ENABLE

European Gram-negative Antibacterial Engine

FACTS & FIGURES

Start Date
End Date
Call
IMI1 - Call 8
Grant agreement number
115583

Contributions
IMI Funding
58 900 000
EFPIA in kind
22 952 360
Other
6 794 042
Total Cost88 646 402

Summary

Antimicrobial resistance (AMR) is a major public health threat. Infections caused by resistant bacteria are increasing and causing Europe to face soaring costs both in terms of lives and public health expenditure. Despite the strong need for new antimicrobials, very few new, effective antibiotics have been brought to the market in the last decades. The ENABLE project, within IMI’s New Drugs for Bad Bugs (ND4BB) programme, is working to advance the development of potential antibiotics against Gram-negative bacteria, such as Escherichia coli. The ultimate goal of the project is to develop attractive antimicrobial candidates for testing in the clinic, bringing the possibility of new antibiotics to treat Gram-negative infections one step closer to patients.

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.

Achievements & News

ENABLE scientists discover a new way to target drug-resistant bacteria
June 2017

Scientists from IMI’s ENABLE project have found a new mechanism to target drug-resistant bacteria, opening up a promising new pathway for further research. The mechanism involves DNA gyrase, a well-known enzyme that is a target of already existing antibiotics. ENABLE scientists found a new way to inhibit this enzyme and kill drug-resistant bacteria in the laboratory. In the study, published recently in the Proceedings of the National Academy of Sciences, they identified and characterised two new compounds, which have the ability to kill bacteria resistant to quinolones, a family of broad-spectrum antibiotic drugs, in this novel way.### Although the work on these specific compounds will not continue within the ENABLE project because the compounds showed toxicity, the new mechanism which was uncovered holds potential for future research. ‘This study is very significant, but not because these specific compounds are likely to end up as clinical drugs’, said Anthony Maxwell of the John Innes Centre in the UK, one of the ENABLE project partners who played a key role in this study. ‘It is significant because it has revealed a novel way of targeting a well validated anti-bacterial target, DNA gyrase, and that new way of targeting this enzyme is not subject to pre-existing resistance to antibiotics. It is very exciting. Eventually this could lead to the development of the new antibiotics.’

IMI gives boost to a promising, new antibiotic programme
Two IMI flagship projects, the European Lead Factory and ENABLE, have together propelled a promising, new antibiotic programme, which could result in new antibiotics for patients. ###A researcher from the University of Oxford, Chris Schofield, kick-started the process through his group’s focus on a potential target within gram-negative bacteria that could eliminate resistance against antibiotics. He applied to the European Lead Factory project, where the target was screened against their library of about 300,000 compounds. Small molecule hits with very promising activity against the target were identified. The Oxford and ELF teams worked further to improve the hits, resulting in highly potent compounds that create a strong base for further development. Schofield then turned to the ENABLE project, which has the mission to develop attractive antibacterial candidates for testing in the clinic. The application was deemed to have high novelty and potential for development and was accepted by the project. Schofield’s group is now collaborating with ENABLE partners in the pharmaceutical industry, SMEs and universities from across Europe to develop these early stage compounds towards clinical trials. ‘Through collaborative efforts across Europe, we have been able to take a potential antibiotic target and identify compounds active against it, improve them and start development towards the holy grail of new antibiotics for patients’, said Schofield. ‘This is transforming an almost impossible task for an individual academic group into a solid scientific and commercially viable pathway.’ And there is more in the pipeline: ELF is currently working on another 5 antibiotic programmes and ENABLE accommodates 8 active programmes.
 - Read the press release
(November 2016)

ENABLE project seeks antibiotic experts to join project
IMI antimicrobial resistance project ENABLE is looking for partners to join its consortium. Specifically, the team is looking for organisations with expertise in bacterial potentiation or small molecule uptake. ###Details of the expertise required, the types of organisations that are eligible for funding, and information on how to apply, can be found on the project website. The project will also hold a webinar on the process on 31 August. The deadline for submitting expressions of interest is 9 September 2016. Meanwhile, ENABLE’s open Call for innovative anti-infective programmes remains open. The Call provides early stage anti-infective programmes with an exciting opportunity to progress through the challenging, earlier stages of drug development and draw on the extensive expertise of the ENABLE consortium. (July 2016)

French SME joins antimicrobial resistance project ENABLE
French SME Nosopharm has joined IMI’s antimicrobial resistance project ENABLE. Thanks to this move, Nosopharm will be able to advance the development of a novel antibiotic it has created called NOSO-95179, which is designed to treat multidrug-resistant hospital-acquired infections. ### Specifically, Nosopharm will be able to access significant technical expertise and financial support to complete further studies. Nosopharm will also participate in collaborative research with ENABLE’s expert partners across Europe. Finally, the project will strengthen the company’s intellectual property as all NOSO-95179 results will be owned by Nosopharm. ‘Being selected for ENABLE strengthens Nosopharm’s position among the most innovative companies in the antibacterial R&D community,’ said Philippe Villain-Guillot, president of Nosopharm. ‘This is a major milestone in the development of our NOSO-95179 candidate. We would like to warmly thank the IMI and the ENABLE team for their trust and support.’ Meanwhile IMI Executive Director Pierre Meulien said: ‘IMI is delighted that projects such as ENABLE can support SMEs to advance programs through the most challenging phases of development. This is an example of how public-private partnerships such as IMI can address critical scientific and commercial challenges for the benefit of patients.’

ENABLE Calls for antibacterial programmes: next deadline March 27
IMI’s antimicrobial resistance project ENABLE has a rolling programme of Open Calls for promising Gram-negative antibiotic programmes, and the next deadline for submissions is on 27 March 2015. If you have an interesting Gram-negative programme ###that targets Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and/or Acinetobacter baumannii and that meets the minimum activity thresholds specified within the call text, this is an opportunity to join the ENABLE project. Selected programmes can join the ENABLE consortium and gain access to the ENABLE discovery pipeline, which can develop a programme through to phase I clinical trials and significantly accelerate your work. Following earlier Calls, the project has started three programmes, with a further two due to start soon. Details of how to apply can be found on the Open Calls page of the ENABLE website. Questions? Contact opencall[AT]nd4bb-enable.eu.

ENABLE project seeks promising antibiotics
IMI antimicrobial resistance project ENABLE is seeking promising early stage Gram-negative programmes to join the €85 million project which has the mission to bring at least one candidate to phase 1 clinical trial. ###Small and medium-sized enterprises (SMEs) and research groups from Europe working on direct acting systemic Gram-negative programmes are invited submit a three-page Expression of Interest to the project. Successful applicants will be invited to join the ENABLE consortium - retaining full ownership of their programme and having a skilled international consortium working on accelerating their programme to clinic. Details of how to submit applications can be found on the Open Calls page of the project website. The project is also organising webinars on its procedures on 3 and 24 November and 8 December. Registration for the webinars is via the project website.


ENABLE launches Call for antibiotic development programmes
IMI’s antimicrobial resistance project ENABLE launched in May its second open call for promising Gram-negative programmes. The deadline for applications was 27 June 2014. ###
This was a good opportunity for universities and research organisations working on Gram-negative programmes targeting Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and/or Acinetobacter baumannii to join the ENABLE project. The selected programmes will gain access to the ENABLE discovery pipeline, which can develop a programme through to phase I clinical trials and significantly accelerate their work. The full details of the call and a template for completing the short expression of interest are still available on the open calls page of the project website. 
   -   Questions? Contact opencall[AT]nd4bb-enable.eu.
(May 2014)

ND4BB – the story so far, in Nature Reviews Microbiology
IMI’s antimicrobial resistance (AMR) programme New Drugs for Bad Bugs (ND4BB) is the focus of a recent comment piece in Nature Reviews Microbiology by John Rex of AstraZeneca, who is involved in ND4BB. The article explains how ###IMI and other projects around the world are tackling the biggest challenges in antibiotic research and development. For example, TRANSLOCATION is investigating how to transport antibiotics into bacteria, while COMBACTE focuses on the design and implementation of more efficient clinical trials. ENABLE, IMI’s newest AMR project, is creating a drug discovery platform to fast-track the development of promising molecules. The article also highlights IMI project RAPP-ID, which is working on point-of-care tests, as well as a number of US-based initiatives. Looking to the future, the article notes that IMI has a project in development which will investigate new business models and economic strategies to incentivise the development of new antibiotics.
The article concludes: ‘Although the [AMR] crisis is far from resolved, the leadership of the European Commission are to be commended for their far-sighted approach to creating ND4BB and its projects, all of which provide hope that the global community will have access to an adequate pipeline of novel antimicrobial agents with which to address the challenge of AMR.’
(April 2014)


ENABLE launches Call for Gram-negative programmes
IMI’s antimicrobial resistance project ENABLE has launched its first open call for promising Gram-negative programmes.
If you have an interesting Gram-negative programme that targets ###Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and/or Acinetobacter baumannii and that meets the minimum activity thresholds specified within the call text, this is an opportunity to join the ENABLE project. Selected programmes will gain access to the ENABLE discovery pipeline, which can develop a programme through to phase I clinical trials and significantly accelerate your work.
The first deadline is 31 March 2014, and regular six-month deadlines will be scheduled following this, with the next deadline planned for mid-September. 
If you are interested in applying, please visit the open calls page of the project website for full details and a template for completing the three-page expression of interest.
   -   Questions? Contact opencall[AT]nd4bb-enable.eu.
(March 2014)

Participants Show participants on map

EFPIA companies
  • AstraZeneca AB, Södertälje, Sweden
  • Basilea Pharmaceutica International AG, Basel, Switzerland
  • Glaxosmithkline Research And Development LTD, Brentford, Middlesex, United Kingdom
  • Sanofi-Aventis Research and Development, Chilly Mazarin, France
Universities, research organisations, public bodies, non-profit groups
  • Agencia Estatal Consejo Superior De Investigaciones Cientificas, Madrid, Spain
  • Asclepia Outsourcing Solutions BVBA, Destelbergen, Belgium
  • Aston University, Birmingham, United Kingdom
  • Cardiff University, Cardiff, United Kingdom
  • Centre National De La Recherche Scientifique, Paris, France
  • European Biotechnology Network aisbl, Brussels, Belgium
  • Forschungszentrum Borstel, Borstel, Germany
  • Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucia MEDINA, Granada, Spain
  • Helmholtz-Zentrum Fuer Infektionsforschung GMBH, Braunschweig, Germany
  • John Innes Centre, Norwich, United Kingdom
  • Københavns Universitet (University of Copenhagen), Copenhagen, Denmark
  • Latvijas Organiskas Sintezes Instituts, Riga, Latvia
  • National Medicines Institute (Narodowy Instytut Lekow), Warsaw , Poland
  • Region Hovedstaden, Hilleroed, Denmark
  • SP Process Development, Södertälje, Sweden
  • Servicio Madrileno De Salud-Fibhug, Madrid, Spain
  • St George’s Hospital Medical School (trading as St George's University of London), London, United Kingdom
  • Stichting VU, Amsterdam, Netherlands
  • The University Court of the University of St Andrews, St Andrews, Fife, United Kingdom
  • Universitaet Zuerich, Zürich, Switzerland
  • University of Helsinki, University of Helsinki, Helsinki, Finland
  • University of Liège, Liège, Belgium
  • University of Oxford, Oxford, United Kingdom
  • Universität de Barcelona, Barcelona, Spain
  • Uppsala universitet, Uppsala, Sweden
Small and medium-sized enterprises (SMEs)
  • Beactica AB, Uppsala, Sweden
  • Bioresources Technology & Engineering GmbH, Giessen, Germany
  • Helperby Therapeutics Ltd, London, United Kingdom
  • Inspiralis Ltd, Norwich, United Kingdom
  • Juvabis GmbH, Furigen, Switzerland
  • Molecular Discovery LTD, London, United Kingdom
  • Mutabilis, Paris, France
  • Northern Antibiotics Oy, Helsinki, Finland
  • Nosopharm SAS, Nimes, France
  • OT Chemistry, Uppsala, Sweden
  • Redx Pharma Ltd, Liverpool, United Kingdom
  • Spero Europe Limited, Godalming, Surrey, United Kingdom
  • The Research Network Ltd., Sandwch, United Kingdom
Third parties
  • Redx Anti-Infectives Ltd, Manchester, United Kingdom
  • Statens Serum Institut, Copenhagen S, Denmark

CONTACT

Project coordinator
Neil Pearson
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD
Neil.Pearson[at]gsk.com
Managing entity
Anders Karlén
Uppsala University
Anders.Karlen[at]orgfarm.uu.se