On May 10, 2021 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") a next generation immunotherapy company pioneering novel therapies for cancer and infectious diseases, reported financial results for the quarter ended March 31, 2021 (Press release, BioNTech, MAY 10, 2021, View Source [SID1234579546]).
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"BioNTech has continued to execute the delivery of our COVID-19 vaccine globally to more than 90 countries and territories. Through our continued innovation, we are expanding access to new populations and geographies, and addressing emerging variants," said Ugur Sahin, BioNTech’s Co-founder and CEO. "We are moving into later stage testing for three of our oncology programs in the near future and plan to launch multiple new products over the next five years. Looking ahead, we will further optimize our technologies and expand our pipeline into additional therapeutic indications, as we meet our ambition to become a global, fully-integrated immunotherapy company."
First quarter 2021 and subsequent updates
Infectious disease
COVID-19 vaccine program – BNT162b2
In March 2021, BioNTech announced its Full Year 2020 Financial Results and Corporate Update as a part of the Annual Report filed on Form 20-F, highlighting developments relating to its COVID-19 vaccine program between January 1 and March 30, 2021 (Link to press release). A summary of these developments as well as full details of subsequent developments that occurred after March 30, 2021 is provided below.
As of May 6, 2021 BioNTech and Pfizer have shipped approximately 450 million doses of BNT162b2 to 91 countries and territories around the world.
To date, the companies have signed orders of approximately 1.8 billion doses for delivery in 2021, and they have also signed the first contracts for 2022 and beyond. Further discussions for additional dose commitments are ongoing for 2021 and beyond. BioNTech expects BNT162b2 annual manufacturing capacity to reach 3 billion doses by the end of 2021, and expects to have capacity to manufacture more than 3 billion doses in 2022.
Multiple clinical trials are ongoing to expand the authorization of BNT162b2 to additional population groups, such as children from 6 months to 11 years of age, and to collect further data in healthy pregnant women.
To date, there is no evidence that an adaptation of BioNTech’s current COVID-19 vaccine against key identified emerging variants is necessary. Despite this, BioNTech has developed a comprehensive strategy to address these variants should the need arise in the future. As part of BioNTech’s strategy to contend with the variant challenge, BioNTech submitted to the U.S. Food and Drug Administration (FDA), and the FDA has approved an additional amendment to the study protocol of the global Phase 1/2/3 trial which includes: (1) an assessment of the impact of a third dose of BNT162b2 in prolonging immunity against COVID-19 and in protecting against COVID-19 caused by potential newly emerging SARS-CoV-2 variants, and (2) an assessment of a modified, variant-specific version of BNT162b2. The aim of this study is to explore the regulatory pathway that BioNTech and Pfizer would pursue if SARS-CoV-2 were to change enough to require an updated vaccine. This trial started in March 2021.
In the first quarter of 2021, BioNTech also advanced its work to broaden access through improvements to its cold chain distribution systems and processes. Both the FDA and the European Medicines Agency (EMA) have approved the transportation and storage of undiluted frozen vials of BNT162b2 at temperatures (-20°C) commonly found in pharmaceutical freezers for a period of up to two weeks. Further stability data have been assessed and formulation optimization activities are ongoing, including a study to evaluate a lyophilized (or freeze-dried) and a ready-to-use formulation of BNT162b2.
BNT162b2 clinical development updates
On March 31, 2021, BioNTech and Pfizer announced that BNT162b2 demonstrated 100% efficacy and robust antibody responses in a Phase 3 trial in adolescents aged 12 to 15 with or without prior evidence of SARS-CoV-2 infection. The trial enrolled 2,260 adolescents in the United States. In the trial, 18 cases of COVID-19 were observed in the placebo group (n=1,129) versus none in the vaccinated group (n=1,131). Vaccination with BNT162b2 elicited high SARS-CoV-2 neutralizing antibody titers, demonstrating strong immunogenicity in a subset of adolescents one month after the second dose. BNT162b2 administration was generally well tolerated.
On March 31, 2021, BioNTech and Pfizer began evaluating the administration of a single booster dose five to seven months after receiving the second dose of BNT162b2. To demonstrate duration of protection, and protection against the emerging variants of concern, an additional dose of BNT162b2 or of BNT162b2SA (encoding for the spike protein of the variant B.1.351) is being given to about 600 Phase 3 participants. About 30 participants that received BNT162b2SA will be given another dose of BNT162b2SA. A new cohort of approximately 300 participants will be enrolled who are COVID-19 vaccine-naïve (i.e., including BNT162b2-naïve) and have not been infected with COVID-19. They will receive BNT162b2SA given as a two-dose series, separated by 21 days. The objective of this Phase 1/2/3 protocol amendment is to describe the safety and tolerability profile of BNT162b2SA, to evaluate its non-inferiority compared to BNT162b2, and to analyze the immune response generated by BNT162b2SA. By evaluating BNT162b2SA as a prototype vaccine, the companies aim to inform the development of an efficient regulatory pathway for testing future modified mRNA vaccines, using the current pathways for flu vaccines as models (blueprint study).
On April 1, 2021, BioNTech and Pfizer announced updated topline results confirming high efficacy and no serious safety concerns through up to six months following the second dose. Topline efficacy was based on an analysis of 927 confirmed symptomatic cases of COVID-19 observed in the pivotal Phase 3 study through March 13, 2021. BNT162b2 was 91.3% effective against COVID-19, measured seven days through up to six months after the second dose. The vaccine was also 100% effective against severe disease, as that term is defined by the U.S. Centers for Disease Control and Prevention, and 95.3% effective against severe COVID-19 as that term is defined by the FDA. Safety data collected from more than 12,000 vaccinated participants who had a follow-up time of at least six months after the second dose demonstrated a favorable safety and tolerability profile.
In an additional exploratory analysis of 800 trial participants enrolled in South Africa, where the B.1.351 lineage is prevalent, nine cases of COVID-19 were observed, all in the placebo group, indicating vaccine efficacy of 100%. Of these cases, eight were of the B.1.351 lineage, confirming efficacy against B.1.351 virus. These data support previous results from immunogenicity studies demonstrating that BNT162b2 induced a robust neutralizing antibody response to the B1.351 variant, and although lower than to the wild-type strain, it does not appear to affect the observed high efficacy against COVID-19 caused by this variant, as published in the New England Journal of Medicine.2
On April 1, 2021, BioNTech and Pfizer started a Phase 3, randomized, observer-blind study to evaluate the safety, tolerability, and immunogenicity of multiple formulations of BNT162b2, administered on a two-dose (separated by 21 days) schedule in adults aged 18 to 55. Part 1 of the study is comparing the safety and tolerability of lyophilized (or freeze-dried) BNT162b2 to the current frozen-liquid formulation of BNT162b2 and is evaluating non-inferiority of the immune response. Part 2 of the study will evaluate the safety and immunogenicity of a ready-to-use formulation of BNT162b2, and will be initiated in May 2021. The study, which is being conducted in the United States, will enroll approximately 610 participants. BioNTech and Pfizer expect to obtain results from both study parts in the third quarter of 2021.
Regulatory updates
On April 9, 2021, BioNTech and Pfizer requested amendments to the U.S. Emergency Use Authorization to expand the use of BNT162b2 to adolescents aged 12 to 15.
On April 30, 2021, BioNTech and Pfizer submitted to the EMA a variation to the European Conditional Marketing Authorization (CMA) for COMIRNATY to request an extension of the indication for use in adolescents 12 to 15 years of age. If the EMA approves the variation, the amended CMA will be valid in all 27 member states of the European Union.
On April 30 and May 4, 2021, BioNTech and Pfizer submitted new stability data of BNT162b2 to the FDA and EMA in order to update the product’s label to extend the storage at standard refrigerator temperatures of 2°C to 8°C to four weeks.
On May 5, 2021, BioNTech and Pfizer Canada announced that Health Canada has expanded the Interim Order authorization for BNT162b2 to include individuals 12 to 15 years of age. This is the first COVID-19 vaccine authorized in Canada for use in this age group.
On May 7, 2021, BioNTech and Pfizer announced the initiation of a Biologics License Application (BLA) with the FDA for approval of BNT162b2 to prevent COVID-19 in individuals 16 years of age and older. Data to support the BLA will be submitted by the companies to the FDA on a rolling basis over the coming weeks, with a request for Priority Review. BioNTech is the Marketing Authorization Holder in the European Union, and the holder of emergency use authorizations or equivalent in the United States (together with Pfizer), United Kingdom, Canada and other countries in advance of a planned application for full marketing authorizations in these countries.
Commercial updates
On April 19, 2021, BioNTech and Pfizer announced an agreement with the European Commission (EC) to supply an additional 100 million doses of its COVID-19 vaccine, as a result of the EC’s decision to exercise its option. The total number of doses to be delivered to the European Union by the end of 2021 is now 600 million.
In April 2021, Pfizer and BioNTech entered into an agreement with Israel to supply several million doses in 2022, with an option to purchase additional doses. The companies also entered into an agreement with Canada to supply up to 125 million doses in 2022 and 2023, with options to purchase up to 60 million additional doses in 2024. Discussions for additional dose commitments with governments and territories worldwide are also ongoing for 2021 and beyond.
On May 6, 2021, BioNTech and Pfizer announced that they have signed a Memorandum of Understanding with the International Olympic Committee to donate doses of COVID-19 Vaccine to help vaccinate athletes, and their delegations, participating in the Olympic and Paralympic Games Tokyo 2020, which are scheduled to take place in July 2021.
On May 7, 2021, the EC announced that BioNTech and Pfizer plan to supply the EC with 900 million doses of COMIRNATY, the Companies’ COVID-19 vaccine, to the 27 European Union (EU) member states beginning December 2021 through 2023, with an option for the EC to request up to an additional 900 million doses. This contract is expected to close upon final confirmation by the EC.
Manufacturing updates
BioNTech expects capacity to reach up to 3 billion doses by end of 2021, and expects to have capacity to manufacture more than 3 billion doses in 2022.
In March 2021, the EMA approved the manufacturing of BioNTech’s COVID-19 vaccine drug product at its facility in Marburg, Germany. This manufacturing facility is one of the largest mRNA vaccine manufacturing sites worldwide with an annual production capacity of up to one billion doses of COVID-19 vaccine, once fully operational. The first batches of vaccines manufactured at the Marburg facility were delivered in mid-April.
BioNTech plans to deliver up to 250 million doses of BNT162b2 in the first half of 2021.
Oncology
BioNTech is accelerating the development of a broad oncology pipeline, which has now advanced 14 product candidates in 15 ongoing trials. In April 2021 the Company started a first-in-human Phase 1 trial for the T cell therapy, targeting personalized neoantigens, named BNT221. Additional important milestones in the advancement of BioNTech’s immuno-oncology pipeline in the first quarter of 2021 included the initiation of first-in-human trials for CARVac (BNT211) and RiboCytokines (BNT151). BioNTech also expects to further advance its oncology pipeline in 2021 with up to three additional programs expected to move into randomized Phase 2 trials. Additionally, three preclinical programs are expected to move into Phase 1 trials in the second half of 2021.
During the remainder of 2021, BioNTech expects at least four data updates from its ongoing clinical trials.
mRNA programs
FixVac
BNT111 – In collaboration with Regeneron, a randomized Phase 2 trial for the treatment of patients with advanced melanoma progressing during or after prior therapy with a PD-1 inhibitor, utilizing a combination of BNT111 and Regeneron and Sanofi’s Libtayo (cemiplimab) is planned to start in the first half of 2021.
BNT113 – A Phase 2 trial evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma (HNSCC) expressing PD-L1, is planned to start in the first half of 2021 in the United States and the European Union. BNT113 has not been combined with anti-PD1 before and the Phase 2 trial will start with a run in portion designed to demonstrate the safety of the combination of BNT113 and pembrolizumab. These data are required to address the partial clinical hold on the subsequent randomized part of the Phase 2 trial.
Individualized neoantigen specific immunotherapy (iNeST)
BNT122 (Autogene Cevumeran) – BioNTech’s iNeST product candidate is partnered with Genentech.
For the adjuvant treatment of colorectal cancer, first patient dosing in a randomized Phase 2 trial in circulating tumor DNA positive, surgically resected Stage 2 (high risk)/Stage 3 colorectal cancer is now planned in the second half of 2021.
RiboCytokines
BNT151 – A Phase 1/2a dose escalation trial evaluating BNT151 with expansion cohorts in multiple solid tumor indications is ongoing.
BNT152+153 – BioNTech plans to start a Phase 1 trial for BNT152 (encoding IL-7) plus BNT153 (encoding IL-2) in multiple solid tumors in the first half of 2021.
RiboMabs
BNT141 – In February 2021, the FDA approved the IND for a Phase 1 first-in-human clinical trial for BNT141. BioNTech plans to start the trial in the second half of 2021.
BNT142 – BioNTech plans to start a Phase 1 clinical trial for BNT142 in the second half of 2021.
Antibodies
Next-generation checkpoint immunomodulators
BNT311 and BNT312 are partnered with Genmab.
BNT311/GEN1046 – A Phase 1/2a dose escalation trial with multiple expansion cohorts in patients with malignant solid tumors is ongoing. A data update for the trial is planned in the second half of 2021.
BNT312/GEN1042 – A Phase 1/2a dose escalation trial with expansion cohorts in patients with solid tumors is ongoing. The first data disclosure for the trial is planned in the second half of 2021.
Cell therapies
CAR-T cell immunotherapy
BNT211 – A first-in-human Phase 1/2a open-label, multi-center dose escalation and dose expansion basket trial of BNT211 with Claudin-6 CAR-T cells as monotherapy, or in combination of Claudin-6 CAR-T cells with Claudin-6 CARVac, is ongoing. The trial is enrolling patients with CLDN6-positive relapsed or refractory advanced solid tumors including ovarian, testicular, lung, gastric and endometrial cancers. The combination of CLDN6 CAR-T cell immunotherapy and CARVac is expected to improve expansion and persistence of CLDN6 CAR-T.
BioNTech plans to present early data from the ongoing BNT211 Phase 1/2a trial on three patients treated with a starting dose of CLDN6 CAR-T cells at the upcoming 18th Association for Cancer Immunotherapy (CIMT) (Free CIMT Whitepaper) Annual Meeting 2021. In these heavily pretreated patients with solid tumors, neither acute nor dose-limiting toxicities were observed and all adverse events were transient and mild to moderate. Robust CAR-T cell engraftment could be detected in all three patients, as well as early signs of clinical activity. Following completion of the first dose level with CAR-T cell monotherapy, the trial is now progressing to the next dose level and a combination treatment involving CAR-T cells with an RNA vaccine, which BioNTech refers to as CARVac. A data update is planned in the second half of 2021.
Neoantigen-targeting T cell therapy
BNT221 – In April 2021, the first patient was dosed in a first-in-human Phase 1 dose escalation trial for the treatment of metastatic melanoma in patients who are refractory or unresponsive to checkpoint inhibitors. Part 1 consists of the monotherapy dose escalation of BNT221. In part 2, BNT221 will be added to anti-PD1 after first-line therapy. The primary objectives of the trial are to evaluate the safety and feasibility of administering BNT221, in addition to an evaluation of immunogenicity and clinical efficacy.
BNT221 (NEO-PTC-01) is a personal neoantigen-targeted T cell therapy candidate derived from patients’ peripheral blood cells. The product candidate consists of multiple CD8+ and CD4+ T cell populations targeting multiple selected neoantigens unique to each patient’s tumor. The proprietary stimulation process allows for the induction of T cells from the naïve as well as expansion of T cells from the memory compartment.
Small molecule immunomodulators
Toll-like receptor binding agonist
BNT411 – A Phase 1/2a dose-escalation trial of BNT411 as a monotherapy in patients with solid tumors, and in combination with atezolizumab, carboplatin and etoposide in patients with chemotherapy-naïve extensive-stage small cell lung cancer (ES-SCLC) is ongoing. A data update from this trial is planned in the second half of 2021.
Corporate development
On May 9, 2021, BioNTech agreed the heads of terms with Fosun Pharma to establish a 50/50 Joint Venture (JV) to manufacture the COVID-19 vaccine in Mainland China. The establishment of a JV will be conditional on BioNTech receiving approval for its COVID-19 vaccine in Mainland China and agreement with Fosun Pharma on a definitive JV agreement, in addition to other conditions. As part of its global supply strategy, BioNTech believes that establishing local manufacturing capacity for the COVID-19 vaccine could substantially increase the Company’s ability to supply vaccines to China upon approval.
On May 10, 2021, BioNTech announced plans to expand its global footprint to Asia with the establishment of its first regional headquarters for south east Asia in Singapore. In addition to selecting Singapore as its future regional headquarters, BioNTech plans to establish a fully integrated mRNA manufacturing facility in Singapore with support from the Singaporean Economic Development Board (EDB). The new facility will leverage cutting-edge manufacturing and digital infrastructure and will be equipped to produce a range of novel mRNA vaccines and therapeutics. The envisioned site will bring highly automated and end-to-end mRNA production capabilities. The facility, with an estimated annual capacity of several hundred million doses, will provide regional and global supply capacity, as well as a rapid response capability for south east Asia to address potential pandemic threats. BioNTech plans to open its Singapore office and initiate construction of the manufacturing facility in 2021, subject to planning approval, and anticipates the site could be operational as early as 2023.
First quarter 2021 financial results (unaudited)
Revenues: Total revenues were estimated to be €2,048.4 million1 for the three months ended March 31, 2021, compared to €27.7 million for the three months ended March 31, 2020. The increase was mainly due to rapidly increasing the supply of COVID-19 vaccine worldwide. Under the collaboration agreements, territories have been allocated between BioNTech, Pfizer and Fosun Pharma based on marketing and distribution rights. BioNTech’s commercial revenues include an estimated amount of €1,751.9 million1 comprising BioNTech’s share of gross profit from COVID-19 vaccine sales in Pfizer’s territories, which represents a net figure, as well as sales milestones. In addition, €63.9 million sales to BioNTech’s collaboration partners of products manufactured by BioNTech and €199.8 million direct COVID-19 vaccine sales to customers in BioNTech’s territory have been recognized.
Cost of Sales: Cost of sales were estimated to be €233.1 million1 for the three months ended March 31, 2021, compared to €5.9 million for the three months ended March 31, 2020. Estimated cost of sales of €223.2 million1 were recognized with respect to BioNTech’s COVID-19 vaccine sales and include Pfizer’s share of gross profits earned by BioNTech.
Research and Development Expenses: Research and development expenses were €216.2 million for the three months ended March 31, 2021, compared to €65.1 million for the three months ended March 31, 2020. The increase was mainly due to an increase in research and development expenses for BioNTech’s BNT162 program, recorded as purchased services with respect to those expenses, which were initially incurred by Pfizer and subsequently charged to BioNTech under the collaboration agreement. The increase was further driven by an increase in wages, benefits and social security expenses from increasing headcounts and recognizing expenses incurred under the new share-based-payment arrangements.
General and Administrative Expenses: General and administrative expenses were €38.9 million for the three months ended March 31, 2021, compared to €15.8 million for the three months ended March 31, 2020. The increase was mainly due to higher expenses for professional services, an increase in wages, benefits and social security expenses from increasing headcounts and recognizing expenses incurred under the new share-based-payment arrangements as well as higher insurance premiums.
Income Taxes: Interim income taxes were €514.2 million for the first quarter of 2021 and were recognized using the estimated annual effective income tax rate of approximately 31%.
Net Profit / (Loss): Net profit was €1,128.1 million for the three months ended March 31, 2021, compared to €53.4 million net loss for the three months ended March 31, 2020.
Cash Position: Cash and cash equivalents as of March 31, 2021 were €891.5 million.
Shares Outstanding: Shares outstanding as of March 31, 2021 were 241,521,065.
Update on current signed COVID-19 vaccine order book:
Estimated COVID-19 vaccine revenues to BioNTech upon delivery of currently signed supply contracts of ~1.8 billion doses is ~€12.4 billion.
This revenue estimate reflects:
Expected revenues from direct COVID-19 vaccine sales to customers in BioNTech’s territory
Expected revenues from sales to collaboration partners of products manufactured by BioNTech
Expected sales milestone payments from collaboration partners
Expected revenues related to share of gross profit from COVID-19 vaccine sales in the collaboration partners’ territories
Additional revenues related to further supply contracts for deliveries in 2021 expected with first contracts in place for 2022 and beyond.
Full year 2021 manufacturing capacity now targeting 3 billion doses and more than 3 billion doses for the year 2022.
On Track with Previously Stated 2021 Financial Outlook:
Planned Full Year 2021 Expenses and Capex3
R&D expenses €750 million – €850 million
Ramp-up of R&D investment in the second half of 2021 and beyond planned to broaden and accelerate pipeline development.
SG&A expenses Up to €200 million
Capital expenditures €175 million – €225 million
Estimated Full Year 2021 Tax Assumptions
German tax group corporate tax rate ~31%
The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Quarterly Report on Form 6-K, filed today with the SEC and available at View Source
1 Estimated figures based on preliminary data shared between the collaboration partner and BioNTech as fully described in the Annual Report on Form 20-F as well as the Quarterly Report as of and for the Three Months Ended March 31, 2021, which is filed as an exhibit to BioNTech’s Current Report on Form 6-K. Changes in the share of the collaboration partners’ gross profit will be recognized prospectively.
2 New England Journal of Medicine. Neutralizing Activity of BNT162b2-Elicited Serum; March 8, 2021. Available at View Source
3 Figures reflect current base case projections.