EME Inc. is working on the research and development of new-generation biopharmaceuticals, using VHH antibodies, cyclic peptide aptamers, and new scaffold molecules, and also working on their application to cell therapy and gene therapy.
- Research and development of the pharmaceutical seeds using VHH antibodies and cyclic peptide aptamers
- Application in drug delivery systems (DDSs)
- Application in the fields of regenerative medicine and gene therapy
- Application in high-sensitivity detection systems and diagnostic fields
- Acquisition of structural information for designing low-molecular compounds
- Research and development of artificial enzymes
Paradigm Shift in Biopharmaceutical development
Since the 1980s, biotechnology-based recombinant proteins, such as insulin and erythropoietin, were launched as pharmaceuticals. Later, when the first humanized antibody technology was launched in 1987, antibody-drug discovery got the spotlight as next-generation biomedicines. Research and development of antibodies against many target molecules have been promoted along with the development of genome-based drug discovery since the 1990s, and antibody drugs grew to 62% of the biopharmaceutical market in 2018. While antibody drugs are expected to be developed with the next-generation antibodies in the future based on innovative technology and concepts, the limitations of antibody drugs have started to be apparent.
VHH, on the other hand, was discovered in 1993 by Professor Hamers at Vrije Universiteit Brussel in Belgium. Although it has many features favoring drug discovery, it never attracted attention from the major companies because it was discovered at the same time when antibody drugs began to attract attention as next-generation biopharmaceuticals. However, a bio-venture company that aimed to commercialize VHH was launched in Belgium, and as one of the low-molecular antibody drugs, research and development of VHH were promoted. Then, EMA in 2018, and FDA in 2019, approved caplacizmab as the first VHH antibody drug against von Willebrand Factor for the treatment of acquired thrombotic thrombocytopenic purpura.
What is a VHH antibody?
Camelids such as alpacas (Vicugna pacos) and llamas (Lama glama) produce not only IgG antibodies consisting of heavy chains (H chains) and light chains (L chains) (A) but also antibodies consisting of only heavy chains (heavy-chain antibodies, HCAb) (B). The single variable domain of HCAb is calld VHH with a molecular weight of 12−15 kDa (C).
Comparison between IgG antibody (A), heavy-chain antibody (B), and VHH (C)
VHH has high antigen specificity and affinity like that of a conventional IgG antibody. While an IgG antibody forms antigen-binding sites with the three complementarity determining regions (CDRs) of each of VH and VL, VHH recognizes antigens with only three CDRs (yellow parts in the figures below). CDR3, in particular, is an important region for antigen binding. VHH preferentially recognizes clefts and cavities in the target molecules.
Conformation of VHH
EME Inc. has successfully constructed a phenotype-genotype linked library using the cDNA display method, and it has higher stability and larger diversity than any other library of the other companies. EME Inc. has also developed a high throughput screening system with a combination of flow cytometry (FCM) and next-generation sequencing (NGS) to maximize screening efficiency.
Innovative Drug Discovery