BioNTech Profile
BioNTech SE operates as a global next-generation immunotherapy company.
The company focuses on harnessing the power of the immune system to address human diseases with unmet medical need and major global health burden. The company’s fully integrated model combines decades of research in immunology, translational drug discovery and development, a technology agnostic innovation engine, good manufacturing practices (GMP) manufacturing, and commercial capabilities to rapidly discover, develop and commercialize its marketed products and other candidate vaccines and therapies.
The company has built a broad toolkit across multiple technology platforms, including a diverse range of potentially first-in-class therapeutic approaches. This includes mRNA vaccines and therapeutics, cell and gene therapies, targeted antibodies and small molecule immunomodulators.
The company’s approach has created a robust and diversified product pipeline across infectious disease and oncology, including Comirnaty, its COVID-19 vaccine and first marketed product, over 25 clinical stage product candidates and more than 30 research projects.
Strategy
The key elements of the company’s strategy are to further COVID-19 vaccine launches; accelerate pipeline development; ramp up research and development (R&D) investments; pursue complimentary acquisitions and collaborations; and expand global organization.
The BioNTech Approach
The company focuses on developing next-generation immunotherapies by employing a multi-platform strategy, powered by a technology agnostic approach rooted in decades of research in immunology coupled with expertise in emerging technologies in messenger ribonucleic acid (mRNA) and synthetic biology. With the approval of its COVID-19 vaccine, the company has entered into a new era of mRNA technology as a drug class.
The company’s immunotherapy product candidates that are being tested in clinical trials span four distinct drug classes:
mRNA Vaccines and Therapeutics: The company utilizes mRNA to deliver nucleic acid messages to cells, where such information is used to express proteins for pharmacological effect. In infectious disease, the company is developing mRNA-based prophylactic vaccines to address COVID-19, shingles, malaria, tuberculosis, HSV-2, and other infectious diseases. In oncology, the company is developing a portfolio of mRNA-based therapeutics to treat cancer, including FixVac, iNeST in collaboration with Genentech, and mRNA encoded cytokines and antibodies, or antibacterials.
Cell Therapies: The company is developing a range of cell therapies against solid tumors, including CAR-T cell therapies, neoantigen-based T-cell therapies and TCR therapies, in which the patient’s T cells are modified or primed to target cancer-specific antigens. The company is also combining its mRNA FixVac platform with its first CAR-T product candidate to enhance the persistence of CAR-T cells in vivo.
Antibodies: In addition to its mRNA-based antibacterials, the company is developing targeted cancer antibodies utilizing its in-house capabilities, and are developing next-generation antibodies, in collaboration with Genmab, that are designed to modulate the patient’s immune response to cancer.
Small Molecule Immunomodulators: The company intends to use small molecules to augment the activity of other drug classes by inducing specific and discrete patterns of immunomodulation. The first program is a small molecule toll-like receptor 7, or TLR7, immunomodulator for the treatment of solid tumors.
The company plans to accelerate the build-out of its oncology commercial capabilities in 2023-24 with the goal of commercial readiness in the United States, European Union and other selected regions to support first oncology launches from 2026 onwards. Longer-term, the company sees applications for its technologies in the fields of autoimmune diseases, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, and regenerative medicines.
Marketed Products: Comirnaty, COVID-19 Vaccine Program (BNT162)
The company’s first commercial product, Comirnaty, was the first-ever approved mRNA-based product, and, to its knowledge, represents the fastest ever developed prophylactic vaccine from viral sampling to approval. As of December 2022, the company’s original COVID-19 vaccine product has been authorized or approved for emergency or temporary use or granted marketing authorization in more than 100 countries and regions worldwide and its efforts have resulted in more than 4 billion doses shipped globally.
Under its collaboration with Pfizer, the comopany is the Marketing Authorization Holder in the U.S., the European Union, the United Kingdom, Canada and other countries, and the holder of emergency use authorizations or equivalents in the U.S. (jointly with Pfizer) and other countries. Pfizer has marketing and distribution rights worldwide with the exception of China, Germany, and Turkey. Fosun Pharmaceutical Industrial Development, Co., Ltd, or Fosun Pharma, has marketing and distribution rights in Mainland China, Hong Kong Special Administrative Region, or SAR, Macau SAR and the region of Taiwan. The company has the marketing and distribution rights to Comirnaty in Germany and Turkey.
Commercial Update
In 2022, the company and Pfizer continued its global COVID-19 vaccine leadership with the first-to-market Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine directed against both the original COVID-19 virus and the Omicron BA.4-5 adapted COVID-19 virus. The company has three commercial COVID-19 vaccine products on the market: the original COVID-19 vaccine, and two Original/Omicron-adapted bivalent vaccines: Original/BA.1- and Original/Omicron BA.4-5-adapted bivalent vaccines, which are all referred to as Comirnaty.
In June 2022, Pfizer entered into a new vaccine supply agreement with the U.S. government. Under the terms of the agreement, the U.S. government received 105 million doses, including 30 µg, 10 µg and 3 µg doses, including the Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine for adults. The U.S. government also has the option to purchase up to an additional 195 million doses, bringing the potential total to 300 million vaccine doses.
As of mid-December 2022, the company and Pfizer have shipped approximately 550 million doses of Original/Omicron-adapted bivalent vaccine.
In December 2022, the company and Fosun Pharma provided approximately 11,500 doses of Comirnaty which were delivered to Mainland China to enable a vaccination campaign for German expatriates. The delivery contained both the Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine and the original COVID-19 vaccine.
Manufacturing and Distribution
The company and Pfizer continue to collaborate with governments and health ministries around the world to efficiently distribute Comirnaty. The company has developed a global COVID-19 vaccine supply chain and manufacturing network spanning four continents to meet the ongoing global demand of Comirnaty.
Clinical Development
Original Covid-19 Vaccine
In April 2022, the company and Pfizer announced positive results from a Phase 2/3 clinical trial evaluating the safety, tolerability and immunogenicity of a 10-µg booster (third) dose of the original COVID-19 vaccine administered approximately six months after the second dose of the original COVID-19 vaccine 10-µg primary series in 140 healthy children 5 through 11 years of age.
In May 2022, the company and Pfizer announced top-line safety, immunogenicity and vaccine efficacy data from a Phase 2/3 trial evaluating a third 3-µg dose of its original COVID-19 vaccine in 1,678 children 6 months through 4 years of age.
In August 2022, the company and Pfizer announced updated efficacy data from a Phase 2/3 trial evaluating a three 3-µg dose series of the original COVID-19 vaccine in children 6 months through 4 years of age, reinforcing previously reported interim vaccine efficacy data collected in March and April 2022.
Adapted Bivalent Vaccines
In January 2022, the company and Pfizer initiated a clinical study to evaluate the safety, tolerability and immunogenicity of three different regimens of the Omicron BA.1-adapted vaccine candidate or the original COVID-19 vaccine in healthy adults 18 through 55 years of age. The study also drew upon some participants from the companies’ Phase 3 COVID-19 booster study.
In June 2022, clinical data from this Phase 2/3 trial showed that a booster dose of the company’s and Pfizer’s Original/Omicron BA.1-adapted bivalent vaccine elicited a superior immune response against the Omicron BA.1 sublineage compared to the original vaccine.
In October 2022, the company and Pfizer reported data from a randomized Phase 2/3 trial evaluating the safety, tolerability, and immunogenicity of the Original/Omicron BA.4-5-adapted bivalent vaccine in individuals aged 12 years and older.
A 30-µg booster demonstrated a substantial increase in the Omicron BA-5 neutralizing antibody response above pre-booster levels based on sera taken seven days after administration, with similar responses seen across individuals aged 18 to 55 years and those older than 55 years of age (40 participants in each age group).
In September 2022, the company and Pfizer initiated a Phase 1/2/3 study to evaluate the safety, tolerability and immunogenicity of different doses and dosing regimens of the Original/Omicron BA.4-5-adapted bivalent vaccine in children 6 months through 11 years of age.
In November 2022, the company published preclinical data that demonstrate mono- and bivalent Original/Omicron BA.4-5-adapted vaccine boosters may enhance neutralization breadth against Omicron sublineages BA.1, BA.2, BA.2.12.1 and BA.4-5.
In November 2022, the company and Pfizer reported updated 30-day clinical data from the randomized Phase 2/3 trial evaluating the safety, tolerability and immunogenicity of the companies’ Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine, given as a 30-µg booster dose.
In November 2022, the company and Pfizer announced results from an analysis examining the immune response induced by the Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine against newer Omicron sublineages, including BA.4.6, BA.2.75.2, BQ.1.1 and XBB.1.
Regulatory Updates
In 2022, the company’s and Pfizer’s COVID-19 vaccine received multiple regulatory approvals and authorizations, including for Original/Omicron-adapted bivalent vaccines, label expansions for pediatric vaccinations and ongoing conversions from conditional or emergency approvals or authorizations to full regulatory approvals worldwide. The company’s and Pfizer’s Original/Omicron BA.4-5-adapted bivalent vaccine has received approvals, authorizations for emergency or temporary use, or marketing authorizations in more than 65 countries and regions in 2022.
Pipeline of Product Candidates
The company is advancing a broad portfolio of product candidates derived from its four drug classes and multiple platforms, and are focused on immunotherapies for the potential treatment of cancer and mRNA vaccines to potentially prevent or treat infectious diseases.
Oncology Programs
The company’s diverse toolkit of different technologies and modes of action has potential to address a broad range of solid tumors in different disease stages. The company’s immuno-oncology strategy is based on pioneering approaches to harness the immune response to treat cancer. The company has multiple clinical stage assets across different therapeutic classes and platforms, which have the potential to tackle tumors using complementary strategies, either by targeting tumor cells directly, or by modulating the immune response against the tumor.
mRNA Product Class in Oncology
FixVac is the company’s wholly owned, systemic, off-the-shelf mRNA-based cancer immunotherapy approach, from which it is developing several first-in-human and potential first-in-class product candidates. The company’s FixVac product candidates leverage its uridine mRNA (uRNA) technology to prime T cells and booster T-cell immunity against common tumor-specific non-mutated antigens, resulting in a strong antigen-specific immune response. FixVac product candidates feature its immunogenic mRNA backbone and proprietary RNA-LPX delivery formulation for intravenous administration, which are designed to trigger both innate and adaptive immune responses and may be of clinical utility in combination with anti-PD1 in patients with lower mutational burden tumors, including those who have already experienced checkpoint inhibitor, or CPI, therapy.
BNT111 Clinical Trials
In 2021, the company received from the FDA both Fast Track Designation for BNT111 in combination with cemiplimab in patients with anti-PD-1--refractory/relapsed, unresectable Stage III or IV melanoma and Orphan Drug Designation for the treatment of stage IIB through IV melanoma.
BNT112 for the Treatment of Prostate Cancer
BNT112 is being studied in an ongoing Phase 1/2a clinical trial.
BNT112 Targets
BNT112 is designed to elicit an immune response to five prostate cancer-specific antigens, including prostate-specific antigen, or PSA, a transmembrane protein that is expressed by virtually all prostate cancers, prostatic acid phosphatase, or PAP, and three additional tumor-associated antigens.
BNT113 for the Treatment of HPV16+ Head and Neck Cancer
The company is studying BNT113 in a randomized Phase 2 clinical in combination with pembrolizumab as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma, or HNSCC, expressing PD-L1. An additional investigator sponsored Phase 1/2 basket trial is ongoing.
BNT113 Targets
BNT113 encodes 2 oncoproteins exclusively expressed in pre-malignant and malignant tissue. HPV-associated cancers are increasing, with HPV16+ HNSCC typically occurring in younger people. Most patients with HPV16+ HNSCC are diagnosed at more advanced clinical stages.
BNT113 Clinical Trials
In December 2022, the company presented preliminary safety data from Part A of the trial at the ESMO Immuno-Oncology Annual Congress.
Ongoing Phase 1/2 Basket Trial (Investigator-Sponsored)
BNT113 is being studied by the University of Southampton in an investigator-sponsored open-label, Phase 1/2 dose escalation basket study with two different arms in approximately 44 patients with HPV16+ head and neck and other cancers.
BNT115 for the Treatment of Ovarian Cancer
BNT115 is being studied in an ongoing investigator-initiated and -sponsored Phase 1 trial.
BNT115 Targets
BNT115 is designed to elicit an immune response to selected antigens that are found in epithelial ovarian cancers.
BNT115 Clinical Trial
BNT115 is being studied in an investigator-initiated and -sponsored first-in-human, open label, Phase 1 dose escalation trial in ovarian cancer patients eligible for standard-of-care treatment with (neo-) adjuvant chemotherapy. Although the original recruitment period was extended, the target number of evaluable patients defined in the study protocol was not reached and recruitment for the trial was stopped at this stage.
BNT116 for the Treatment of Non-small Cell Lung Cancer
BNT116 is being evaluated in a Phase 1 clinical trial alone and in combination with cemiplimab (anti-PD-1, Regeneron’s Libtayo) or in combination with docetaxel in patients with advanced or metastasized NSCLC.
In March 2022, the company announced the expansion of its strategic collaboration with Regeneron. Under the agreement, the company and Regeneron will jointly conduct trials to evaluate the combination of BNT116 and cemiplimab in different patient populations.
BNT116 Targets
BNT116 is designed to elicit an immune response to six tumor-associated antigens that cover up to 100% of patients in all major histologic subtypes of non-small cell lung cancer.
Autogene cevumeran (BNT122) for Multiple Potential Indications
The company and its collaborator Genentech are developing autogene cevumeran (BNT122) for the treatment of adjuvant and metastatic solid tumors. The company and its collaborator Genentech are conducting a randomized Phase 2 trial of autogene cevumeran in combination with pembrolizumab in first-line melanoma. In collaboration with Genentech, it studied autogene cevumeran as a monotherapy and in combination with atezolizumab in a Phase 1a/1b study of patients with locally advanced or metastatic solid tumors (including melanoma, non-small cell lung cancer, bladder cancer, as well as other solid tumors) and moved into the adjuvant treatment space with a randomized Phase 2 trial in colorectal cancer patients. An additional Phase 2 trial in the adjuvant setting in patients with pancreatic ductal adenocarcinoma (PDAC) is planned to open in 2023. An open-label Phase 1a (monotherapy)/1b (in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab) basket trial, as well as an investigator-initiated Phase 1 clinical trial in combination with atezolizumab and chemotherapy are also ongoing.
Autogene cevumeran (BNT122) Targets
Autogene cevumeran (BNT122) is an individualized neoantigen-specific immunotherapy. Each autogene cevumeran dose includes up to 20 different neoantigens selected on a patient-by-patient basis.
Clinical Data from Phase 1 Investigator-Initiated Trial in PDAC
The company and Genentech plans to open a randomized Phase 2 study to further evaluate the efficacy and safety of autogene cevumeran in combination with atezolizumab and chemotherapy in patients with resected PDAC in 2023.
mRNA Intratumoral Immunotherapy
The company started developing intratumoral immunotherapies utilizing its proprietary mRNA technology in collaboration with Sanofi. These immunotherapies have been designed to be administered directly into the tumor in order to alter the tumor microenvironment and enhance the immune system’s ability to recognize and fight cancer cells within the tumor (proximal), as well as in other non-injected tumor sites (distal).
BNT131 (SAR441000) Targets
BNT131 (SAR441000) comprises four mRNAs encoding the cytokines IL-12sc, IL-15sushi, IFN-a and GM-CSF, that the company has identified as mediators of tumor regression across different murine tumor models.
BNT131 (SAR441000) Clinical Trial
Sanofi, in collaboration with us, commenced a first-in-human, multi-center, open-label, Phase 1, dose escalation and expansion trial to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of BNT131 (SAR441000) administered intratumorally as monotherapy and in combination with cemiplimab. In this trial, 77 patients with certain advanced solid tumors have been enrolled.
RiboMabs
The company’s RiboMab product candidates, BNT141 and BNT142, are mRNAs that encode cancer cell targeting antibodies. These product candidates leverage the company’s proprietary optimized mRNA technology combining nucleoside modifications to minimize immunogenicity with its improved mRNA backbone designs with the aim of maximizing protein expression. RiboMab product candidates are formulated using liver-targeting LNPs for intravenous delivery.
BNT141 for the Treatment of Solid Tumors
BNT141 is being studied in an ongoing Phase 1/2 trial. The company’s RiboMab product candidate encodes an IgG antibody which upon injection is secreted into the bloodstream.
BNT141 Targets
BNT141 is designed to target CLDN18.2, expressed in high unmet medical need tumors, including multiple epithelial solid tumors, such as gastric, biliary and pancreatic cancers.
BNT141 Clinical Trial
Ongoing Phase 1/2 trial
In January 2022, the company dosed the first patient in an open-label, multi-site, Phase 1/2 dose escalation, safety, and pharmacokinetic trial of BNT141 followed by expansion cohorts in patients with CLDN18.2-positive tumors.
BNT142 for the Treatment of Solid Tumors
BNT142, the company’s second RiboMab product candidate for the treatment of solid tumors, is being studied in an ongoing Phase 1/2a trial.
BNT142 Targets
BNT142 is designed to encode bispecific T-cell engaging antibodies that target CD3, a T-cell receptor component that plays a key role in the activation of T cells, and CLDN6, a highly specific oncofetal cell surface antigen that is found in solid tumors, such as testicular and ovarian cancers but not in normal cells.
BNT142 Clinical Trial
Ongoing Phase 1/2 trial
In July 2022, the first patient was dosed in an open-label, multi-center Phase 1/2 dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy in patients with CLDN6-positive advanced solid tumors, including ovarian, endometrial, testicular, non-squamous NSCLC and Not Otherwise Specified (NOS) tumors, including rare tumors and cancers of unknown primary.
The company’s RiboCytokine product candidates BNT151 and BNT152+BNT153 are nucleoside-modified mRNAs encoding human cytokines fused to human serum albumin. The modified mRNA is formulated with liver-targeting lipid nanoparticles, or LNPs, for intravenous delivery.
BNT151 for the Treatment of Solid Tumors
BNT151 is being studied in an ongoing Phase 1 trial.
BNT151 Target
BNT151 comprises the company’s nucleoside-modified mRNA that encodes mRNA for a function-modified or optimized IL-2. IL-2 is a key cytokine in T-cell immunity, supporting the differentiation, proliferation, survival and effector functions of T cells. BNT151 is designed to stimulate T cells without triggering immunosuppression in the tumor microenvironment.
BNT152+BNT153 Targets
BNT152+BNT153 comprise the company’s nucleoside-modified mRNAs that encodes mRNA for cytokines IL-7 and IL-2 respectively.
BNT152+BNT153 Clinical Trials
BNT152+BNT153 are being studied in an ongoing Phase 1 trial.
Oncology Cell Therapy Product Candidates
BNT211 is a chimeric antigen receptor (CAR) directing T cells against the novel target CLDN6 that is tested alone and in combination with a CAR-T-cell Amplifying RNA Vaccine, or CARVac, encoding CLDN6. CARVac is also based on a pharmacologically optimized uRNA backbone delivered in the company’s proprietary RNA-LPX formulation. CLDN6 CAR-T cells are equipped with a second-generation CAR of high sensitivity and specificity for the tumor-specific carcino-embryonic antigen CLDN6. CARVac is intended to drive in vivo expansion of transferred CAR-T cells to increase their persistence and efficacy. BNT211 aims to overcome CAR-T-cell therapy limitations in patients with solid tumors.
BNT211 for the Treatment of CLDN6+ Solid Tumors
BNT211 is being studied in an ongoing Phase 1/2 trial.
BNT211 Target
BNT211 targets Claudin 6, or CLDN6, a highly specific oncofetal cell surface antigen that is expressed in multiple cancers, including ovarian, testicular and lung cancers, but not in healthy tissue.
The company is planning a Phase 2 trial with BNT211 in patients with testicular cancer with a potential start in 2024.
Neoantigen-Targeting T Cells.
The company’s neoantigen-targeting T-cell stimulation platform can be utilized to develop product candidates across several neoantigen-targeting non-engineered and engineered T-cell therapies. The company’s lead product candidate under this platform is its individualized neoantigen-targeting T-cell therapy, BNT221.
BNT221 (NEO-PTC-01) for the Treatment of Cancer
BNT221 (NEO-PTC-01) is the company individualized neoantigen-targeting T-cell therapy which targets selected sets of individualized tumor neoantigens.
BNT221 (NEO-PTC-01) Target
BNT221 (NEO-PTC-01) is a personal neoantigen-targeted T-cell therapy candidate derived from patients’ peripheral blood cells. The product consists of multiple CD8+ and CD4+ T-cell populations targeting multiple selected neoantigens from each patient’s tumor. The neoantigens are selected using the company’s proprietary Recon bioinformatics engine.
Antibody Product Candidates in Oncology
Next-Generation Immune Checkpoint Modulators
The company is developing, in collaboration with Genmab AS (Genmab), antibodies that function as tumor-targeted and dual immunomodulators, applying Genmab’s proprietary technologies in combination with its joint target identification and product concept expertise. BNT311, BNT312, BNT313 and BNT322 are partnered with Genmab as part of a 50:50 collaboration.
BNT311 (GEN1046) a Jointly Owned PD-L1x4-1BB Bispecific Antibody for the Treatment of Solid Tumors
BNT311 (GEN1046), the company’s jointly owned PD-L1x4-1BB product candidate, is a potential first-in-class bispecific antibody combining PD-L1 checkpoint inhibition with 4-1BB checkpoint activation. BNT311 (GEN1046) is being evaluated in two clinical trials—a Phase 1/2 trial for the treatment of malignant solid tumors and a randomized Phase 2 trial with BNT311 as monotherapy and in combination with pembrolizumab in patients with recurrent/refractory metastatic NSCLC.
BNT311 (GEN1046) Targets
BNT311 (GEN1046) is a PD-L1x4-1BB bispecific antibody that induces activation of T cells through conditional 4-1BB stimulation which is dependent on simultaneous binding to PD-L1. In addition, the PD-L1-specific arm of DuoBody-PD-L1x4-1BB functions as a classical immune checkpoint inhibitor by blocking the PD-1/PD-L1 axis, even in the absence of 4-1BB binding. PD-L1 is a validated target that is expressed on tumor cells. 4-1BB is a trans-membrane receptor belonging to the TNF receptor superfamily and is expressed predominantly on activated T cells. DuoBody is a registered trademark of Genmab.
BNT312 (GEN1042), a Jointly Owned CD40x4-1BB Bispecific Antibody for the Treatment of Solid Tumors
BNT312 (GEN1042) is a jointly owned, novel, agonistic, bispecific antibody that combines targeting and conditional activation of the costimulatory molecules CD40 and 4-1BB on immune cells.
BNT312 (GEN1042) Targets
BNT312 (GEN1042) is a bispecific antibody designed to enhance an anti-tumor immune response by crosslinking CD40 on antigen presenting cells with 4-1BB+ T cells to induce conditional stimulation and co-stimulatory activity in both types of cells. It has demonstrated increased tumor infiltrating lymphocyte expansion in human tumor tissue cultures ex vivo, and induces activation of B cells in the presence of 4-1BB+ cells. Both 4-1BB and CD40 are members of the tumor necrosis factor receptor superfamily.
BNT313 (GEN1053), a Jointly Owned agonistic CD27Antibody for the Treatment of Malignant Solid Tumors
In August 2022, the company announced the expansion of its global strategic collaboration with Genmab for the joint development of BNT313 (GEN1053).
BNT313 (GEN1053) Targets
BNT313 (GEN1053) is a novel CD27 antibody with an IgG Fc domain engineered to induce CD27 agonist activity independently of Fc gamma receptor-bearing cells.
In November 2022, a Phase 1 trial was initiated to evaluate the safety, tolerability, and preliminary efficacy of BNT313 as a monotherapy for the treatment of malignant solid tumors.
BNT322 (GEN1056), a Jointly Owned Antibody
BNT322 (GEN1056) is an antibody product being co-developed with Genmab and for the treatment of solid tumors and for use in combination with other products. The first CTA was submitted for BNT322 (GEN1056) in July 2022. A first-in-human Phase 1 trial of BNT322 (GEN1056) in patients with advanced solid tumors was initiated in November 2022.
Targeted Cancer Antibodies
BNT321 for the Treatment of Pancreatic Cancer
In 2019, the company acquired certain antibody assets from MabVax Therapeutics Holding, Inc., including BNT321, a clinical-stage targeted cancer antibody. BNT321 is a fully human IgG1 monoclonal antibody targeting sialyl Lewis A (sLea), an epitope on CA19-9 that is expressed in pancreatic and other gastrointestinal cancers that plays a role in tumor adhesion and metastasis formation, and is a marker of an aggressive cancer phenotype.
BNT321 is being investigated in an open-label, multi-center, non-randomized dose escalation/expansion Phase 1 trial evaluating the safety and recommended Phase 2 dose of BNT321 as monotherapy and combination with mFOLFIRINOX in approximately 108 patients with pancreatic and other CA19-9+ malignancies.
BNT411, a Small Molecule TLR7 Agonist for the Treatment of Solid Tumors, Including Small Cell Lung Cancer
BNT411 is a TLR7 agonist that is designed to activate both the adaptive and innate immune system through the TLR7 pathway. This activity and the release of cytokines and chemokines are designed to result in the potent stimulation of antigen-specific CD8+ T cells, B cells and innate immune cells, such as NK cells and macrophages.
Infectious Disease Programs
Next-generation COVID-19 vaccine – BNT162b5 and BNT162b2 + BNT162b4
In July 2022, the company and Pfizer initiated a randomized, active controlled, observer-blind Phase 2 study to evaluate the safety, tolerability and immunogenicity of a 30-µg dose of an enhanced spike antigen vaccine candidate, BNT162b5. This is the first of multiple vaccine candidates with an engineered design, aimed to increase the magnitude and breadth of antibody neutralization response to better protect against COVID-19.
In November 2022, the company and Pfizer initiated a Phase 1 study to evaluate the safety, tolerability and immunogenicity of a next-generation COVID-19 vaccine component, BNT162b4, dosed in combination with the Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine, that aims to enhance and broaden SARS-CoV-2 T-cell responses.
COVID-19 – Influenza Combination mRNA Vaccine Program – BNT162b2 + BNT161
In October 2022, the company and Pfizer initiated a Phase 1 open-label, dose-finding study to evaluate the safety, tolerability and immunogenicity of a combination of the COVID-19 and influenza mRNA vaccines in 180 healthy adults 18 to 64 years of age. The combination vaccine consists of the company’s Original/Omicron BA.4-5-adapted bivalent COVID-19 vaccine and Pfizer’s quadrivalent modified RNA (modRNA) influenza vaccine.
In December 2022, the company and Pfizer announced that the companies have received Fast Track Designation from the U.S. FDA for the mRNA-based combination vaccine candidate for influenza and COVID-19.
Influenza Vaccine Program – BNT161
In 2018, the company and Pfizer agreed to collaborate on an mRNA program in influenza. The collaboration was established to develop an influenza vaccine based on its suite of mRNA platforms to better address the burden of influenza and further reduce the yearly rates of the severe outcomes, including hospitalization and death. WHO estimates that influenza is responsible for 290,000 to 650,000 deaths annually on a global scale (WHO 2023). The research collaboration period ended in August 2021, and Pfizer has the sole responsibility, authority and control of the development, manufacturing and commercialization of all candidates and products.
In July 2022, Pfizer reported data from the Phase 2 clinical trial of BNT161 in subjects 65 years of age and older showing first evidence of substantial induction of strain specific CD4+ and CD8+ T-cell responses.
HSV-2 Vaccine Program – BNT163
BNT163 encodes three HSV-2 glycoproteins with the aim of helping to prevent HSV cellular entry and spread, as well as counteract immune evasion properties of HSVs.
In December 2022, the company dosed the first subject in a first-in-human Phase 1 clinical trial evaluating the safety, tolerability and immunogenicity of BNT163, an HSV vaccine candidate for the prevention of genital lesions caused by HSV-2 and potentially HSV-1.
Tuberculosis Vaccine Program – BNT164
The company has collaborated with the Bill and Melinda Gates Foundation since 2019 to develop vaccine candidates aimed at preventing tuberculosis infection and disease. Tuberculosis is a worldwide leading cause of death due to an infectious disease, second only to COVID-19. In 2021, approximately 10.6 million people developed active tuberculosis and 1.6 million people died from this disease. The WHO estimates that 25% of the world’s population is latently infected with Mycobacterium tuberculosis, the bacteria responsible for the disease, and approximately 5 to 10% of infected individuals will develop tuberculosis disease.
A clinical trial for the tuberculosis vaccine candidate, BNT164, is planned to begin in 2023.
Malaria Vaccine Program – BNT165
BNT165b1 encodes certain parts of the circumsporozoite protein (CSP). The WHO estimated that there were 247 million cases of malaria and 619,000 associated deaths in 2021 (WHO 2022). P. falciparum caused the majority of deaths in sub-Saharan Africa. Sub-Saharan Africa (SSA) carries the heaviest malaria burden, with an estimated 234 million cases (95%) and 593,000 deaths (96%) in 2021. Children under 5 years old represent the most vulnerable population, due to a high risk of severe disease progression and chronic complications.
Announced in July 2021, the company’s Malaria project aims to develop a well-tolerated and highly effective mRNA vaccine with durable immunity to prevent blood-stage malaria infection, thereby reducing morbidity and mortality, as well as onward transmission, and to develop sustainable vaccine production and supply solutions on the African continent.
In December 2022, the company initiated a first-in-human study with BNT165b1, the first candidate from its BNT165 program, to develop a multi-antigen malaria vaccine candidate. The company will initially evaluate a set of mRNA-encoded antigens of the malaria-causing parasite Plasmodium falciparum (P. falciparum) to help select the multi-antigen vaccine candidate to proceed to planned later-stage trials. This first clinical trial (NCT05581641) will evaluate the safety, tolerability and exploratory immunogenicity of the vaccine candidate BNT165b1.
Shingles Vaccine Program – BNT167
In January 2022, the company and Pfizer announced a global agreement to develop the first mRNA-based shingles vaccine candidate. Under the terms of the agreement, the companies will leverage a proprietary antigen technology identified by Pfizer’s scientists and the company’s proprietary mRNA platform technology used in the companies’ COVID-19 vaccine.
In February 2023, the company and Pfizer began a Phase 1/2 clinical trial exploring the safety, tolerability, and immunogenicity of BNT167 in up to 900 healthy volunteers 50 to 69 years of age. The Phase 1 clinical trial will help select the optimal mRNA vaccine candidate, dose level, dosing schedule, and formulation for advancement to Phase 2 testing.
Anti-Bacterial Programs
BioNTech R&D (Austria) GmbH is a wholly owned subsidiary of the company focused on the development of novel anti-bacterial drugs to treat persistent bacterial infections. The development programs are based on the proprietary LysinBuilder platform, which allows the targeted development of precision anti-bacterials. The development pipeline focuses on chronic bacterial infections where antibiotics fail to cure or destroy the natural microbiomes.
Research Collaboration with University of Pennsylvania
The company’s mRNA portfolio includes BNT162b2, its mRNA-based COVID-19 vaccine, which has received emergency or temporary use authorization or approval or has been granted conditional marketing approval in over 100 countries.
The company’s mRNA pipeline addresses each of these therapeutic areas.
General Principles of mRNA Pharmacology
The company’s mRNA drugs are synthesized from a DNA template. With the exception of the 5’ cap, the template determines all structural elements of the mRNA.
mRNA Backbone Concepts and Technologies
The company’s mRNAs all contain basic structural elements, including the 5’ cap, the untranslated regions and the poly(A) tail, in addition to a coding sequence, that are encoded by its DNA template.
The company has also invented a novel mRNA purification method that greatly impacts translatability of its mRNA.
Optimized Uridine mRNA (uRNA)
The company has further optimized its uridine mRNA for immunogenicity (augmented antigen presentation on MHC I and MHC II) and pharmacological activity (enhanced stability and translational efficiency).
Nucleoside-Modified mRNA (modRNA)
The company has profound expertise in incorporating naturally-occurring modified nucleosides into its therapeutic mRNAs. The company has demonstrated that the presence of a variety of modified nucleosides in the manufactured mRNA suppresses its intrinsic immune activation, while leading to superior protein production for long duration.
Self-Amplifying mRNA (saRNA)
The company’s self-amplifying mRNA, or saRNA, drugs use the concept of viral replication, while not being an infectious, disease-causing agent itself. saRNA resembles conventional mRNA encoding the protein of interest, but also encoding a polymerase, called replicase, that multiplies part of the mRNA within the target cell. The company’s scientific team has designed this mRNA technology to act as a potent tool for prophylactic vaccination, with the potential application in infectious diseases with high medical needs.
Trans-Amplifying mRNA (taRNA)
The company has also expanded on its self-amplifying mRNA capabilities, developing a novel mRNA amplification technology by separating the target mRNA to be amplified and the replicase encoding mRNA. The company’s trans-amplifying mRNA is a proprietary mRNA format that is particularly well-suited for prophylactic vaccines to prevent infectious diseases.
mRNA Delivery Formulation Technologies
The company has deep and broad expertise in the targeted delivery of mRNA therapeutics.
Lipoplex: The company’s lipoplex formulation, or LPX, embeds the mRNA between a lipid bilayer, which is used for its FixVac and iNeST platforms. The company uses a proprietary size- and charge-based non-viral mRNA lipoplex that was developed to deliver mRNA to dendritic cells in lymphoid compartments, such as the spleen for optimal antigen presentation and immune response activation.
LNPs: For other applications, the company encapsulates its mRNA in lipid nanoparticles, or LNPs. These formulations are suitable for the company’s RiboMab, RiboCytokine and rare disease protein replacement platforms. The company’s LNP formulations can be adjusted according to its needs for delivery to particular target tissues, such as the liver in the case of its rare disease protein replacement platform.
Polyplexes: The company’s portfolio also comprises polyplexes, which are being utilized in certain of its discovery programs, in which the mRNA is bound to a polymer and then forms nanoparticles.
RNA-LPX Technology
To advance from local to systemic dendritic cell, or DC, targeting, the comopany developed an innovative liposome-based RNA-lipoplex formulation, RNA-LPX, that allows for intravenous administration of the company’s mRNA cancer immunotherapies. The company has demonstrated in the clinic that systemic DC targeting by mRNA cancer immunotherapies can result in potent activity at very low doses.
RNA-LPX Technology: The company’s proprietary RNA-LPX formulation is designed to deliver vaccine mRNA precisely into DCs and macrophages in the spleen and other lymphoid compartments.
The company’s RNA-LPX technology is designed to target a wide variety of antigens and address cancer patients with all possible HLA haplotypes. Utilizing RNA-LPX, it can target fixed groups of known shared antigens with its FixVac platform and a whole new class of patient-specific neoantigen targets with its iNeST platform.
RNA-Lipid Nanoparticle Formulation for Infectious Disease Vaccines
The company’s COVID-19 Vaccine BNT162b2 is based on an RNA-LNP platform of nucleoside modified RNA, which has blunted innate immune sensor activating capacity and thus augmented antigen expression. BNT162b2 encodes a P2 mutant S (P2 S) and is formulated in LNPs. Encapsulation into LNPs enables transfection of the RNA into host cells after intramuscular injection.
mRNA Platforms
The company is developing multiple mRNA-based therapeutic platforms. These include FixVac, iNeST, mRNA-based intratumoral immunotherapy, RiboMabs and RiboCytokines in the oncology space. In addition, the company has implemented mRNA platforms for the development of infectious disease vaccines and protein replacement therapies for rare diseases.
mRNA Platforms: The company has multiple mRNA-based platforms utilizing different mRNA formats and delivery formulations, directed at a range of biological targets in oncology and infectious and rare diseases.
Sales, Marketing and Distribution
The company’s commercial organization focuses on supporting sales of its COVID-19 vaccine in Germany. The company’s commercial organization is responsible for promoting its products to health care providers and providing information to stakeholders, including governmental organizations, in Germany and Turkey. The company’s commercial organization is also responsible for preparing and obtaining reimbursement from third-party payors, including governmental organizations, for its COVID-19 vaccine and will have the same responsibilities for its clinical-stage oncology product candidates, if approved.
Manufacturing
The company operates four GMP-certified manufacturing facilities in Germany, where it manufactures mRNA therapeutics and engineered cell therapies for its own pipeline and for external customers, including a state-of-the art, multi-platform, GMP-certified manufacturing facility located in a life science industrial park in Marburg, Germany, which it acquired in October 2020 from Novartis AG to increase manufacturing capacity of its COVID-19 vaccine for commercial supply.
Third-Party Collaborations
The company’s collaborations include:
Pfizer for the company’s COVID-19, influenza and joint COVID-19/influenza vaccine programs, which leverage technology from its infectious disease mRNA-based platform;
Fosun Pharma for the company’s COVID-19 vaccine program;
Genentech for the company’s iNeST platform in its mRNA drug class; and
Genmab for the company’s next-generation checkpoint immunomodulator platform in its antibodies drug class.
Pfizer COVID-19 Collaboration
On April 9, 2020, effective as of March 17, 2020, the company entered into a Collaboration Agreement with Pfizer for the research and development of immunogenic compositions comprising RNA encoding a SARS-CoV-2 polypeptide or fragment thereof for prophylaxis against SARS-CoV-2 in humans, which it refers to as the Pfizer Corona Field. On January 29, 2021, effective as of March 17, 2020, the comopany entered into an amended and restated Collaboration Agreement with Pfizer for the research, development and commercialization of immunogenic compositions comprising RNA in the Pfizer Corona Field, which it refers to as the Pfizer Agreement.
On March 13, 2020, the company entered into a Development and License Agreement with Shanghai Fosun Pharmaceutical Industrial Development, Co., Ltd, or Fosun Pharma, for the development and commercialization in mainland China, Hong Kong special administrative region, or SAR, Macau SAR and in the region of Taiwan, or collectively the Fosun Collaboration Territory, of immunogenic compositions generated by the company and comprising uridine RNA, modified RNA and/or replicon technology for prophylaxis against SARS-CoV-2 in humans. The company refers to this agreement as the Fosun Agreement.
Genentech iNeST Collaboration
Collaboration Agreement
On September 20, 2016, the company and BioNTech RNA entered into a Collaboration Agreement with Genentech and F. Hoffman-La Roche Ltd, which, as amended on June 1, 2018 and December 6, 2019, the company refers to as the Genentech Collaboration Agreement, to jointly research, develop, manufacture and commercialize certain pharmaceutical products that comprise neoepitope RNAs, or the Genentech Collaboration Products, which include its iNeST development candidates, for any use worldwide.
Manufacturing Development and Supply Agreement
Concurrent with the Genentech Collaboration Agreement, the company entered into a Manufacturing Development and Supply Agreement with Genentech and F. Hoffman-La Roche Ltd, or the Genentech Manufacturing Agreement, which governs the manufacturing, related manufacturing development activities and supply of Genentech Collaboration Products. Pursuant to the Genentech Manufacturing Agreement, the company is responsible for clinical manufacturing and supply, for developing and implementing manufacturing processes (including pursuant to specified target turnaround times), and for constructing, commissioning, qualifying and obtaining permits for the clinical facilities. The company is permitted to subcontract certain steps in the clinical manufacturing process to its affiliate, BioNTech IMFS.
Genmab Next-generation Immunomodulator Collaboration
On May 19, 2015, the company entered into a License and Collaboration Agreement with Genmab (together with all amendments and side letters thereto, collectively referred to as the Genmab Agreement) to jointly research, develop and commercialize polypeptide-based bispecific antibodies against certain target combinations for the treatment of cancer worldwide, or the Genmab Agreement Field, using certain Genmab technology.
Pfizer-Influenza Collaboration
On July 20, 2018, the company and BioNTech RNA entered into a Research Collaboration and License Agreement with Pfizer, or the Pfizer Influenza Agreement, for the research, development and Pfizer’s commercialization of immunogenic compositions comprising modified RNA and/or replicon technology for prophylaxis against influenza in humans, which it refers to as the Pfizer Influenza Agreement Field.
Research and Development
For the year ended December 31, 2022, the company’s research and development expenses included €1,537.0 million.
Intellectual Property
As of January 1, 2023, the company’s overall owned and in-licensed patent portfolio included more than 300 patent families, each of which includes at least one filing in the U.S. or Europe, and several of which are pending or granted in multiple jurisdictions. The patent families include at least 100 patent families that are solely or jointly owned by the company, including certain families acquired through its acquisitions and others that it has licensed from a third party.
Trademark Portfolio
The company’s trademark portfolio includes, but is not limited to, Comirnaty, BioNTainer, FixVac, RiboCytokine, RiboMab, Recon, Neo-Stim, Precision Neo-Stim, and Maptac, including logo versions of some of these trademarks.
Government Regulation
The company is required to comply with strict data protection and privacy legislation in the jurisdictions in which it operates, including the General Data Protection Regulation (EU) 2016/679, or GDPR.
History
BioNTech SE was founded in 2008. The company was incorporated under the laws of the Federal Republic of Germany in 2008.
