The development of protein therapeutics can be time consuming and cumbersome and often requires a trade-off between enhancing the biological effect of a protein and its stability and solubility. More specifically, the biophysical properties often highlighted as important for the developability of proteins are aggregation propensity, viscosity, adsorption, stability and solubility.

This presentation discusses how in-vitro assay guided optimization of antibody developability correlates with developability indicators obtained using in-silico tools.

Despite the fact that anti-TNF-alpha antibodies have significantly improved the treatment of rheumatic diseases, anti-drug antibody immune response pushes a fraction of patients to discontinue treatment due to ineffectiveness or adverse reactions.

Here is presented how rational design strategy can be used to modify variable region of the fully human IgG1 Adalimumab and reduce immunogenicity risk while retaining TNF-alpha binding activity.

Ultimately, germlining engineering improved mAb biophysical properties, leading to generation of Adalimumab biobetter.

First-generation gene therapies for Haemophilia A exhibited large patient-to-patient variations in FVIII levels and a lack of durability that may at least in part be caused by the large size of the FVIII expression cassette, resulting in vector genome sizes exceeding the optimal capacity of the wild type AAV genome.

Here we present the design and preliminary characterization of FLT210, a next generation AAV-FVIII cassette, which we believe possesses the attributes required to become the best-in-class vector to treat Haemophilia A patients. It includes the optimisation to the ‘FVIII-SQ’ protein and coding sequence by in-silico design and the enhancement of the level of FVIII expression and secretion by de-novo design of the regulatory regions.