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H2020

MIMESIS Report Summary

Project ID: 739086

Periodic Reporting for period 1 - MIMESIS (A novel systems biology approach to develop preclinical assets from innovative drug discovery starting points inspired by viruses)

Reporting period: 2016-11-01 to 2017-10-31

Summary of the context and overall objectives of the project

Today, significant unmet medical needs persist in many therapeutic areas.
The pharmaceutical development of new drugs has been limited by rising development costs, patent expiries and high attrition rates. As a consequence, this activity is characterized by:
- A low level of innovation,
- A focus on a restricted number of drug targets recognized as tractable,
- The emphasis put on developing “me-too” products.

In this context, ENYO Pharma is bringing a new drug discovery process to develop first-in-class drugs. This approach mimics the viruses’ strategy to modulate human cell functions and enables:
• The discovery of new cellular targets, previously considered untractable
• The use of phenotypic screens with superior capacity to successfully identify new molecular entities
• The development of new drugs against infectious diseases and in oncology.

For its MIMESIS project, ENYO Pharma has designed a proprietary library of 10,000 developable small molecules, currently screened in phenotypic assays against four viruses (Influenza virus, RSV, Zika virus and HRV), one mycobacterium (Mycobacterium tuberculosis) and as inducers of Immunogenic Cell Death in triple negative breast cancer.

MIMESIS project is completing the scaling-up of ENYO Pharma’s innovative drug discovery engine with the support of the European Commission.
With €3.6 million spending over 24 months, ENYO Pharma will lead five therapeutic starting points to modulate the function of novel human targets. This holds the promise for new drug development for many indications with still unmet needs and for the access to new treatments in the future.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

After one year, ENYO Pharma has achieved great first results:

1. Design of a unique library:
The MIMESIS library, inspired by viral strategies to modulate host cell biology, is a unique compound collection enriched with a higher than expected percentage of active molecules.
2. Completion of primary screenings
Three primary phenotypic screens are now completed; RSV, Zika Virus and Triple negative
Breast cancer (induction of Immunogenic Cell Death – ICD).
ENYO Pharma has already defined a list of more than 50 active small molecule structures and a second wave of primary screens on HRV, Influenza virus (Flu) and Mycobacterium
tuberculosis (TB) will be completed by the end of 2017.
3. Validation of hits
Hit validation has been completed on the output from the RSV, Zika Virus and ICD screens.
ENYO Pharma confirmed the validity of a high proportion of primary hits and activity of structural analogues has been confirmed in the original screening assay.
A second wave of hit validation will be completed by Q1 2018 on HRV, Flu and TB.
4. Prioritization of validated hits
ENYO Pharma has selected several top priority hit chemical series to progress
into hit-to-lead development with an expectation that more will be identified in Q1 2018.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

1. Expected results until the end of the project
MIMESIS project will launch internally five hit-to-lead optimization programs, resulting in five
partially derisked ‘Lead’ chemical series. These series will be ready for further optimization
into potent, selective, well tolerated candidates for clinical testing. ENYO Pharma will explore options to internally optimize or further optimize its best chemical series up to clinical proof of concept in partnership with other pharmaceutical companies.


2. Progress beyond the state of the art and potential impact of the project
The MIMESIS approach goes beyond the state of the art on three aspects of major importance in the pharmaceutical field. They include:
• A unique library: the MIMESIS library, inspired by viral strategy, comprises an unprecedented number of active molecules. In addition, it allows to expand the scope of cellular targets and to identify first-in class molecules.
• A powerful screening strategy: Phenotypic screening is the most successful approach in identifying first-in- class new molecular entities. This approach, combined with the MIMESIS library, positioned ENYO Pharma in the forefront of the state of art.
• The emergence of new therapeutic strategies: The MIMESIS project offers a pioneering and disruptive technology to identify new starting points for drug candidates in the fields of both infectious diseases and oncology. The approach is also applicable to a very large number of pathologies with various etiologies since it is targeting cellular human pathways, with no risk of emerging resistance.

In conclusion, the MIMESIS project succeeds in offering a pioneering and disruptive technology to identify new starting points for drug candidates in the fields of both infectious diseases and oncology. The approach is also applicable to a large number of pathologies with various etiologies since it targets cellular human pathways.

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