Biontech SE (BNTX) 2021 Q2 法說會逐字稿

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 9th of August 2021.

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

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 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-19 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 detailed and important safety information regarding our COVID-19 vaccine. I'm joined today by our CEO and Co-Founder, Ugur Sahin; 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 Ugur Sahin.

Thank you, Sylke. 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 transformed 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 this global pandemic.

We have also had a strong first half year. In terms of the number of new trial starts in oncology and the accelerated development of our broad pipeline. Ozlem 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 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 pipeline to total 15 clinical stage programs and 18 ongoing trials. I expect our pipeline 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 technology fields. We believe in a future where 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, 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 launching marketable products in the next 5 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 6 trials in the first half of 2021. This includes randomized Phase II trials for our BNT111, FixVac in checkpoint inhibitor with 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 II trial for adjuvant colorectal cancer. In addition to this later-stage trial, we initiated first-in-human trials for the first programs from 3 novel 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 RiboCytokine platform, where we encode cytokines in vivo using messenger RNA. 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 deep experience as 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 EUR 5.3 billion, driven by the ramp-up of the COVID-19 vaccine production and delivery worldwide.

Finally, we recently announced the acquisition of Kite's personalized TCR research and development platform and 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 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-19 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 mRNA vaccines with durable protective immunity for prevention of malaria with the initiation of a clinical path by the end of 2022. Malaria is a disease 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 eradicateMalaria initiative by the kENUP Foundation.

The second layer of our malaria 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 with our partners or on our own. Our efforts are supported by the joint convening powers of the WHO and the Africa Centers 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 offered 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 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 messenger RNA vaccine candidates for various infectious diseases with unmet medical need. With multiple programs in 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 and up to double-digit royalties for this program through our licensing agreement with Pfizer.

On Slide 10, we show a depiction of the broad tool kit we are building across our technology platform, which includes a diverse range of potentially first-in-class therapeutic approaches. While our focus historically has been on immuno-oncology, we are investing to expand the application spectrum of our technology tool kit 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 that channels 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 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 have 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 or 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 proteins, such as our RiboMab and RiboCytokine platforms.

And finally, we believe our tool kit could lead to new, disruptive modalities at the intersection of mRNA and cell therapies, 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 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-19 program.

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 the 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 contract 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, 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 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 the BioNTech and Pfizer global supply chain and manufacturing network now spans 3 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 fill-and-finish 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 6 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 6 months to 2 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 6 months to 5 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 III trial of the vaccine, where the vaccine's efficacy and favorable side effect profile were observed up to 6 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 III trial is evaluating ready-to-use and 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 viral variants, 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 Ozlem.

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-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 6 months after the second dose was 95.7%. In 800 participants in South Africa, where the Beta variant was prevalent at that time, 9 cases of COVID-19 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 (sic) [Slide 16]. One is neutralizing antibodies. We constantly assess sera from vaccine recipients in the trial for ability to neutralize emerging variants. Sera from participants, who received 2 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. While the neutralization titers against Delta are clearly lower than against the original strain, USA WA2020 (sic) [USA-WA1/2020], the neutralization is still robust.

T cell responses are a second layer of defense. Those elicited by BNT162b2 target multiple epitopes within the spike protein. The sequences of the epitopes recognized by these T cells are shown and aligned for 5 SARS-CoV-2 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 BNT162b2 resulted in a vaccine effectiveness against symptomatic infection from Delta of 87% and 100% protection against hospitalization. A nationwide surveillance study involving 4.4 -- 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 disease 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%.

Waning 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 Israel's vaccination program relative to the rest of the world, and that many high-risk populations have 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. Variances 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 preemptively a development and regulatory pathway for a variant-specific prototype approach, as shown on Slide 17. This approach also aims to address the question whether boosting with the ancestral BNT162b2 only may suffice or variant adaptations may be required.

Our prototype approach includes 4 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 will be assessed for efficacy of the 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 300 fully BNT162b2-vaccinated participants as well as 2 doses of a Beta-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 trials 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 third BNT162b2 dose 7 to 9 months after dose 2. The graph on the top right shows that in elderly adults, neutralization has almost fallen to the level of detection by this assay after 7 to 9 months. Boosting with the third dose between 7 and 9 months after dose 2 induces a robust neutralization response beyond what was originally observed after dose 2. Sera obtained from participants 1 month after this dose 3 elicits 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 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 variants. And the third 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 a third 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 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 immunotherapy 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 3 Phase II trials. In our FixVAc 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 iNeST Phase II 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 Genmab.

And there will be a data update for our Claudin-6 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 Claudin CAR-T (sic) [Claudin-6 CAR-T] cells in which the CARVac vaccine to selectively stimulate this adoptively transferred, engineered cells, have been conducted. BNT211 is our second cell therapy program in solid tumors, which started first-in-humans clinical testing this year as well.

Moving now to Slide 22, I will discuss our wholly owned FixVac platform, which has 5 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 used 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 body-wide delivery of tumor antigen, selectively to lymphatic compartment-resident dendritic 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 I trial and for HPV16+ head, neck cancer in the BNT113 Phase I trial. Our clinical trials and preclinical studies have demonstrated that FixVac primes activates and expands a complementary pool of CD4 and CD8 T cells; and also that these newly generated T cells benefit from PD-1 blockade; that vaccines based on nonmutant, tumor-associated antigens may be of particular clinical utility in combination with anti-PD1 for tumor control in patients with a lower mutational burden, including those who have already experienced checkpoint inhibitor therapy.

Two FixVac programs just moved in Phase II trials: BNT111 in checkpoint inhibitor refractory or resistant melanoma, and BNT113 in HPV16+ head and neck cancer. In addition, we have an ongoing Phase I 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 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-1 blockade. While checkpoint inhibitors leads 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 or relapsed have an especially poor prognosis, with survival as short as 6 months, depending on the risk factors.

Our FixVac candidate, BNT111 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 I/II 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 II trial in patients with anti-PD1 refractory or relapsed unresectable Stage III or IV melanoma. This global trial, which we are conducting in collaboration with Regeneron, is outlined on Slide 25. 120 patients will be randomized 2:1:1 in the free treatment arm, evaluating BNT111 in combination with Regeneron's cemiplimab and each drug as a monotherapy. The primary end point is overall response rate in the BNT111 plus cemiplimab arm. We will consider the study a success if 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+ cancers 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 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 BNT113, that has the potential to augment clinical responses in patients being treated with checkpoint blockers.

Moving to Slide 27. The BNT113 is designed 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 targets for immunotherapy and have proven to be highly immunogenic and are not subject to immune escape. 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 a checkpoint blockade.

Slide 28 shows early clinical data in HPV16+ head and neck cancer from our ongoing Phase I/II 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 II 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 in combinations with the checkpoint inhibitor pembrolizumab versus pembrolizumab monotherapy as first-line treatment. Overall survival and objective response rate are key end points 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 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 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 versus watchful waiting in resected Stage II, high risk, and Stage III colorectal cancer patients, who are ctDNA positive following 3 to 6 months of adjuvant chemotherapy as standard of care. In a first screening round, 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 latter 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 third (inaudible). Eligible patients will then be randomized 1:1 into the main treatment arms to compare the efficacy of BNT122 versus watchful waiting. The patients in the experimental arm will receive 6 weekly vaccinations followed by 2 biweekly vaccination. 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 our RiboCytokine 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 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-2, 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 reaction and liver toxicity.

Our RiboCytokines 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 encodes the cytokines fused to human albumin. The RNA backbone is optimized for high protein production, and this 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-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 physiological counter-regulatory mechanism, also activates suppressive regulatory T cells via 1 of its 3 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 I trial is ongoing.

Our BNT152+153 product candidate has 2 components: BNT153 encodes for natural IL-2 with maintained high affinity binding to CD25-positive T cells. Accordingly, it stimulates recently activated antitumor T cells and regulatory T cells. BNT152, the second component of this product candidate, encodes IL-7, which sensitizes T cells to IL-2, while it controls refraction of immunosuppressive regulatory T cells. We believe BNT152+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 first patient in June 2021 in the first human Phase I 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 4 more data updates for our oncology programs. We have started 2 randomized Phase II clinical trials, with 1 more expected to start in the second half of 2021. 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, 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. 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 second quarter of 2021, as shown on Slide 35. I'll start with total revenues estimated to be approximately EUR 5.3 billion for the second quarter of 2021 compared to EUR 41.7 million for the comparative period in 2020. For the period of 6 months ended June 30, 2021, we report an estimated total revenue of around EUR 7.4 billion compared to EUR 69.4 million 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.

A breakdown of our commercial revenues is shown on Slide 36. Our second quarter 2021 commercial revenues include approximately EUR 4.1 billion and EUR 5.8 billion for the first 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 EUR 168.6 million for the second quarter and EUR 415.8 million 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, 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 EUR 138.1 million in sales to our collaboration partners of products manufactured by us and around EUR 1 billion of direct COVID-19 vaccine sales to customers in our territory, Germany and Turkey. For the period of 6 months ended June 30, 2021, we had sales to our collaboration partners of EUR 202 million and approximately EUR 1.2 billion direct COVID-19 sales in Germany and Turkey.

Now returning back to Slide 35 and moving to cost of sales, which were estimated to be EUR 883.8 million for the second quarter of 2021 compared to EUR 5.6 million for the comparative period in 2020. For the 6 months ended June 30, 2021, total cost of sales were estimated to be around EUR 1.1 billion compared to EUR 11.5 million for the comparative prior year period. The increase was driven by an estimated amount of EUR 872.1 million for the second quarter of 2021 and around EUR 1.1 billion for the period of 6 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 EUR 201.1 million for the second quarter of 2021 compared to EUR 95.2 million for the comparative period in 2020. For the 6 months ended June 30, 2021, research and development expenses reached EUR 417.3 million compared to EUR 160.3 million 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 2 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 of EUR 47.8 million for the second quarter of 2021 compared to EUR 18.8 million for the comparative period in 2020. For the 6 months ended June 30, 2021, general and administrative expenses were EUR 86.7 million compared to EUR 34.6 million 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 EUR 1.2 billion for the second quarter of 2021 and around EUR 1.7 billion for the 6 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 EUR 2.8 billion compared to a net loss of EUR 88.3 million for the comparative period in 2020. For the 6 months ended June 30, 2021, total net profit was approximately EUR 3.9 billion compared to a total net loss of EUR 141.7 million for the comparative prior year period.

As of June 30, 2021, cash and cash equivalents totaled EUR 914.1 million. Please note that the contractual settlement of a gross profit share under our COVID-19 collaboration with Pfizer has a temporal offset of more than one calendar quarter. As Pfizer's fiscal 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 EUR 15.9 billion. This estimate reflects expected revenues from direct COVID-19 vaccine sales to customers in our territory, expected revenues from sales to our collaboration partners, expected sales milestone payments from our collaboration partners and expected revenues related to our share of gross profit from COVID-19 vaccine sales in the collaboration partners' territories. 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&D expenses in the range of EUR 950 million to EUR 1.05 billion, 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 EUR 250 million to EUR 300 million. Capital expenditures for the year 2021 are expected to be in the range of EUR 175 million to EUR 225 million. These figures have again been 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 a 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.

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 tool kit 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 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 therapy.

Slide 41 highlights the 3 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 uses 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 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 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-19 vaccine is continuing to have a major impact in addressing the 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 4 data readouts in our oncology programs and the start of our fourth randomized Phase II 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 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.

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

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 now there's, 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?

I can take this question, right, Cory. So at the moment, our studies, which we have performed with lab experiments clearly show that subjects who have received a third dose 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 fivefold 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.

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

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 in 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 specified plan of boosting just when you have different variants emerging?

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 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 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 cross neutralizing against Delta, but also again 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 in naive subjects, but also subjects who have received the first 2 dose series with the ancestral strain. This 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 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.

The next question comes from the line of Chris Shibutani of Goldman Sachs.

I did want to ask some practical questions about the booster. It seems as if we will get the Phase III 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?

So I can take the question. So what we expect is that based on the data that's generated, including the safety data, our recommendations for use of booster doses would come in different regions. So there are already recommendations, for example, in Israel to use booster doses. Also, Germany recommended the use of booster doses in elderly, and this will happen. This happens under emergency use.

And what needs to be or what is going on is, on the one side, in parallel -- and 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, to -- if this is recommended to enable booster vaccination for those who have received and prime boost vaccination 5 or 6 months ago to ensure an increase of antibody titers. So that means these things will happen in parallel, and country-wise or region-wise recommendations may support different policies.

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

Yes, it is. So you would need really region-wise, different approaches for Europe. And it's, first of all, the approval, which is the first step. And then in different countries, and there are either recommendations by the vaccine committee or policies, which are coming from governments. So it is really different per region as the region will come up with a solution. It will be a mixed solution and mixed policies.

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 the health authorities, and how exactly the implementation of third 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.

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

I wonder if you could talk a bit more about your business development approach, and what you're looking to do. Is it 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?

Daina, was the question about the business strategy or about the development strategy?

Business development for licensing and acquisition strategy.

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, yes, if it fulfills the criteria that we are seeking.

We have, at the moment, own IO molecules also with a PD-1 blockade function in development as you know, and anti-PD-L1 plus 4-1BB 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 with deals, allowing us to increase our pipeline to further gain combination partners for the vaccines and immune modulators that we have already in place.

The next question comes from the line of Zhiqiang Shu of Berenberg.

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. Ugur, 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 (inaudible)?

Also, I want to ask about the oncology pipeline regarding FixVac. How should we think about the look across -- read across different cancer types? Is that related to pathology of the tumor types or related to the selection of neoantigen?

Let me start with the first question, role of T cells. So we have 2 layers of immunity against this virus. The 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 the virus has managed to enter the cells, yes, 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 -- kill the cells as well as CD40 cells, which help to further accelerate antibody and T cell responses to restore the antibody response.

And we know that in animal experiments, this is known for SARS virus for more than 20 years, that 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, yes. 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 real-world studies. So even though the decreasing antibody titers, there are more breakthrough infections, yes, most of the infections are mild, yes, and severe disease is -- it's 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 breakthrough infections. But most of the 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.

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

I think, yes. We have 2 approaches for inducing antigen-specific immune responses in cancer patients. It's the FixVac. The FixVac is a combination of antigens, which are specifically tailored for certain cancer types. For example, we have FixVac melanoma. We are developing a FixVac lung cancer. We have a FixVac non-small cell, FixVac ovarian cancer, FixVac head and neck cancer. So these are collections of antigens for specific cancer types, yes.

And the complement of the approach is the iNeST approach, which is targeting cancer with -- in an individualized session, 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 vaccine. And since this approach is universal in its nature, it could be applied to many, many different cancer types.

So we have the iNeST clinical trial running in melanoma. We have a basket trial in multiple indications running. It's still a Phase I study. And we have just recently started a iNeST trial using essentially the same approach for colorectal cancer.

Your next question comes from the line of Arlinda Lee of Canaccord.

I was also curious about the booster and maybe your broader strategy on the COVID situation. I know it's fluid, but on the multivalent, 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. 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 variant. So this is technically possible, and we are already doing that in frame of 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 more a general question, yes, for the health authorities and for the public, when is the best time to change a strain. So we have a situation for example in -- for influenza, the strains are defined every year by the WHO, and manufacturers just could use the vaccines for the relevant strain. And 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, South Africa, where other variants 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 hit the right variant, yes? And whether this is a single variant -- and we had such a case, for example, with the Alpha variant, where there was a single variant, which is really a 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 plus signs might emerge, yes? So it's 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 it's 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 parental strain is completely sufficient, yes. There is no need to change the variant, and we don't know what is happening, it's going to happen in the next few months. So if it turns out that, for example, in 6 or 9 months new variants emerge, which require a booster, we will -- we need then to understand if you go with a monovalent vaccine, that's this new variant, or if there are multiple variants, if we go with a 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.

And our final question comes from the line of Simon Baker from Redburn.

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?

So we had communicated that we can do a change in less than 100 days, yes. And the technical progress with 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 Sierk 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 development depends highly on the mixture. So if the revenues are coming from our collaboration with Pfizer or from 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 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.

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

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

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