Technology

Natural evolution technology for optimization of protein therapeutics activity and toxicity

GO pioneered the vision that natural evolution of the human specie has lead to the generation of natural protein therapeutic variants with superior pharmacological properties (specific activity, safety) than first generations protein drug variants that still constitute standards of care.

Seek evolution-derived beneficial protein mutations and convert the human genome revolution into straight drugs

GenOdyssee’s pioneer technology capitalizes on natural human genetic diversity to identify in the population genetic variants of human proteins with improved therapeutic properties.

GenOdyssee’s patent-protected technology was built to produce novel proteins characterized by:

Superior efficacy as compared to the reference blockbuster protein therapeutic variants isolated and developed in the 80s, which currently constitute standard of care

And /or decreased toxicity leading to lower risk and greater tolerability compared to standard of care

GenOdyssee identifies and develops natural and functional human genetic protein variant compounds with anticipated lower than already identified risk in man associated with artificial genetic mutant proteins

Similar safety is anticipated in man as first generations natural protein therapeutic drugs

GenOdyssee identifies and develops natural and functional human genetic protein variant compounds carrying only one mutation and already functional and tolerated in man, they are in that regard similar to first-and second-generations of natural human protein drugs, that are also natural human genetic variants of proteins, that were successfully brought to market

in 30 years no natural genetic variant of human protein drugs has ever failed in clinical trials for toxicity issues

We therefore anticipate with our compounds lower than already identified safety risk in man associated with artificial genetic mutants proteins

To address hard-to-treat patients, we believe intrinsic improvement of core protein therapeutic specific activity and safety is a superior approach to long-lasting or slow release technologies

Intrinsic improvement of pharmacological properties with a more active or a safer variant should demonstrate better efficacy to address hard-to-treat patients, as compared to long-lasting or slow release technologies using the standard product

The company has assembled a fully integrated functional genomics platform that is implemented by a network based on the screening of 380 different human genomes from healthy individuals representing more than 90% of the human population genetic diversity. These genomes are screened for novel and inventive naturally occurring “functionally relevant” protein variants with superior therapeutic utility as compared to first generations variant products on the market. Screening procedure included sophisticated bio-informatics tools including including the following: building of protein structures: homology modelling; analysis of charges distributions; analysis of hydrophobicity; analysis of protein conformations; protein-protein interactions analysis: protein docking; and low-frequency movements calculation of protein domains. Expression in appropriate cell systems and GLP production of lead candidates is performed followed by an extensive screening using state-of-the art human diseases’ pre clinical models, of lead candidates’ pharmacological properties performed in independent and academic European laboratories. Such laboratories must have a reknown research and clinical expertise in diseases and disease areas of interest for the company

GenOdyssee has discovered natural variants of human proteins with higher therapeutic index than marketed versions of the same class of proteins

Thanks to the DNA collection database of the Corriel Institute, GenOdyssee screened over 380 genomes whose gene pool is optimized to cover more than 90 per cent of human genetic diversity

The screening hits are variants of the relevant proteins, which could be

– Cytokines
– Growth factors
– Blood clotting factors
– Human beta-glucocerebrosidase
– Tissue Plasminogen Activators
– Insulin
– Bone repair proteins
– Reproductive hormones
– Zinc Finger Proteins
– Enzymes

Screening makes use of functional annotation, sophisticated molecular modeling and structure-function predictions based on the conformational behavior of known first-generation proteins. In particular, GenOdyssee seeks natural changes in the three-dimensional structure and in electrostatic isopotentials at the active sites of therapeutic protein variants Once improved versions of the desired proteins have been identified, the Company expresses and produces the chosen variants under GLP conditions Independent and internationally renowned academic laboratories are called upon to evaluate the pharmacologic properties of the therapeutic variants, seeking correlation of innovative variant structures with improved therapeutic index and the “best cases” are selected These drug candidates are tested head-to-head against reference proteins from which are derived first- and chemically-modified long-lasting second-generation blockbuster human protein therapeutics on the market