Earnings Call: Q2 2021

Aug 9, 2021

Thank you for standing by, and welcome to the BioNTech Second Quarter 2021 Update Call. At this time, all participants are in a listen only mode. There will be a presentation followed by a question and answer I must advise you the call is being recorded today on Monday, 9th August, 2021. I would now like to hand the call over to your Vice President of Investor Relations and Strategy, Silke Maas. Please go ahead. Good morning and good afternoon. Thank you for joining us today to review BioNTech's Q2 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, our current estimated COVID-nineteen vaccine revenues based on current contracted supply orders and our estimated financial results for 2021, the continued global demand for our COVID-nineteen vaccine, our target vaccine production capacity for 2021 and beyond, our ability to supply our COVID-nineteen vaccine, The planned next steps in our pipeline programs, the timing for enrollment initiation, completion and reporting of data from our clinical trials and 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 34 provides detailed and important safety information regarding our COVID-nineteen vaccine. I'm joined today by our CEO and Co Founder, Guarzarin, Urs Naim Toureji, our Chief Medical Officer and Co Founder Jean Marat, our Chief Business and Commercial Officer Jens Holstein, Our Chief Financial Officer Ryan Richardson, our Chief Strategy Officer, Ingrid Petting, our Chief Operating Officer. I'll now turn the call over to Ugur Sahin. Thank you, Silke. Good morning and good Thank you to everyone joining the call today. Slide 6, I will provide an update on the last quarter's performance before inviting my team to go into further detail. Our performance in the second quarter Continue to be strong as we transform BioNTech and accelerate our pipeline of novel immunotherapies. I'm happy to report that we and our partner have cost the €1,000,000,000 mark for COVID-nineteen vaccine doses We still have to further to go to reach our ambitious targets for the full year, But we are on track with where we wanted to be at this time. We are truly humbled by the impact Our vaccine and our company is having in addressing the global pandemic. We have also had a strong first Half year in terms of the number of new trial starts in oncology as we accelerate development of our BOLD pipeline. Wertheim will go in further detail on some of these new trials in our prepared remarks. Moving to Slide 7. Our strategy remains focused on developing A broad pipeline of next generation immunotherapies and vaccines and bring them to people worldwide to address unmet medical need in cancer, infectious disease, as well as in a growing list of other diseases. To accomplish this, we are building a fully integrated global immunotherapy company anchored around deep To be more concrete, what this means. In addition to shipping more than 1,000,000,000 doses of our first authorized product In the Q2, we expanded our oncology pipeline to total 15 clinical stage programs and 18 ongoing trials. I expect our pattern to continue to broaden as we broaden our research and development and initiate additional clinical cards over the next to 24 months. We are also increasing investment to strengthen our cost capabilities, including our digital technology spectrum. In the first half of the year, we have initiated a number of new research and development projects, which aim to exploit the artificial intelligence and machine learning technologies across our research and development organization to discover and to optimize new immunotherapies. BioNTech will become a technology company of the coming age, Exploring and exploiting innovations at the border of various rising technology fields. We believe in a future that our innovations Can make a difference for many people around the world with diseases that cannot be effectively treated today. Finally, to accelerate the accomplishment of these objectives, we have continued to hire exceptional people around the world, Going our firm to more than 2,500 team members in Europe, North America and now Asia. We remain focused on innovating and accelerating our pipeline with the aim launching multiple products in the next Slide 8 shows the key highlights for the Q2. Starting with COVID-nineteen, we have now distributed vaccine doses to more than 100 countries and regions globally. As of July 21, we and our partner have signed supply contracts for delivery of approximately 2,200,000,000 dose in 2021. 3rd, We have committed to supply more than 2,000,000,000 doses of our vaccine to low and middle income countries within this year and the next. This is a considerable commitment that is only possible due to the investment We have made with our partners over the past 12 months to continuously increase our joint manufacturing capacity, now being well over 3,000,000,000 doses per year. In oncology, we have initiated 6 trials in the first half of twenty twenty one. This includes randomized Phase 2 trials for our BNT-one hundred and eleven fix back in checkpoint inhibitor with refractory melanoma and for BNT-one hundred and thirteen, 6x drug in HBV positive head and neck cancer. For our IMS program, BNT122, we began screening patients in our Phase II trial for acute colorectal cancer. In addition to this later stage trial, we initiated 1st in human trials for the 1st programs from 3 novel platforms in the first half of the year. This includes Our first car back, car tisaprogram, our Neostim, ex vivo tisaprogram, and the first program from our ribocitokine platform where we include cytokines in vivo using mesenchyarnib. All of these programs are targeting solid tumors and are wholly owned by BioNTech. We welcome Jens Holstein as our new CFO, who joined our executive management team on July 3. Jens is an accomplished executive who brings deep experience as financial steward and operator. His appointment will enable Zerk to fully focus on his role as COO going forward. We recorded Q2 revenues of approximately €5,300,000,000, driven by the ramp up of the COVID-nineteen Finally, we recently announced the acquisition of CART's personalized TCR, research and development platform and the clinical stage cell therapy manufacturing facility in Gettysburg, Mavenclad in the United States. This transaction strengthens our position in cell therapy by giving us a turnkey clinical stage cell therapy manufacturing site on both sides of the Atlantic. The site will support our going clinical stage cell therapy pipeline. The acquisition will also provide us With a team of more than 50 highly specialized cell therapy experts and personalized TCR platform, which complements our pipeline of individualized cancer therapies where we aim to build a long term leadership position. Turning to Slide 9. We see infectious disease as a long term growth pillar for BioNTech. We believe the technology behind COVID-nineteen vaccine has the potential against a range of other infectious diseases as well as potential to play an important role in future pandemic preparedness programs. We are investing in mRNA vaccine programs to address diseases with a massive health burden, in particular in lower income countries, such as malaria, tuberculosis and HIV. As part of this, we recently announced our plan to develop Sustainable solutions to address infectious disease on the African continent. We aim to develop the first Arne vaccines with durable protective immunity for prevention of malaria with the initiation of a clinical trial by the end of 2022. Malaria is a disease that affects more than 200,000,000 people worldwide every year, The worst affected being young children who have no immunity against this pathogen. Our malaria project is part of the eradicate malaria initiative by the Ken Abs Foundation. The second layer of our malaria project is dedicated to the development of sustainable vaccine production and end to end supply solutions on the African continent. We are exploring possibilities for establishing state of the art manufacturing facilities in Africa, either with our partners or on our own. Our efforts are supported by the joint Convening powers of the WHO and the Africa Center For Disease Control and Prevention. Besides the The European Commission and other organizations have been involved in the early planning phase of our malaria project and offer their support to identify and set up needed infrastructure. As a reminder, we have multiple product candidates In preclinical development for tuberculosis and HIV in collaboration with the Bill and Melinda Gates Foundation. We plan to start the clinical trial for our tuberculosis vaccine candidate in 2022, only about 2.5 years after initiation of the research program. As part of our collaboration with the University of Pennsylvania, We are developing up to 10 mesangeline vaccine candidates for various infectious diseases with unmet medical need. With multiple programs and preclinical development, we expect to bring the 1st product candidate in the clinic by the next year. Finally, BNT-one hundred and sixty one, the influenza vaccine program. Our partner Pfizer expects to initiate the 1st immuno trial In the Q3 of 2021, we are eligible to receive milestone payments and up to double digit royalties for this program to our licensing agreement with Pfizer. On Slide 10, we show a depiction of the broad toolkit we are building across our technology platform, which includes a diverse range of potentially 1st in class therapeutic approaches. While our focus Historically has been on immuno oncology. We are investing to expand the application spectrum of our technology toolkit to address an even broader range of immunological targets and mechanisms of action. This means building out our platforms and even developing new complementary approaches, which harness the power of the immune system. To conclude on Slide 11, we believe that the broad spectrum of our technologies will enable us To bring forward new product paradigms that have the potential to broaden the disease horizon Beyond oncology and infectious disease to allergy, autoimmune disease and inflammatory diseases And even with regenerative medicine, we believe that the new product paradigms that we are creating have the potential to expand on traditional therapeutic approaches. This includes mRNA vaccines for other infectious diseases Well, we believe our technology has the potential to improve efficacy or producibility beyond what has been achievable with other vaccine modalities. We also see the opportunity for new modalities such an mRNA therapeutic cancer vaccines or immunotherapies based on mRNA encoded proteins, such as our riboMab and riboserta client platform. And finally, we believe our toolkit could lead to new disruptive modalities At the intersection of mRNA and cell therapy, such as our CARWAC approach, where we use mRNA to address T cell persistence in vivo. We will continue to combine our immuno oncology expertise and powerful seat of technologies to unlock this new therapeutic universe of opportunities. I will now turn the call over to Sean, who will provide updates on our COVID-nineteen program. Thanks, Zukor. It's a pleasure to be speaking with everyone today. Our partnerships with Pfizer and Fosun Pharma have enabled us to establish a global development program and distribution network. It remains our goal to deliver as many doses of our COVID-nineteen vaccine as possible to people around the world to help end this pandemic and facilitate the return to a normal life. As a leading provider of COVID-nineteen vaccines globally, The demand for our vaccine remains high. We have a strong order book in place for 2021 and several contracts already signed for 2022 and beyond, shown on Slide 13. Discussion for additional contracts remains ongoing. As of 21st July, we, along with Pfizer, have secured orders for approximately 2,200,000,000 doses of the vaccine to be delivered in 2021. We expect the number of doses to continue to grow through additional orders. For example, we recently announced that the U. S. Government purchased an additional 200,000,000 doses, bringing the total number of doses under the existing supply agreement to 500,000,000. We expect to deliver 110,000,000 of the additional doses by December 31, 2021, and the remaining 90,000,000 doses no later than April 20, 2022. We also have a contract to supply 900,000,000 doses to the European Union for the years 2022 to 2023 inclusive, with an option for an additional 900,000,000 doses. This is a historic development as it is the largest supply contract in the history of the pharmaceutical industry. We have also contracted for more than 1,000,000,000 doses of our COVID-nineteen vaccine today for 2022 and beyond. Both the United States government and the European Commission also have the option to acquire an updated version of the vaccine to address potential variants and also new formulations, is available and authorized. We are serious about our responsibility to help combat COVID-nineteen globally and are committed to ensuring that low- and middle income countries, many of which are experiencing serious outbreaks, Receive our vaccine. We anticipate that a significant amount of the remaining 2021 Vaccine manufacturing capacity will be delivered to middle and low income countries where we price in line with income levels or at a not for profit price. To this end, as Ugur mentioned, we have pledged 2,000,000,000 doses over the next 18 months to ensure global equitable vaccine access. This includes our plan to provide the U. S. Government 500,000,000 doses of our COVID-nineteen vaccine at a not for profit price, of which 200,000,000 doses are in 2021300,000,000 doses are in the first half of 2022. The U. S. Government will, in turn, donate the Pfizer BioNTech vaccine doses to low and middle income countries and organizations that support them. This will further support the multilateral efforts to address the surge of infection Recently, we, along with our partner Pfizer, announced that we had signed a letter of intent to collaborate with BioVac for the manufacture and distribution of our COVID-nineteen vaccine in Africa. All vaccine doses manufactured at this new CMO site will exclusively Within the 55 member states that make up the African Union. Moving now to Slide 14. As we've done on previous calls, I will provide an update of our key levers to expand the global reach of our vaccine. Starting with manufacturing, we have been continuously increasing our capacity and the BioNTech and Pfizer global supply chain Our manufacturing network now spans 3 continents and includes more than 20 facilities. At this time, we expect to have up to 3,000,000,000 doses manufacturing capacity in place by the end of this year and up to 4,000,000,000 doses capacity in 2022. We will continue to expand our multi continent manufacturing I just mentioned our new collaboration with BioVac, which is located in Cape Town, South Africa, and which will perform manufacturing and distribution We and our partner Pfizer have immediately begun technology transfer, on-site development and equipment installation at the new site. At full operational capacity, BioVac's annual fill and finish will exceed 100,000,000 doses, allowing for more rapid distribution across the African continent. We expect to begin delivery of vaccine doses from this site by 2022. In our efforts to expand our vaccine label to more population, we are pleased that we have received expanded authorizations Adolescents 12 years of age and older in the United States, the European Union and many other countries. As we have discussed in detail previously, we have multiple ongoing clinical trials to support further label expansions, including in pregnant women and in children aged 6 months to 11 years. We expect data from the study in children 2 to 11 years in the Q3 of this year and data from children 6 months to 2 years in the Q4 of this year. If the results from the study are positive, We expect to submit the data to regulators, including the FDA and EMA for Potential label expansion for children 5 to 11 years old in the September to October 2021 timeframe and soon after for children 6 months to 5 years. On the regulatory front, our U. S. BLA submission for our COVID-nineteen vaccine was recently accepted by the FDA and granted priority review designation. The Prescription Drug User B Act or PDUFA date for a decision by the FDA is in January 2022. The BLA includes Clinical data from the pivotal Phase III trial of the vaccine, where the vaccine's efficacy and favorable side effect profile were observed to 6 months after the 2nd dose. They're also pursuing submissions for standard approval in additional countries where emergency authorizations are currently in place. In China, our BLA submission is underway too. In terms of optimizing vaccine formulations to simplify global access, we have received regulatory approval from both The EMA and FDA for storage at 2 to 8 degrees Celsius for up to 31 days. An ongoing Phase 3 trial is evaluating ready to use and lyophilized formulations with data expected in the Q3 of As we continue to learn about emerging variants, our teams are rapidly responding to the dynamics the pandemic by adapting technology, manufacturing and regulatory processes to ensure we continue to have a robust vaccine that protects humanity from COVID-nineteen. To address potential waning immunity and emerging We have expanded trials to expand both variant specific versions of BNT162b2 as well as a third dose of BNT162b2 given 6 to 12 months after the second dose. Initial data from the BNT162b2 booster trial have been recently disclosed, and Ozlem will now provide you further details on our boosting and variant strategy. I'll now turn the call over to Aslan. Thank you, Sean. To pick up where Sean stopped, We believe that duration of vaccine induced protection and cross protection against variants are interdependent outcomes. Slide 15 shows follow-up data from our landmark trial that enrolled more than 46,000 participants at more than 150 sites around the globe. These data show vaccine efficacy to remain high, 91.2%, for up to 6 months following the dose 2 of our vaccine. Of the 971 confirmed Symptomatic cases of COVID-nineteen in the trial, 889 cases were in the placebo group and 82 cases We're in the BNT162b2 group and the trial vaccine efficacy against severe disease at 6 months after the 2nd dose is 95.7%. In 800 participants in South Africa, where the beta variant was prevalent at that time. 9 cases of COVID-nineteen with 8 being the beta variant were observed all in the placebo group demonstrating clinical protection against the beta strain. What about the delta variant, which is currently a major concern? There are several data sources to look into, shown on Slide 6. 1 is neutralizing antibodies. We constantly assess sera from vaccine recipients in the trial for ability to neutralize emerging variants. Sarah from participants who received 2 doses of BNT162b2 demonstrate preserved in vitro neutralizing activity against several variants of concern, including delta and delta related ones, as shown in the left panel. While the neutralization titers against Delta appear lower than against the original strain, US AWA 2020, the neutralization is still robust. T cell responses are a second layer of defense. Those elicited by BMG162b2 target multiple epitopes within the spike protein. The sequences of the epitopes recognized by these key cells are shown and aligned for 5 SARS CoV-two Lineages in the figure on the top right showing that these epitopes are highly conserved across a variety of different variants, including the delta variant. Additionally, there is real world data for vaccine effectiveness that helps to assess protection against emerging variants. A recent study by Public Health England found that full vaccination with BNT162b2 was 88% effective against symptomatic disease from the delta variant and provided 96% vaccine effectiveness against hospitalization caused by the delta variant. A study from Canada found that full vaccination with BNP-one hundred and sixty two(two) resulted in a vaccine effectiveness against symptomatic infection from delta of 87% and 100% protection against hospitalization. A nationwide surveillance study involving 5,400,000 people from Scotland estimated that BNT162b2 was 79% effective against delta. In July, the Israel Health Ministry reported that BNP-162b2 mediated effectiveness in preventing both infection and symptomatic disease had fallen to 39% from 64% earlier in July, while effectiveness against severe COVID-nineteen disease, including prevention of hospitalization, continued to be as high as 91.4%. Wainting vaccine effectiveness observed in Israel coincides with the spread of Delta and the end of social distancing restrictions in Israel. We believe that another important factor is the early start date of this vaccination program relative to the rest of the world and that many high risk populations had received their second dose more than 6 months prior July ago, which increases the risk of infection in these individuals. So the point I want to make is, broadly speaking, As of now, evidence points to robust vaccine effectiveness against circulating variants in the real world setting, including a high vaccine effectiveness against severe disease. Varieties across different geographies, Such as public health measures and restrictions that are in place will also have an impact on how this plays out in the real world setting. Continued monitoring of real world data and immunogenicity data is warranted to understand when a booster or a variant adapted Vaccine will be required, which of course is at the discretion of global health authorities. To be prepared for the scenario That a response to a variant of concern may become necessary soon, we are establishing preemptively a development and regulatory pathway for a variant specific prototype approach, as shown on Slide 17. This approach Also aim to address the question whether boosting with the ancestral BNT162b2 Only mazes suffice or variant adaptations may be required. Our prototype approach includes 4 work streams. The first to evaluate a third dose of BNT162b2 in fully BNT162b2 vaccinated participants. 300 participants were assessed for safety and immunogenicity, And I'm going to show data on the next slide. Another 10,000 participants will be assessed for efficacy of a 3rd dose of BNT162b2 62b2 with data expected in Q4 this year. The 3rd ongoing evaluate safety and immunogenicity of BNT162b2 or a better variant specific vaccine version of it in 340 BNT162b2 vaccinated participants as well as 2 doses of a better specific version in 300 vaccine naive participants. Data from this trial is expected in Q3 2021. Also, we are planning to start a trial that will evaluate a delta variant specific version, an alpha variant specific version and also multivalent vaccine, including both versions of BNT162b2. This trial will include about 600 vaccinated participants and 300 naive participants. Data from the trial is expected in Q4. We expect the data from these to significantly enlarge our knowledge about vaccine protection and variants of concern and also help to inform the optimal path Going forward, pieces of data from our comprehensive endeavor are in fact already available. Recently published data from the First work stream is shown on Slide 18, evaluating the administration of a 3rd BNT162b2 dose 7 to 9 months after dose 2. The graph on the top right shows that an elderly adult Neutralization has almost fallen to the level of detection by this assay after 7 to 9 months. Boosting with a 3rd dose between 7 9 months after dose 2 induces a robust neutralization response beyond what was originally observed after those 2. Sera obtained from participants 1 month after this dose 3 elicits a high neutralization titers Against the original ancestral strain and also against the beta variant and the delta variant. Neutralization titers against the delta variant are over fivefold over those observed after the dose After dose 2 in the age group 18 to 55 years and even over 11 fold in the older age group, 65 to 85 year old, as shown in the graph on the bottom right. Furthermore, the difference in neutralizing titers against the ancestral virus and the beta variant narrowed after the 3rd dose compared to after the second dose, implying that in addition to prolonging protection, a booster dose may increase the breadth of neutralizing of a neutralizing response against SARS CoV-two variants. And the first dose is safe and tolerant according to our data. These data are being prepared for submission for regulatory authorities globally to support the potential introduction of a booster dose, a third one in the product information. We continue to believe it is likely that the 1st dose booster may be needed within 6 to 12 months after full vaccination to maintain the highest level of protection. Therefore, we are in ongoing discussions with regulatory agencies regarding a potential 3rd dose booster of our current vaccine. Transitioning to our oncology pipeline on Slide 20. Ugur has already outlined our immune oncology strategy, which is based on several first in class immune therapy approaches to modulate the immune response against cancer. Each of our therapeutic platforms has at least 1 product candidate In the clinic and several of our product candidates have a potential to be combined synergistically with other pipeline programs. Slide 21 provides updates on select oncology programs. We now have 15 product candidates in 18 clinical trials, including 3 Phase II trials. In our 6 sec platform, we have started 2 Phase II trials in the last 2 months. I will discuss those programs in more detail in a few moments. We also anticipate dosing the first patient in our INS Phase II trial in the adjuvant colorectal cancer setting in the second half of twenty twenty one. We expect data readouts across both of the next generation immunomodulators, BNT-three eleven and BNT-three twelve, that we developed with our colleagues from Genmab. And there will be a data update for our claudine 6 CAR TCEP European BNT-two eleven in the second half of the year. Enrollment into higher dose levels is ongoing in that trial, and we have also treated the 1st patient with claudine CAR T Key cells in which the CAR VAC vaccine to selectively stimulate this adoptively transferred engineered cells has been conducted. BNT-twenty one is our 2nd cell therapy program in solid tumors, which started 1st in human clinical testing this year as well. Moving now to Slide 22, I will discuss our wholly Our own fixed track platform, which has 5 product candidates for multiple indications in clinical trials. Each FICC product candidate targets a set of shared tumor associated antigens, which are commonly stressed by a significant portion of patients in a given cancer type. RNA technology design elements used for FICC VAC include an RNA backbone optimized for high protein yield, augmentation of induction of innate and immune responses, LPX formulation for systemic administration. Our RNA lipoPlex approach has been optimized For body wide delivery of tumor antigens, selectively to turn to lymphatic compartment resident dendritic cells to induce As shown on the bottom of this slide, we have observed strong vaccine induced CD8 T cell responses across different cancer types against non mutated shared tumor associated antigens for melanoma in the BNT-one hundred and eleven Phase one trial and for HPV16 positive head and neck cancer in the BNT-one hundred and thirteen Phase 1 trial. Our clinical trials and preclinical studies have demonstrated that 6xFrIME activates and expands a complementary pool of CD4 and CD8 T cells and also that these newly generated T cells benefit from PD-one blockade. Thus, vaccines based on non with anti PD-one for tumor control in patients with a lower mutational burden, including those who have already experienced checkpoint inhibitor therapy. 2 fixed fat programs just moved in Phase II trials, BNT-one hundred and eleven in checkpoint inhibitor refractory or resistant melanoma and BNT-one hundred and thirteen In HPV 16 positive head and neck cancer. In addition, we have an ongoing Phase 1 trial for our BNT12 program in metastatic castrate resistant prostate cancer. On Slide 23, there has been a nearly 50% increase of melanoma globally over the last decade. And it is predicted that by 2025, the number of melanoma deaths will increase by a further 20%. The latest therapeutic advancement we've seen in the standard of care are immune checkpoint inhibitors, in particular PD-one blockade. While checkpoint inhibitors lead to durable responses in a small fraction of patients, In the majority of patients, duration of responses is short and more than half of the patients are refractory to or relapse on immune checkpoint inhibitors. Those who are refractory 2, these compounds are roulettes, have an especially poor prognosis with survival as short as 6 months depending on the risk factors. Our fixed rate candidate BNT-one hundred and eleven on Slide 24, encodes a fixed set of 4 shared antigens covering more than 90% of cutaneous melanoma patients. In 2020, we published promising preliminary data from our Phase III trial in nature, BNT-one hundred and eleven as immunotherapy and in combination with anti PD-one showed a tolerable safety profile and durable objective responses in checkpoint inhibitor experienced melanoma patients with evaluable disease. We believe that these positive data provides compelling support for BNT-one hundred and eleven in combination with anti PD-one. In June 2021, our BNT-one hundred and 11 program moved into a Phase II trial in patients with anti PD-one refractory or relapsed unresectable stage 3 or 4 melanoma. This global trial, which we are conducting in collaboration with Regeneron, is outlined on Slide 25. 120 patients will be randomized 2 to 1 to 1 in the free treatment arm, evaluating BNT-one hundred and eleven in combination with Regeneron cemiplimab and each drug as a monotherapy. The primary endpoint is overall response rate in the BNT-one hundred and eleven plus simipimab arm. We will consider the study a success if data shows an overall response rate of 30% and the duration of response of more than 15 months. On Slide 26, we have our fixed fab product candidate BNT-one hundred and thirteen for the treatment of HBV-sixteen positive head and neck cancer. Our pharyngeal cancer is the most common head and neck cancer type accounting for 70% of head and neck cancers and up to 90% of those cancers are HPV-sixteen positive. In contrast to Other types of head and neck cancer, HPV-sixteen positive cancers typically occur in younger people and are not associated with typical risk factors such as tobacco or alcohol. The majority of patients are diagnosed at more advanced clinical stages and are usually treated with chemotherapy, surgery and radiation. The immune checkpoint inhibitors pembrolizumab and nivolumab are approved For treatment of recurrent or metastatic head and neck cancer, empembrolizumab is approved as first line therapy in patients who present with unresectable or metastatic disease. The historical overall response rates for pembrolizumab and nivolumab in recurrent metastatic head and neck cancer are in the range of 13.3% to 17%. For those patients who fail or progress on checkpoint inhibitors, there are only limited treatment options. We see a significant opportunity to improve the treatment landscape with BNT-one hundred and thirteen that has the potential to augment clinical responses in patients being treated with checkpoint blockers. Moving to Slide 27. BNT-one hundred and thirteen is designed to target the well characterized HBV-sixteen derived oncoproteins E6 and E7. These proteins are strongly immunogenic Viral neoantigens that are found in HBV-sixteen positive solid tumors. They are exclusively expressed in malignant cells. Viral oncogenes are commonly acknowledged as safe and promising targets for immunotherapy, have proven to be highly immunogenic and are not subject to immuno escape. Given the high number of patients with HPV-sixteen positive head and neck cancer who are also PD L1 positive, We believe that there is potential for a synergistic anti tumor effect when BNP-one hundred and thirteen is combined with checkpoint blockade. Slide 28 shows early clinical data in HBV-sixteen positive Head and neck cancer from our ongoing Phase III trial with strong vaccine antigen specific CD8 and or CD4 T cell responses in the majority of patients. As shown in preclinical experiments, these newly primed T cells Benefit from immune checkpoint blockade. We have started our BMD-one hundred and thirteen Phase 2 clinical trial shown on Slide 29 and recently dosed the first patient in the safety run-in PART. In the subsequent randomized PERT patients with unresectable recurrent or metastatic at the neck cancer Positive for HBV-sixteen and expressing PD L1 will be treated with BNT-one hundred and thirteen in combination with the checkpoint inhibitor pembrolizumab versus pembrolizumab monotherapy, a first line treatment. Overall survival and objective response rate are key endpoints of this trial with targeted Median overall survival of 18 months and an overall response rate of 40% in the combination treatment arm. We are co developing a PCR based companion diagnostic to select patients for treatment with BNT-one hundred and thirteen, which will be clinically validated as part of this trial. Moving to Slide 30 now, I would like to provide a short update on our INS program, BNT122, which is partnered with Genentech Roche. BNT122 is designed to target patient specific neoantigens and is a fully individualized cancer vaccine with 2 ongoing trials in metastatic cancers. We are now moving into the adjuvant treatment space with a Phase II trial in colorectal cancer being the first such indication. The study will compare the efficacy of BNT122 We're just watchful waiting in resected Stage 2 high risk and Stage 3 colorectal cancer patients who are ctDNA positive following 3 to 6 months of adjuvant chemotherapy as standard of care. In the first screening round, the circulating tumor DNA or ctDNA status of the patient will be determined for eligibility, which is the main risk factor for disease recurrence. In a second screening of eligible patients, neoantigen selection Based on the patient's individual tumor will be performed and BNT122 manufacturing will be initiated. The letter takes about 3 to 6 weeks, while patients undergo usual 3 to 6 months of adjuvant standard of care therapy. Final eligibility for the study will be assessed in a firm. Eligible patients will then be randomized 1 to 1 into the main treatment arms to compare the efficacy of BNT122 versus watchful weighting. The patients in the experimental arm will receive 6 weekly vaccinations, followed by 2 weekly vaccinations. Thereafter, vaccinations will be given every 6 weeks for up to 12 months. The trial also has a biomarker cohort that includes patients irrespective of ctDNA status. A second exploratory cohort will include patients who had recurrent disease at the first screening. Patients in both of these cohorts will be dosed with BNT122. Recruitment has started for this study and we anticipate dosing the first patient later this year. Coming up next On Slide 31 is the ribo cytokine platform, which is one of the examples of a high diversification of our RNA technology, which depending on the design elements we choose from our toolbox to use can be used for varying purposes. In this case, we use our RNA technology to encode Key cell homeostatic cytokines, which otherwise would be administered as recombinant proteins. Cytokines encoded by mRNA and produced in the patient have a potential for improved safety and therapeutic efficacy and more favorable cost of goods over their recombinant protein based counterparts. Recombinant protein based IL-two, for example, has been shown to induce durable responses in some tumor types, but has significant drawbacks. A short half life requiring frequent and high dosing associated with toxicities such as infusion reactions and liver tox. Our ribocitokines are designed for improved pharmacokinetic properties with a prolonged serum half life and high bioavailability. This allows for lower and less frequent dosing, which may result in better tolerability. Our ribocytokines encodercytokines fused to human albumin. The RNA backbone is optimized for high protein production And it is nucleoside modified and thus non immunogenic. The RNA is encapsulated in liver targeting LNP that allow for intravenous systemic delivery. Shown on Slide 32, we have 2 ribocytokine product candidates in the clinical trials that feature IL-two, A key cytokine in T cell immunity supporting differentiation, proliferation, survival and effector functions of T In addition to activating effector T cells, IL-two as a Physiological counter regulatory mechanism also activates suppressive regulatory T cells via one of its 3 cellular receptors, namely the IL-two receptor alphaswap unit, also referred to as CD25. BNT-one hundred and fifty one is a sequence modified IL-two engineered to reduce binding to this subunit was maintained binding to the other IL-two receptor. Thus, without extensively triggering immunosuppressive regulatory T It activates effector anti tumor T cells with a preference for those effectors that have low to no expression of CD25. As such, we anticipate that BNT-one hundred and fifty one is an optimal combination partner for anti PD-one or anti PD L1 PRP with BNT-one hundred and fifty one Phase 1 trial is ongoing. Our BNT-one hundred and fifty two-one hundred and fifty three product candidate has 2 components. BNT-one hundred and fifty three Encode's natural IL-two was maintained high affinity binding to CD25 positive T cells. Accordingly, it simulates recently activated anti tumor T cells and regulatory T cells. BNT-one hundred and fifty two, the 2nd component of its product candidate, encodes IL-seven, which sensitizes T cells to IL-two, while it controls the fraction of immunosuppressive regulatory cells. We believe BNT-one hundred and fifty two plus 153 could be a potent combination for a partner for cancer vaccines as vaccine induced T cells express high levels of CD25. We dosed the 1st patient in June 2021 in a first human Phase 1 trial in patients with solid tumors. We plan to combine this combination of T cell homeostatic cytokines with other products of our pipeline, for example, with our SiXact platform. Now to wrap up my part for today, Slide 33, which highlights a number of key milestones achieved so far this year as well as significant milestones we back on the back half of twenty twenty one. In addition to our multiple clinical updates from our COVID-nineteen vaccine program, we expect Four more data updates for our oncology programs. We have started 2 randomized Phase 2 clinical trials with 1 more expected to start in the second half of twenty twenty one. We have started 4 first in human clinical trials of our diverse therapeutic programs and expect 3 more this year. We have made significant progress with regard to accelerating our pipeline in the first half of this year, and I look forward to updating you on upcoming milestones in the near future. So I now turn over to our Chief Financial Officer, Jens Holstein, who will discuss our financial results. Thank you, Eslam, and a warm welcome to those of you on the phone. I've been in my role a few weeks now, And I'm delighted to have joined BioNTech at this exciting time in the company's growth trajectory. With great pleasure, I look forward to supporting my colleagues in our mission to make a significant impact on human health. Let me now start my section by moving to our financial results for the Q2 of 2021 as shown on Slide 35. I'll start with total revenues estimated to be approximately EUR 5,300,000,000 for the compared to €41,700,000 for the comparative period in 2020. For the period of 6 months ended June 30, 2021, we report an estimated total revenue of around €7,400,000,000 compared to €69,400,000 for the comparative period prior year period. Total revenues increased due to the rapid increase in supply and sales of our COVID-nineteen vaccine worldwide. As a reminder, under our COVID-nineteen collaborations, A breakdown of our commercial revenues is shown on Slide 36. Our Q2 2021 commercial revenues include Approximately €4,100,000,000 €5,800,000,000 for the 1st 2 quarters of 2021 that comprise our gross profit share generated by our collaboration partners in their respective territories as well as sales milestones. The sales milestones included in the figure just mentioned amounted to €168,600,000 for the 2nd quarter €415,800,000 for the period of 6 months ended June 30, 2021. Similar to previous quarters, the figure for our profit share are estimated based on Preliminary data shared between Pfizer and us, it may be subject to adjustments pending final data on input parameters like sales volume in values as well as transfer prices. Any changes in our share of the collaboration partner's gross profit will be recognized prospectively. Our COVID-nineteen vaccine commercial revenues in the 2nd quarter also include €138,100,000 In sales to our collaboration partners, products manufactured by us and around €1,000,000,000 of direct COVID-nineteen vaccine sales to customers in For the period of 6 months ended June 30, 2021, we had sales to our collaboration partners of €202,000,000 and approximately €1,200,000,000 direct COVID-nineteen sales in Germany and Turkey. Now returning back to Slide 35 and moving to cost of sales, which were estimated to be €883,800,000 for the Q2 2021 compared to €5,600,000 for the comparative period in 2020. For the 6 months End of June 30, 2021, total cost of sales were estimated to be around €1,100,000,000 compared to €11,500,000 for the comparative prior year period. The increase was driven by an estimated amount of €872,100,000 for the Q2 of 2021, around €1,100,000,000 for the period of 6 months ended June 30, 2021, respectively, that was recognized as cost of sales with respect to our COVID-nineteen vaccine sales and included the share of gross profit that we owe to our collaboration partner Pfizer or sales. Research and development expenses were €201,100,000 for the Q2 of 2021 compared to €95,200,000 for the comparative period in 2020. For the 6 months ended June 30, 2021, Research and development expenses reached EUR 417,300,000 compared to EUR 160,300,000 for the comparative prior year period. The increase was mainly due to an increase in research and development 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, development costs are shared equally between the two companies. The increase was further driven by an increase in wages, benefits and Social Security expenses due to increases in headcounts, recognizing Inventor compensation expenses as well as expenses incurred under the new share based payment arrangements. General and administrative expenses were €47,800,000 for the Q2 of 2021 compared to €18,800,000 for the comparative period in 2020. For the 6 months ended June 30, 2021, General and administrative expenses were €86,700,000 compared to €34,600,000 for the comparative prior year period. The increase was mainly due to an increase in wages, benefits and social security expenses for increasing headcounts and recognized expenses incurred under the new share based Payment arrangements, higher expenses for purchased management, consulting and legal fees as well as a higher insurance premium. Interim income taxes were approximately €1,200,000,000 for the Q2 of 2021, around €1,700,000,000 for the 6 months ended June 30, 2021 and were recognized using the estimated annual effective income tax rate of approximately 31%. For the Q2 of 2021, net profit reached approximately EUR 2,800,000,000 compared to a net loss of €88,300,000 for the comparative period in 2020. For the 6 months ended June 30, 2021, total net profit was approximately €3,900,000,000 compared to a total net loss of €141,700,000 for the comparative prior year period. As of June 30, 2021, cash and cash equivalents totaled €914,100,000 Please note that the contractual settlement of the gross profit share under our COVID-nineteen collaboration with Pfizer has a temporal offset of more than one Calendar quarter. As Pfizer's sister quarter for subsidiaries outside the United States differs from ours, creates an additional time lag between the recognition of revenues and the payment received. Consequently, trade receivables, which were outstanding As of June 30, 2021, were received as payments only in July 2021, improving our cash position relative to the amount of June 30, 2021. Moving to Slide 37. Our 2021 financial outlook has been updated as we expand and accelerate the development or broad pipeline. Based on the current contractual supply orders of approximately 2,200,000,000 doses, We're providing estimated COVID-nineteen vaccine revenues to BioNTech in 2021 of approximately EUR 15,900,000,000 This estimate reflects expected revenues from direct COVID-nineteen 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-nineteen vaccine sales in the collaboration partner's territories. Please note that this figure has been estimated at constant foreign exchange rates. We expect additional revenues related to further supply contracts for deliveries in 2021 with contracts in place for 2022 and beyond. Please keep in mind that we will deliver a significant amount of doses to middle and low income countries where prices are in line with income levels or at non for profit basis to serve the poorest. In terms of guidance for the full year 2021, We expect to incur R and D expenses in the range of €950,000,000 to €1,050,000,000 reflecting a ramp up, especially in the second half of twenty twenty one, given our plans to expand and accelerate our pipeline development. SG and A expenses are estimated to be in a range of €250,000,000 to €300,000,000 Capital expenditures for the year 2021 are expected to be in the range of €175,000,000 to €225,000,000 These figures have again, being estimated at constant foreign exchange rates and reflect our current base case projections. Finally, please note that in terms of a full year 2021 tax impact, we still expect our BioNTech Group estimated annual effective income tax of approximately 31%. And with that, I turn the call to our Chief Strategy Officer, Ryan Richardson, for an update on our corporate development Thank you, Jens. Moving now to Slide 39. I'd like to briefly discuss our recently announced acquisition Kite Pharma's personalized TCR platform and manufacturing facility in Gaithersburg, Maryland. Cell therapy forms an important component of our immuno oncology toolkit Alongside our mRNA cancer vaccines, antibodies, small molecule immunomodulators, engineered biologicals and next generation immunomodulators. This acquisition adds to our cell therapy capability and specialized infrastructure to support our growing cell therapy pipeline, which spans CAR T cell therapy, neoantigen ex vivo T cell therapy and personalized TCR T therapy. Turning to Slide 40. The Gaithersburg facility we've acquired will provide a turnkey production site to support clinical trials in the United States, complementing our existing cell therapy manufacturing facility in The new U. S. Site will support the development of our expanding pipeline of novel cell therapies, including cancer product candidates based on our CARVAC program and Neostim platforms as well as the newly acquired individualized neoantigen TCR program from Kite. Further, as a result of the acquisition, BioNTech will gain a team of more than 50 professionals with deep expertise in cell and gene therapy, including a cell therapy production team and a personalized neoantigen TCR research team. This acquisition further supports our leadership position in individualized cancer Slide 41 highlights the 3 individualized treatment platforms we are developing in house at BioNTech to address solid tumors. These include BNT122 I Nest and BNT221 Neostim and our personalized TCR T program. Each of these modalities exploits a distinct mechanism of action and is uniquely suited to specific tumor types, broadening the types of solid tumors we can target. Individualized mRNA cancer vaccines use the patient's own cancer mutations to generate neoantigen specific CD4 and CD8 T cell responses in vivo. We believe this modality is well suited to early adjuvant stage cancers. NeoStim is our individualized neoantigen T cell therapy, which uses PBMCs to induce and expand multiple CD4 and CD8 neoantigen T cell populations ex vivo. This modality is expected to end the clinic in 2021, targeting checkpoint non responsive tumors. Finally, the QI TCR platform acquisition strengthens our own in house personalized TCR T cell therapy program, which leverages ex vivo engineered neoantigen specific We believe the breadth of these therapeutic modalities position us well to usher in a new era of individualized cancer therapy. To conclude on Slide 42, we have strong momentum in our business as we move into the second half of the year. Our COVID-nineteen vaccine is continuing to have a major impact addressing the global pandemic and there is early data supporting the potential benefits of an additional booster dose. Moreover, Our oncology pipeline continues to expand with the 1st wave of programs now advancing into later stage trials. We expect a number of significant clinical trial updates in the second half of twenty twenty one. These include 4 data readouts in our oncology programs and the start of our 4th randomized Phase 2 trial. Additionally, we're on track to start 2 more first in human trials this year. We are transforming our business through additional investments into our technology platforms, Building out our global team and expanding our list of collaborators. We believe that we are well positioned for success as we execute on our strategy to achieve our vision of harnessing the immune system's full potential to fight human disease and our strong financial position enables us to invest more than ever and our firm and our innovation engine with the aim to build true long term value for patients, shareholders and society. We thank our shareholders and partners for their ongoing collaboration and support. And with that, we'll conclude our presentation and open up the floor for questions. Thank you. Your first question comes from the line of Cory Kasimov of JPMorgan. Please ask your question. Great. Good morning, good afternoon, everyone. Thanks for taking the question. I wanted to ask you about your booster strategy with the new delta trial and the ongoing You're doing for the beta specific vaccine. Now this is not surprisingly talk about the emergence of additional variants. Is it your expectation that The original vaccine will ultimately be best to use for boosting, especially given the emerging data that you have there? Or do you think this is going to trend towards some type of multivalent product in the future. And just kind of related to that, I'd be interested in your thoughts around some of The commentary out of organizations like the CDC around boosters and whether you think it's going to take a surge in breakthrough infections to really mobilize the idea of boosters on a broader basis? Thank you. I can take this question. Hi, Kobi. So at the moment, our studies, which we have performed with lab experiments, Clearly show that subjects who had received a Those had show increased neutralization antibody titers, Not only against the original variant, but almost with the same level also against the delta variant. So we believe that the best approach at the moment to deal with the situation is to continue With a booster dose with the existing wild type strain, which creates antibody responses, which are about 5 foot higher than the antibody titers neutralizing antibody titers after the second shot. It is quite possible that in the next 6 to 12 months, Further variants emerge and that would require adaptation of the vaccine, But it is at the moment not yet the case. Thank you. Your next question comes from the line of Tazeen Ahmad of Bank of America. Please ask your question. Hi, good morning. Thanks for the very thorough update. My one question is in relation to the strategy around booster. How much of the view that a third dose of the original vaccine is sufficient and the current environment is based on the is sufficient and the current environment is based on potentially not enough of the population being vaccinated, thus allowing the virus to continue to spread. And so if the pace of vaccination does increase, In the future, would you continue to believe that the booster of the original, shot would be sufficient? Or do you think that we would move to a more the specified plan of boosting just when you have different variants emerging? Thanks. I can take this one. Tazeen, as Ugo has pointed out, the current strategy, which is based on the Currently available data is to continue with the ancestral strain, so with The current variant with the original vaccine and rather than adapting just to boost with that And a large part of this data of the supporting data comes from, For example, neutralizing antibody assessments, I have presented one piece of data, but there is also other data from other groups out there, which shows that the vaccine, the ancestral vaccine generates antibody titers anti neutralizing antibodies, which are cross reactive, Even those after the second dose and cross neutralizing towards other strains, including the delta variant and Specifically, our 3rd dose data, we have also shown this after the 2nd dose, our 3rd dose data shows that the Highly boosted antibody neutralizing antibodies and as you've seen they are above the ones we generate with the second dose are also cross neutralizing against delta, but also against beta. So it is a robust Strategy to continue with boosting with the ancestral strain. I have also shown our Plans going forward in terms of producing additional data and a better understanding What adapting the strain could bring in terms of added value and added Safety margin, this is the data from our planned and ongoing clinical trials where we will Vaccinate naive subjects, but also subjects who have received The first two dose series with the ancestral strain, these will be vaccinated with the South African variant, but also with the Delta and alpha variant as individual vaccines, but also as multivariant vaccines. And these studies will tell us once we are able to investigate and map the immune responses and understand So the efficacy, whether it is required and what in terms of additional benefit it would bring to adapt the vaccine. So this is definitely something which will be investigated and might be then the strategy for the future. Thank you. The next question comes from the line of Chris Shibutani of Goldman Sachs. Please ask your question. Thank you very much. I did want to ask some practical questions about the booster. It seems as if we will get the Phase 3 readout in the 4th order. Would you anticipate that, that is a data requirement for an emergency use authorization for the booster? And in that scenario that we get a full approval of the initial doses, how would it work practically speaking in the commercial realm where you may have the initial doses fully approved and a booster on an EUA. Thank you. So I can take the question. So what we expect is That based on the data that were generated, including the safety data, Recommendations for use of booster doses, booster doses would come in different regions. So there are already recommendations, for example, Israel To use booster doses also, Germany recommended the use of booster doses in elderly And this will happen. And this happens under emergency use. And what needs to be or what is What's going on is on the one side in parallel, and this is, of course, something that we can't directly influence, It's the primary vaccination of those who had not received the vaccine to really reduce the infection. And on the other side, to if this is recommended, to enable booster vaccination For those who had received and prime boost vaccination 5 or 6 months ago To ensure an increase of antibody titers. So that means these things It happened in parallel and country wise or region wise recommendation May support different policies. So are you implying that an EUA has the potential to be A designated 5 risk populations for the booster, particularly with the U. S. FDA? Yes, it is. So you would need really a reason why different projects for France for Europe. There is, 1st of all, the approval, which is the first step. And then In different countries, and they are either recommendations by the vaccine committee or policies which are coming from government. So it is really different, Parisian and every region will come up with a solution. It will be a mixed solution and mixed policies. And then if I may add here, this is a because this is a pandemic situation, it's also An unusual situation in terms of regulatory pathway. So we are working with the health And how exactly the implementation of 3rd doses within EUAs or Full submissions at some point should be implemented in order to ensure that this all serves for overall health strategy of the respective Region or country, this is something which really needs to be worked out together with the health authorities, which will guide us. So I would not want to speculate what exactly is later in the label of the full approval or in the EUA. This is really work in progress in the interaction with the respective regulatory authorities and in the U. S. With the FDA. Okay. Thank you. Sounds quite dynamic. We'll keep tabs. Appreciate it. Yes. Thank you. Thank you. The next Question comes from the line of Dana Graybosch of SVB Leerink. Please ask your question. Hi, good afternoon, good morning. Thanks for the question. I wonder if you could talk a bit more about your business development approach And what you're looking to do is that maybe near term and long term in terms of capabilities, capacity, targets or modalities? And also with that, do you believe that you need your own PD-one to support your rich portfolio of IO program. Hi, Dana. What's the question about the business strategy or about The development strategy? Business development, so licensing and acquisition strategy. I see. I see. So Dana, we are at the moment on the one side Accelerating and broadening our internal pipeline. And of course, we are That's interested also in complementing our pipeline with additional IO molecules. So and PD-one molecule Could be an option, yes. If it's for first the criteria that we are seeking, We have at the moment own IO molecules also with the PD-one blockade function In development, as you know, and anti PD L1 plus For 1 DB bispecific is one of the molecules. And we have Internal programs, also addressing additional IO pathways. And in the next 12 to 18 months, we will certainly come up This deals allowing us to increase our pipeline to Further, again, combination partners for the vaccines and immune modulators that we have already in place. Very helpful. Thank you. Thank you. The next question comes from the line of Xiquing Xu of Berenberg. Please ask your question. Hi. Good morning. Good afternoon. Thanks for taking my questions. I'd like to also ask the booster opportunity here. Given the waning protection of the vaccine, I think A critical question is about the T cell response. Can you talk about based on our current understanding, What is the role of T cell response, particularly memory T cells and B cells here in terms of conferring The protection. Also, I want to ask about the oncology pipeline regarding VAK. How should we think about the look across read across different cancer types? Is it related to biology of the tumor types or related to the selection of the neoantigen? Thanks very much. Let me start with the first question, role of T cells. So we have 2 layers of immunity against this virus. The first layer It's the neutralizing antibody response and the first layer is responsible for inhibiting the uptake of the virus Inhibiting the infection. And the second layer is once the virus has managed to enter the cells, Yes. Then the T cells, the 2nd layer, these are CD8 T cells, which are able to recognize infected cells and kill the recognized The SAD as well as CD4 T cells, which help to further Accelerate antibody and T cell responses to restore the antibody response. And we know In animal experiments, it is known for SARS virus for more than 20 years. The T cells Protecting against severe disease and there are a number of publications now indicating that this is the case also for SARS Got 2. So that means the presence, the sheer presence of T cells is Inhibiting the development of severe disease. And this is in line with what we are observing in real world studies. So even though the decreasing antibody titers, there are more breakthrough infections, Most of the infections are mild, yes, and severe disease is still protected. The reason for that is that the T cell response is lasting longer. T cell responses can last up to many years. But we and therefore, the situation is that we will get wait for infections, but most Of the subjects, there'll be of the people will be protected against severe disease. So this was your first question. And Can you repeat your second question, please? I forgot it. Yes. The same question I'd like to ask about the kind of The real cross different tumor types regarding your fixed back, obviously, you have positive Quite the current data in melanoma. And how should we think about other types? Yes, we have 2 approaches for inducing antigen specific immune responses in cancer patients. It's The fixed pack. The fixed pack is a combination of antigens, which are Specifically tailored for certain cancer type. So we have a fixed back melanoma. We are developing a fixed back lung cancer. We have a fixed back non small cell fixed back ovarian cancer, fixed back head and neck cancer. So these are collections of antigens for specific cancer types. And the complementary approach It's the INES approach, which is targeting cancers with in an individualized fashion where We use a universal approach, so that means this approach could be universally applicable to all kinds of cancers. And it is based on the concept that we identify personal neoantigens and tailor an individual And since this approach is universal in its nature, it could be applied to many different cancer types. So we have We have the INES clinical trial running in melanoma. We have a basket trial in multiple indications running it Phase 1 study and we have just recently started IMS trial using essentially Same approach for colorectal cancer. Great. Thanks very much. Congrats on the progress. Thank you. Thank you. Your next question comes from the line of Arlinda Lee of Canaccord. Please ask your question. Hi, guys. Thanks for taking my questions. I was also curious about the booster and maybe your broader strategy on The COVID situation, I know it's fluid, but on the multivalence, Could that include other SARS CoV-two proteins? And I saw that you guys were looking at adding for additional variants. And then I guess maybe as a follow-up to that, how easily can your manufacturing setup change to manufacture some of these variants? Thank you. Okay. Thank you. So starting with the last question, we have the ability to rapidly change The strain for manufacturing, the only step that we need to do is to use another The A template for a new variant and then we can keep the complete manufacturing process without any changes And generate a vaccine, which is adapted to the variant. So this is technically possible, and we are already doing that in Claim of clinical trials. So we have a running trial for the beta variant, and we are going to So in this month, also a trial against the delta variant. So the key question is And this is not only a question for BioNTech, but it is more a general question, yes, For the health authorities and for the public, when is the best time to change of plans. So we have a situation, for example, in for influenza, the Claims defined every year by the WHO and manufacturers just produce The vaccines for the relevant claim. We do not yet have such a situation for the coronavirus. Yes. And the challenge at the moment, the global challenge is that there are different variants on different continents, Even though the delta variant is dominating most regions, there are other regions, for example, in South Africa, The other variants are more prevalent. And therefore, we would really need to get the perfect timing To make a decision for a new variant vaccine. And the decision should be based On first, the understanding that the existing vaccine, a booster of the existing vaccine will not work or is suboptimal, Yes. And the second understanding is that we really get the right variant, yes? And whether this is a single variant, And we had such a case, for example, with the alpha variant. There was a Single variant, which is really dominant one. But with the delta variant, we are now at the moment seeing the delta variant and delta plus variant. It is not yet clear which of the past volumes might emerge, yes? So Making a decision at the moment might turn out to be wrong in 3 or 6 months if another variant is dominating. Therefore, the timing of the decision must be appropriate. And this is also the reason one of the reasons why it does not make sense to change to a delta variant the vaccine now. At the moment, we have a good understanding that the booster vaccine with the Parenteral strain is completely sufficient, yes? There is no need to change the variant, and we don't know what It's happening it's going to happen in the next few months. But if it turns out that for example in 6 9 months new variants emerged, which require booster. We will we need then To understand if you go with the monovalent vaccine, just with this new variant or if there are multiple variants, if you go with with a vaccine which has several variants. All of these options are technically executable With mRNA vaccines, we prepare ourselves to ensure regardless what kind of solution is needed That we can execute that. Thank you. Thank And our final question comes from the line of Simon Baker of Redburn. Please ask your question. Thank you very much for taking my question. Just continuing on the issue of boosters and in relation to the last question, Could you give us an idea of the lead time from identification of the Desirable variant for new vaccine to how quickly you could get it into volume manufacturing. And if I may, just a very quick P and L question. Could you give us an idea of how representative this quarter's gross margin is for the rest of the Thanks so much. So we had communicated that we can do a change in less than 100 days, Yes. And this technical progress, this 100 days will become shorter with time because we are improving our methods And making it more efficient. That's the first part of the answer. And maybe Ryan or Zurg Can or Sean could answer the next question? Yes, happy to take that question, Simon. This is Jens. Of course, the revenue development as well as the gross margin depends highly on the mixture. So if the revenues are coming from our collaboration with Pfizer or for milestones or from delivering products to our collaboration partners. And that obviously influences the gross margin to a great extent. In addition, please keep in mind that going forward, there will be also quite a number of deliveries of products From ourselves, but mainly from our partners, of course, where we deliver to middle and low income countries For which we have lower prices, of course, or non for profit prices. So that influences the gross margin going forward to some extent. So Towards the year end, I would expect that maybe in Q3 or Q4, you will see a slight decrease of the margin that you have seen in Q2. Perfect. Thanks so much. Thank you. I will now hand the call back to Silkemaas To close, Thank you again for joining the call today. We look forward to speaking with you in future. Thank you. Bye bye. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.