European Gram Negative AntiBacterial Engine
ENABLE

ENABLE's initial objectives:

To identify three leads and two development candidates, and progress one compound into preclinical and phase I clinical studies - were surpassed with

• 6 lead declarations

• 3 candidate declarations
  

• 2 compounds into preclinical GLP studies

• 1 phase I study completed 

What have we achieved?

During its 7 years, the ENABLE project delivered:

• Creation of an European discovery engine for anti-infective development

• Review and contact with European SMEs within anti-infectives
  

• Attraction of over 110 expressions of interest from SMEs and research organisations

• Integration of over 25 programmes within its portfolio

ENABLE’s portfolio was continuously integrating new programmes through an open call process. The open call resulted in 110 expressions of interest (EoIs):

Dissemination activities

The entire ENABLE team is busy discussing, presenting and writing. Find a selection of the results below:

Publications

• Page, M.G.P.; Bush, K. (2014): Discovery and development of new antibacterial agents targeting Gram-negative bacteria in the era of pan-drug resistance: is the future promising?, Curr. Op. Pharm. 2014; 18; 91-97

• Kostyanev, T. et al (2016): The Innovative Medicine Initiative (IMI) New Drugs for Bad Bugs (ND4BB) programme - European Public Private Partnership for the Development of New Strategies to Tackle Antibiotic Resistance, J Antimicrob Chemother (2016) 71 (2): 290-295.

• Bill, R.M., vab der Haar, T. (2015): Hijacked then lost in translation: the plight of the recombinant host cell in membrane protein structural biology projects, Current Opinion in Structural Biology Volume 47

• Kitchen, P. et al (2015): Beyond water homeostasis: Diverse functional roles of mammalian aquaporins, Biochimica et Biophysica Acta (BBA) - General Subjects

• Rabanal, F. et al (2015): A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity, Nature Scientific Reports | 5:10558 | DOI: 10.1038/srep10558

• Uppsala University (2015): A world without antibiotics, Pre-conference publication: Uppsala health Summit

• Kitchen, P. et al (2016): Structural Determinants of Oligomerization of the Aquaporin‐4 Channel. Journal of Biological Chemistry

• Grau‐Campistany, A.et al (2016): Tryptophan‐containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria. Biochimica et Biophysica Acta (BBA)‐Biomembranes 1858 (2), 333–343 (2016)

• Rabanal, F. et al (2016): Therapeutic Potential of antimicrobial peptides in "New Weapons to Control Bacterial Growth, Springer International Publishing Switzerland, 2016

• Rudilla, H. et al (2016): Synergistic antipseudomonal effects of synthetic peptide AMP38 and carbapenems Molecules

• Kostyanev et al (2016): The Innovative Medicines Initiative’s New Drugs for Bad Bugs programme: European public–private partnerships for the development of new strategies to tackle antibiotic resistance, J Antimicrob Chemother 2016; 71: 290–295

• Chan et al (2017): Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase. In: Proc. Natl. Acad. Sci. USA May 30;114(22).

• Rabanal et al (2017): Design, Synthesis and Activity of New Polymyxins, in: Proceedings 2017, 1(6), 662; doi:10.3390/proceedings106066

• Segovia et al (2017): Design of New Polymyxins with Reduced Nephrotoxicity, in: Proceedings of the 3rd Int. Electron. Conf. Med. Chem., 1–30 November 2017;
  Sciforum Electronic Conference Series, Vol. 3, 2017 ; doi:10.3390/ecmc-3-04689

• Vaara et al (2017): The polymyxin derivatives NAB739 and NAB815 are more effective than polymyxin B in 3 murine Escherichia coli pyelonephritis, in: J Antimicrob Chemother. 2018 Feb 1;73(2):452-455. doi: 10.1093/jac/dkx394.

• Vaara, M., Vaara, T. and Tyrrell, J.M. (2017): Structure-activity studies on polymyxin derivaties carrying three positive charges only reveal a new class of compounds with strong antibacterial activity. In: Elsevier, Peptides, Volume 91, May 2017, Pages 8-12

• Jeannot, F. et al (2018): Imidazopyrazinones (IPYs): novel non-quinolone bacterial topoisomerase inhibitors showing partial cross-resistance with quinolones. In: J Med Chem. 2018 Apr 26;61(8):3565-3581. doi: 10.1021/acs.jmedchem.7b01892.

• Dumont et al (2018): Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm. In: Life Science Alliance, DOI: 10.26508/lsa.201800242

• Racine et al (2018): In vitro and In vivo characterization of NOSO-502, a novel inhibitor of bacterial translation. In: Antimicrob Agents Chemother. 2018 Aug 27;62(9), doi: 10.1128/AAC.01016-18

Articles & Press Releases

• Rex, J.H. (2014): ND4BB: addressing the antimicrobial resistance crisis, Nature Reviews Microbiology 12, 231-232

• Press releases (2014): €85 million European programme targets novel antibiotic, Aston, Biomol, CSIC, EBN, Liege, Medina, Northern Antibiotics, OTC, Asclepia, SP, Redx

• Karlén, A. (2014): Swedish researchers makes an attempt to tackle a problem of the world, Article in Economic magazine

• Karlén, A., Hughes, D. (2014): Non-even fight against resistance, Article in popular science magazine “Naturvetaren”

• Karlén, A. (2014): Svenska forskare tar itu med världsproblem. Di Almedalen.
  

• ENABLE participants (2014): Large effort in antibiotic research, Swedish Radio – Science (20 minutes special on ENABLE and hurdles of developing an antibacterial drug)

• Yli-Kauhaluoma, J (2014): Uudet antibiootit haussa eurooppalaisena yhteistyönä, University of Helsinki

• Yli-Kauhaluoma, J (2014): Suomen Lääkärilehti - Finnish Medical Journal: Uusia antibiootteja etsitään eurooppalaisessa yhteistyössä, University of Helsinki

• Kiuru, P. (2014): Antibiootin kehitys on kilpajuoksua, Satakunnan Kansa (the 2nd oldest Finnish daily newspaper)

• Kiuru, P. (2014): Kuuden vuoden kilpajuoksu muuntuvia bakteereita vastaan, Aamulehti (Front page news story)

• Horizon Magazine (2014): Complex molecules could beat drug resistant bacteria.
  

• Press release UB (2015): UB researchers develop a new family of bioinspired antibiotic compounds. 

• European Biotechnology News (2015): Time is running out. 

• Press release Nosopharm (2015): Nosopharm joins European Gram-negative Antibacterial Engine (ENABLE) project to combat antibiotic resistance, Nosopharm

• Uppsala University (2015): The Drug Push. Interview in Science, 2015, Vol 348, 850-853

• ENABLE Press Release (2017): Three lead structures from SMEs identified for novel antibiotics
  

• Nordic Life Science Magazine (2017): Antibiotic advances from new drugs 4 bad bugs

• ENABLE Juvabis Press Release (2018): Tackling Antimicrobial Resistance: ENABLE Selects First Clinical Candidate

• ENABLE Mutabilis Press Release (2019): ENABLE selects new antibiotic candidate

• ENABLE Juvabis Press Release (2019): Swiss start-up Juvabis announces start of Phase I study of its best-in-class aminoglycoside antibiotic apramycin

• ENABLE Press Release (2020): Goals achieved - Mission continues 

• ENABLE Juvabis (2020): Juvabis announces positive Phase 1 results of EBL-1003 in the Innovative Medicines Initiative's ENABLE Consortium

• ENABLE Mutabilis (2021): Mutabilis' EBL-1463 programme graduates from ENABLE with Development Candidate and continues to progress with funding and support from CARB-X

Lectures & Presentations

• Karlén, A. (2014): ENABLE (IMI) presentation of activities, seminar in Brussels

• Karlén, A. (2014): ENABLE - A European antibacterial drug discovery platform, Lecture at Uppsala University

• Karlén, A. (2014): Tackling Antimicrobial Resistance, Lecture in Stockholm

• Karlén, A. (2014): New antibiotics- a common responsibility or the responsibility of the industry, Lecture at antibiotic seminar in Gotland,

• Karlén, A. (2014): IMI project experience: "Project ENABLE: European Gram-negative Antibacterial Engine, Lecture at IMI seminar in Oslo

• Karlén, A. (2014): Examples of partnerships between public and private partners - Innovative Medicine Initiative, Lecture at antibiotic seminar in Stockholm

• Karlén, A. (2015):Are collaborations in Public-Private Partnerships a model for discovery of new antibiotics, Lecture at seminar in Stockholm - The Royal Swedish Academy of Engineering Sciences (IVA)

• Schipper, N. (2014): Framtidens infektionshot kräver gränslösa samarbeten, Presentation at Swedish National Life Science days

• Genilloud, O. (2014): Discovery of Novel Antibacterials from microbial natural Products, Presentation at ICAAC2014

• Stokes, N. (2014): Innovative approaches from industry: Developing new treatment, Presentation at BSAC AMR Round Table series

• Hughes, D. (2014): Antibiotics and resistance, University of Uppsala

• Maxwell, T. (2014): Combating AMR: how can topoisomerases and insect gut bacteria help?, Presentation 

• Stavenger, R. (2015): Current European Collaborative Plans: ENABLE Keystone Symposia on Gram-Negative Resistance Granlibakken, Tahoe City (USA)

• Asclepia (2015): Collaboration and funding to clinical trials for European anti-infective Gram negative programmes, Lecture: Innova Balt Drug Discovery conference Riga

• Asclepia (2015): Collaboration and Funding through Preclinical Development and Phase I Clinical Trial for Anti-Infective Gram-Negative Programs, Lecture: Re-Entering Antibacterial Drug Development Summit, Boston, MA

• EBN (2015): Webinars on Funding for Gram negative anti-infective programmes

• Yli-Kauhaluoma, J. (2015): Professori Jari Yli-Kauhaluoma pitää juhlapuheen Karvian kotiseutujuhlassa, Helsinki

• Medina (2015): The challenge of discovering and developing novel microbial natural product antibiotics to fight infectious diseases, Lecture: 5th CPA - RSCSymposium on Antibacterial Agents: Chemistry and Mechanism of Action.
  

• Uppsala (2015): IMI-ENABLE: A European Antibacterial Drug Discovery Platform, Lecture at ICAAC2015 San Diego

• Uppsala (2015): Antibacterial drug discovery and development. Challenges, opportunities and ways forward., Lecture at AIMECS 2015: 10th AFMC International Medicinal Chemistry Symposium, Jeju, Korea

• Uppsala (2015): Experiences from Horizon 2020 and IMI funded projects, Lecture at "National Information Day on Health, demographic change and well-being in Horizon 2020"

• Uppsala (2015): ENABLE - European Gram Negative AntiBacterial Engine, Participate in 10th European Workshop in Drug Design in Sienna (XEWDD). PresentPoster on ENABLE. Discuss ENABLE computaitional chemistry platform and training in use of program developed by ENABLE partner.

• CNB (2016): Bacterial celldivision: Orchestrating the ring cycle, EMBO Workshop Prague

• EBN (2016): Workshop: Showcasing global anti‐infective innovation at the BIO Convention

• GSK (2016): IMI TRANSLOCATION & ENABLE: Collaborative Drug Discovery in Action, Oral presentation at workshop to take aim at Bacteria, Lehigh University, USA

• JIC (2016): DNA Topoisomerases in Bacteria and Plants: Mechanism and Drug Targeting, Lecture: Univ W. Australia, Perth

• JIC (2016): Exploiting DNA topoisomerases for antibiotic development, Lecture University of Sydney

• JIC (2016): New ways to target DNA gyrase: a well‐validated target for antimicrobial chemotherapy, Lecture: Gordon Research Conference, Sunday River, Maine, USA

• JIC (2016): Supercoils and superbugs: exploiting DNA topoisomerases as targets for antibacterial chemotherapy, Lecture: Trinity College, Dublin, Ireland

• University of Uppsala (2016): The Swedish contribution to IMI‐ENABLE: A European antibacterial drug discovery platform, Lecture:Embassy of Sweden, Washington DC, USA

• University of Uppsala, GSK (2016): Frontiers in Antibiotic Drug Discovery (FiADD, Symposium: Antibacterial Drug Discovery, Stockholm Sweden

• University of Uppsala (2016): Challenges and progress inthe development of novel Gram‐negative antibiotics. Lecture at The NorwegianAcademy of Science and Letters (DNVA) in Oslo, Norway, “Turning the tide of Antimicrobial Resistance Conference – TTA goes Nordic”

• Bacqué, E.: IMI-ENABLE: A European Antibacterial Drug Discovery Platform.

• Stavenger, R.: Addressing the challenges of antibacterial R&D through public-private partnerships at the BIO convention.

• Schofield, C. (2017): From Antibiotics to Oxygen Sensing and Back Again, seminar at the University of Durham 

• Karlén, A. (2017): The ENABLE project. Presentation at the Berlin Conference on Novel Antimicrobials. 

• Griestop, L. (2017): The ENABLE project. Presentation at the General Assembly of the EU funded PharmaSea project. 

• Bacqué, E. (2017): The ENABLE project. Presentation at the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) during the “Early Discovery of New Antibiotics Workshop”

• Uppsala University (2017)- Interview for a report about ENABLE in the Nordic Life Sciences titled "Antibiotic Advances"

• Brem, J. (2017): "Tackling anti-microbial resistance, development of novel metallo-ß-lactamase inhibitors", presentation at PSWC 2017
  

• Tyrrell, J. (2018): Presentation of ENABLE at Oxford university on July 18th.

• Karlén, A (2018): Presentation of ENABLE at the Almedalen Week in Visby, Sweden from July 1st - July 7th.

• Karlén, A. & Bölcker, K. (2018): ENABLE Präsentation auf der Berlin Conference on AMR in Berlin
  

• Bacqué, E. (2018): Presentation of ENABLE at the Innovative Medicines Initiative2 (IMI2) AMR Accelerator‐Expert‐Workshop in Bonn on June 29th.

• Schofield, C. (2018): Presentation of ENABLE at the Innovative Medicines Initiative (IMI) event in Brussels on June 27th: celebrating 10 years of medical innovations. 

• Maxwell, T. (2018): Presentation at the Gordon Research Conference on DNA Topoisomerases in Biology & Medicine: "Microcin B17, a Microbial Toxin that Targets DNA Gyrase: Activity, Biosynthesis and Impact on Human Health"

• Baranczewski, P. (2018): Presentation of the DMDG-SPS Joint meeting in Göteborg, 16-18 October 2018

• Nilsson, C. (2018): Presentation at the Swedish Veterinary Institute on their Research Days

• Schofield, C. (2018): “From Penicillins to Epigenetics – Adventures at the Interface ofChemistry and Biology”, presentation at the University of Queensland, Brisbane,
  Australia

• Schofield, C. (2018): “Structural, Functional and Inhibition Studies on Enzymes Involved in the Regulation of Protein Biosynthesis”, presentation at the University of Queensland, Brisbane, Australia

• Schofield, C. (2018): “From Penicillins to Epigenetics – Adventures at the Interface of Chemistry and Biology”, presentation at Adelaide University, Adelaide, Australia

• Schofield, C. (2018): “From Penicillins to Epigenetics – Adventures at the Interface of Chemistry and Biology”, presentation at Sydney University, Sydney, Australia

• Schofield, C. (2018): “From Penicillins to Epigenetics – Adventures at the Interface of Chemistry and Biology”, presentation at Institut Pasteur, Paris, France

• Schofield, C. (2018): “From Penicillins to Epigenetics – Adventures at the Interface of Patents Conferences Chemistry and Biology”, presentation University of Dundee, Dundee
  

Patents

WO2018/215800 - (Link) "The present invention relates to certain compounds that function as inhibitors of bacterial metallo-beta-lactamases. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of a bacterial infection."

WO2018/215799 - (Link) "The present invention relates to compounds of Formula (I) that function as inhibitors of bacterial metallo-beta-lactamases. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of a bacterial infection. (Formula (I))" Posters

Posters

• UIT (2015): Combating antibiotic resistance

• GSK (2016): IMI ENABLE: The European Gram-Negative AntiBacterial Engine, Poster Presentation at Melinda and Bill Gates Foundation Grand Challenges.

• Kiuru, P. (2016): ENABLE: Northern Antibiotics Polymyxin Programme, Flash poster presentation at the symposium on frontiers on antibiotic drug discovery (FiADD) in Stockholm 

• University of Uppsala (2016): Gordon Research Conference: New Antibacterial Discovery & Development, Poster presentation, Gordon Research Conference, Renaissance Tuscany Il Ciocco in Lucca (Barga) Italy

• Stavenger, R. (2016): IMI ENABLE: The European Gram-Negative AntiBacterial Engine presented at BMGF Grand Challenges Annual Meeting, Oct 2016, London

• Bölcker, K. (2017): Poster presentation ENABLE at the ECCMID in Vienna

• Gising, J. and Karlén, A. (2018): ENABLE – European Gram Negative AntiBacterial Engine 

• Racine et al (2018): NOSO-502, a novel antibacterial compound active against Carbapenem-Resistant-Enterobacteriaceae.

• Salisbury et al (2018): In Vitro Evaluation of Novel Bacterial Topoisomerase Inhibitors
  

Video

• ENABLE (2018): ENABLE Call for Action - European Gram-negative Antibacterial Engine