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The BioNTech SE (short for Biopharmaceutical New Technologies) is a Nasdaq-listed biotechnology company headquartered in Mainz, Germany, focused on the development and manufacture of active immunotherapies for a patient-specific approach to the treatment of cancer and other serious diseases. BioNTech's primary focus is on the discovery of mRNA-based drugs. These are potential candidates for individualized cancer immunotherapies, vaccines against infectious diseases, and protein replacement therapies for rare diseases. Besides, the company is active in the research of programmable cell therapies ("Engineered Cell Therapy"), novel antibodies, and small molecule immunomodulators ("small molecules") as treatment options for cancer.

BioNTech was the first company to develop an mRNA-based human therapeutic agent for intravenous administration, to bring individualized mRNA-based cancer immunotherapy into clinical trials, and to establish its manufacturing process for such a product candidate. In November 2020, the company announced that the coronavirus vaccine BNT162b2, developed in cooperation with the pharmaceutical company Pfizer, offered a vaccine efficacy of 95% to protect against COVID-19 disease.

Foundation (2008–2013)
BioNTech was founded in 2008 based on many years of research work by Uğur Şahin, Özlem Türeci, and Christoph Huber. The company's activities focus on the development and production of technologies and drugs for individualized cancer immunotherapy. with a starting capital of around 180 million U.S. dollars and Michael Motschmann and Helmut Jeggle were involved in the company's founding. In 2009, the acquisition of EUFETS and JPT Peptide Technologies took place. The same year saw Phase 1 clinical studies with MERIT (Melanoma RNA Immunotherapy; a fixed combination of cancer-specific antigens) and IVAC MUTANOME (first study with individualized neoepitopes). The initial seed financing was completed in 2009.

Expansion (2014–2018)
Between 2014 and 2018, extensive publications of the research results were made in Nature, among others. Besides, extensive collaborations and joint development and commercialization programs were concluded with various companies and scientific institutions starting in 2015. During this period, BioNTech filed several patent applications and developed a multi-layered strategy to protect its intellectual property in the various technology platforms and their application in the treatment of cancer and other serious diseases.

Nasdaq IPO (2019)
The focus of 2019 was the IPO on the Nasdaq. Since October 10, 2019, BioNTech has been publicly traded as American Depository Shares (ADS) on the Nasdaq Global Select Market under the ticker symbol BNTX. This makes BioNTech one of eight German companies listed on the U.S. technology exchange. Before this, one of the largest European Series B financings was closed in July. BioNTech was able to generate total gross proceeds of 150 million dollars from the IPO. Originally, proceeds of 250 million dollars had been expected from the IPO. The consortium leaders were the investment banks J.P.Morgan, Merrill Lynch, UBS, and SVB Leerink. With a valuation of around 3.1 billion euros based on the issue price of 15 dollars per share, BioNTech established itself in the top group of the German biotech scene based on its market capitalization.

In 2019, six clinical studies were initiated using four therapeutic platforms and covering two classes of compounds. A total of ten product candidates were processed in eleven clinical studies in 2019. Also, the antibody production business of MAB Discovery, antibody assets of MabVax Therapeutics, and Lipocalyx were acquired in 2019.

Current situation
Currently, BioNTech is working on the development of a vaccine against SARS-CoV-2. When the outbreak of a new virus in China became public at the beginning of 2020, the global development project Lightspeed began as early as mid-January to develop a well-tolerated, potent vaccine against the SARS-CoV-2 virus in as short a time as possible. For this purpose, BioNTech has allied with two partners, Pfizer and Fosun Pharma. Studies have been successfully initiated in the USA, Europe, China, Latin America, and South Africa. The first clinical trials were conducted as early as April. In November 2020, BioNTech announced that the coronavirus vaccine developed together with Pfizer offered a vaccine efficacy of over 95% to protect against COVID-19 disease.

Corporate structure
BioNTech is a limited liability corporation founded in Germany and based in Germany. BioNTech's shares have been publicly traded as American Depository Shares (ADS) on the Nasdaq Global Select Market since October 10, 2019. With effect from March 8, 2019, the company's name and legal form were changed from BioNTech AG to BioNTech SE. BioNTech's business is managed in two overarching business units, the Biotech Division and the External Services Division. The External Services division represents the interface through which medical devices are sold to third parties.

Shareholders
The registered share capital of BioNTech amounts to €232,304,250, and it is divided into 232,304,250 bearer shares with a nominal value of one Euro. Each issued ordinary share is fully paid up.

AT Impf is the largest single shareholder with a stake of over 50%. Other institutional investors associated with the Management Board and Supervisory Board members are Medine, MIG Verwaltung, and FMR. In total, companies of these board members hold almost 72% of the shares in BioNTech.

Management Board
The Board of Directors of BioNTech consists of five members. Since its foundation, Uğur Şahin has been the Chairman of the Board (Chief Executive Officer). Other members are Sean Marett (since 2012, Chief Business Officer and Chief Commercial Officer), Sierk Poetting (since 2014, Chief Financial Officer and Chief Operating Officer), Özlem Türeci (since 2018; Chief Medical Officer), and Ryan Richardson (since 2020, Chief Strategy Officer).

Supervisory Board
The Supervisory Board consists of four members. The Chairman is Helmut Jeggle, who has held senior positions at Athos Service since 2007. He has been Chief Executive Officer and Chief Operating Officer since 2015. Before that, he held various positions at Hexal. Other members are Ulrich Wandschneider (since 2018, from 2011 to 2016 Chief Executive Officer of the Asklepios Kliniken), Michael Motschmann (since 2008, co-founder of the MIG administration) , and Christoph Huber (Austrian hematologist, oncologist, and immunologist with a research focus on tumor defense and stem cell transplantation. From 1990 until his retirement in 2009, he was director of the III. Medical Clinic and Polyclinic at the University Medical School of the Johannes Gutenberg University Mainz.

Scientific Advisory Board
Since its foundation, BioNTech has been supported by a scientific advisory board headed by Rolf Zinkernagel and Hans Hengartner. Rolf Zinkernagel is professor emeritus at the University of Zurich and former head of the Institute for Experimental Immunology in Zurich. In 1996, Zinkernagel received the Nobel Prize for discovering how the immune system recognizes virus-infected cells. Hengartner is an immunologist and professor emeritus at the Swiss Federal Institute of Technology (ETH) Zurich and the University of Zurich.

Locations
The headquarters of BioNTech is located in the district of Mainz. The company's headquarters were built on the Generalfeldzeugmeister-Kaserne barracks site, which will be completely cleared by the German Armed Forces by 2022. BioNTech has already acquired additional land in Mainz in March 2020 in order to be able to expand. The company operates several GMP-certified production facilities in Germany to manufacture mRNA therapeutics and programmable cell therapies ("Engineered Cell Therapies"). The locations are Idar-Oberstein (BioNTech Innovative Manufacturing Services), Martinsried (BioNTech Small Molecules), Neuried (BioNTech), and the fourth facility in Berlin, which offers peptide-based services and products for various areas of biomedical research (JPT Peptide Technologies).

In 2019, the sites were expanded by a subsidiary in San Diego, USA (BioNTech Research & Development). In 2020, Neon Therapeutics was acquired and became BioNTech US. Neon was founded in 2015 by scientists, including a Nobel Prize winner, and was based on insights gained in the development of neon antigen therapies focusing on vaccines and T-cell therapeutics. The complementary skills and resources for neon antigen-based therapeutics in cancer medicine and immunology were thus combined. The merger enabled BioNTech to further expand its capabilities in the T-cell receptor field and strengthen its position in programmable T-cell therapies. Neon's common stock was delisted from the stock exchange in May 2020. BioNTech US is based in Cambridge, Massachusetts, and is a fully integrated subsidiary, strengthening BioNTech's presence in the U.S.

In September 2020, Novartis Vaccines and Diagnostics sold its Marburg plant to BioNTech, which has since been managed as BioNTech Manufacturing Marburg. The Marburg plant is a state-of-the-art multi-platform GMP-certified production facility employing around 300 people. It is equipped for the production of recombinant proteins and cell and gene therapies. It has cell culture laboratories and production capabilities to manufacture viral vectors, with the possibility of long-term expansion. The plant's acquisition enables BioNTech to expand its commercial production capacities for the manufacture of the mRNA-based COVID-19 vaccine candidate BNT162. The facility has two of BioNTech's existing GMP-certified sites that manufacture COVID-19 vaccine candidates for clinical trials and will become one of the most extensive production facilities for mRNA in Europe, along with four Pfizer sites in the U.S. and Europe. Subject to regulatory approval, production of the mRNA, and LNP formulation of a COVID-19 vaccine is expected to begin in Marburg, Germany. In the plant, which employs about 300 people, annual production of 750 million vaccine doses is planned.
 * BioNTech Manufacturing Marburg

The production facility in Marburg was built in 1904 by Emil von Behring for. He developed the antidote for diphtheria and tetanus. He used the prize money he received for his Nobel Prize in Medicine in 1901 to finance the production facility.

Employees
BioNTech employs over 1,300 people from more than 60 countries (as of December 2019). The proportion of women is over 56%; a quarter of the employees hold a doctorate. The average age is about 35 years. Well-known employees include Katalin Karikó and Alexandra Kemmer-Brueck.

Key figures
(Sources: Annual Reports of BioNTech SE)

Research and technology
BioNTech's research approach is based on the view that the use of complementary, potentially synergistic mechanisms of action increases the probability of therapeutic success, reduces the risk of secondary resistance mechanisms, and also opens up a larger potential market. The key is a technology-agnostic approach to provide the most appropriate therapeutic platform or combination of platforms for each patient and disease. Bioinformatics is crucial for the production of individualized therapies. The validated patient-centered bioinformatics process enables the application of complex algorithms to patient data in the context of drug manufacturing. The bioinformatics processes are robust, scalable, and rely on handling genome data with high data processing rates. BioNTech's research is designed to enable the production of individualized on-demand immunotherapies for commercial use.

mRNA therapeutics
BioNTech is researching active ingredients based on the messenger molecule messenger RNA (mRNA) as a potential new drug class. mRNA brings genetic information to the ribosomes, the place in the cell where proteins are formed. In the ribosomes, the genetic information of mRNA is translated into corresponding proteins. First mRNA-based product candidates have already entered clinical development as cancer immunotherapeutics and vaccines against infectious diseases. As a drug, the produced mRNA provides instructions to a target cell to produce a desired therapeutic protein. In cancer treatment, the produced protein is directed against target structures that are directly derived from the mutations of the cancer cells. In this way, the cancer is to be fought.

BioNTech has developed several formats and formulations of mRNA to deliver genetic information to cells used for the body's protein production for therapeutic purposes. BioNTech is exploring several mRNA-based therapeutic platforms for cancer immunotherapy, in particular for individualized cancer immunotherapy.

With four classes of active substances, the paradigm shift towards individualized immunotherapy is to be initiated. BioNTech's approach combines different mechanisms of action of the different drug classes to make cancer treatment more coordinated and precise than is possible with currently available therapies. The four different mRNA formats are expected to result in five different platforms for the treatment of cancer.

mRNA formats
The nucleotide sequence of the mRNA determines the amino acid sequence of the protein. Also, the type of nucleosides used to produce mRNA drugs can influence the immune system's recognition of the molecule.
 * Optimized unmodified mRNA (uRNA)

Immunogenic reactions against mRNA drugs must be avoided in applications where therapeutic proteins are produced, for example on our two platforms RiboMab and RiboCytokines.

Our product candidates with self-amplifying mRNA (saRNA) are based on the concept of viral replication but are neither infectious nor pathogenic. saRNA is similar to conventional mRNA: it encodes the respective protein on the one hand and a polymerase. This so-called replicase multiplies a part of the mRNA within the target cell. During self-amplification within the cell, a double-stranded RNA is formed as an intermediate stage, which is recognized by intracellular immune sensors. This enables us to achieve a robust activation of the immune system with saRNA.
 * Self-amplifying mRNA (saRNA)

This technology is a further development of the saRNA platform. We have expanded the range of applications by separating the target mRNA to be amplified from the replicase-encoding mRNA. This makes therapeutic mRNAs more flexible since the replicase can amplify mRNA that encodes not only one protein but several different proteins.
 * Transamplifying mRNA (taRNA)

mRNA platforms
Three of the platforms are currently in clinical trials. Two additional platforms are also under development.
 * FixVac, standard immunotherapy based on common antigens owned by BioNTech
 * iNeST, individualized neo-antigen-specific immunotherapy in collaboration with Genentech
 * Intratumoral immunotherapy in collaboration with Sanofi
 * RiboMabs, a new class of mRNA-encoded monoclonal antibodies that aim to produce the desired antibodies directly in the patient's body using the corresponding mRNA.
 * RiboCytokines, a new class of mRNA-based therapeutics designed to directly translate cytokines in the patient. Cytokines play a central role in controlling the immune response to pathogens and malignant cells.

Engineered cell therapies
BioNTech is developing a series of new cell therapies (Engineered Cell Therapies) to modify the patient's T-cells to target cancer-specific antigens. Research is being conducted into programmable cell therapies and an expanded patient universe. Several new cell therapies are being developed in which the patient's T cells are modified to target cancer-specific antigens. These include two platforms to treat solid tumors: a platform for chimeric antigen receptor T cells (CAR T cells) and a platform for T cell receptor (TCR) programs. BioNTech is investigating a CAR-T product candidate, BNT211, which targets claudin-6 (CLDN6). The CLDN6 antigen is specific for solid tumors.

Antibodies
BioNTech is developing next-generation antibodies (checkpoint immunomodulators and targeted cancer antibodies) to modulate the patient's immune response to cancer.

In collaboration with Genmab, BioNTech is researching bispecific antibodies that act as dual immunomodulators. For this purpose, the company applies the DuoBody technology developed by Genmab. In 2019, BioNTech acquired an antibody (MVT-5873 or BNT321) with a novel mode of action from MabVax.

Small molecule immunomodulators
BioNTech researches small molecules for specific immunomodulation. The aim is to increase the activity of other drugs through immunomodulation. In this context, the company is developing a small molecule toll-like receptor-7 (TLR7) based immunomodulator to treat solid tumors. TLR7 plays an essential role in the activation of the innate immune response. In many types of cancer, tumors are protected by an anti-inflammatory environment. This reduces the ability of the immune system to attack cancer cells. TLR7 agonists can trigger a direct cellular immune response in this case. Small molecule immunomodulators or low-molecular cancer therapeutics can be used to control cancer tumors' growth, stop the formation of blood vessels in tumors, and release toxins to cancer cells. They can also be used as markers of cancer cells to make them recognizable to the immune system and destroy them. Unlike cancer therapies with larger antibody molecules, low-molecular compounds are often directed against target structures inside cells.

Research is carried out at BioNTech Small Molecules in Martinsried.

Oncology
Cancer is caused by abnormalities known as somatic mutations. These mutations can accumulate in the genome of cells over time and lead to malignant transformation. The process of carcinogenesis involves the immune system's inability to recognize and eradicate such transformed cells.

Immunotherapy in oncology aims to use the immune system to recognize malignant cells as "foreign" and overcome mechanisms by which cancer cells evade the immune defense. The immune system should be activated in such a way that it can limit tumor growth and destroy malignant cells. Due to their random nature, carcinogenic genetic changes lead to a set of mutations (the "mutanome") unique to each patient's tumor. The research uses the patient-specific mutanome to develop drugs for individualized cancer immunotherapy. In this process, the treatment is tailored to the individual patient. The development of cancer immunotherapies that are individually tailored to each patient is the focus of BioNTech's research activities.

Technologies such as Next-Generation Sequencing (NGS for short) have undoubtedly confirmed the problematic diversity of tumors at the interindividual patient level. Simultaneously, NGS enables fast, cost-effective, and precise high-resolution mapping of a patient's disease. The application of these groundbreaking technologies leads to a change in drug development. It has the potential to significantly change the oncological treatment landscape. It is possible to incorporate comprehensive molecular mapping of tumor genes into treatment decisions and make individualized therapeutics available. This is the focus of the development of the next generation of cancer therapies.

The necessary technology for such groundbreaking advances is now available in oncology. However, a radical paradigm shift in drug development is required to exploit this potential.

Infectious diseases
In addition to the field of oncology, BioNTech has also implemented mRNA platforms for the development of mRNA-based vaccines against infectious disease pathogens. The vaccine candidates against infectious diseases contain modified mRNA-encoding antigens specific to a target pathogen to activate T cells and B cells and instruct them to fight the pathogen.

Collaborations exist with Pfizer and the University of Pennsylvania. In August 2019, BioNTech entered into an investment agreement with the Bill & Melinda Gates Foundation to advance immunotherapies' development to prevent and/or treat HIV, tuberculosis, and up to three other infectious diseases.

On March 17, 2020, Pfizer and BioNTech announced an agreement to develop and distribute a potential mRNA-based coronavirus vaccine to prevent COVID-19 infection. To this end, the Paul Ehrlich Institute approved a Phase 1/2 clinical study for the BNT162 vaccine program on April 22, 2020. By the end of April, the first group of twelve volunteers had received the first vaccination.

On November 9, 2020, interim results of the pivotal study for the coronavirus vaccine were published. The reported efficacy is thus 90 percent. The risk for study participants to contract Covid-19 was more than 90 percent lower than without vaccination. Serious side effects did not occur. The approval is therefore expected to be granted in the USA in November.

Rare and other diseases
In rare diseases, BioNTech has implemented platforms for the development of mRNA-based protein replacement therapies. The aim is to encode and produce the required proteins directly in the patient's body using mRNA. BioNTech shares the costs and profits with Genevant Sciences. Protein-based replacement therapies have been developed to treat rare diseases by administering recombinant proteins. Such therapies are limited to diseases in which the missing protein function is extracellular. However, mRNA-based protein replacement therapy can potentially treat diseases with intracellular protein defects as long as the mRNA can be introduced into the affected cells.

BioNTech uses several protein replacement platforms for rare diseases:
 * Concept: Therapeutic proteins encoded by mRNA and produced in the patient as an alternative to recombinant protein replacement.
 * mRNA format: Nucleoside-modified mRNA, deimmunized to avoid immune activation to translate the therapeutic protein in the cells.
 * mRNA delivery formulation: LNPs targeting the liver.

Collaborators
BioNTech has entered into several collaboration agreements with biopharmaceutical and scientific partners to expand its science and development resources. These include several agreements that allow BioNTech to maintain significant control over its development programs and participate in its products' future. The aim is to expand the potential of the technology platforms and exploit the extensive applicability of the mRNA class of drugs beyond cancer therapy to other indications. The collaborations concern oncology as well as infectious diseases and rare diseases. The biopharmaceutical partners include Genentech, Sanofi, Genmab, Genevant Sciences, Eli Lilly, Bayer, and Pfizer. Besides, BioNTech maintains research collaborations with the University of Pennsylvania ("Penn") and the TRON (Translational Oncology) Research Institute at the University Medical Center of the Johannes Gutenberg University of Mainz.

Partner programs

 * Genmab: BioNTech's first collaboration was signed in May 2015 with Genmab under a licensing and collaboration agreement. The purpose of the agreement is to jointly discover, develop, and commercialize bispecific polypeptide-based antibodies. These antibodies are intended to be used against certain target structure combinations to treat cancer patients worldwide. The first product candidate is being investigated in a phase 1/2a study in solid tumors since June 2019.
 * Eli Lilly: Together with Eli Lilly and Company, new tumor target structures and associated T-cell receptors (TCRs) have been developed since May 2015.
 * Siemens: BioNTech has maintained a strategic partnership with Siemens since June 2015. The goal is to establish a fully automated, paperless, and digitized commercial cGMP production facility for individualized vaccines.
 * Sanofi: In November 2015, BioNTech and Sanofi announced an agreement for the licensing, co-development, and commercialization of mRNA-based therapeutics for intratumoral application in solid human tumors. In March 2018, Sanofi selected the first product candidate for further development and commercialization. For this candidate, which entered clinical development in January 2019, an option to co-develop and co-promote was exercised.
 * Bayer Animal Health: Since May 2016, BioNTech has been collaborating with Bayer Animal Health to develop novel, "first-in-class" mRNA vaccines and therapeutics specifically for use in animals.
 * Genentech: A collaboration agreement was signed with Genentech and F. Hoffman-La Roche in September 2016. The purpose of the agreement is to jointly discover, develop, manufacture and commercialize certain pharmaceutical products containing neoepitope mRNAs for worldwide use. These include our development candidates for individualized neoantigen-specific immunotherapy (iNeST).
 * Genevant: In July 2018, a collaboration was signed with Genevant to develop mRNA-based therapeutics for rare diseases.
 * Pfizer: In collaboration with Pfizer, mRNA-based vaccines are being developed for Influenza prevention. The agreement was announced in August 2018.
 * Bill & Melinda Gates Foundation (BMGF): In August 2019, a research and development agreement was signed with the BMGF in HIV and tuberculosis and up to three other infectious diseases. The foundation's commitment can be up to USD 100 million. The funds will be used to identify and preclinically develop vaccine and immunotherapy candidates for the prevention of HIV and Tuberculosis infections as well as for sustained antiretroviral therapy-free remission of HIV disease.
 * InstaDeep: In November 2020, BioNTech announced a strategic partnership with the British company, including creating an A.I. Innovation Lab to develop new immunotherapies.

Science and medicine
For clinical trials, BioNTech cooperates with a large number of universities and medical centers in Europe and the USA.


 * Translational Oncology at the University Medical Center of the Johannes Gutenberg University of Mainz (TRON)' is a biopharmaceutical research institute at the University of Mainz that develops new diagnostics and drugs for the treatment of cancer and other serious diseases.
 * Ci3 is a non-profit association with more than 500 scientists, which networks players from science, hospitals, and relevant authorities. The goal is to realize groundbreaking individual immune therapies.
 *  (DZIF): The DZIF aims to close the gap that has existed until now between the discovery of new treatment approaches, preclinical and clinical research.
 * Neoantigen Initiative "Tumor Neoantigen Selection Alliance" (TESLA) of the Parker Institute for Cancer Immunotherapy. This non-profit organization brings together researchers from the fields of science, non-profit organizations, pharmacy, and biotechnology to collaborate in the treatment of the most deadly cancers.
 * University of Pennsylvania: A research collaboration with the University has been in place since October 2018. BioNTech has the exclusive option to develop and commercialize mRNA immunotherapies to treat up to ten indications of infectious diseases.

Patents
In the area of patents, BioNTech has developed a multi-layered strategy to protect intellectual property rights for the various technology platforms and their application in the treatment of cancer and other serious diseases. A key focus of the intellectual property strategy is protecting the platforms and product candidates developed by BioNTech that are currently in development. In this context, the emphasis is also on protecting intellectual property for assets that may be used in future development programs and/or that may be of interest to employees or otherwise prove valuable in this field.

BioNTech has more than 200 patent families in total ownership, including in-licensed patent portfolios and more than 100 patent families owned exclusively or jointly by BioNTech. All patents cover at least one occupation in the E.U. or the U.S.; several are pending in several countries or have been granted in several jurisdictions.

BioNTech has held patents on mRNA for years. mRNA is successfully used in medical and immunological applications but is inherently very short-lived. Externally introduced, injected mRNA is normally degraded before it could start the protein production for the immune response with the pathogen's construction plan. For this purpose, a method was discovered and patented years ago to stabilize injected mRNA very well. This was discovered and patented by a Polish team led by Jacek Jemielity, who had already entered into a partnership with BioNTech in 2008 to further develop the process. BioNTech has already licensed the stabilized mRNA technology to major pharmaceutical companies, including the French company Sanofi (in 2015) and Genentech (2016). Moderna, GSK - and the two German companies BioNTech and CureVac own almost half of all patent applications for mRNA vaccines.


 * Selected patents



Antibodies

 * Microbodies


 * Bispecific antibodies


 * Virus-like-particles