mRNA Therapeutics

Why mRNA represents a disruptive new drug class

In the last decade mRNA has progressed into a promising new class of medicine, with the potential to treat a wide variety of diseases with high unmet medical needs. mRNA is a long, polymeric molecule, composed of four different building blocks called nucleotides. In mRNA, hundreds or thousands of these nucleotides are linked in a unique order to convey genetic information to cells, where it is used to express proteins with biological effects.

Considering that all mRNA is generated with four different building blocks, but with unique sequence order, all therapeutic mRNAs have highly similar compositions, while having the capacity to encode a variety of different proteins. These characteristics allow for rapid development of mRNA therapeutics that are broadly applicable for treatment of many diseases, including cancer, infectious diseases and rare diseases. Our mRNA pipeline addresses all of these therapeutic areas.

Our mRNA technologies

The structural elements of the mRNA have an impact on its performance. This includes potential immunogenicity, efficacy of translation and stability of the molecule. We leverage our extensive experience to design, synthesize, manufacture and formulate our therapeutic mRNA, and adapt its composition to suit the desired application.

Our mRNAs all contain basic structural elements that we believe are critical for successful development:

  • 5’ cap: Incorporation of a unique cap analogue into the mRNA helps to achieve superior translational performance by stabilizing the mRNA molecule and directing the immune response.
  • 3’ untranslated region: The composition and structure of the 3’ untranslated regions of the mRNA molecule are important determinants of the intracellular stability of mRNA.
  • Poly(A) tail: We have performed extensive research on the structure of the poly(A) tail and the translational performance of mRNA and customized our template design accordingly.

Our mRNA Oncology Platforms

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.

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.

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.

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.