Under the global umbrella of IMI’s AMR Accelerator, the Gram-Negative Antibacterials NOW (GNA NOW) Consortium is a six-year project aimed at bringing together key European and private experts in antibiotic discovery and development. The Consortium is committed to developing completely novel compounds derived from previously unknown natural compounds with new modes of action. Ultimately, the goal of GNA NOW is to progress one compound through completion of Phase I studies, another compound to Investigational New Drug (IND) stage, and/or up to two more compounds to clinical development candidate stage.

Our approach is to leverage the support of a network of platforms with key expertise in research and development of antibiotics, which is required for a new molecular entity to progress from Lead or pre-candidate/candidate stages up to completion of Phase I studies. Moreover, GNA NOW aims to contribute significantly to preclinical antibacterial development in the widest sense with capacity and knowledge exchange. To this end, GNA NOW aims to favour the participation of project members in international scientific conferences and topic-related training courses. Furthermore, we will develop and integrate Patient and Public Involvement (PPI) into compound development and perform an evaluation of its impact. Finally, we will also develop a quality management system for the use of PK/PD models in preclinical science for better predictions of clinical outcomes which will have clear benefits for the whole AMR community.

The team will run three programmes in parallel, each focusing on a different drug candidate with an innovative mode of action. All drug candidates will undergo a range of tests to ensure their safety and efficacy and to understand and optimise how they work. The project hopes to complete phase 1 clinical trials for at least one candidate and advance at least one more to the stage where it is ready to enter clinical trials.


NOSO-502 is the first clinical candidate in the novel antibiotic class called Odilhorhabdins that was discovered by Nosopharm. It inhibits the bacterial ribosome with a new mechanism of action and is intended for the treatment of complicated Urinary Tract Infections (cUTI) and complicated Intra-Abdominal Infections (cIAI), including infections caused by polymyxin– and carbapenem-resistant Enterobacteriaceae (CRE). NOSO-502 has proven to be effective in vivo in Enterobacteriaceae infection models and demonstrated antibacterial activity in vitro against multi-drug resistant clinical isolates (KPC, NDM and OXA among others).


NOSO-2G is a lead optimization program to develop a second-generation Odilorhabdin clinical drug candidate for the treatment of hospital-acquired pneumonia and ventilation-associated pneumonia (HAP/VAP), including infections caused by carbapenem-resistant Pseudomonas aeruginosa.


The natural product Corramycin is a novel scaffold with antibacterial activity against multi resistant Gram negative pathogens such as Enterobacteriaceae and Acinetobacter Baumannii causing severe hospital bacterial infections (cUTI, and cIAI). Corramycin has no cross resistance with other classes of antibiotics and has a unique mode of penetration into Gram negative pathogens. After a lead optimisation program, a frontrunner has been selected by Evotec for its efficacy in animal models of infection. The goal within GNA NOW is to determine this compound’s molecular target and to advance it to Phase I.

Figure 1: Three drug discovery programmes (NOSO-502, NOSO-2G & CORRA) are running in parallel under the GNA NOW project, supported by eight drug development platforms.

Figure 2: The six year project aims to complete phase 1 clinical trials for at least one programme and advance at least one more to clinical development candidate stage


Initially, GNA NOW is working on three programmes with assets provided by the compound owners Evotec and Nosopharm. While there is a realistic chance of reaching the pre-set objectives,  these compounds are subject to stringent criteria before milestones can be reached.

Potential attrition will be managed by including new compounds that would benefit from the GNA NOW expertise and enabling platforms in order to progress. The consortium has therefore put in place robust governance and management structures to ensure that the most promising compounds are pursued diligently.

About Lygature

Lygature is a not-for-profit foundation that catalyzes the development of new medical solutions for patients by driving public-private partnerships (PPPs) between academia, industry and society. Lygature has extensive expertise in program management of large pan-European PPPs such as the IMI European Lead Factory (ELF), the IMI RADAR program and the IMI ADAPT SMART program. As independent enabler, Lygature functions as coordinator of GNA NOW and will provide operational, management, financial and legal support to the project. In addition, the development of the consortium’s communication and dissemination strategy is also part of Lygature’s GNA NOW responsibilities, as well as providing a secured web-based IT platform enabling all partners to safely share general project information.


Kristina Orrling: kristina.orrling@lygature.org
Karin de Ruiter: karin.deruiter@lygature.org

About Evotec

Evotec SE has built a strong, productive and successful business model serving as a partner to a variety of organisations (pharma and biotech companies, academic groups, foundations) to rapidly and efficiently advance assets from the discovery space to filing INDs (INDiGO) and on to early clinical development across multiple therapeutic areas. With the acquisition of Sanofi’s infectious diseases unit adding to the company’s already existing ID capacity, Evotec can serve as a key strategic partner for infectious diseases R&D. An internal team of the infectious diseases unit is dedicated to drug discovery and development, including in vitro and in vivo pharmacology, chemistry, development, and project management. Evotec will contribute to the enabling platforms by providing medicinal chemistry and design, in vitro and in vivo microbiological efficacy data, safety and ADME data. It will analyse PK/PD relationships, decipher modes of action, carry out CMC and fermentation and support clinical studies and modelling.


Sophie Lagrange: Sophie.lagrange@evotec.com
Eric Bacque: Eric.Bacque@evotec.com

About Nosopharm

Nosopharm is an innovative biotechnology company headquartered in Lyon (France) and specialized in the research and development of new molecules to combat antimicrobial resistance (AMR). The innovative anti-infective drug discovery platform developed by Nosopharm is based on the therapeutic exploitation of a very original bioresource: the bacterial genera Xenorhabdusand Photorhabdus. The mission of Nosopharm is to discover and develop novel first-in-class anti-infectives addressing unmet medical needs.


Philippe Villain-Guillot: p.villainguillot@nosopharm.com
Emilie Racine: e.racine@nosopharm.com


Created in April 2012 by l’Institut Pasteur and Lyonbiopole health competitiveness cluster, following the initiative of the French government, BIOASTER Technology Research Institute (TRI) is working to develop an unique technological and innovative model to support the latest challenges in microbiology. In particular, BIOASTER aims to fight antimicrobial resistance, improve vaccine safety and efficacy, quickly diagnose infections, and take full advantage of human and animal microbiota.


Magali Sarafian: magali.sarafian@bioaster.org
Gilles Courtemanche: Gilles.COURTEMANCHE@bioaster.org

About Helmholtz Centre for Infection Research

The Helmholtz Centre for Infection Research (HZI) and its affiliate Helmholtz Institute for Pharmaceutical Science Saarland (HIPS) will support GNA NOW in several work packages.  At HZI, we will apply our mass spectrometry-based technology to quantify compound uptake in subcellular compartments of Gram-negative bacteria. For different antibiotic series under study, the kinetics of uptake in periplasm, cytoplasm and membrane fractions will be determined. These experiments will be conducted in at least four different species of Gram-negative bacteria of high medical interest and defined genetic mutants thereof.


Mark Brönstrup: Mark.Broenstrup@helmholtz-hzi.de

About Helmholtz Institute for Pharmaceutical Research Saarland

The Helmholtz Centre for Infection Research (HZI) and its affiliate Helmholtz Institute for Pharmaceutical Science Saarland (HIPS) will support GNA NOW in several work packages.  At HIPS, we aim to establish biotechnological production platforms for antibiotics under study. Emphasis will be given on building blocks difficult to make by total synthesis to achieve a reduction in cost-of-goods. In addition, this work will help generate further derivatives of selected examples. We will employ our in-house platform for target elucidation of natural products by identifying and characterising self-resistance markers of natural producers. In addition, biophysical interaction studies and resistance development in pathogens with subsequent determination of underlying genetic factors will be used.


Rolf Müller: Rolf.Mueller@helmholtz-hips.de

About North Bristol Trust

Within the Department of Infection Sciences at North Bristol NHS Trust (NBT), there is more than 25 years of experience in performing in vitro PK/PD experiments for drug development programmes. NBT will contribute a number of basic microbiology techniques to GNA NOW, such as MIC, MBC, Time Kill Curve experiments, determination of post-antibiotic effects and antibiotic interaction studies. Moreover, patient and public involvement (PPI) is well established in antimicrobial research at NBT. The team are well convinced of the benefits of PPI in both ensuring that research is relevant and appropriate for patients, but also that the quality of research is enhanced by including the patient’s perspective and therefore has an established PPI panel.


Alasdair Macgowan: Alasdair.Macgowan@nbt.nhs.uk
Tony Timlin: tony.timlin@nbt.nhs.uk


About University of Liverpool

The Centre for Antimicrobial Pharmacodynamics (CAP) is based in the Department of Clinical and Molecular Pharmacology, Institute of Translational Medicine, University of Liverpool. Antimicrobial resistance is a growing threat and there has been a global push to address to develop new drugs. The CAP is one of relatively few academic laboratories in the world that can develop pharmacodynamic packages for new antimicrobial agents. We study how antimicrobial agents are distributed in the body (pharmacokinetics) and their effect on killing microorganisms (pharmacodynamics). CAP provides preclinical and early phase clinical support to ensure new drugs are developed in a streamlined manner.


Shampa Das: Shampa.Das@liverpool.ac.uk


Founded in 1964, Inserm is a public scientific and technological institute which operates under the joint authority of the French Ministries of Health and Research. The institute is dedicated to biomedical research and human health, and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.


About Université de Poitiers

The University of Poitiers is symbiotically rooted in its region, getting as close as possible to institutional, economic, cultural and academic actors. The University of Poitiers is located mainly in Greater Poitiers, on the campuses of central Poitiers, Poitiers-East and Futuroscope. It has also developed campuses in Niort and Angoulême, where it offers undergraduate (including the 2-year DUT diplomas) and postgraduate studies. It also has sites in Châtellerault and Segonzac.


Université de Poitiers is involved as a Linked Third Party of INSERM.

William Couet: william.couet@univ-poitiers.fr
Sandrine Marchand: Sandrine.Marchand@univ-poitiers.fr

About Erasmus MC

In the different platforms, the Department of Medical Microbiology and Infectious Diseases of the Erasmus MC will focus on determining the pharmacokinetics/dynamics (PK/PD) of the new compounds in different mouse models (e.g. lung infection model, urinary tract infection model, thigh infection model). The drug monitoring of the plasma samples and the subsequent mathematical modeling will be performed in close collaboration with the Department of Pharmacy of the Erasmus MC. Besides determination of PK/PD parameters, Erasmus MC will also perform the in vitro mutation frequency determinations of the compounds for different reference organisms. In addition, an in vitro urinary tract model will be applied to monitor the resistance selection during the course of an infection and subsequent antibiotic treatment.


Wil Goessens: w.goessens@erasmusmc.nl

About MedUni Vienna

The Medical University of Vienna (briefly: MedUni Vienna) is one of the most traditional medical training and research facilities in Europe. With its 26 university hospitals, three clinical institutes, 12 theoretical medicine centres and numerous highly specialised laboratories, it is included among the most important cutting-edge research institutes of Europe in the area of biomedicine. The role of MUW in the programme will be to plan, perform and analyse clinical first in man studies in healthy subjects and studies in specific patient populations with all compounds developed by the consortium. The clinical assessment will cover safety and tolerability. After biochemical quantification of the pharmacokinetic samples in a certified laboratory, pharmacokinetic analysis will be performed to optimize preclinical models as well as PK/PD modelling in other work packages.


Markus Zeitlinger: markus.zeitlinger@meduniwien.ac.at


About Fraunhofer-IME

Fraunhofer-IME leads the data management aspects of GNA-NOW, supported by the innovative informatics company, GRIT42, which will supply software tools to the consortia. A key part of Fraunhofer’s role is to help increase the impact of GNA-NOW by establishing the FAIR (Findable, Accessible, Interoperable and Reusable) principles in overall data management. These principles underpin how the consortia will work with data generated in each of the platforms. They will help facilitate the use of Machine Learning and similar techniques to extract additional value from the results and support the work of the wider antibiotic drug discovery community.


Philip Gribbon: Philip.Gribbon@ime.fraunhofer.de

GNA NOW Project Contact

Dr. Sophie Lagrange


GNA NOW Project Contact

Kristina Orrling



This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No 853979. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA companies’ in kind contribution.