Antimicrobial resistance (AMR) is a major global public health threat. Bacteria are becoming increasingly resistant to existing antibiotics, with the rising mortality rate and extended hospitalisation for patients translating into soaring treatment and societal costs. In Europe alone, AMR causes 25 000 deaths every year; two thirds of these are due to Gram-negative bacteria such as E. coli. The clinical burden associated with AMR is estimated to cost Europe approximately €1.5 billion per year.
Increasingly resistant bacteria trigger the continuous need for new, effective antibiotics. Nonetheless, only two new classes of antibiotics have been brought to the market in the last 30 years and many drug developers have left the field. This mainly due to two factors: firstly, the discovery, development and delivery of new and effective antibiotics is hampered by both scientific and regulatory challenges; secondly, antibiotics have a low return on investment compared to other medicines, making it an unattractive area for drug developers.
Accelerating the delivery of new antibiotics
While there is a strong need for new medicines to treat resistant Gram-negative infections, the industrial pipeline of new drugs remains quite limited. The ENABLE project will create and manage a drug discovery platform for testing and optimising molecules that are still in the earlier stages of drug discovery but have the potential to become future drug candidates capable of treating resistant Gram-negative infections. Once up and running, the platform will be able to run several drug discovery programmes in parallel.
Researchers in the ENABLE project who have interesting molecules that could benefit from the platform will have the opportunity to collaborate with a diverse range of experts in microbiology, pharmacology and chemistry to help advance their molecule through the drug development process until it is an attractive candidate for clinical testing.
The project will focus on the discovery and pre-clinical stages of drug development, as well as (potentially) phase 1 clinical trials, during which a new drug is tested in humans for the first time. Molecule owners wishing to continue with more advanced clinical trials will be able to do so outside the ENABLE project.
More specifically, the project is working towards:
- identifying three antibacterial lead molecules which, following extensive testing, have been identified as having promising antimicrobial activity;
- identifying two antibacterial clinical candidate molecules. At this stage, the final structure of the molecule is set. The candidate then undergoes more preclinical testing before being studied in humans;
- progressing at least one compound into preclinical and phase 1 clinical studies, i.e. early clinical safety testing in humans.
In a nutshell, the unprecedented scientific collaboration carried out within the ENABLE project will improve early-stage antibacterial drug discovery and advance the progress of new medicines through the scientific pipelines so that they are ready for testing in patients.
The new antibiotics programmes run by the ENABLE platform will come from European research institutions and small and medium-sized enterprises (SMEs). There are initially seven programmes in the ENABLE portfolio. In addition, a programme arising from an alliance between GSK and Sanofi will also make use of the platform.
This portfolio of programmes will be expanded through open calls for additional antimicrobial programmes from the academic and SME community, to create the most promising portfolio of drug candidates to treat Gram-negative infections. The project has funding to advance a minimum of eight programmes through early testing, with the ultimate goal of obtaining at least one drug molecule for early testing in humans by 2019.
Boosting European scientific competitiveness
Spanning 13 countries, ENABLE brings together an initial set of 32 partners including 11 SMEs. The unique scientific collaboration stemming from ENABLE will greatly contribute to making Europe a world leader in antimicrobial drug discovery. The creation of a cooperative environment will respond to Europe’s fight against antibiotic resistance and make a sustainable impact on the future of antibacterial drug discovery.
ENABLE is the third project of IMI’s New Drugs 4 Bad Bugs (ND4BB) programme – a series of projects designed to directly address the scientific, regulatory and economic challenges associated with antibacterial drug discovery and development.
The need for public-private collaboration
AMR is a multi-faceted and complex issue, and no single organisation or country can tackle it alone. A public-private partnership thus provides unique opportunities for collaboration between leading European academic researchers, SMEs and the pharmaceutical industry – working together to discover new drugs to treat Gram-negative infections.
It is expected that this joint effort by top experts from different fields will maximise scientific excellence and ensure that the drug discovery programmes selected in ENABLE will progress much more efficiently than if they had been pursued in isolation.
SMEs participating in ENABLE will benefit from access to the top antimicrobial drug discovery and development expertise brought in by other partners to see their molecules further developed. ENABLE also puts into practice some principles of collaboration and open innovation through an unprecedented intellectual property (IP) agreement that was tailored to meet the needs of the project. A key aspect of the agreement is that it allows improvements made to a molecule within the project to be assigned to the original molecule owner. At the same time, agreed mechanisms to compensate those partners that contributed to the improvements were found. The project therefore represents a clear opportunity to enhance in an open and transparent way the collaborative impact of pharmaceutical research, and the IP policy could prove inspirational for R&D collaborations in other disease areas.