BioNTech SE (BNTX) Q2 2021 Earnings Call Transcript

BioNTech SE (BNTX 1.63%)
Q2 2021 Earnings Call
Aug 09, 2021, 8:00 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Thank you for standing by and welcome to the BioNTech second-quarter 2021 update call. [Operator instructions] I must advise you the call is being recorded today on Monday, the August 9, 2021. I would now like to hand the call over to your vice president of investor relations and strategy, Sylke Maas. Please go ahead.

Sylke Maas -- Vice President-Sales & Marketing

Good morning and good afternoon. Thank you for joining us today to review BioNTech's second-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 Investor 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 vaccine revenues based on current contracted supply orders and our estimated financial results for 2021. The continued global demand for our COVID-19 vaccine, our target vaccine production capacity for 2021 and beyond. Our ability to supply our COVID-19 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 Slides 3 and 4 provide detail and important safety information regarding our COVID-19 vaccine. I'm joined today by our CEO and co-founder, Uğur Şahin; Ozlem Tureci, our chief medical officer and co-founder, Sean Marett, our chief business and commercial officer; Jens Holstein, our chief financial officer; Ryan Richardson, our chief strategy officer; and Sierk Poetting, our chief operating officer.

I'll now turn the call over to Uğur Şahin.

Uğur Şahin -- Chief Executive Officer

Thank you, operator. Good morning and good afternoon and 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 continued to be strong as we confirmed BioNTech and accelerate our pipeline of novel immunotherapies.

I'm happy to report that we and our partner have crossed the 1 billion mark for COVID-19 vaccine doses shipped worldwide. 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 price starts in oncology and the accelerated development of our broad pipeline. Ozlem will go in further detail on some of these new parts 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 in our growing list of other diseases. To accomplish this, we are building a fully integrated global immunotherapy company, anchored around deep expertise in immunology and complemented by an expanding set of capabilities to be more concrete what this means. In addition to shipping more than 1 billion doses of our first authorized product, in the second quarter, we expanded our oncology patent to total 15 clinical-stage programs and 18 ongoing trials. I expect our patent to continue to broaden as we broaden our research and development and initiate additional clinical trials over the next 12 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 power of 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 technologies. We believe in the future that our innovation 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 growing 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 of launching marketable products in the next five years. Slide 8 shows the key highlights for the second quarter. Starting with COVID-19, we have now distributed vaccine doses to more than 100 countries and regions globally.

As of July 23, we and our partner has signed supply contracts for delivery of approximately 2.2 billion doses in 2021. Further, we are committed to supplying more than 2 billion doses of our vaccine to low- and middle- income countries between 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 billion doses per year. In oncology, we have initiated six trials in the first half of 2021.

This includes randomized Phase 2 trials for our BNT111, FixVac in checkpoint inhibitor refractory melanoma. And for BNT113, FixVac in HPV-positive head and neck cancer. For our iNeST program, BNT122, we began screening patients in our Phase 2 trial for adjuvant colorectal cancer. In addition to this later stage trial, we initiated first-in-human trials for the first programs from three other platforms in the first half of the year.

This includes our first CARVac, CAR-T cell program, our NEOSTIM, ex-vivo TCR program. And the first program from our Ribo Cytokines current platform, where the important cytokines in vivo using intravenously. 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 1.

Jens is an accomplished executive, who brings his experience as a financial steward and operator. His appointment will enable Sierk to fully focus on his role as COO going forward. We recorded Q2 revenues of approximately 5.3 billion euros, driven by the ramp-up of the COVID-19 vaccine production and delivery worldwide. Finally, we recently announced the acquisition of Kite, personalized TCR research and development platform and the clinical stage cell therapy manufacturing facility in Gaithersburg, Maryland 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 growing clinical stage cell therapy pipeline. The acquisition will also provide us with a team of more than 50 highly specialized cell therapy experts and personal 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-19 vaccine has the potential against a range of other infectious diseases as well as the potential to play an important role in future pandemic preparedness programs. They are investing in mRNA vaccine programs to address the thesis with a massive burden in particular, in lower-income countries such as malaria, tuberculosis and HIV. As part of this, we have recently announced our plan to develop sustainable solutions to address infectious disease on the African continent.

We aim to develop the first mRNA vaccines with durable protected immunity for prevention of malaria with the initiation of a clinical path by the end of 2022. Malaria is a disease that that attacks more than 200 million 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 kENUP Foundation. The second layer of our planned project is dedicated to the development of sustainable vaccine production and end-to-end supply solution on the African continent.

We are exploring possibilities for establishing state-of-the-art mrNA manufacturing facilities in Africa, either as our partners or on our own. Our efforts are supported by the joint convening power of the WHO and the Africa Center for Disease Control and Prevention. Besides the WHO, 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 & Melinda Gates Foundation.

We plan to start the clinical trial power tuberculosis vaccine can be made 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 messenger RNA vaccine candidates for various infectious diseases with unmet medical need. With multiple programs and preclinical development, we expect to bring the first product candidate in the clinic by the next year. Finally, BNT161, the influenza vaccine program.

Our partner, Pfizer, expects to initiate the first-in-human trial in the third quarter of 2021. We are eligible to receive milestone payments up to double-digit royalties for this program to our licensing agreement with Pfizer. On Slide 10, we show a depiction of the board toolkit we are building across our technology platform, which includes a diverse range of potentially first-in-class therapeutic approaches. But our focus historically has been on immuno oncology, we are investing to expand the application spectrum of our technology toolkit to address an even holder range of immunological targets and mechanisms of action.

This means building out our platforms and even developing new complementary approaches that channels the power of the new system. To conclude on Slide 11. We believe that the broad spectrum of our technologies will enable us to bring further new product paradigms that have the potential to broaden the disease horizon beyond oncology and infectious disease for allergy, autoimmune disease and inflammatory diseases and even regenerative medicine. We believe that the new product paradigms that we are creating has the potential to expand on traditional therapeutic approaches.

This includes mRNA vaccines for other infectious diseases where we believe our technology has the potential to improve efficacy of producibility beyond what has been achievable with other vaccine modalities. We also see the opportunities for new modalities such as mRNA therapeutic cancer vaccines or immunotherapies based on mRNA encoded protein, such as our RiboMabs and Ribo Cytokines kind of platform. And finally, we believe our toolkit could lead to new disruptive modalities at the intersection of mRNA therapy, such as our CARVac approach that use mRNA to address T cell persistence in vivo. We will continue to combine our immuno-oncology expertise and powerful set 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-19 progress.

Sean Marett -- Chief Business & Commercial Officer

Thanks, Ugur. 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-19 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-19 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 of July, we, along with Pfizer, have secured orders for approximately 2.2 billion 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 million doses bringing the total number of doses under the existing supply agreement to 500 million. We expect to deliver 110 million of the additional doses by December 31, 2021 and the remaining 90 million doses no later than April 20, 2022.

We also have a contractor to supply 900 million doses to the European Union for the years 2022 to 2023 inclusive, with an option for an additional 900 million 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 billion doses of our COVID-19 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 if available and authorized. We are serious about our responsibility to help combat COVID-19 globally and are committed to ensuring that low and middle-income countries, many of which are experiencing serious outbreaks received a 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 billion doses over the next 18 months to ensure global equitable vaccine access. This includes our plan to provide the U.S.

government 500 million doses of our COVID-19 vaccine at a not-for-profit price of which 200 million doses are in 2021 and 300 million doses are in the first half of 2022. The U.S. government will, in turn, donate the Pfizer-BioNTech vaccine doses to lower- and middle-income countries and organizations that support them. This will further support the multilateral efforts to address the surge of infection in many parts of the world.

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-19 vaccine in Africa. All vaccine doses manufactured at this new CMO site will exclusively be distributed within the 55 member states that make up the African Union. Moving now to Slide 14. As we have 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 BioNTech and Pfizer global supply chain manufacturing network now spans three continents and includes more than 20 facilities. At this time, we expect to have up to 3 billion doses manufacturing capacity in place by the end of this year and up to 4 billion doses capacity in 2022. We will continue to expand our multicontinent manufacturing capabilities in the future by establishing new facilities in additional geographies. I just mentioned our new collaboration with BioVac, which is located in Cape Town, South Africa and which will perform manufacturing and distribution activities in the region.

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 billing finished capacity will exceed 100 million 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 for 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 six months to 11 years. We expect data from the study in children 2 to 11 years in the third quarter of this year and data from children six months to two years in the fourth quarter 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 time frame and soon after for children six months to five years. On the regulatory front, our U.S.

BLA submission for our COVID-19 vaccine was recently accepted by the FDA and granted priority review designation. The Prescription Drug User Fee Act or PDUFA date for a decision by the FDA is in January 2022. The BLA includes clinical data from the pivotal Phase 3 trial of the vaccine, where the vaccine's efficacy and favorable side effect profile works served up to six months after the second dose. We're also pursuing submissions for a 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 evaluate and ready to use in lyophilized formulations with data expected in the third quarter of 2021. As we continue to learn about emerging variants, our teams are rapidly responding to the dynamics of the pandemic by adapting technology, manufacturing and regulatory processes to ensure we continue to have a robust vaccine that protects humanity from COVID-19.

To address potential waning immunity and emerging bio variants, we have expanded trials to expand both variant specific doses of BNT162b2 as well as a third dose of BNT162b2, given six to 12 months after the second dose. Initial data from the BNT162b2 booster trial have been recently disclosed and Osman will now provide you further details on our boosting and variant strategy. I'll now turn the call over to Ozlem.

Ozlem Tureci -- Chief Medical Officer

Thank you, Sean. To pick up where Sean talked. 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 six months following the dose two of our vaccine. Of 971 confirmed symptomatic cases of COVID-19 in the trial, 889 cases were in the placebo group and 82 cases were in the BNT162b2 group. In the trial vaccine efficacy against severe disease at six months after the second dose at 95.7%. In 800 participants in South Africa, where the Beta variant was prevalent at that time, nine cases of COVID-19 with eight 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. One is neutralizing antibodies. We constantly assess serum from vaccine recipients in the trial for ability to neutralize emerging variants. Serum from participants, who received two doses of BNT162b2, demonstrate preserved in vitro neutralizing activities against several variants of concern, including Delta and Beta-related ones, as shown in the left panel.

Why the neutralization titers against Delta are clearly lower than against the original strain, QSAWA 2020, where neutralization is still robust. T cell responses are a second layer of defense, those illustrated by BNT162b2 target multiple epitopes within the spike protein. The sequences of the epitopes recognized by these T cells are shown and aligned for five SARS-CoV-2 variants 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 work 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. The study from Canada found that full vaccination of BNT162b2 resulted in the vaccine effectiveness against symptomatic infection from Delta of 87% and 100 protection against hospitalization. A nationwide surveillance study involving Scotland from -- 5.4 million people from Scotland, estimated that BNT162b2 was 79% effective against Delta. In July, the Israel Health Ministry reported that BNT162b2 mediated effectiveness in preventing both infection and symptomatic diseases had fallen to 39% from 64% earlier in July, while effectiveness against severe COVID-19 disease, including prevention of hospitalization continued to be as high as 91.4%.

Growing vaccine effectiveness observed in Israel, coincides with the spread of delta at the end of social distancing restrictions in Israel. We believe that another important picture is the early start date of the frist vaccination program relative to the rest of the world and that many high-risk populations have received their second dose more than six months prior July ago, which increases the risk of infection in these individuals. So the point I want to make is growth is peaking 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. New rises 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 adaptive 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 pre-emptively a development and regulatory pathway for variant specific prototype approach as shown on Slide 17. This approach also aims to address a question whether boosting with the ancestral BNT162b2 only may suffice or variant adaptations may be required. Our prototype approach includes four work streams: the first to evaluate the first 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, who were assessed for efficacy of a first dose of BNT162b2, with data expected in Q4 this year. The third ongoing trial evaluates safety and immunogenicity of BNT162b2 or a Beta variant specific vaccine version of it in 340 BNT162b2 vaccinated participants as well as two doses of a beta specific version in 300 vaccine net new 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.

And iNEST variant specific version and also multivalent vaccine, including both versions of BNT162b2. This trial will include about 600 vaccinated participants and 300 net new participants. Data from the trial is expected in Q4. We expect the data from these trials to significantly enlarge our knowledge about vaccine protection and variance of concern and also have 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, as shown on Slide 18, evaluating the administration of the third BNT162b2 dose seven to nine months after dose two. The graph on the top right shows that in elderly adults neutralization has almost fallen to the level of detection by this, say, after seven to nine months, boosting with the first dose between seven and nine months after those two induces a robust neutralization response beyond what was originally observed after dose 2. Serum obtained from participants one month after this dose three elicits a high neutralization titers against the original ancestral strain, all end 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 two in the age group 18 to 55 years and even over 11fold 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 Delta variant, narrowed after the third 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-2 variant. 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 third dose would come -- may be needed within six to 12 months after full vaccination to maintain the highest level of protection. Therefore, we are in ongoing discussions with regulatory agencies regarding the potential third dose booster of our current vaccine. Transitioning to our oncology pipeline on Slide 20. Ugur has already outlined our immuno-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 have at least one 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 three Phase 2 trials. In our FixVAc platform, we have started two Phase 2 trials in the last two months.

I will discuss those programs in more detail in a few moments. We also anticipate dosing the first patient in our iNEST Phase 2 trial in the adjuvant colorectal cancer setting in the second half of 2021. We expect data readouts across both of the next-generation immune modulators, BNT311 and BNT312, that we developed with our colleagues from Genevant. And there will be a data update for our CLDN6 CAR-T cell therapy, BNT211, in the second half of the year.

Enrollment into higher dose levels is ongoing in that trial and we have also treated the first patient with CLDN6 CAR-T cells in which the CARVac vaccine to selectively stimulate this adoptively transferred engineered trials have been conducted. BNT221 is our second cell therapy program in solid tumors, which started first in doing clinical testing this year as well. Moving now to Slide 22, I will discuss our wholly owned FixVac platform, which has five product candidates for multiple indications in clinical trials. Our -- each FixVac product candidate targets a set of shared tumor-associated antigens, which are commonly expressed by a significant portion of patients in a given cancer type.

RNA technology design elements moved for FixVac 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 bodywide delivery of tumor antigen, selectively to lymphatic compartment resistent regenerative cells to induce strong T cell responses. 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 BNT111 Phase 1 trial and for HPV-16 positive head, neck cancer in the BNT113 Phase 1 trial. Our clinical trials and preclinical studies have demonstrated that FixVac trials activates and expands a complementary pool of CD4 and CD8 T cells and also that these newly generated pieces benefit from PD-1 blockade.

But vaccines based on nonmutant tumor-associated antigens may be of particular clinical utility in combination with anti-PD-1 for tumor control in patients with no mutational burden, including those who have already experienced checkpoint inhibitor therapy. Two FixVac programs just moved in Phase 2 trials, BNT111 in checkpoint inhibitor refractory or resistant melanoma and BNT113 in HPV-16 positive head and neck cancer. In addition, we have an ongoing Phase 1 trial for our BNT112 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 debts will increase by a further 20%. The latest therapeutic advancement we've seen in the standard of care immune checkpoint inhibitors in particular PD-1 blockade. While checkpoint inhibitors to reach 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 to these compounds are relapse, having especially poor prognosis with survival as short as six months depending on the risk factors.

Our FixVac candidate, BNT111, on Slide 24, encodes a fixed set of four shared antigens covering more than 90% of cutaneous melanoma patients. In 2020, we published promising preliminary data from our Phase 1/2 trials in Nature. BNT111 as a monotherapy and in combination with anti-PD1 showed a tolerable safety profile and durable objective responses in checkpoint inhibitor experienced melanoma patients with evaluable disease. We believe that these positive data provide compelling support for BNT111 in combination with anti-PD1.

In June 2021, our BNT111 program moved into a Phase 2 trial in patients with anti-PD1 refractory or relapse 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 2:1 to 1 in the free treatment arm, evaluating BNT111 in combination with Regeneron, cemiplimab and each drug as a monotherapy. The primary endpoint is overall response rate in the BNT111 plus cemiplimab.

We will consider the study if success this data shows an overall response rate of 30% and a duration of response of more than 15%. On Slide 26, we have our FixVac product candidate BNT113 for the treatment of HPV16+ head and neck cancer. Oropharyngeal cancer is the most common head and neck cancer type accounting for 70% of head and neck cancer and up to 90% of those cancers are HPV16+. In contrast to other types of head and neck cancer, HPV16+ cancer typically occur in younger people 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 and pembrolizumab is approved as first-line therapy in 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 BNT113 that has a potential to augment clinical responses in patients being treated with checkpoint blockade. Moving to Slide 27. The BNT130 is in line to target the well-characterized HPV16 derived oncoproteins E6 and E7. These proteins are strongly immunogenic viral neoantigens that are found in HPV16+ solid tumors.

They are exclusively expressed in malignant cells. Viral oncogenes are commonly acknowledged as safe and promising target for immunotherapy and have proven to be highly immunogenic and are not subject to immunotherapy. Given the high number of patients with HPV16+ head and neck cancer who are also PD-L1 positive, we believe that there is potential for a synergistic antitumor effect when BNT113 is combined with checkpoint blockade. Slide 28 shows early clinical data in HPV16+ head and neck cancer from our ongoing Phase 1/2 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 BNT113 Phase 2 clinical trial shown on Slide 29 and recently dosed the first patient in the safety run in part. And the subsequent randomized part patients with unresectable recurrent or metastatic head and neck cancer, positive for HPV16 and expressing PD-L1 will be treated with BNT113 new combinations with the checkpoint inhibitor pembrolizumab versus pembrolizumab monotherapy at first-line treatment. Overall survival and objective response rate are key endpoints of this trial was targeted median overall survival of 18 months and an overall response rate of 40% in the combination treatment arm.

We are codeveloping a PCR-based companion diagnostic to select patients for treatment with BNT113, 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 iNEST program, BNT122, which is partnered with Genentech/Roche. BNT122 is designed to target patient-specific neoantigens and is a fully individualized cancer vaccine with two ongoing trials in metastatic cancers.

We are now moving into the adjuvant treatment space. with a Phase 2 trial in colorectal cancer being the first such indication. The study will compare the efficacy of BNT122 versus watchful waiting in refractory Stage 2 high risk and Stage 3 colorectal cancer patients who are ctDNA positive following three to six months of adjuvant chemotherapy as standard of care. In the first screening around the circulating tumor DNA or ctDNA status of the patients 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 data takes about three to six weeks, while patients undergo their usual three to six months of adjuvant standard of care therapy. Final eligibility for the study will be assessed in the first screen. Eligible patients will then be randomized 1 to 1 into the main treatment arm to compare the efficacy of BNT122 versus watchful waiting.

The patients in the experimental arm will receive six weekly vaccinations followed by two weekly vaccination. Thereafter vaccinations will be given every six 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 our Ribo Cytokines platform, which is one of the examples of high a diversification of our RNA technology, which depending on the design elements we choose from our toolbox to use. It can be used for varying purposes.

In this case, we use our RNA technology to encode T cells commonly known static 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 a more favorable cost of goods over their recombinant protein-based counterparts. Recombinant protein-based IL-2, for example, has been shown to induce durable responses in some tumor types but have significant drawbacks. The short half-life requiring frequent and high dosing associated with toxicities such as infusion reaction and liver toxicity.

Our Ribo Cytokines are designed for improved pharmacokinetic properties with a prolonged tier half-life and high bioavailability. This allows for lower and less frequent dosing, which may result in better tolerability. Our Ribo Cytokines encoded cytokines fused to human environment. The RNA backbone is optimized for high protein production and it is nuclear vie 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 two ribocytokine product candidates in the clinical trials that feature Il-2, a key cytokine in T-cell immunity, supporting differentiation, proliferation, survival and effector functions of T cells. In addition to activating effector T cells, IL-2 as a season logical counter-regulatory mechanism also activates suppressive regulatory T cells via one of its three cellular receptors, namely the IL-2 receptor alpha subunit, also referred to as CD25. BNT151, is a sequence modified IL-2 engineered to reduce binding to this subunit with maintained binding to the other IL-2 receptor.

But without extensively triggering immunosuppressive regulatory T cells. It activates effector antitumor T cells with a preference for dose effectors that have low to no expression of CD25. As such, we anticipate that BNT151, is an optimal combination partner for anti-PD1 or anti-PD-L1 therapy. With BNT151, a Phase 1 trial is ongoing.Our BNT152, 153 product candidate has two components: BNT153 encode for natural IL-2 was maintained high affinity binding to CD25-positive T cells.

Accordingly, stimulates recently activated antitumor T cells and regulatory T cells. BNT152, the second component of this product candidate encode IL-7, which sensitizes T cells to IL-2, while it controls refraction of immunosuppressive regulatory T cells. We believe BMT152 plus 153 could be a potent combination from a partner for cancer vaccines -- vaccine-induced T cell express high levels of CD25. We dosed the first patient in June 2021 in the 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 FixVac 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 expect in the back half of 2021. In addition to our multiple clinical updates from our COVID-19 vaccine program, we expect four more data updates for our oncology programs. We have started two randomized Phase 2 clinical trials with 1 more expected to start in the second half of 2021.

We have started four plus in human clinical trials of our diverse therapeutic programs and expect three 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.

Jens Holstein -- Chief Financial Officer

Thank you, Ozlem 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. The 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 second quarter of 2021, as shown on Slide 35.

I I'll start with total revenues estimated to be approximately 5.3 billion euros for the second quarter of 2021 compared to 41.7 million euros for the comparative period in 2020. For the period of six months ended June 30, 2021, we report an estimated total revenue of around 7.4 billion euros compared to 69.4 million euros for the comparative period -- prior-year period. Total revenues increased due to the rapid increase in supply and sales 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.

The breakdown of our commercial revenue is shown on Slide 36. Our second-quarter 2021 commercial revenues include approximately 4.1 billion euros and 5.8 billion euros for the first two 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 168.6 million euros for the second quarter and 415.8 million euros for the period of six 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 and may be subject to adjustments pending final data and input parameters like sales volume in values as well as transfer prices.

Any changes in our share of the collaboration partners gross profit will be recognized prospectively. Our COVID-19 vaccine commercial revenues in the second quarter also include 138.1 million euros in sales to our collaboration partners, products, manufacturers for us and around 1 billion of direct COVID-19 vaccine sales to customers in our territory in Germany and Turkey. For the period of six months ended June 30, 2021, we had sales to our collaboration partners of 202 million euros, approximately 1.2 billion euros direct COVID-19 sales in Germany and Turkey. Now returning back to Slide 25 and moving to cost of sales, which were estimated to be 883.8 million euros for the second quarter of 2021 compared to 5.6 million euros for the comparative period in 2020.

For the six months ended June 30, 2021, total cost of sales were estimated to be around 1.1 billion euros compared to 11.5 million euros for the comparative prior-year period. The increase was driven by an estimated amount of 872.1 million for the second quarter of 2021 and around 1.1 billion euros for the period of six months ended June 30, 2021, respectively, that was recognized as cost of sales with respect to our COVID-19 vaccine sales and included the share of gross profit that we owe to our collaboration partner Pfizer on our sales. Research and development expenses were 201.1 million euros for the second quarter of 2021 compared to 95.2 million euros for the comparative period in 2020. For the six months ended June 30, 2021, research and development expenses reached 417.3 million euros compared to 160.3 million euros 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 purchase 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 headcount, recognizing inventor compensation expenses as well as expenses incurred under the new share-based payment arrangement. General and administrative expenses were of 47.8 million euros for the second quarter of 2021 compared to 18.8 million for the comparative period in 2020.

For the six months ended June 30, 2021, general and administrative expenses were 86.7 million euros compared to 34.6 million euros for the comparative prior-year period. The increase was mainly due to an increase in wages, benefits and social security expenses for increasing headcount 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 1.2 billion euros for the second quarter of 2021 and around 1.7 billion euros for the six months ended June 30, 2021 and were recognized using the estimated annual effective income tax rate of approximately 31%. For the second quarter of 2021, net profit reached approximately 2.8 billion euros compared to a net loss of 88.3 million for the comparative period in 2020.

For the six months ended June 30, 2021 total net profit was approximately 3.9 billion euros compared to a total net loss of 141.7 million euros for the comparative prior-year period. As of June 30, 2021, cash and cash equivalents totaled 914.1 million euros. Please note that the contractual settlement of a gross profit share under our COVID-19 collaboration with Pfizer has a temporary offset of more than 1 calendar quarter. As far as assisted quarter for subsidiaries outside the United States differs from ours, it 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 of our broad pipeline. Based on the current contractual supply orders of approximately 2.2 billion doses, we're providing estimated COVID-19 vaccine revenues to BioNTech in 2021 of approximately 15.9 billion euros.

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 of 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 progress.

In terms of guidance for the full-year 2021, we expect to incur R&D expenses in the range of 950 million euros to 1.05 billion euros, reflecting a ramp-up especially in the second half of 2021, given our plans to expand and accelerate our pipeline development. SG&A expenses are estimated to be in the range of 250 million euros to 300 million euros. Capital expenditures for the year 2021 are expected to be in the range of 175 million euros to 225 million euros. These figures have again been estimated at constant foreign exchange rate and reflect our current base case projections.

Finally, please note that in terms of 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 activities and concluding remarks.

Ryan Richardson -- Chief Strategy Officer

Thank you, Jens. Moving now to Slide 39. I'd like to briefly discuss our recently announced acquisition of 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 Idar-Oberstein, Germany. 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 personals 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 therapy. Slide 41 highlights the three individualized treatment platforms we are developing in-house at BioNTech to address solid tumors.

These include BNT122, iNEST 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 gives 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 in early and 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 enter the clinic in 2021 targeting checkpoint or nonresponsive tumors. Finally, the Kite TCR platform acquisition strengthens our own in-house personalized TCR-T cell therapy program, which leverages ex-vivo engineered neoantigen-specific TCR-T cells to address advanced tumors. We believe the breadth of these therapy 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-19 vaccine is continuing to have a major impact in addressing our global dynamic and there is early data supporting the potential benefits of an additional booster dose. Moreover, our oncology pipeline continues to expand with the first wave of programs now advancing into later-stage trials. We expect a number of significant clinical trial updates in the second half of 2021.

These include four data readouts in our oncology programs and the start of our fourth randomized Phase 2 trial. Additionally, we're on track to start two 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 immune systems' full potential to fight human disease and our strong financial position enables us to invest more than ever in 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.

Questions & Answers:

Operator

[Operator instructions] Your first question comes from the line of Cory Kasimov of J.P. Morgan. Please ask your question.

Cory Kasimov -- J.P. Morgan -- Analyst

Great. Good morning, good afternoon, everyone. Thanks for taking my question. I wanted to ask you about your booster strategy.

With the new Delta trial and the ongoing testing you're doing for the beta-specific vaccine not surprising to 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 toward some type of multivalent product in the future? 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.

Uğur Şahin -- Chief Executive Officer

I can take this question. Hi, Cory. At the moment, our studies, which we have performed with net experiments clearly show that subjects who have received a third dose, those had show increased neutralization antibody titers, not only against the original variants, 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 faster or higher than the antibody titers -- neutralizing antibody titers after the second shot.

It is quite possible that in the next six to 12 months, further variants emerge and that would require adaptation of the vaccine. But it is, at the moment, not yet the case.

Operator

Thank you. Your next question comes from the line of Tazeen Ahmad of Bank of America. Please ask your question.

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Hi. Good morning. Thanks for the update. My 1 question is in relation to the strategy around booster.

How much of the view that a third dose of the original vaccine is decision in the current environment is based on potentially not enough with the population being vaccinated, thus allowing the virus to continue to spread. And so the pace of acclimation 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 specified plan of boosting just when you have different variants emerging? Thanks.

Ozlem Tureci -- Chief Medical Officer

I can take this one. Tazeen, as Ugur 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 or with the original vaccine. And rather than adapting just to boost with that strain. And a large part of this data -- of the supporting data comes from, for example, neutralizing antibody assessment.

I have presented 1 piece of data, but there is also other data from other groups out there, which shows that the vaccine -- ancestral vaccine generates antibody titers, anti-neutralizing antibodies, which are cross-reactive even those after the second dose and cross neutralizing toward other strains including the Delta variant and specifically our third dose data, we have also shown this after the second dose, our third dose data shows that the highly boosted antibody neutralizing antibodies. And as you have seen, they are above the ones we generate with the second dose, also cost neutralizing against Delta, but also again beta. So it is a robust strategy to continue with boosting with ancestral strain. I have also shown our plans going forward in terms of producing additional data and a better understanding what adapting this 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 in least subjects, but also subjects who have received the first two dose series with the ancestral strain. This will be vaccinated with the South African variant, but also with 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 met the immune responses and understand also 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.

Operator

Thank you. The next question comes from the line of Chris Shibutani of Goldman Sachs. Please ask your question.

Chris Shibutani -- Goldman Sachs -- Analyst

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 fourth quarter, 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.

Uğur Şahin -- Chief Executive Officer

So I can take the question. So what we expect is that based on the data that's generated, including the safety data has recommendations for use of booster doses. Booster doses would come in different regions. So there are already recommendations, for example, in East 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 going on is, on the one side, in parallel.

This is, of course, something that we can't directly influence is the primary vaccination of those who had not received a vaccine to really reduce the infection. And on the other side, if this is recommended to enable booster vaccination for those who have received and time boost vaccination five or six months ago to ensure increase of antibody titers. So that means these things will happen in parallel and country-wise or region-wise recommendations may support different policies.

Chris Shibutani -- Goldman Sachs -- Analyst

So are you implying that an EUA has the potential to be a designated bot risk populations for the booster, particularly with the U.S. FDA?

Uğur Şahin -- Chief Executive Officer

Yes, it is. So you would need really region wise different projects filed for Europe. And it's, first 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.

But it is really different as a region will come up with a solution. It will be mixed solution and mix policies.

Ozlem Tureci -- Chief Medical Officer

Yes. If I may add here, this is because this is a pandemic situation. It's also unusual situation in terms of regulatory pathway. So we are working with health authorities and how exactly the implementation offer 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 a 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 in the U.S. with the FDA.

Chris Shibutani -- Goldman Sachs -- Analyst

OK, thank you. Sounds quite dynamic. We'll keep tabs. Appreciate it.

Ozlem Tureci -- Chief Medical Officer

Yeah. Thank you.

Operator

Thank you. The next question comes from the line of Daina Graybosch of SVB Leerink. Please ask your question.

Daina Graybosch -- SVB Leerink -- Analyst

Hi. Good afternoon, good morning. Thanks for the question. Wondered if you could talk a bit more about your business development approach.

And what you're looking to do it 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-1 to support your rich portfolio of IO program?

Uğur Şahin -- Chief Executive Officer

Daina, what's the question about the business strategy or about the development strategy?

Daina Graybosch -- SVB Leerink -- Analyst

Business development for licensing and acquisition strategy.

Uğur Şahin -- Chief Executive Officer

I see, I see. So Daina, we are, at the moment, on the one side, accelerating and broadening our internal pipeline. And of course, we are interested also in complementing our pipeline with additional IO molecules. So a PD-1 molecule could be an option if it fulfills the criteria that we are seeking.

We have, at the moment, own IO molecules also with the PD-1 blockade function in development as you know and anti-PD-L1 plus for 41BB bispecific is one of the positives. And we have internal programs also addressing additional IO passes. And in the next 12 to 18 months, we will certainly come up with this deals, allowing us to increase our pipeline to further gain combination partners for the vaccines and immune modulators that we have already in placed.

Daina Graybosch -- SVB Leerink -- Analyst

Very helpful. Thank you.

Operator

Thank you. The next question comes from the line of Zhiqiang Shu of Berenberg. Please ask your question.

Zhiqiang Shu -- Berenberg Capital Markets -- Analyst

Hi. Good morning, good afternoon. Thanks for taking my question. I'd like to also ask at 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 in memory T cells and B cells here in terms of confirming the protection? Also I want to ask about the oncology pipeline regarding FixVac. How should we think about the look across different cancer types? Is it related to biology of the tumor types or related to the selection of the neoantigen? Thanks very much.

Uğur Şahin -- Chief Executive Officer

Let let me start with the first question, role of T cell. So we have two layers of immunity against this virus, but first layer is 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 virus has managed to enter the cells, then the T cells, the second layer, this has to be a T cell, which are able to recognize infected cells and kill the recognized cell as well as CD40 cells, which have to further accelerate antibody and T cell responses to restore the antibody response. And we know that in animal expense is known for virus for more than 20 years, the T cells are protecting against severe disease and there are a number of publications now indicating that this is the case also for SARS-CoV-2, but 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 large studies. So even though the decrease in antibody titers, there are more breakthrough infections. Most of the infections are mild 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 too many years. But we -- and therefore, the situation is that we will get paid for infections, but most of the after subjects will 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.

Zhiqiang Shu -- Berenberg Capital Markets -- Analyst

Yes. The same question I'd like to ask about the kind of the real cost different tumor trends regarding your FixVac. Obviously, we have positive quite recurring data in melanoma. And how should we think about other types?

Uğur Şahin -- Chief Executive Officer

Yes. We have two approaches for inducing in using antigen-specific immune responses in cancer patients, it's FixVac. The FixVac is a combination of antigens, which are specifically tailored for certain cancer types. For example, FixVac melanoma.

We are developing a FixVac lung cancer. We have a FixVac ovarian cancer, FixVac head and neck cancer. So these are collections of antigens for specific cancer types. And the complement of the approach is the iNEST approach, which is targeting cancer with -- in the last session, 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 tailored and individual vaccine. And since the support is universal in its nature, it could be applied to many different cancer types. So they have a iNEST clinical trial running in melanoma. We have a basket trial in multiple indications, still a Phase 1 study.

And we have just recently started iNEST trial using essentially same approach for colorectal cancer.

Zhiqiang Shu -- Berenberg Capital Markets -- Analyst

Great. Thanks very much. Congrats on the profits.

Uğur Şahin -- Chief Executive Officer

Thank you.

Operator

Thank you. Your next question comes from the line of Arlinda Lee of Canaccord. Please ask your question.

Arlinda Lee -- Canaccord Genuity -- Analyst

Hi, guys. Thanks for taking my question. I was also curious about the booster and maybe your broader strategy on the COVID situation. I know it's fluid, but on a multivariant, could that include other SARS-CoV-2 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.

Uğur Şahin -- Chief Executive Officer

OK, 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 DNA 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 value.

So this is technically possible and we are already doing that in same clinical trials. And so we are running trials for the Beta variant and we are going to start in this month also a trial against the Delta variant. The key question is -- and this is not only a question for BioNTech, but it is a general question for the half order we see and for the public, when is the best time to change our plan. So we have a situation for example in -- for influenza the trends are defined every year by the WHO and manufactures just could use the vaccines for the relevant strain.

And we do not yet have such a situation for the coronavirus. 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 North region, there are other regions like South Africa, the other variant 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 boost that is the existing vaccine will not work or is it that optimal.

And the second understanding is that we really hit 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 senior variant, which is really the dominant one. But with the Delta variant we are now at the moment, seeing the Delta variant and Delta plus variant. And it's not yet clear, which of the tough signs might emerge.

So it's making a decision at the moment might turn out to be wrong in three or six months if another variant is dominating. Therefore, the timing of the decision must be appropriate. And it's also the reason -- one of the reasons that it does not make sense to change to a Delta variant vaccine now. At the moment, we have a good understanding that the booster vaccine with the parental strain is completely sufficient, yes.

There is no need to change the variant and we don't know what is happening -- is going to happen in the next few months. If it turns out that in six or nine months new variants emerge, which require a booster, we will -- we need then to understand if you go with a monovalent vaccine, that is the new variant or if there are multiple variants, if we go with the vaccine which has several variants. All of these options are technically executable with mRNA vaccines and we prepare our staff to ensure regardless what kind of solution is needed, that we can execute that.

Arlinda Lee -- Canaccord Genuity -- Analyst

Thank you.

Operator

Thank you. And our final question comes from the line of Simon Baker from Redburn. Please ask your question.

Simon Baker -- Redburn -- Analyst

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 a new vaccine to how quickly you could get it into volume manufacturing. And if I may, just a very quick P&L question. Could you give us an idea of how representative this quarter's gross margin is for the rest of the year?

Uğur Şahin -- Chief Executive Officer

So we had communicated that we can do a change in less than 100 days. And the technical progress is 100 days will become shorter with time because we are improving our methods and making it more efficient. That's the first part of answer and maybe Ryan or Sierk or Sean could answer the next question.

Sean Marett -- Chief Business & Commercial Officer

Yes, happy to take that question, Simon. This is Sean. Of course, the revenue development as well as the gross margin development 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 not-for-profit prices. So that influences the gross margin going forward to some extent. So toward 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.

Simon Baker -- Redburn -- Analyst

Perfect. Thanks so much.

Operator

Thank you. I will now hand the call back to Sylke Maas to close.

Sylke Maas -- Vice President-Sales & Marketing

Thank you again for joining the call today. We look forward to speaking with you in the future. Thank you. Bye bye.

Operator

[Operator signoff]

Duration: 98 minutes

Call participants:

Sylke Maas -- Vice President-Sales & Marketing

Uğur Şahin -- Chief Executive Officer

Sean Marett -- Chief Business & Commercial Officer

Ozlem Tureci -- Chief Medical Officer

Jens Holstein -- Chief Financial Officer

Ryan Richardson -- Chief Strategy Officer

Cory Kasimov -- J.P. Morgan -- Analyst

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Chris Shibutani -- Goldman Sachs -- Analyst

Daina Graybosch -- SVB Leerink -- Analyst

Zhiqiang Shu -- Berenberg Capital Markets -- Analyst

Arlinda Lee -- Canaccord Genuity -- Analyst

Simon Baker -- Redburn -- Analyst

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