Biontech SE (BNTX) 2021 Q1 法說會逐字稿

Thank you for standing by, and welcome to the BioNTech First Quarter 2021 Update Call. (Operator Instructions) I must advise you this call is being recorded today, Monday, the 10th of May 2021.

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

Good morning, and good afternoon. Thank you for joining us today to review BioNTech's first quarter 2021 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: BioNTech's efforts to combat COVID-19; the collaboration between BioNTech and Pfizer regarding a COVID-19 vaccine; our expectations regarding the potential characteristics of BNT162b2 in our ongoing trials and/or in commercial use based on data observations to date, including real-world data gathered; the ability of BNT162b2 to prevent COVID-19 caused by emerging virus variants; the expected time point for additional readout on trial data of BNT162b2 in ongoing trials; the timing for submission of data for, or receipt of, any marketing approval or emergency use authorization; our contemplated shipping and storage plan, including our estimated product shelf life at various temperatures; the ability of BioNTech to supply the quantities of BNT162 to support clinical development and, if approved, market demand, including our production estimates and targets for 2021 and 2022; the planned next steps in our pipeline programs and specifically, including, but not limited to, statements regarding plans to initiate clinical trials of our product candidates or expansion in Southeast Asia; expectations for data announcements with respect to our clinical trials, our current estimated COVID-19 vaccine revenues based on current contracted supply orders; our projected expenses -- capital expenditures and tax rate for 2021; our target vaccine production capacity for 2021 and '22; our reported vaccine revenue, which are subject to numerous estimates as more fully described in our annual report on Form 20-F and quarterly report for the 3 months ended March 31, 2021; and our 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 during today -- shared today during this conference call and webcast.

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

Slide 4. On the call from BioNTech's management today will be Ugur Sahin, our Chief Executive Officer and Co-Founder; Ozlem Tureci, 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 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 discuss our continued progress in the first quarter, leaving us well positioned to achieve the milestones we have planned for this year and beyond.

Slide 5. During our last quarterly update only 6 weeks ago, we detailed BioNTech's transformation into a fully integrated biopharmaceutical company within a remarkable time frame as we had also the challenge of a global pandemic. We have stayed true to our vision of harnessing the full potential of the immune system to overcome the therapeutic challenges of today by combining excellence in immunology and innovative technology.

Our core competencies and resources established over the last decades were validated by our success in developing the first approved mRNA vaccine against COVID-19. The success has become the foundation of our exciting and ambitious journey to change treatment paradigms in a range of disease areas.

Our robust pipeline with more than 20 product candidates, addressing oncology, infectious diseases and beyond reflects this ambition. We are in a quite unique position to strategically invest cash flow from our COVID-19 vaccine into further maturing the company deliver multiple product launches over the next 5 years.

Forward to Slide 6. Our global goal is to build a 21st century immunotherapy powerhouse. Firstly, we continue to increase our global footprint with new offices beyond our subsidiary in the United States. This includes our commercial subsidiary in Germany, in Turkey, and planned regional headquarters in Singapore that we will discuss later in the call.

Second, we are expanding our integrated infrastructure for strategic investment in scientific and technological innovation. This is in the heart of everything we do. These investments, spanning clinical, commercial, manufacturing excellence, including digital capabilities, will support future product launches. Our success is driven by people, therefore, attracting and retaining top talent remains a crucial imperative for us.

Lastly, we see a tremendous opportunity as we advance our robust pipeline in infectious diseases and oncology and expand to new therapeutic areas, accelerated by our vaccine revenues. Our pipeline currently consists of 14 products in 15 ongoing clinical trials. Building on compelling data, we are poised to initiate multiple potentially registrational studies and first-in-human trials in 2021. Our dynamic and rich internal R&D efforts will be complemented with strategic in-licensing.

Slide 7. Slide 7 highlights key achievements since our last update on March 30. With respect to our oncology pipeline, we have started 3 first-in-human oncology trials in 2021. These include 2 T cell therapies, namely BNT211, our CARVac program, and BNT221, our NEO-STIM neoantigen-targeting T cell therapy. The third is our first RiboCytokine program featuring an optimized interleukin-2 variant. Ozlem will detail this programs in her remarks.

With respect to our COVID-19 vaccine, I remain delighted by the exceptional excellence of our team, along with our partner, Pfizer, has exhibited. To date, we delivered more than 450 million doses of our COVID vaccine to 91 countries and territories worldwide. For 2021, the number of contracted doses has increased to about 1.8 billion, with first contracts in place for 2022 and beyond.

Last week, we announced, together with Pfizer, the signing of a memorandum of understanding with the International Olympic Committee to donate doses of our COVID-19 vaccine to vaccinate athletes and their delegations participating in Olympic and Paralympic Games, which are scheduled to take place in Tokyo in July 2021. The strong execution across our entire organization, along with our partner, Pfizer, led to the recognition of EUR 2 billion in COVID-19 vaccine revenues in our first quarter of COVID-19 commercialization.

Our COVID-19 vaccine continues to demonstrate robust clinical results. Since our last call, we disclosed 2 additional significant positive clinical updates, including top line results from our phase III trial that confirmed high efficacy with no serious safety concerns to the -- up to 6 months following the second dose. In this analysis, 927 confirmed symptomatic cases of COVID-19, BNT162b2 demonstrated 91.3% vaccine efficacy. The vaccine was 100% effective in preventing severe disease as defined by the U.S. CDC and 95.3% effective in preventing severe disease as defined by the FDA. The data also showed the vaccine was highly effective in preventing COVID-19 cases in South Africa where B1351 lineage is prevalent. We anticipate publication in peer-reviewed journal and plan to submit this data to regulators in the upcoming weeks.

We also announced positive top line data of our U.S. pivotal study of 2,260 adolescents, 12 to 15 years of age, demonstrating 100% efficacy in participants with or without prior SARS-CoV-2 infections. BNT162b2 was well-tolerated, demonstrated strong immunogenicity with SARS-CoV-2 neutralizing antibody titer 1 month after the second dose.

We remain focused on 6 key levers to expand our COVID-19 vaccine, which -- we remain focused on 6 key levers to expand our COVID-19 vaccine reach globally and across different demographics, as shown on Slide 8. We are now targeting our manufacturing capacity to reach up to 3 billion doses by the end of 2021 and more than 3 billion doses in 2022. The first shipments from our Marburg facility were delivered mid-April, a remarkable accomplishment for BioNTech manufacturing scale-up.

In Singapore, we plan to establish a regional headquarter that will also include highly automated end-to-end mRNA manufacturing facility. We continue to broaden our vaccine's label. We expect to hear back shortly from the FDA on our application for expanded Emergency Use Authorization for our COVID-19 vaccine to include individuals 12 to 15 years of age. We also expect feedback from EMA on our submitted label expansion for the same age group. As announced last week, Health Canada has authorized to use BNT -- the use of BNT162b2 in that age group already.

Ongoing trials include a global Phase II/III in healthy pregnant women and a study in children 6 months to 11 years of age. We expect to announce safety data from those studies in the third and fourth quarter 2021. We are determined to contribute to vaccine access globally, and our vaccine has been approved for emergency or temporary use or granted conditional marketing authorization in more than 70 countries and regions including emergency use listing from the WHO in January.

In addition, I would highlight that the regulatory submission for Mainland China is now underway in collaboration with our partner, Fosun. For broadened and decentralized vaccine access, we initiated the rolling Biologics License Application in the United States for BNT162b2. We will seek full approval of our vaccine in countries where regulatory submissions have been made and Emergency Use Authorization or equivalents are currently in place.

Both the FDA and EMA have updated our label with 2-week storage and transport at minus 25 to minus 50 Celsius degrees. Recently, we have submitted new stability data to the FDA to broaden our label to standard refrigerator temperature, that means 2 to 8 degrees of Celsius, for up to 4 weeks. We are also developing ready-to-use and lyophilized formulations with improved time of stability profile to reduce dependency on cold chain infrastructure. We have initiated a trial to evaluate a lyophilized and ready-to-use formulation with data expected in the third quarter.

Our understanding of SARS-CoV-2 is evolving as new data is generated, and we understand that immunity may wane over time and that new variants emerge. I do believe that booster will be of high value to reestablish full immunity. We do not know yet when, how frequently this will be needed.

Also, there is currently no evidence that an adaptation of our current vaccine against any of the circulating variants necessary, and we continue to monitor real-world efficacy against emerging variants. However, we want to learn and preemptively prepare today to respond fast in case a dose [or strain] adaptation will be required in future.

Slide 9. To this end, we have developed a comprehensive strategy that uses the South African variant as a prototype for potentially emerging [strain variants]. In subjects who have been vaccinated with 2 doses of BNT162b2, we evaluate a third dose of either BNT162b2 or of the BNT162b2 South African variant version. The trial will also enroll a group of BNT162b2-naive participants who will receive 2 doses of the BNT162b2 South African variant first.

The data will inform us about safety and additional booster -- boostability of the immune response and effects of these additional boosters on immunity against the circulating virus and potential new emerging SARS-CoV-2 variants. First data expected in the second quarter of 2021. This effort will also provide a blueprint for a trial design, regulatory pathway and platform character of the manufacturing process for each future variant.

I will now turn over to Sean to provide an update on our COVID-19 order book and manufacturing status. Sean?

Thank you, Ugur. Great to be with everyone today. Moving to Slide 10 for an update on the distribution progress of our vaccine. We now have contracted orders for approximately 1.8 billion doses in 2021, which includes increased orders from the EU and U.K. and a number of developing countries.

Multiyear contracts with 2022 and beyond are being negotiated with a number of countries around the world, demonstrating that there will be demand for our vaccine in the post-pandemic market. We have reached an agreement with Israel to supply millions of doses in 2022, and with Canada to supply up to 125 million doses in 2022 and 2023, with options to supply up to 60 million additional doses in 2024. We look forward to expanding supply to additional geographies beyond those shown here.

Turning our attention to Slide 11. We are aiming to increase our supply capacity to up to 3 billion doses in 2021. And we expect to be able to manufacture more than 3 billion doses in 2022. This increase was driven by the critical need that remains in many parts of the world, requiring access to vaccine supply as well as vaccinations.

Looking at BioNTech's manufacturing network, I would like to point out that BioNTech has manufactured more than 50% of the drug substance rolled out to date worldwide. Our Marburg facility has made significant progress. We have established mRNA manufacturing at the Marburg site in less than 6 months, including EMA's approval of the manufacturing of our COVID-19 vaccine product at the facility in late March.

As Ugur noted, the first batches of vaccine from the Marburg site were delivered in mid-April, which is truly a remarkable achievement. With the Marburg site fully operational, BioNTech's annual vaccine manufacturing capacity will be approximately 1 billion doses on an annual run rate. Beyond COVID-19, this large in-house manufacturing capability position us for future success with additional pipeline products that we anticipate launching in the coming years.

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

Thank you, Sean. I will provide updates on selected immuno-oncology programs, which have recently advanced in clinical stage or for which we expect to reach significant milestones this year. For further details on other programs, please refer to our annual report, which was filed with the U.S. Securities Exchange Commission on March 13 and our quarterly update which will be filed with the SEC today.

Despite the undeniable impact of COVID-19 pandemic on our clinical operations, we expect to present several data sets and initiate multiple new trials. Slide 13 provides a snapshot of our immuno-oncology platforms across distinct drug classes. Our pipeline covers a broad range of immune therapy approaches that leverage powerful mechanisms of action and a diverse array of novel targets to address the unique molecular signature of each patient's tumor. We believe that harnessing complementary modes of action increases the likelihood of therapeutic success and unlocks a larger potential market.

Combination therapies of drugs that work synergistically are expected to be particularly useful for therapy-resistant tumor types, for which chemotherapy and targeted approaches have failed. Our platforms are being developed to address these limitations and provide a pipeline of potentially combinable products which complementary -- with complementary and synergistic immune modulatory modes of action. CARVac is one of our opportunities already in clinical testing. It combines our FixVac immunotherapy with our novel CAR-T therapies.

Our pipeline highlights several other product candidates with the potential for synergistic combinations that are currently in clinical trials. Our most advanced oncology programs, including upcoming near-term milestones, are shown on Slide 14.

For our FixVac product candidates, BNT111 and BNT113, we expect to start Phase II trials soon. BNT111 is for the treatment of advanced melanoma, and I will detail further momentarily. BNT113, our mRNA vaccine encoding E6 and E7 proteins of human papillomavirus 16 will be evaluated in combination with pembrolizumab versus pembrolizumab alone as a first-line treatment in patients with unresectable recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma expressing PD-L1.

For BNT122, our autogene cevumeran for individualized neoantigen-specific immunotherapy, partnered with Roche Genentech, the Phase II trial in first-line treatment of metastatic melanoma and the Phase I basket trial in solid tumors remain ongoing. Based on promising data seen for iNeST, we decided to move into adjuvant treatment settings, starting with colorectal cancer.

Due to slow enrollment caused by the ongoing pandemic, we are updating our guidance and expect to dose the first patient in the second half of this year in a randomized Phase II trial evaluating BNT122 in circulating tumor, DNA-positive, surgically resected, Stage 2 high-risk or Stage 3 colorectal cancer patients. Together with Genentech, we are evaluating other options for treating early-stage cancer patients with BNT122.

Then there is our next-generation checkpoint immune modulator program, which is partnered with Genmab. We expect to provide a data update in the second half of 2021 for the ongoing Phase I/II trial of BNT311, which targets PD-L1 and 4-1BB. We remain very encouraged by the results seen to date and believe this product has significant potential across multiple oncology indications given the unmet need for improved checkpoint immunotherapies. We also plan to present data in the second half of 2021 from the ongoing Phase I/II trial of BNT312, which is -- which conditionally targets CD40 and 4-1BB.

Slide 15 provides an overview of our next wave oncology assets, including 6 programs across 4 different technology platforms that has the potential to advance innovation beyond current boundaries. Three of these 6 highly innovative programs are in preclinical stage. Our first CARVac product candidate has entered clinical testing, and we will be presenting first early data for BNT211 at the ongoing CIMT 2021 Meeting.

Also the first product from our NEO-STIM T cell therapy program, BNT221, has entered clinical testing. The first patient was dosed in a Phase I trial in April. I will discuss both therapy programs in greater detail shortly. On last quarter's call, we also noted that for BNT151, our first RiboCytokine program, encoding a modified IL-2, the first patient was dosed in a Phase I trial in solid tumors in February. A Phase I trial of BNT152/BNT153, our IL-2/IL-7 RiboCytokine combination in multiple solid tumors is expected to also start this year. As our Phase 1 trials in multiple solid tumors for BNT141 and BNT142, our first RiboMabs program.

Moving to Slide 16. Our lead FixVac product candidate, BNT111, will soon be advancing into a randomized Phase II trial. This intravenous vaccine encodes a fixed set of 4 cancer-specific antigens expressed in our mRNA backbone optimized for immunogenicity and delivered in our RNA-lipoplex formulation. The 4 antigens encoded in BNT111 are common to about 95% of all melanoma patients.

As previously published in Nature, BNT111, in monotherapy and even more so in combination with anti-PD-1, has shown promising data in CPI experienced patients with advanced melanoma in our Phase I trial. Tolerable safety, durable objective responses and checkpoint inhibitor experienced patients with evaluable disease at baseline and high magnitude and persistent CD4 and CD8 T cell responses have been observed.

We believe that these strong positive data provide compelling support for advancement of BNT111 in combination with anti-PD-1 into a Phase II study in a high medical need setting, namely patients with anti-PD-1 refractory or relapsed unresectable Stage 3 or 4 melanoma.

This global study is the collaboration with Regeneron and is outlined on Slide 17. 120 patients will be randomized 2:1:1 into 3 treatment arms, evaluating BNT111 plus Regeneron's cemiplimab and each drug as a monotherapy. The primary endpoint is overall response rate in the BNT111 plus cemiplimab arm.

Now moving to Slide 18. BNT211 is BioNTech's first clinical stage chimeric antigen receptor product candidate. BNT211 targets a tumor-specific antigen, Claudin 6, and was developed in combination with a CAR-T cell amplifying RNA vaccine, short CARVac, in preclinical studies. In those studies, we demonstrated that CARVac treatment leads to in vivo expansion of adoptively transferred CAR-T cells, resulting in increased persistence and superior functionality.

BNT211 is expected to overcome CAR-T cell therapy limitations that hamper efficacy in patients with solid tumors and thus limit widespread use of CAR-T cell therapies. CLDN6 is the target antigen for BNT211 and an ideal candidate for CAR-T cell therapy due to its absence in healthy adult tissues and its frequent expression in high medical need cancers. The ongoing Phase I/II trial is currently recruiting patients with Claudin 6-positive, relapsed or refractory advanced solid tumors such as ovarian, testicular, lung, gastric and endometrial cancer.

Slide 19 shows the trial design of the first-in-human Phase I/II trial of BNT211, evaluating the safety and efficacy of increasing dose levels of CLDN6 CAR-T cells first without and then with CARVac. We have completed dose level 1 of a monotherapy arm with 3 patients and the next dose level is open for clearance.

While the initial Phase I data from this trial is expected in the second half of this year, we are presenting some very early data from the trial at the ongoing CIMT 2021 Annual Conference.

Slide 20 shows preliminary data from the first dose cohort with 3 patients that were treated with the starting dose of CLDN6 CAR-T cell monotherapy. The underlying diseases were ovarian carcinoma, sarcoma and testicular carcinoma, all heavily pretreated. To date, we have not observed any acute toxicities or dose-limiting toxicities in these patients. All observed adverse events were transient and mild to moderate.

We are very excited to report that an analysis of CLDN6 CAR-T cell magnitude in peripheral blood revealed detectable CAR-T cells with CAR-T engraftment in all patients. CAR-T cells in Patient 1 declined after 2 weeks; for Patient 3, a 90-fold expansion was seen; CAR-T cells of Patient 2 expanded further, reaching a 700-fold expansion and a stable plateau from day 24 onwards. Tumor shrinkage was observed for this patient with 11% to 38% reductions in 2 or 3 target lesions 6 weeks after CAR-T cell transfer. So while early, the initial data from the trial are very encouraging, and we look forward to presenting additional data in the second half of the year.

Moving to Slide 21. I'm excited to discuss our NEO-STIM BNT221 program. BNT221 is a fully personalized neoantigen-targeted adoptive T cell therapy candidate consisting of T cells, targeting the most therapeutically relevant neoantigens from each patient's tumor. We believe BNT221 offers several significant advantages as compared to TIL therapy. The T cells are derived from the patient's own peripheral blood, which is advantageous with respect to accessibility since tumor acquisition may be limited.

TIL therapy approaches typically rely on existing T cell repertoires in the tumor sample. We use the RECON bioinformatics platform to select the most therapeutically relevant neoantigens, specific to each patient. We then custom manufacture neoantigen peptides for each patient, which are used to activate and expand neoantigen-specific T cells, recognizing patient-specific neoantigens ex vivo.

T cell responses from both the naive repertoire and the memory compartment are expanded. This results in CD4 and CD8 T cells against multiple tumor-specific targets, reducing risk of antigen escape and off-target toxicity. BNT221-induced T cell cultures directly recognize autologous patient tumor material providing strong support for our approach.

Many adoptive T cell therapy approaches are supported by high dose interleukin-2 to facilitate engraftment. BNT221 does not require IL-2, providing an important advantage in terms of product safety and tolerability. We believe this approach has potential to drive a robust and persistent antitumor response with improved safety and reduced antigen escape over other therapies. In April 2021, the first patient was dosed in the first-in-human Phase I dose escalation trial in metastatic melanoma, refractory or unresponsive to checkpoint inhibitors.

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

Thank you, Ozlem. I will summarize our financial results for the first quarter of 2021, as shown on Slide 23. I will start with the total revenues, which were estimated to be EUR 2,048.4 million for the first quarter of 2021 compared to EUR 27.7 million for the first quarter of 2020. Total revenues increased due to rapidly increasing the supply of our COVID-19 vaccine worldwide. As a reminder, under our COVID-19 collaborations, territories have been allocated between us, Pfizer and Fosun Pharma, based on marketing and distribution rights.

A breakdown of our commercial revenues is shown on Slide 24. Our first quarter 2021 commercial revenues include an amount of EUR 1,751.9 million, comprising our share of gross profit from COVID-19 vaccine sales in the collaboration partners territory, which represents a net figure as well as sales milestones. This figure is 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 partners' gross profit would be recognized prospectively.

Our COVID-19 vaccine commercial revenues also include EUR 63.9 million in sales to our collaboration partners of products manufactured by us and EUR 199.8 million of direct COVID-19 sales to customers in our territory.

Now returning back to Slide 23 and moving to cost of sales, which were estimated to be EUR 233.1 million for the first quarter of 2021 compared to EUR 5.9 million for the first quarter of 2020. The increase was driven by the estimated EUR 223.2 million cost of sales, which were recognized with respect to our COVID-19 vaccine sales and include Pfizer's share of gross profit earned by us.

R&D expenses were EUR 216.2 million for the first quarter of 2021 compared to EUR 65.1 million for the comparable period in 2020. The increase was primarily due to an increase in R&D expenses related to our BNT162 program recorded as purchased services with respect to those expenses which were initially incurred by Pfizer and subsequently charged to us under our collaboration agreement. As a reminder, those costs are shared equally between the 2 companies. The increase was further driven by an increase in wages, benefits and social security expenses from increasing headcounts and the recognition of expenses incurred under the new share-based payment arrangements.

G&A expenses were EUR 38.9 million for the first quarter of 2021 compared to EUR 15.8 million for the comparable period in 2020. The increase was mainly due to the higher expenses for professional services, an increase in wages, benefits and social security expenses from increasing headcount and the recognition of expenses incurred under the new share-based payment arrangements as well as higher insurance premiums.

Interim income taxes were EUR 514.2 million for the first quarter of 2021 and were recognized using the estimated annual effective income tax rate of approximately 31%. For the first quarter of 2021, net profit was EUR 1,128.1 million compared to a EUR 53.4 million net loss for the first quarter of 2020. As of March 31, 2021, cash and cash equivalents totaled EUR 891.5 million.

Moving to Slide 25. We remain on track to achieve our 2021 financial outlook. Based on the current contracted supply orders of approximately 1.8 billion doses, we are providing estimated COVID-19 vaccine revenues to BioNTech of approximately EUR 12.4 billion. This estimate reflects expected revenues from direct COVID-19 vaccine sales to customers in our territory, 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 partners' territories. We expect additional revenues related to further supply contracts for deliveries in 2021 with first contract in place for 2022 and beyond.

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

Finally, please note that in terms of full year 2021 tax impact, we still expect German tax group corporate tax of approximately 31%. And with that, I turn the call to Ryan for an update on our corporate development activities and concluding remarks.

Thank you, Sierk.

Turning to Slide 27. We continue to expand our geographic footprint in the first quarter. In addition to establishing a subsidiary in Turkey to commercialize our COVID-19 vaccine, we are pleased to announce today plans to expand our footprint to Asia with the establishment of a regional headquarters for Southeast Asia in Singapore. We plan to establish a fully integrated mRNA manufacturing facility in Singapore. It will be equipped to produce a range of novel mRNA vaccines and therapeutics for regional and even global supply and add resiliency to our global supply network.

Based on our current plans in partnership with the government of Singapore, facility will also form part of a rapid response capability for Southeast Asia to address future potential pandemic threats. Pending the necessary regulatory approvals, we plan to initiate construction of the manufacturing facility in 2021 and expect the site could be operational as early as 2023. So with this planned expansion, we expect to have boots on the ground in Asia Pacific by the end of this year, building on our existing footprint in Europe, United States and Turkey.

Slide 28 highlights our expected pipeline milestones for the remainder of 2021. Since the start of the year, we have initiated 3 first-in-human clinical trials in oncology, and we expect to initiate 3 more before the end of the year. We remain on track to start 3 potentially registrational Phase II trials with our wholly owned FixVac and iNeST programs this year.

In infectious diseases, BNT161, our seasonal flu vaccine program, partnered with Pfizer, is expected to enter a Phase I clinical trial in the third quarter of 2021. We are moving multiple other programs towards the clinic and plan to provide further updates on our infectious disease pipeline throughout the year.

Finally, we expect data updates on up to 5 different programs in 2021, including our next-generation checkpoint immunomodulators, BNT311 and BNT312, in the second half of the year.

Turning to a few closing remarks on the next slide. We remain focused on ramping up supply of our COVID-19 vaccine with the goal of vaccinating more than 1 billion people this year and potentially even more in 2022. We believe we have a responsibility to supply large quantities of our vaccine throughout the world, including to the developing world, and are working hard to make that happen.

In parallel to executing against COVID-19, we will accelerate our pipeline development in our core therapeutic areas of immuno-oncology and infectious diseases. We intend to advance mRNA vaccines against a range of pathogens, building on our 9 active preclinical programs. We will provide more details on some of these exciting programs over the course of this year.

Finally, we intend to ramp up investment in our clinical, commercial and manufacturing infrastructure and teams as we transform BioNTech into a global biopharmaceutical company and prepare to bring next-generation immunotherapy to people around the world.

And with that, I'll conclude our presentation and open up the floor for questions.

(Operator Instructions) And your first question comes from the line of Cory Kasimov from JPMorgan.

I will stick to 1. I'm curious like what your views are on all the controversy last week on the patent waiver front. And kind of what do you see as the potential impact here for BioNTech and kind of next steps you're waiting to hear on this topic?

Yes. I can take the question. Cory, thanks for the question. So first of all, of course, we understand the importance of global distribution of our vaccine. And let me just shortly summarize the status quo, which we have at the moment. We have delivered our vaccine to over more than 90 countries and -- so far, and we continue to support the global supplies, including the lower and middle income countries. So our capacity -- our initial capacity for 2021 was in the range of 1.3 billion doses. We have now scaled the manufacturing capacity up to 3 billion doses in 2021. And more than 40% of these doses is expected to go to mid- and low-income countries.

The only near-term solution that we see is really to ensure that we produce from the existing network, we have increased our existing manufacturing network, and ensure that the vaccines, which is produced in the United States and in Europe, can be -- continues to be delivered also to the low-income countries. And waiving of IP would not increase short or medium-term supply of the vaccine.

So the setting up of the manufacturing process is complex. It will take at least 1 year, not even more, to set up a new manufacturing, and we do not see any value in waiving patents. We are, as we discussed this morning, already expanding our manufacturing network from Europe also to Asia. We are setting up manufacturing in Singapore. And we'll also implement manufacturing in our JV in China. And we believe, together with the other vaccine developers, in the next 9 to 12 months, there will be more than enough vaccine produced, and there is absolutely no need for waiving patents.

Your next question comes from Tazeen Ahmad from Bank of America.

For me, I wanted to just ask a little bit more about the booster. And Ugur, are you thinking that the booster for the original formulation that you had manufactured for the Wuhan variant would be sufficient for future protection? Or do you think that the rate of change of each of the variants would necessitate any kind of change to the actual vaccine itself?

And if it's the latter, if you do have to modify the vaccine, how, if in any way, does that change your rate of production plans for the need of boosters starting, let's say, next year and beyond?

Yes. Yes. Excellent question. So at the moment, we don't see a need for changing our vaccine. As you know, we have done in the last 6 months, we have evaluated more than 30 different variants for -- and evaluated immune responses, antibody responses induced with the wild type vaccine for neutralization, and we see for the most variants almost equal neutralization. We have, in the meantime, also real-world data for the effectivity of our vaccines, for example, against the U.K. variant, more than 90% in the Israel real-world data, almost 90% from the real-world data from Qatar.

And we have also seen, last Friday, a publication, showing real-world data from Qatar, showing that our vaccine is able also to prevent infection, PCR-concerned infection, with a 75% of effectiveness. We have also seen, in our laboratory experiments, that increase in the neutralization antibody titer results also in increase of neutralizing antibody titer and almost normal neutralization antibody titers in -- against, for example, South African variant.

So at the moment, we don't see any reason to adapt our vaccine but we are working on establishing a process and a regulatory framework by executing a blueprint prior to ensure that. The potential change to a new variant would only impact, as far as we can see at the moment, just the DNA template without changing any other process. The manufacturing process appears to be absolutely robust for all kinds of variants. So that means once we have a decision for a new variant, we can just change the DNA template and without losing any production capacity, come up with supply of the new variant vaccine.

And your next question comes from Daina Graybosch from SVB Leerink.

Thanks for the question, and it's a follow-up right on the conversation you just had. Given this really impressive real-world effectiveness against B1351, I think you mentioned Qatar was 75%. I'm wondering how you plan to select between the 4 different booster strategies that you currently have in the clinic? Do you think that you can get a differentiating predictive signal immunogenicity data? Or is that decision going to require a larger outcomes trial?

Daina, so the clinical trial that we are performing is really evaluating different questions. One question is what is the immune response that we get if we use homologous booster. And this will be, of course, analyzed against the wild type strains but also against mutants. So that will answer the question that a single booster is improving also the response against the variants.

And then we have the question whether a booster vaccine with a variant is able to produce very specific immune responses. And we will analyze that again, evaluating wild type and variant virus, virus neutralization assays. And then the last question is that a variant -- vaccination with a variant in naive subjects induces variant-specific immune responses in the same way as we have seen with the vaccination of the wild type in naive subjects.

So these are different types of questions. Some of the questions are scientific and address also future adaptation strategies, some are more pragmatic in aiding just a change of our vaccine and providing the regulatory framework.

Sorry, just a quick follow-up on that. So when you have all this immunogenicity data against the wild type in variant, what's the regulatory path? Just the one that has the best neutralization profile, you'll go forward?

No, it's just -- the regulatory path is really enabling a flexible response. So the trial is not in the sense of decision-making. The trial is -- has 2 objectives. One objective is really providing the regulatory path to enable based on a non-inferiority analysis that variant vaccine can be established whenever needed. That's the one. And the second is the set of scientific questions that I just elaborated.

Your next question comes from Daniel Wendorff from Commerzbank.

I would have also a follow-up question on the potential regularity of booster shots to be given, looking into 2022, 2023, and you mentioned already a few contracts with customers having been signed here, e.g., Canada. How do you think the booster vaccination campaign would look like? Would it be largely elderly people then receiving the booster shots again? Would it be more younger people in order to establish a certain level of immunity amongst the younger generation? So any idea or views you have currently on this topic would be much appreciated.

Sure. Sure. I can take this question. These questions about prioritization and concrete rollout of a potential booster campaign. The successions, we, as vaccine developers and manufacturers, cannot decide. These are policy questions that have to be decided by the respective regulatory authorities or governments.

With regard to the necessity of booster shots, we believe -- while we believe that booster shots will be of high value to reestablish full immunity and most likely also expanded against emerging variants, we do not know yet when and how frequently we are -- these are needed. The upcoming data from follow-up of immune responses and also the real-world data regarding protection will inform us about this.

Your next question comes from Akash Tewari from Wolfe Research.

This is Leo for Akash. We have 1 question regarding about WTO's IP waiver. So can WTO compel BioNTech to share tech transfer information such as undisclosed information or trade secrets outside of published patents?

Ryan, can you take this question?

Sure. So as I understood it, the question was, can the WTO compel manufacturers to release information beyond the patent. Is that the question?

Yes.

Yes. Yes. I think it's too -- I think it's a little bit premature to try to pinpoint precisely what a hypothetical resolution may or may not include. I think our position on the resolution was mentioned earlier by Ugur, and that is the IP is an important part of proprietary asset for BioNTech. It's something that we've spent over a decade of investment has gone into our IP portfolio. However, we don't believe that it's the bottleneck to accelerating production or supply of our vaccine to the world.

And actually, when you look at our global supply network that we already have assembled, it includes actually 15 different production nodes in that network. So we've already taken great steps to try to expand our supply footprint on both sides of the Atlantic and now with the next steps announced today into Asia.

So that would be my response to the question, but I think it's a little bit early to tell how this will play out.

Your next question comes from Arlinda Lee from Canaccord.

I was wondering on the -- on your comment on becoming a fully integrated global immunotherapy company. What areas of emerging therapeutics like you'd be interested in? You had a paper recently on autoimmune disease. Can you maybe talk about that a little bit?

So I believe this is a more general question, which is the direction which we are addressing with our M&A development. So in the last years, we have shown that our mRNA vaccine technology platforms allow us to develop classical cancer vaccines, personalized cancer vaccines. We have now a program that we use mRNA vaccine to stimulate CAR-T cells. So that means that the first step from the cancer vaccine to the T cell space.

Then we have shown that mRNA vaccines can be used also in preclinical setting to evaluate autoimmune disease. And this is, for sure, a direction which we will address in the next years in [clinical spaces], of course. Moreover, we are using mRNA to deliver therapeutic proteins. As I stated, we have now the first mRNA-encoded cytokine molecule in clinical testing. There are more cytokine -- mRNA-encoded cytokines in our pipeline. We have mRNA-encoded antibodies, which includes IgG antibodies as well as bispecific antibodies.

So that means our clinical pipeline already today covers a number of pharmaceutical molecules to be delivered by mRNA and we will certainly expand that. And we will certainly also address -- accelerate the clinical development of some of these molecules towards the market.

Your next question comes from Zhiqiang Shu from Berenberg.

I'd like to ask about the flu vaccine you're going to move forward in the clinical trial with Pfizer. I was wondering what kind of is the mRNA construct? Is that -- I recall, in 2017, you published a self-amplifying mRNA version in a preclinical study. And related to that, do you plan to share results in your self-amplifying COVID vaccine? I remember it is also tested in Phase I trial.

Yes. Thank you for the question. We have not yet disclosed which specific vaccine platform and format -- mRNA format will be used in the cooperative development of the flu vaccine together with Pfizer. With regard to the other platforms we are working on, for example, the self-amplifying vaccine platform, where there will be data sometime next year, which we will disclose from our ongoing assessments, also clinical assessments.

We will now take our last question, and this comes from the line of Simon Baker from Redburn.

On the P&L, if I may, please. Two parter. Firstly, for the gross margin, were there any distorting factors in the gross margin this quarter related to previously expensed inventory? Or is that a good run rate for the rest of the year?

And also on tax, it doesn't look like you've utilized any tax carryforward losses in the quarter given the rate was close to the German corporate rate. Do you intend to use those later on in the year? Or is 31% a reasonable indication for the effective tax rate for 2021?

This is Sierk. Let me quickly take the question. There are some phase milestones actually in the numbers. So this is a little bit of a distortion. But keep in mind that the sales that we are showing is predominantly part is like Pfizer's gross contribution after 50-50 split already. So what Pfizer and we share as profit comes into our P&L as a sales item. So that's why there is some -- not call it distortion, but you can pro rata go with like the volume that we sell to the market. Yes, so this is one effect. But yes, in this number, there's also phase milestones included and especially the gross margin from Pfizer. So this is comment one.

And comment two, yes, we're going to lose our tax loss carryforward. They are partially included already in this tax calculation. This is -- the tax that we are calculating is, we have -- like 24% of the tax loss carryforward is already in this quarter. We are actually updating the calculation with the deferred tax asset that we have from last year, plus also the tax loss carryforward. So we will see a net rate of 31% roundabout in the end.

We have no further questions at this time. I would now like to hand you back to Sylke Maas for closing remarks.

Thank you, again, for joining the call today. We look forward to speaking to you in the future. Thank you, and bye-bye.

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