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Our vision: individualize cancer medicine
Platforms
Oncology
FixVac
Our FixVac product candidates contain selected combinations of unmodified, pharmacologically optimized mRNA, encoding known cancer-specific shared antigens. They feature our proprietary immunogenic mRNA backbone and proprietary RNA-lipoplex, or RNA-LPX, delivery formulation, designed to enhance stability and translation, target dendritic cells and trigger both innate and adaptive immune responses. We are currently evaluating three FixVac product candidates in clinical trials, including BNT111 in a Phase 1 trial in metastatic melanoma, BNT113 in a Phase 1 trial in HPV-positive head and neck cancers and BNT114 in a Phase 1 trial in triple negative breast cancer.
FixVac
At a glance: Our FixVac Platform
- Concept: Cancer immunotherapies targeting shared antigens that we have identified to be frequently expressed across patients with a specific cancer type.
- mRNA Format: Optimized mRNA providing superior immunogenicity.
- mRNA Delivery Formulation: Proprietary size- and charge-based RNA-LPX targeting DCs.
- Development Approach: Worldwide rights; wholly owned.
- Lead Candidate: BNT111 for metastatic melanoma.
- Data Highlights: Four partial responses and eight stable diseases in 22 patients with metastatic lesions at enrollment, following BNT111 monotherapy.
Individualized Neoantigen Specific Immunotherapy (iNeST)
We are a pioneer and global leader in developing fully individualized cancer immunotherapies. We have developed a first of its kind, on-demand manufacturing process to treat each individual patient based on the mutation profile of the patient’s tumor. We have validated this treatment approach in the clinic in collaboration with Genentech.
INDIVIDUALIZED NEOANTIGEN SPECIFIC IMMUNOTHERAPY
Our iNeST immunotherapies contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, and also feature our proprietary RNA-LPX formulation. We are conducting, in collaboration with Genentech, two clinical trials of our iNeST product candidate, RO7198457 (BNT122), including a randomized Phase 2 trial in first-line metastatic melanoma in combination with pembrolizumab, a checkpoint inhibitor, and a Phase 1a (monotherapy)/1b (in combination with atezolizumab) trial in multiple solid tumors.
iNeST
At a glance: Our iNeST Platform
- Concept: Individualized cancer immunotherapy targeting neoantigens identified on a patient by patient basis and selected for immunogenicity.
- mRNA Format: Optimized mRNA providing superior immunogenicity.
- mRNA Delivery Formulation: Proprietary size- and charge-based RNA-LPX targeting DCs.
- Development Approach: 50:50 cost share with Genentech.
- Lead Indication: RO7198457 (BNT122) as a first-line melanoma therapy in combination with pembrolizumab.
- Data Highlights: In a previous Phase 1 trial of BNT121, we observed first-in-human data in 13 patients with metastatic melanoma demonstrating stable progression-free survival in nine patients for up to 41 months, and additional objective responses in three of five patients with metastatic disease at time of treatment with iNeST including one patient receiving combination therapy. We also observed a significant decrease in the cumulative recurrence rate post-treatment as compared to pre-treatment.
Intratumoral Immunotherapies
Intratumoral immunotherapies are designed to promote innate and adaptive immune responses against tumors, without toxicities related to systemic administration. Our intratumoral immunotherapy involves injection of cytokine-encoding mRNA directly into a tumor in order to alter the tumor microenvironment and promote greater T cell activity. This approach has been found in preclinical studies to boost cancer-specific immune responses locally, while also producing tumor responses in remote parts of the body due to the circulation of properly activated anti-tumor immune cells, known as an abscopal effect. We are developing our mRNA-based intratumoral platform in collaboration with Sanofi.
At a glance: Our Intratumoral mRNA Platform
- Concept: Immunomodulator-encoding mRNA injected directly into the tumor in order to avoid off-target toxicities.
- mRNA Format: Nucleoside-modified mRNA engineered for minimal immunogenicity in order to avoid immune detection and allow translation of the encoded cytokines to occur within the cells.
- mRNA Delivery Formulation: Various formulations, delivered by intratumoral injection.
- Development Approach: Co-development and co-commercialization, at our option, in collaboration with Sanofi.
- Lead Candidate: SAR441000 (BNT131) for advanced solid tumors as a monotherapy and in combination with cemiplimab.
RiboMabs
Ribomabs represent the next generation of antibody-based drugs. Antibody drugs are a leading class of biologics for the treatment of various diseases, but have a number of limitations. The development of antibodies is currently challenged by demanding and costly procedures of production, purification and formulation of a recombinant protein, which we believe hampers the rapid development and clinical testing of new drugs in this class. mRNA not only involves a simpler and less expensive manufacturing process, but also is effective in much lower volumes than are required to produce similar effects using recombinant proteins. RiboMabs simply involve the encoding of a sequence in the mRNA, and the body does the production work itself. This simplicity allows for both shorter development times and a greater diversity of druggable targets.
At a glance: Our RiboMab Platform
- Concept: Antibodies encoded by mRNA and produced in the patient as an alternative to recombinant antibodies.
- mRNA Format: Nucleoside-modified mRNA engineered for minimal immunogenicity in order to avoid immune detection and allow translation of the encoded antibodies to occur within the cells.
- mRNA Delivery Formulation: Various liver-targeting LNP formulations, delivered intravenously, to ensure systemic availability and prolonged production of the antibody in vivo.
- Development Approach: Worldwide rights; wholly owned.
- Lead Candidate: BNT141 in multiple solid tumors.
RiboCytokines
Cytokines represent a large group of relatively small proteins (<30 kDa) that regulate a variety of biological functions as they elicit signaling for immune and non-immune cells. In particular, cytokines play a pivotal role in orchestrating the initiation, execution and extinction of innate and adaptive immunity against pathogens as well as malignant cells. Due to their natural role as immunomodulators, recombinant cytokines are currently used for the treatment of a number of infectious, inflammatory, autoimmune and malignant diseases. One of the major challenges associated with the therapeutic use of cytokines relates to their short serum half-life and low bioavailability. This impedes therapeutic efficacy as it necessitates high and frequent dosing, which often results in dose-limiting toxicities. We have developed a wholly owned, novel mRNA-based platform technology called RiboCytokines, designed to address the limitations of recombinantly expressed cytokines.
At a glance: Our RiboCytokine Platform
- Concept: Cytokines encoded by mRNA and produced in the patient as an alternative to recombinant cytokines.
- mRNA Format: Nucleoside-modified mRNA engineered for minimal immunogenicity in order to avoid immune detection and allow translation of the encoded cytokines to occur within the cells.
- mRNA Delivery Formulation: Various liver-targeting LNP formulations, delivered intravenously, to ensure systemic availability and prolonged production of the cytokine in vivo.
- Development Approach: Worldwide rights; wholly owned.
- Lead Candidate: BNT151 in multiple advanced malignancies.
CAR T Cell Platform
The tailored reprogramming of autologous T cells from cancer patients to recognize and attack their tumors has become a disruptive medical innovation. Retargeting of T cells can be achieved via introduction of tumor-specific receptors into patient-derived T cells.
At a glance: Our CAR T Platform
- Concept: Second-generation CAR T therapy designed to overcome the shortcomings of CAR T therapy in solid tumors.
- Mechanism: T cells with CARs engineered to target cancer-specific antigens, including novel antigens selected from our proprietary antigen library and administered with a FixVac immune booster to enhance CAR-T cell expansion and persistence.
- Development Approach: Worldwide rights; wholly owned.
- Lead Candidate: BNT211 for multiple solid tumors.
T Cell Receptor (TCR) Cell Platform
We are developing T cell receptor therapies for the treatment of cancer, including in collaboration with Eli Lilly. Under our collaboration, Eli Lilly has an exclusive option to pursue clinical development of certain potential TCR product candidates. We and Eli Lilly have concluded the research phase of the collaboration and Eli Lilly is evaluating whether to exercise its option.
Checkpoint Immunomodulators
Following the success of immune checkpoint blocking antibodies targeting CTLA-4, PD-1 or PD-L1 in cancer treatment, bispecific antibody formats represent the next generation of emerging immunotherapies with the potential to further improve clinical efficacy. We are developing, in collaboration with Genmab, bispecific antibodies that function as dual immunomodulators, applying Genmab’s proprietary DuoBody technology in combination with our target identification expertise. These next-generation checkpoint immunomodulators are thought to induce beneficial co-stimulation, promoting specific T cell activation, survival, proliferation and T cell effector functions.
At a glance: Our Next-generation Checkpoint Immunomodulators
- Concept: Bispecific antibodies for dual immunomodulation, initially targeting 4-1BB, an immune checkpoint that is expressed on T cells and NK cells and can enhance immune cell proliferation and activation, in combination with simultaneous checkpoint inhibition.
- Mechanism: Conditional activation of 4-1BB checkpoint only upon simultaneous binding of PD-L1 or CD40 (in the case of our initial candidates), potentially avoiding toxicities seen in prior attempts at 4-1BB agonism by localizing 4-1BB activation to the tumor environment.
- Development Approach: 50:50 cost and profit share with Genmab, combining our and Genmab’s immunostimulatory antibodies and extensive immunology expertise with Genmab’s DuoBody bispecific antibody platform.
- Lead Candidate: GEN1046 (BNT311), our PD-L1x4-1BB product candidate for multiple solid tumors.
Targeted Cancer Antibodies
Our multiple antibody discovery engines significantly expand our targeting repertoire and enable us to directly, rapidly and efficiently produce new mAb candidates. With the acquisition of MAB Discovery GmbH’s antibody generation unit in 2019, we integrated a unique and proprietary rabbit-based antibody discovery platform that can generate and develop high quality, functional mAbs targeting traditional proteins and receptors as well as a wide variety of more challenging targets. HuMab, our human antibody discovery engine acquired from MabVax Therapeutics in 2019, led to the clinical development of our fully human IgG1 monoclonal antibody product candidate targeting Sialyl Lewisa (sLea), a carbohydrate moiety that is present in over 90% of pancreatic and a large percentage of gastrointestinal cancers.
Small Molecule Immunomodulators
Our immunomodulatory small molecule product class focuses on Toll-like receptors (TLRs). We believe TLRs represent a promising target class for cancer immunotherapy, particularly for inflammatory re-programming of the tumor microenvironment. In many cancers, tumors are protected by an anti-inflammatory environment, which reduces the ability of the immune system to attack the cancer cells.
TLR7 agonists are able to initiate a direct cellular immune response, for example, by activating immature dendritic cells, cytotoxic T cells and NK cells, as well as stimulating the release of signal molecules such as cytokines and chemokines including IFN-α and IP-10, which can be directed against tumor cells. The activation of the innate and adaptive immune system and the release of cytokines and chemokines, for instance by our small molecule TLR7 agonist, results in the potent stimulation of antigen specific T cells, B cells and innate immune cells such as NK cells and macrophages.
At a glance: Our Small Molecule Immunomodulators
- Concept: Small molecule therapies, with a specific focus on TLRs, that can be used synergistically with other cancer therapeutics, including other product candidates in our portfolio.
- Development Approach: Worldwide rights; wholly owned.
- Lead Candidate: BNT411, our TLR7 agonist product candidate intended for combination therapies.
Beyond oncology
Infectious diseases
Expanding beyond our research in oncology, we are leveraging our mRNA technologies to direct the immune system more effectively against infectious diseases. Our infectious disease vaccine candidates contain modified mRNA-encoding antigens specific to a target pathogen to activate and direct T cells and B cells to fight the pathogen.
We are collaborating with Pfizer to develop an influenza vaccine using our mRNA-based immunotherapy technology.
The benefits of mRNA influenza vaccines
- Fast manufacturing process (within three months)
- Flexibility to rapidly generate vaccines against genetically drifted seasonal viruses or pandemic strains
- Potentially broader protection through consistent product
We also have a research collaboration with the University of Pennsylvania, under which we have the exclusive option to develop and commercialize prophylactic mRNA immunotherapies for the treatment of up to 10 infectious disease indications.
At a glance: Our Infectious Disease Vaccine Platform
- Concept: mRNA-based vaccines targeting infectious disease pathogens.
- mRNA Format: Self-amplifying mRNA providing high immunogenicity with smaller amounts of mRNA.
- mRNA Delivery Formulation: Lipid nanoparticles (LNPs).
- Development Approach: Collaboration with Pfizer and exclusive option arrangement with the University of Pennsylvania.
- Lead Candidate: Influenza vaccine.
Rare diseases
Current protein-based replacement therapies were developed to treat rare diseases by administering recombinant proteins. Such therapies are limited to diseases where the missing protein function is extracellular. However, mRNA-based protein replacement therapy also has the potential to treat illnesses with intracellular protein defects, as long as the mRNA can be delivered into the affected cells.
At a glance: Our Protein Replacement Platform 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 in order to allow for translation of the therapeutic protein in the cells.
- mRNA Delivery Formulation: Liver-targeting LNPs.
- Development Approach: 50:50 cost and profit share with Genevant.
