A novel systems biology approach to develop preclinical assets from innovative drug discovery starting points inspired by viruses

Informations projet

MIMESIS

N° de convention de subvention: 739086

DOI

10.3030/739086

Projet clôturé

Date de signature de la CE 15 Novembre 2016

Date de début 1 Novembre 2016

Date de fin 31 Octobre 2018

Financé au titre de

• INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies – Biotechnology

Coût total

€ 3 568 898,75

Contribution de l’UE

€ 2 498 229,00

Coordonné par

ENYO PHARMA
France

Periodic Reporting for period 2 - MIMESIS (A novel systems biology approach to develop preclinical assets from innovative drug discovery starting points inspired by viruses)

Période du rapport: 2017-11-01 au 2018-10-31

Résumé du contexte et des objectifs généraux du projet

ENYO Pharma has developed an original drug discovery engine allowing the development of innovative programs regarding several intracellular targets which were untapped by the pharmaceutical industry until now. Indeed, only a thousand of human proteins are currently targeted by the pharmacopeia over ten of thousands. ENYO Pharma is inspired by the ability of viruses to modulate certain cellular functions of the host to discover new intracellular targets and develop innovative small molecule therapeutics (with a new mode of action) in many indications. By identifying and targeting the human proteins engaged by viruses, ENYO Pharma is identifying and developing novel classes of small molecules therapeutics directed against human proteins selected by viral evolution. The new molecules are developed in indications where unmet medical needs persist.

The approach has proven to be scalable and has generated valuable starting points for drug discovery. The new developpable hits will bring new hope to patients dealing with diseases with no or poor treatment. Our drug discovery engine can now be leveraged through partnership to further exploit the capacity of the library to deliver first-in-class drug candidates and to co-develop our main hits.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The 2-year MIMESIS project, funded by SME Instrument Phase 2 H2020 program, aimed at expanding the scale of ENYO Pharma’s approach in order to generate multiple starting points for drug discovery in various indications.
ENYO Pharma has designed, during the project, a proprietary library of 10,000 developable small molecules that mimic the pharmacophores on bioactive peptides targeting multiples cellular pathways. The library has been screened in phenotypic assays against four viruses (Influenza, Respiratory Syncytial Virus (RSV), Zika and Human RhinoVirus (HRV)), one mycobacterium (Tuberculosis) and also screened for inducers of Immunogenic Cell Death (ICD) in a triple negative breast cancer cell line.

All primary screens have been performed, a valuable collection of molecules has been validated and several novel starting points for drug discovery have been identified. After two years, the main results are:
• A validated approach: all screens have yielded developable starting points for drug discovery. The approach was repeatedly successful.
• A validated library: highly potent molecules delivered by six screens (low µM scaffolds). This shows an enriched library with a higher than expected percentage of active molecules.
• Four selected promising chemical series: novel and potent chemical series optimized for application in different therapeutic areas.
• A complete validation for ICD with primary cells and animal model data.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The approach is the product of 4 objectives that when combined goes beyond the state of the art in drug discovery:

- Mimicking approaches adopted by viruses to modulate human cell biology
- Identifying novel, developable chemistry mimicking viral strategies
- Understanding the therapeutic relevance of the human target of our chemistry
- Defining the therapeutic focus on the basis of unmet medical need & biological rationale

The strength of this disruptive host-targeted approach lies in its applicability to a broad range of diseases (infectious diseases, metabolic diseases, oncology…) all with unmet medical needs.
The approach has proven to be scalable and has generated valuable starting points for drug discovery. ENYO Pharma is in discussions to partner development of these assets towards clinical testing.

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