revenues from sales to our collaboration partners, expected sales milestone payments from our collaboration partners and expected revenues related to our share of gross profit from COVID-19 vaccine sales in the collaboration partner's territories.

We expect additional revenues related to further supply contracts for deliveries in 2021.

I would like to point out again that we have raised our manufacturing capacity target from 2.0 billion to 2.5 billion doses for the full year 2020 to be able to address increased demand.

In terms of guidance for the full year 2021, we expect R&D expenses to incur in the range of EUR 750 million to EUR 850 million for the full year 2021, reflecting our aspirations to broaden and accelerate our pipeline development, which we plan to ramp up, especially in the second half of 2021.

SG&A expenses are estimated to rise up to EUR 200 million.

Capital expenditures for the year 2021 are expected to be in the range of EUR 175 million to EUR 225 million.

I would like to emphasize that all these figures reflect our current base-case projections.

Finally, please note that in terms of full year 2021 tax impact, we expect the German tax group corporate tax rate of approximately 31%.

We have approximately EUR 450 million accumulated tax loss carryforwards with respect to the German tax group as of December 31, 2020.

And with that, I'll turn the call to Ryan for concluding remarks.

Thank you, Sierk.

Turning to Slide 32, to our 2021 strategic priorities.

Our immediate aim is to supply our COVID-19 vaccine to over 1 billion people this year and be in a position to supply it in large quantities in 2022.

While we work to broaden access to our vaccine, our goal is to build and maintain a leadership position into 2022 and beyond.

With proceeds from the COVID-19 vaccine, we plan to accelerate pipeline development in our core therapeutic areas of immuno-oncology and infectious disease.

We currently have 9 active preclinical programs in the infectious disease field and intend to advance additional mRNA vaccines against other infectious diseases.

We will provide more details on some of these programs over the course of the year.

We remain as committed as ever to our goal of ushering in a new era of immunotherapy for cancer patients.

In 2021 and beyond, we intend to accelerate and broaden our immuno-oncology pipeline, where we see a significant opportunity for BioNTech to lead in the emerging fields of individualized cancer medicine and cell therapy, among others.

Finally, we plan to ramp up investments in our platforms and early product development in select emerging therapeutic areas such as autoimmune disease, inflammatory disease and regenerative medicine.

While these areas will not be a major component of our capital allocation near term, we believe they could become major opportunities for BioNTech in the future.

Slide 33 highlights some of the key pipeline milestones we expect in 2021.

These include trial updates on at least 5 ongoing programs, including BNT311 and 312, 2 bispecific antibodies in Phase I/II trials which we believe have potential as next-generation checkpoint immunomodulators.

We also expect to initiate 3 randomized Phase II trials for our FixVac and iNeST programs in 2021.

Finally, we're on track to initiate up to 6 first-in-human Phase I trials across a range of novel IO platforms.

With the start of Phase I trials for BNT211 and 151 in the first quarter, 2 of the 6 milestones listed here have already been reached.

Importantly, all of the product entering the clinic in 2021 are wholly owned by BioNTech.

We are also pleased to announce our first Capital Markets Day, which will be held in the second half of the year.

We will confirm the date in the coming weeks.

Turning to Slide 35.

We believe we are better positioned than ever to bring innovative immunotherapy to patients by reinvesting the proceeds from our COVID-19 vaccine in trying to accelerate our vision to build a 21st century immunotherapy powerhouse.

We see a tremendous opportunity ahead to build long-term value for patients, our shareholders and society.

To broaden our global reach, we will continue to expand in key strategic locations in the U.S. and Europe and have near-term plans to establish a presence in Asia.

To support our expanding pipeline, we intend to further invest in our clinical, commercial and manufacturing infrastructure, and we'll also make further investments to build out our digital infrastructure and capabilities.

Finally, we will double down on what got us here, through innovation.

Alongside planned increases in internal R&D investment, we will continue to actively source complementary external innovation that fits with our long-term strategy to harness the full power of the immune system to address serious disease.

And with that, I will conclude our presentation.

We thank our shareholders and partners for their ongoing collaboration and support, and we'll now open up the floor for questions.

(Operator Instructions) Your first question today is from the line of Tazeen Ahmad from Bank of America.

As it relates maybe to the COVID vaccine, can you give us a little bit more color, Ugur, about your thoughts about the need for boosters?

Maybe a couple of parts to that.

Do you have any sense of the frequency with which, if needed, people would need boosters?

Secondly, you talked about doing work on the different variants.

So on a go-forward basis, would the booster shots be inclusive of all variants that would be present at the time?

And the last part of the question is do you see value still for switching from the 2-dose vaccine to a 1 dose in the future?

Okay.

Thanks for the questions.

Actually, these topics are related.

So first of all, what is important is that the booster dose and the variant vaccine are somehow related because some variants, for example, the South African variant, come with reduced neutralization titers.

And we, of course, know that antibody titers will drop over time, and we see first drop now after 6 months.

So we definitely will need a first booster dose in -- maybe after 6 months, after 9 months.

And then the question will be, of course, after the boost -- how long after the boost the immune response will continue to stay stable, whether it's 6 months, 9 months or 12 months.

So we strongly believe that booster doses will be required.

And the second reason to ensure that is we are now seeing with mRNA vaccines and with the data coming from Israel that the vaccine indeed enables prevention of infection, which is one of the key parameters reducing also the emergence of variants because every infected person is somehow creating the chance for new mutations.

And if we want to get a full control of this pandemic, we need to ensure to have high antibody titers to ensure prevention of infections.

With regard to the third topic, so we will see, of course, with the upcoming data that the booster doses are required every 12 months, every 18 months.

So this is data coming in.

With regard to single- versus double-dose vaccine, it is very clear that our vaccine is able to provide protection against disease with a single dose but this is limited.

And we see it -- we clearly see that a second dose is required to have a full immunity.

We will have a situation end of this year that in many regions, we will have already a preexisting immunity in the vast majority of the population.

And then we are not anymore dealing with the question whether we need a 2-shot vaccine or single-shot vaccine because everyone who is receiving a vaccine -- additional vaccine will be regarded as a booster dose vaccine.

And we already know from published data and from our own data, if someone had received prior dose or had COVID disease before, then a single dose is sufficient.

So we are now talking about starting -- we need to start to talk in 2020 and beyond about revaccination, and there is not anymore difference between single-dose and 2-dose vaccines here.

(Operator Instructions) The next question is from the line of Cory Kasimov from JPMorgan.

Ugur, I wanted to follow up with you in the comments you just made with -- around boosters.

Are you saying that the participants in your Phase III trial who were vaccinated back in late summer, early fall are now in need of booster shots, that they're no longer adequately protected from COVID?

I guess just a follow-up on that.

How clear is the regulatory process for boosters and variant vaccines for that matter in terms of the burden of proof on your end to enable authorization or licensure?

Yes.

So to the first part of the question, no, I did not say that the participants are not anymore protected.

I'm just saying that we are seeing -- we are starting to see a drop of the antibody response, and there are now clear publications showing a correlation between the neutralizing antibody titers and protection over time.

So we will see a decline of antibody titers, and we have to identify the right timing for a booster dose.

And the right timing of a booster dose comes, of course, with the objective one would like to accomplish.

And if the accomplish (sic) [objective] is really to ensure prevention of infections, the booster dose has to come earlier.

And I believe that we need to go for -- to accomplish in the population a strategy to avoid infections, not only to avoid diseases, and therefore, a booster dose would be needed earlier than later.

So that's the first part of the question.

Can you repeat the second -- your second question, please?

Yes.

Just how clear the regulatory process is for boosters and variant vaccines in terms of the burden of proof to enable authorization.

Yes.

So we have already started a clinical trial with boosting participants who had received 2 doses of our vaccine.

And this will -- at the end of the day, it is more or less an automatic approach based on understanding of titers, protection and the level of improvement that can be accomplished by a booster dose.

The next question is from the line of Arlinda Lee from Canaccord Genuity.

I wanted to maybe clarify something.

You alluded to single and double doses for the booster studies that are planned and underway.

Can you please explain how the study is designed, what you hope to see and when might we see data flow from that?

Özlem, would you like to take the question?

Or should I take the question?

Yes.

Can you please repeat?

The audio is a bit shaky.

It was about future doses?

Right.

You were talking about the single and double dose for the booster studies that would address the variants that are planned and underway.

Can you please explain how that study is designed, what you hope to see and when we might see data flow?

So the studies assess a couple of questions.

One question is that we assess a third dose, meaning after prime booster, the second booster dose of our vaccine in its current form; and will assess how immunogenicity after this dose is boosted and whether it also protects from circulating variants, so not only test neutralization of the vaccine strain but also other variants.

What these studies will also test is boosting of -- BNT162b2 boosters in participants with new strain of interest or of concern.

And here, we will use the South African strain as a representative of variant of concern.

And additional assessments are in participants who are naive for vaccines and will be tested with regard to immunogenicity and protection by vaccine which represents a variant strain, meaning, in this case, the South African strain.

These studies have partly already started as amendment of our ongoing, for example, Phase III trial, where those subjects and participants who have been already vaccinated with Comirnaty are now, for example, getting the first boost with the same vaccine or with the new strain.

And partly, we are -- we have submitted them.

They have not started yet.

The next question is from the line of Daniel Wendorff from Commerzbank.

I have a question on the -- on your development efforts of different formulations.

Can you maybe elaborate a bit on where we stand there?

And is it technically possible also to bring a Comirnaty vaccine to the market which is stable at normal refrigerator temperatures for a longer time?

Is it something you worked on?

So any more color here would be much appreciated.

I can take the question if okay.

Yes, we are continuously working on new formulations but also on extending the use of our current formulation.

So we have recently announced that the existing formulation is -- can be stored for a longer time at minus 20 degrees.

We will update this data also with regard to stability of our formulation at 2 to 8 degrees.

So we had announced that this is ongoing study with the existing formulation to relax the conditions for the existing formulation.

We are developing ready-to-use formulations and lyophilized formulation which will come into the market in the second half of 2021.

And this new formulations will allow much longer stability at fridge temperature 2 to 8 degrees.

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

I'm going to ask another one on the boost and variant.

Specifically, you have suggested that you need to maintain a threshold titer of antibodies.

And I wonder what evidence you have that informs what that target threshold is.

What's the impact of B-cell affinity maturation on the required threshold?

And where do T cells fit in?

And could they come save us and not require multiple boosts?

Yes.

So great questions, Daina, as always.

So what is emerging is really a correlation between prevention of disease and prevention of infection by this different type of vaccines and neutralizing antibody titers.

So it is -- now more and more studies are publishing which provides clear correlation between vaccine effectiveness, vaccine efficacy and neutralizing antibody titers.

And we do not yet have complete numbers, but this will clearly come in the next 6 to 9 months.

And prevention of infection is clearly dependent on neutralizing antibody titers.

Severe disease -- prevention of severe disease and even maybe also prevention of disease is also driven, of course, by T cell responses.

But T cell responses are coming in only if the virus has reached already the target cells and starts replication.

So we are confident that particularly CD8 T cell responses will provide long-term protection against severe disease, including the variants, but they will not be able to prevent effectively infection in combination with neutralizing antibodies.

And of course, there will be -- will most likely be a situation where lower titer -- neutralizing titers can in part be compensated by stronger T cell responses and vice versa.

But this is science to come or data which will be -- which will emerge in the next 6 to 12 months.

The next question is from the line of Navin Jacob from UBS.

I know you said one but hopefully, these 2 questions are very quick.

I just wanted to clarify the lyophilized version of 162 that you're working on.

What -- you mentioned that you're starting the study.

I just wanted to understand, I'm sorry I missed it, but what exactly is required to get that approved.

Is it just immunogenicity data?

Or do you have to run a full outcomes-based study?

Or is it just PK data?

And then of the 450 million doses contracted in "other regions", how much of that is China?

Any color there would be appreciated.

I can take the first question maybe.

And the second question is Ryan or Sean.

Is that okay?

Yes, I can take the question.

That's fine.

Yes.

So the first question is -- so there are different guidelines or guidances at the moment how to approve a process to ensure that new variant vaccine can be introduced.

One way of doing that, and this is the way requested by the FDA, is to show for a variant strain -- that a vaccine addressing variant strain can be manufactured in the same way, released in the same way, then provide safety data for this new variant vaccine and provide immunogenicity data and show comparability of titers accomplished against this variant strain.

And then on the data package -- on the full data package and on the comparability data, this could result in a blueprint -- approved blueprint process so that if a variant vaccine is needed, it could be introduced without the need for an additional clinical trial.

So that's the general way to address that.

There are differences suggested by regulators in U.K. and by EMA.

But at the end of the day, for each of the parties, some sort of study and data will be required.

Yes.

And Navin, on the China question, so the answer is very little has been included in the 1.4 billion currently signed figure.

We've included the doses that have been committed to Hong Kong and Macau, where we have an EUA approval, which is just under 10 million doses.

We've also committed to Fosun, our partner for Mainland China, to supply up to 100 million doses or at least 100 million doses in 2021 if approval occurs, and we're in the approval process as we speak.

But those doses have not been included in the 1.4 billion number.

And the last question today is from the line of Akash Tewari from Wolfe Research.

So Pfizer has publicly made, I would argue, some unusual comments on its desire to go after mRNA themselves moving forward.

Can you comment on your current COVID partnership, how long it lasts, if there are any outs?

And would either company be able to develop a vaccine candidate for SARS-CoV-2 solo at some point?

And then maybe on your PD-L1x4-1BB bispecific, Genmab mentioned one of the reasons they selected the 100 mg dose is they wanted to have optimal trimer formation, and that kind of translates to about 60% to 70% occupancy for the PD-L1 receptor.

How important is that formation of a trimer?

And why not target a higher PD-L1 occupancy from an efficacy perspective?

Okay.

Thanks, Akash, for the question.

So the first question is, first of all, we have an excellent collaboration with Pfizer where the teams are really closely collaborating.

And we -- at the management level, for example, with Albert Bourla, we have daily conversations about the ongoing collaboration but also about future collaboration opportunities.

And with regard to the existing COVID-19 project, it is a partnership.

We have a 50-50 partnership, and there is no room for any of the partners to do something alone.

Everything has to be decided in a partnership manner.

But understanding, of course, that COVID-19 will stay with us most likely for at least a decade, this is a long-term partnership.

With regard to other potential collaborations, Albert Bourla said that they like to work with us but they don't need to do it, and this is actually a comment I made in the same way.

It is a fantastic partnership and we would like to continue to do additional projects with Pfizer but we don't have to do it.

And I think it's an excellent situation where you just enter into a partnership if you see the benefits.

We see a lot of benefits in doing additional projects together, but we will come up with updates about this in the next weeks.

Yes.

And Ugur, I'd just like to add to that.

Of course, I'd just like to remind everyone that we've been developing IP around mRNA for over a decade.

And of course, that's important for any collaborator when they're thinking about entering into the space themselves.

And of course, the other thing we do, do is we continue to talk to other pharmaceutical companies, too, as an ordinary course of business matter.

Yes.

Thanks, Sean, for this additional input.

The trimer formation?

Yes.

The trimer formation is indeed -- the trimer formation is important for the conditional activation of the 4-1BB arm.

And this 100 microgram, we have the sweet spot of PD-L1 or PD-1 blockade plus trimer formation in a sufficiently long time.

So we exploit here the optimal activation or functions of both arms of the antibody.

And this is also in line with the objective responses that we have observed with this compound, which seem to be associated with the dose window.

I now hand back to the speakers.

Yes.

Thank you again for joining the call today.

We look forward to speaking to you in the future.

Thank you, and bye-bye.

Thanks, everyone.

Thank you.

Thank you.

That concludes the conference for today.

Thank you for participating, and you may now disconnect.