Crescendo brings together novel in vivo and in vitro technologies which will enable the Company to generate diverse, stable and optimised human heavy chain (VH) fragments, the smallest functional binding units of an antibody molecule. These fragments offer several potential advantages as starting points for the development of novel therapeutics:
- Topical administration including inhaled and oral
- Ability to penetrate tissues more rapidly and deeply
- Greatest format flexibility including bi-specifics and formats with effector function
- Ability to engineer half-life
- Ability to ensure pure antagonism
- Easy to manufacture and stable
- Potential to bind otherwise inaccessible epitopes
Transgenic Mouse Platform
Heavy chain antibodies (HCAb, immunoglobulin lacking light chains) occur naturally in camelids and sharks, and have been developed as a source of VH fragments which are then humanised prior to therapeutic development. The Crescendo transgenic mouse platform under development is engineered to produce human heavy chain antibodies in response to immunisation, and therefore has the potential to rapidly and predictably generate VH fragments that have no requirement for humanisation, and have evolved high affinity and solubility through in vivo maturation.
The platform is being developed based on observations that HCAb can be generated by engineering of the immunoglobulin constant region and deletion of light chain expression. Dr Marianne Brüggemann, a pioneer in human antibody transgenic technology, has made key contributions to the HCAb field and developed assets which form the basis of the Crescendo mouse platform.
Ribosome Display Platform
Ribosome display technology is a proven method for optimisation of antibody binding affinity, and has advantages based on the very high library diversity that can be achieved and the fact that the entire process is performed rapidly in vitro. Crescendo owns the IP for eukaryotic ribosome display (developed by Drs Mike Taussig and Mingyue He) and is currently adapting the technology for optimisation of VH fragments produced from the transgenic platforms.