ND4BB

IMI's COMBACTE projects are the foundation of ECRAID, a network to support the full range of clinical research into new antimicrobial agents. ###

As it currently stands, clinical studies of new antimicrobial drugs have to be set up from scratch, leading to wasted time and resources. Now a new entity called ECRAID has been set up to be able to quickly and efficiently launch and carry out clinical trials of potential new antibiotics. The new entity will provide the full breadth of clinical studies on infectious diseases, from observational and interventional studies to prevention, treatment, diagnostics, screening, epidemiological, quality of life, and health economics research. It will also support phase one to phase four clinical trials.

ECRAID is an outgrowth of IMI's COMBACTE projects and the EU-funded PREPARE programme. COMBACTE is part of the IMI-funded programme ND4BB (New Drugs for Bad Bugs) progreamme and focuses on improving the clinical development of antibiotics. COMBACTE has been building a high-quality clinical and laboratory research network for new options to treat or prevent bacterial infections in the EU and affiliated countries.

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• Read the article in full

It is known that treating patients with antibiotics is associated with the emergence of resistance - and worse outcomes for patients. But how resistance emerges during infections remains poorly understood.

Now a study published in Nature Communications reports that rapid bacterial evolution interacts with host immunity to shape both the rise, and fall, of resistance during infection. ###This study was performed as part of the IMI COMBACTE-MAGNET project.

COMBACTE-MAGNET is working to find new approaches to combat antibiotic resistance. This new study highlights the need to understand better how our immune system works with antibiotics to suppress bacterial infections.

The research described in the article is part of the ASPIRE-ICU study, which stands for Advanced understanding of Staphylococcus aureus and Pseudomonas aeruginosa Infections in EuRopE – Intensive Care Units.

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• Read the article in full

The US Food and Drug Administration (FDA) has granted ‘fast track designation’ to Da Volterra’s DAV132 for the prevention of Clostridioides difficile infection (CDI). The FDA fast track designation is intended to speed up the review of drug candidates for treating or preventing serious conditions. ###

DAV132 is a first-in-class microbiome protector designed to inactivate antibiotics that are circulating in the colon and disrupting the gut microbiome. It is destined for use in patients for whom microbiome disruption can be life-threatening, such as those with cancer. The product was developed by French SME Da Volterra, which is a partner in IMI’s COMBACTE-NET project.

As part of COMBACTE-NET, Da Volterra is about to launch an international phase 3 clinical trial called MICROCARE to evaluate DAV132 in patients with haematologic malignancies. MICROCARE will assess the efficacy of DAV132 in protecting intestinal microbiome diversity, preventing intestinal colonisation with potentially pathogenic bacteria, preventing bloodstream infections, and improving overall survival.

It will build on the results of ANTICIPATE, a multi-centre, prospective, observational study conducted within COMBACTE-NET to identify microbial factors predictive of CDI, the results of which were published recently in Nature Communications.

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• Read the article in full

COMBACTE-NET partner Da Volterra has been given a green light to move forward with a phase 3 trial of an innovative product to protect the microbiome of cancer patients from antibiotic-induced disruption.###

The microbiome of cancer patients is constantly assaulted by numerous prescribed drugs, in particular life-saving antibiotics. The consequences of this include a higher risk of picking up infections, lower efficacy of anti-cancer treatments, and even potentially lower survival due to interference with the immune system. There is now hope for change.

In a world first, French biotech Da Volterra, a partner in the COMBACTE-NET project, has been granted authorisation to proceed to phase 3 trial to get evidence on the efficacy and safety of its product, DAV132, in patients with hematologic malignancies (cancers of the blood, bone marrow and lymph nodes). The product, they claim, will protect the microbiome of these patients in spite of massive antibiotic use.

The MICROCARE study will enrol 900 patients mainly in Europe and the USA. The objective is to show that DAV132 contributes to decreasing the occurrence of life-threatening complications of hematologic malignancies in people who are undergoing chemotherapy.

The study is a major milestone. It is a testament to the capacity of the quality clinical and laboratory research network set up by COMBACTE-NET and its ability to successfully conduct the first-ever phase 3 study of the project, thus facilitating market access of novel products to combat life-threatening conditions and antimicrobial resistance (AMR).

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• Read the article in full

Antimicrobial resistance (AMR) project COMBACTE-MAGNET has launched a new, freely accessible online tool that allows healthcare professionals and the public to assess the risk of international travellers acquiring (and spreading) antimicrobial-resistant bacteria.###

Travel plays a major role in the spread of AMR, and the new AMR Travel Tool will make it easier for healthcare professionals to evaluate patients’ travel history and associated AMR risk factors. The healthcare professional’s section of the website highlights differences in resistance levels between the travel destination and the host country, for example.

Meanwhile, travellers can enter their travel destination and receive general advice on infection control as well as pathogen-specific advice on the infection risks related to their destination (and tips on how to avoid them).

Find out more

• Visit the AMR Travel Tool

A study in healthy volunteers showed that the antibiotic EBL-1003 is safe and well tolerated. EBL-1003 (a purified form of apramycin) shows promise as a treatment for complex drug-resistant infections. The finding is a great result for the ENABLE project, which set up an antibiotic development platform to provide researchers with the expertise, resources and support needed to advance promising early research stage antibiotics into Phase 1 clinical trials in humans.###

The clinical potential of apramycin was discovered by researchers at the University of Zurich who set up a spin-out company, Juvabis, to develop it further. Juvabis joined ENABLE in 2016. Thanks to the collaboration with ENABLE, Juvabis was able to demonstrate the safety and efficacy of in animal models for various infections, including infections caused by some of the more dangerous drug-resistant bacteria.

The Phase I clinical trial started in 2019; the goal of the trial was to assess the safety and tolerability of the drug as well as how it behaves in the body. Healthy volunteers received single intravenous doses or a placebo.

The results of that trial are now in, and they show that EBL-1003 is both safe and well tolerated. The Juvabis team now plans to run a further Phase I trial in patients with complicated urinary tract infections – one of the disease areas where EBL-1003 shows the most promise.  

If further trials confirm EBL-1003’s antibiotic abilities, it would be a valuable weapon for treating infections involving bacteria that are increasingly resistant to many existing antibiotics.

‘We urgently need new antibiotics to tackle the ever-growing threat of antimicrobial resistance. ENABLE’s successes demonstrate that with the right support from a team of experts from academia and industry, potential antibiotics can be identified and supported through the highly challenging early stages of antibiotic development,’ said IMI Executive Director Dr Pierre Meulien. ‘More broadly, this result demonstrates the strength of public-private partnerships in tackling major health challenges.’

Find out more

• Read the article in full
• Read ENABLE’s press release
• Visit the ENABLE website

A study of potential coronavirus treatments, announced in March by the French national institute of health and medical research (INSERM), is receiving support from an IMI-funded network of clinical trial sites and laboratories. The INSERM coordinators contacted the team behind the IMI-funded COMBACTE-NET project to help recruit patients with COVID-19 and coordinate the clinical sites involved in the multicentre, multi-country study.### DisCoVery is a large, international, open randomised trial studying a number of drugs that could prove effective against SARS-CoV-2, the virus that causes COVID-19.

‘These are drugs that in the lab in vitro and in animal models have an effect on the virus, but we don't know whether that effect can also be reproduced in the patient,’ says Marc Bonten from University Medical Centre Utrecht and academic leader for COMBACTE-NET. ‘What (INSERM) needed was to be able to identify the sites that could move rapidly because this is a race against the clock. We were able to identify in our network the sites that we think can manage this problem of having this set up in in a few weeks’ time.’

COMBACTE-NET will also contribute to the new H2020 project RECOVER; COMBACTE-NET’s established clinical and laboratory networks will be used to study disease spectrum and severity, risk factors, spread and outcomes of COVID-19 in patients in hospital care.

Read more

• The article in full
• Press release: Launch of a European clinical trial against COVID-19
• COMBACTE-NET website

The IMI project ENABLE was launched in 2014 to speed up the development of new antibiotics for the treatment of Gram-negative systemic infections. The project has achieved and surpassed its initial goals, ###having so far identified 5 antibacterial leads, selected 2 antibacterial development candidates and advanced 1 compound into preclinical and phase one clinical studies.

With several promising compounds in the pipeline, IMI granted the project a one year no-cost extension (i.e. total spend will remain within original budget). Here’s a breakdown of the achievements of the research teams so far:

• ENABLE currently has 10 active programmes: 6 are in Hit to Lead, 2 in Lead to Candidate, 1 in Candidate to Phase I and 1 in Phase I.
• ENABLE selected its first candidate – Juvabis’ apramycin programme – in October 2018. Mutabilis’ candidate MUT485 received candidate status in November 2019.
• Juvabis’ clinical candidate apramycin is currently evaluated in a Phase I randomised, double-blind, placebo-controlled single ascending dose study in healthy volunteers. Apramycin is an aminoglycoside antibiotic which has demonstrated promising efficacy against multidrug-resistant bacteria. First results are expected in 2020.

Anders Karlén, leader of ENABLE Managing Entity and professor at Uppsala University, said: 'This achievement is an immense success given the complexity and number of partners involved. We have brought the leading experts in the antimicrobial resistance field together, set up a unique and effective collaboration and delivered.'

Read more

• IMI’s news story
• ENABLE press release: Goals achieved – Mission continues

Researchers recently showed that an injection of monoclonal antibodies can be used to decrease the virulence of Staphylococcus aureus bacteria in patients who are hooked up to breathing machines in hospital. The phase II trial was carried out by the IMI project COMBACTE-NET, as part of the SAATELLITE study, using a monoclonal antibody developed by AstraZeneca called Suvratoxumab.###

Patients in intensive care units (ICUs) who are breathing with the help of ventilating machines are at high risk of contracting pneumonia. The S. aureus bacteria make their way into healthy lungs by attaching to the medical tubing that connects to the outside world. S. aureus is extremely virulent and increasingly resistant to antibiotics. The objective of the trial was to see if patients whose lungs are already colonised by S. aureus could avoid pneumonia by being dosed with a one-off shot that would block the bacteria’s virulence, i.e. the potential for infection.  

The results were promising. The researchers enrolled about 200 ventilated ICU patients in a double blind placebo controlled trial. The percentage of people in the placebo arm that contracted pneumonia was 26%, while those who had received the monoclonal antibodies injection was 18%. This is a relative reduction of 31%. Dr Bruno François from the University Hospital of Limoges, who was involved in the SAATELLITE study, is cautiously optimistic about the results.

‘This was the first trial with this type of drug to be used as a preventative,’ says Dr François. ‘This could represent a true opportunity to decrease the number of pneumonia infections in the ICU without needing any antibiotics. Of course it’s only a phase two so you would need a confirmatory trial, but it’s completely innovative.’

Read more

• IMI’s news story
• The COMBACTE-NET project factsheet
• COMBACTE-NET website
• More AMR stories from IMI projects

Antimicrobial resistance (AMR) is becoming one of the defining problems of our time. As bacteria become resistant to the drugs that are supposed to kill them, scientists, policy makers and the pharma industry are looking at different ways to fix the problem before it’s too late. IMI has invested heavily in AMR research. ###To date, we have invested almost €800 million on 14 projects. Throughout November, we turned the spotlight on some of IMI’s projects in this area and explored the different angles from which they’re tackling the problem.

Read the articles

• Focus on AMR
• New antibiotics won't stop AMR. Luckily, there are other things we can try. – editorial by Pierre Meulien, IMI Executive Director
• Why it's so hard to make new antibiotics
• A very promising antibiotic just started clinical trials
• Technology, not instinct, should guide antibiotic prescribing

Antimicrobial resistance (AMR) is becoming one of the defining problems of our time. As bacteria become resistant to the drugs that are supposed to kill them, scientists, policy makers and the pharmaceutical industry are looking at different ways to fix the problem before it’s too late. IMI has invested heavily in AMR research.### In November, we will be taking a look at some IMI projects and the different angles from which they’re tackling the problem – from rapid diagnostics and public health policy, to permeability and prophylactic vaccines.

We’ll be publishing new stories throughout November in our newsroom; follow @IMI_JU on Twitter for updates. We will also publish links to all the AMR articles in the next edition of the newsletter.

Find out more about IMI’s AMR projects:

• IMI New Drugs for Bad Bugs programme
• IMI AMR Accelerator Programme

COMBACTE-CARE has recruited 2 266 patients to its EURECA study on infections that are resistant to antibiotics called carbapenems, which are considered to be among the most difficult to treat. ###In a statement, the project said: ‘Excellent collaboration between the central team and the study sites has ensured that the study has run smoothly, and in future will lead to results that have a significant impact on the practice of infectious diseases in Europe and elsewhere.’ Cases of infections caused by bacteria known as carbapanem-resistant enterobacteriaceae (CRE) are on the rise, and are most common in healthcare settings. They are extremely hard to treat (very often the only treatment options are combinations of old, toxic antibiotics) and can be fatal. The EURECA study is investigating the risk factors for CRE infection and things that influence treatment outcomes. The samples collected during the study are now being sent to a central site for analysis.

Since its launch in 2014, the ENABLE project has helped researchers in universities and small and medium-sized enterprise (SMEs) to progress potential antibiotics through the challenging earlier stages of drug development. Now, the project has selected one potential antibiotic it has worked on, apramycin, as a clinical candidate. ###The clinical potential of apramycin was discovered by researchers at the University of Zurich who set up a spin-out company, Juvabis, to develop it further. Juvabis joined ENABLE in 2016. Thanks to the collaboration with ENABLE, the Juvabis team has now been able to demonstrate the safety and efficacy of apramycin in animal models for various infections, including infections caused by some of the more dangerous drug-resistant bacteria. This prompted the project to select apramycin as a clinical candidate; the plan is to prepare for a Phase I clinical trial application by the end of 2018. ‘We are pleased that our collaboration with ENABLE has further highlighted the potential of apramycin in the treatment of complicated systemic infections in humans,’ says Sven Hobbie, who leads the programme. ‘The nomination by ENABLE of apramycin as a drug candidate will accelerate the preclinical and clinical development of our product into a life-saving medicine.’

ENABLE is still accepting Expressions of Interests from organisations with interesting molecules that could benefit from the project’s unique platform. For more information, visit the project website and watch their new video.

COMBACTE projects have launched a unique European platform that allows users to explore and visualise data on antibiotic resistant infections in humans and animals across Europe. The website, which is freely accessible, brings together epidemiology data from 32 European countries on the priority list of pathogens released by the World health Organization in 2017.### It also includes data on more recent outbreaks and emerging cases of resistance to newly-developed antibiotics. Data is displayed via colour-schemed maps that allow users to easily track things like the setting, resistance rates, sample sizes and data sources. If users register, they can also select and download data. In a statement, the project explains: ‘The goal is to give industry, policy makers, and public an easy tool to use in order to understand the trends and the epidemiology of antimicrobial resistant infections across Europe using a One Health approach. The platform provides an interactive space, which combines multiple sources and allows to overcome language barriers.’

Antibiotic resistance is a big global public health problem. Of particular concern are multidrug-resistant Gram-negative bacteria, which are among the leading causes of serious, debilitating and life threatening healthcare-associated infections. There is an urgent need for new therapies to treat or prevent infections caused by these bacteria in hospitalised patients. IMI’s COMBACTE-MAGNET project is developing new antibacterial treatments for vulnerable patients, especially the critically ill in intensive care units. ###It is doing this by promoting collaborations between scientific experts. ‘I think the creation of an effective public-private consortium like COMBACTE-MAGNET in itself is a major achievement,’ says project coordinator Hasan Jafri of MedImmune, the global biologics research and development arm of AstraZeneca. ‘The project brings together top researchers and clinicians from five pharmaceutical companies – AstraZeneca, AiCuris, GSK, Basilea Pharmaceutica, and Sanofi – and more than 30 leading academic medical centres from 10 European countries.’ To date, the COMBACTE-MAGNET consortium has established a Pan-European platform called EPI-Net to access epidemiological data; is publishing the first results from an epidemiology study; and is designing innovative clinical trials to advance development of novel molecules against multidrug-resistant Gram-negative bacteria.

• Read the entire story

Researchers from STAT-Net, a group of experts from IMI’s COMBACTE-NET project, have issued a white paper with recommendations for improving the design and analysis of clinical trials of drugs to treat resistant infections. ###In the paper, published in the journal Clinical Infectious Diseases, the team states that the recommendations represent ‘a solid, evidence-based approach to develop new, and established, antibacterials and address this public health challenge’. The clinical development of a new antibacterial is far from easy; for example, using standard clinical trial designs, it is difficult to find enough patients with a resistant infection to adequately assess the safety and efficacy of a new treatment. With this in mind, the COMBACTE-NET team assessed a number of ways of improving the situation, and scored each one on its alignment with regulatory frameworks; its technical feasibility; ease of data interpretation; ease of practical implementation; and the strength of the evidence base for the recommendation. The authors note that not all recommendations will be applicable to all trials, and some score better than others on the different criteria. Nevertheless, they note that ‘they are all relevant to the debate supporting change’. The team concludes: ‘Hopefully, these recommendations and their continued evaluation and evolution will accelerate antibacterial approval and ensure appropriate use of established antibiotics to help those in need as soon and as best as possible.’

A mix of economic drivers and incentives is needed to stimulate antibiotic development, according to the final report of IMI’s DRIVE-AB project. The report, based on input from diverse stakeholders, highlights four incentives that would be the most effective in stimulating the antibiotic pipeline while also ensuring that critical antibiotics are used sustainably and are accessible to all who need them. ###The incentives picked out by the report are:

• Grants: non-repayable funds for R&D given to academic institutions, companies and others;
• Pipeline coordinators: governmental or non-profit organizations that closely track the antibiotic pipeline (or subsets thereof), identify gaps, and actively support R&D projects both financially and technically to fill these gaps;
• Market entry rewards: a series of financial payments to an antibiotic developer for successfully achieving regulatory approval for an antibiotic that meets specific predefined criteria to address a defined public health need, with obligations for sustainable use, equitable availability and supply;
• Long-term supply continuity model: a delinked payment to create a predictable supply of important generic antibiotics.

All of the recommended incentives would include mandatory provisions for equitable access and sustainable use in order to ensure these critical medicines are available to patients who need them globally, and remain effective over time. ‘The models are meant to be complementary and don’t operate in isolation. Instead, they’re designed to form an ecosystem that maximizes R&D while ensuring access and sustainable use of new antibiotics over time,’ said Christine Årdal, DRIVE-AB partner and Senior Advisor at the Norwegian Institute of Public Health.

Read the project’s press release

New antibiotics will have to be used sparingly to preserve their efficacy. IMI’s DRIVE-AB focuses on ways to stimulate their development. A combination of incentives is required, the researchers note. In particular, they highlight the need to ‘delink’ the revenue generated by new drugs from the quantities sold. To do so, they propose a combination of push and pull mechanisms. ### Priority grants could, for example, be used to get the innovation process moving. A system of rewards for market entry could be set up to encourage its completion. This type of approach would contrast with the business model traditionally applied to drugs, where income depends on the volume of sales.

DRIVE-AB ends in December 2017, and the partners are preparing to publish their final report along with detailed recommendations. ‘We have aimed to encourage a balance between innovation and responsible use,’ says Nicole Mahoney of Merck Sharp & Dohme (MSD), one of the project partners. Policymakers and other stakeholders could find ample inspiration in DRIVE-AB’s conclusions. As a first step, the project’s findings might, for instance, feed into pilot studies at national levels, says Mahoney. ‘We may well see individual countries trialling some of these ideas and setting up reward mechanisms that work within their local context,’ she concludes.

• Read the full story

Mutabilis, a French company specialised in developing novel treatments for resistant bacterial infections, has joined IMI antimicrobial resistance (AMR) project ENABLE. Mutabilis works on a family of antibiotics called dabocillins, which are effective against bacteria such as carbapenem resistant enterobacteriaceae (CRE) that are resistant to other antibiotics and are notoriously hard to treat. ### By joining ENABLE, Mutabilis gains not only funding from IMI, but access to the ENABLE project’s expertise and technical resources. ‘Securing this grant is a clear recognision of the quality of our innovative research,’ said Mutabilis Chairman Stéphane Huguet. ‘In accessing its platform of services and receiving the advice of specialists in the field, we have a fantastic opportunity to speed up the development of our compounds and secure the company’s future.’

ENABLE has an open Call for proposals for organisations to join the project and benefit from the platform it has created. More information on how to apply can be found on the project website.

• Read the Mutabilis press release

Scientists from IMI’s Translocation project have uncovered the workings of a ‘molecular vacuum cleaner’ in the outer membrane of certain bacteria. The mechanism, described in a paper in Nature Microbiology, helps to keep the outside of the membrane free of clusters of molecules that could weaken it and the system could prove useful as a target for new antibiotics. ### Gram-negative bacteria like Escherichia coli are enclosed by two membranes which form a significant barrier for many antibiotics, limiting their effectiveness. The outer membrane is asymmentric; while the outside is coated in sugars that ward off many molecules that could be harmful to the bacteria, the inside is lined with phospholipids. Sometimes, phospholipids from the inside of the membrane accumulate on the outside. These clumps of phospholipids represent weak spots in the membrane, rendering it more vulnerable to toxic compounds like antibiotics. In this study, the scientists proposed a functional model of the ‘maintenance of lipid asymmetry’ (Mla) system, which removes phospholipids that have strayed into the outside of the membrane, sucking them back into the inside of the membrane where they belong. ‘Our three-dimensional structures and functional data show that MlaA forms a donut in the inner leaflet of the outer membrane. This binds phospholipids from the outer leaflet and removes these via the central channel, somewhat similar to a vacuum cleaner,’ explains Bert van den Berg of Newcastle University in the UK. ‘Our study illuminates a fundamental and important process in Gram-negative bacteria and is a starting point to determine whether the Mla system of Gram-negative pathogens could be targeted by drugs to decrease bacterial virulence, and to make various antibiotics more effective.’

Read more in the press releases from the University of Newcastle and Jacobs University

IMI’s COMBACTE project has started work on the ASPIRE-ICU study at a site in the Netherlands. ASPIRE is an epidemiological study of healthcare-associated infections caused by Staphylococcus aureus  and Pseudomonas aeruginosa to determine the incidence of infection in different patient populations and the association between factors such as co-morbidities, colonisation status, relevant biomarkers and infection risk.### Getting the study off the ground required intense collaboration between the COMBACTE partners to obtain ethical approval and to ensure the research team had the necessary training in protocols, procedures and particularly importantly, in specimen sample management. The study has two stages. In stage 1, information from existing intensive care unit (ICU) and surgical surveillance databases will be collected and analysed. In stage 2, ICU and surgical epidemiologic data will be collected from ongoing surveillance which includes collecting bacterial isolates and serum samples for in-depth microbiological and immunological studies. There are plans to launch the study in Spain next and the ASPIRE-ICU study team is working closely together with the regional coordinator there to obtain the required approvals in order to start in late summer 2015. Overall, the ASPIRE-ICU will be initiated in about 30 sites across between 10 to 12 countries. COMBACTE is working to improve clinical trials for antibiotics and is one of the seven projects included in IMI’s New Drugs for Bad Bugs (ND4BB) platform. 

COMBACTE has launched an open call for clinical trial programmes or studies to join the project. The open call aims to identify potential replacement antimicrobial agents or approaches developed by EFPIA companies that could fulfil the overall objectives### of the project i.e. to conduct prospective clinical trials with novel trial designs to deliver safety, pharmacology, and proof of efficacy data for novel agents directed towards treatment, prevention or sequelae of infections due to priority pathogens. COMBACTE is one of the first IMI projects to be launched under the ND4BB programme with the aim of developing a broad European network of fully capable and Good Clinical Practice (GCP) compliant clinical investigation sites associated to microbiological labs to execute clinical trials enabling the registration of novel agents to be used in the treatment of patients with bacterial infections. Following the early termination of development of GSK1322322, the first novel agent to be developed within COMBACTE, there is now opportunity for other clinical trial programmes or studies to join the COMBACTE project. A webinar on the open call is planned - details will be published on the COMBACTE website.

• Deadline for submissions: 29 April 2015 at 19:00 Central European Summer Time (CEST).
• Read the open call protocol and guidelines for submitting proposals
• Download the proposal submission template and evaluation criteria

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.’

IMI cited in White House paper on antimicrobial resistance
IMI’s New Drugs for Bad Bugs (ND4BB) programme has been specifically highlighted as a potential collaborator in the recent US National Action Plan for Combating Antibiotic-Resistant Bacteria report issued by the White House in March 2015. The plan outlines steps for implementing and addressing the policy recommendations of the President’s Council of Advisors on Science and Technology (PCAST). ###In setting five goals for collaborative action, the US Government is exploring ways to work with international partners, including the ND4BB programme, in order to incentivise the development of new therapeutics to counter antibiotic resistance which includes finding new, next-generation and alternatives to antibiotics, vaccines, and affordable, rapidly-deployable ‘point-of-need’ diagnostics. IMI projects included in the ND4BB programme are COMBACTE who are creating a pan-European network of clinical sites; TRANSLOCATION who are getting drugs into bugs (and keeping them there); ENABLE which is a drug-discovery platform for antibiotics; DRIVE-AB which is developing new economic models for antibiotic development.
(April 2015)

IMI antimicrobial resistance programme expands with new project
IMI’s antimicrobial resistance programme New Drugs for Bad Bugs has acquired a new project with the launch of COMBACTE-CARE. With 18 academic partners and 3 pharmaceutical companies, the project will bring highly innovative studies and activities related to the treatment of patients with infections caused by Carbapenem-Resistant Enterobacteriaceae (CRE). ###Tough to treat and sometimes deadly, CRE are considered to be one of the most dangerous resistant bacteria in the world. Specifically, the €83 million project aims to understand how patients with CRE infections are managed, with a focus on best available treatment and clinical outcomes. The project will develop new tools to detect CRE and conduct clinical trials with AstraZeneca’s antibiotic combination product Aztreonam-Avibactam (ATM-AVI), in development for the treatment of serious infections due to a difficulty to treat sub-type of CRE infections called metallo‐β‐lactamase producing Gram‐negative pathogens. All clinical and microbiological studies will be conducted in South-Eastern Europe, where infection rates with MDR-GNB are expected to be high. The phase III study is intended to include investigation sites outside Europe to ensure the global assessment of the ATI-AVI combination product.
- Read the project’s press release
(March 2015)

Antimicrobial resistance projects sign memorandum of understanding
IMI’s first antimicrobial resistance projects, COMBACTE and TRANSLOCATION, have signed a Memorandum of Understanding (MoU) to facilitate their collaboration. ### The projects are part of the New Drugs for Bad Bugs (ND4BB) programme. As such, there was always an understanding that the projects would work together – this MoU simply formalises and sets out the framework for collaboration. Specifically, the MoU covers issues such as data sharing (and confidentiality), communication and coordination, as well as the creation of a shared Ethics Committee. One of the tasks of the TRANSLOCATION project is the creation of an Info Centre that would gather data from all ND4BB projects. With this in mind, the MoU also contains a section devoted to data standards and analysis. Looking to the future, the new ND4BB projects that will be set up in the coming months will also be invited to join the MoU.
(December 2013)