It has been more than ten years since you have joined the Innovative Health Initiative (IHI; formerly Innovative Medicines Initiative), what have been for you the most important scientific breakthroughs in antibiotic development made under the Innovative Medicines Initiative public-private partnerships?

As we know antimicrobial resistance (AMR) represents a serious and growing threat to human and animal health worldwide but development of preventive or therapeutic solutions to fight AMR is complex, risky and not linear. Given the number of important advances brought about by IMI projects it is difficult to single out specific developments. However, a key element underpinning all of the achievements has been the collaborations fostered between different stakeholders under the umbrella of IMI. IMI launched its New Drugs 4 Bad Bugs (ND4BB) programme to contribute to the effort of fighting AMR, further to the 2011 EC action plan on antimicrobial resistance and together the ND4BB projects have generated significant results that have impact on the AMR field such as:

• A pan-European network set up of over 1000 clinics and hospitals capable of quickly and reliably recruiting, treating, monitoring and reporting data on the required numbers of patients in multinational, multicenter trials at all stages of clinical drug development. CLIN-NET is completed by large network of over 900 microbiology laboratories, LAB-NET, delivering high-quality and standardised information on microbial strains and antibiotic resistance. These networks are the foundation of ECRAID, a network to support the full range of clinical research into new antimicrobial agents https://www.ecraid.eu.
• Support of clinical development of several assets including assets targeting WHO priority pathogens (e.g aztreonam-avibactam intended to treat serious Gram-negative bacterial infections in patients with limited or no treatment options, novel approaches like monoclonal antibodies (suvratoxumab against Staphylococcus aureus alpha toxin in mechanically ventilated adult and adolescent subjects).
• EPI-Net surveillance database providing up-to-date information to track prevalence and incidence of AMR and HAI, AMR outbreaks, and emergent antibiotic resistances (Epi-net.eu) as well as the AMR travel tool https://epi-net.eu/travel-tool/overview/.
• New knowledge on infections (e.g., estimation of incidence, risk factors, etc.) generated through several observational studies conducted.
• Generating data to support novel methodological approaches and change in current practices; interaction with regulators (e.g use of composite endpoints, adaptive platform trials focusing on VAP).
• EU Bronchiectasis (BE) registry EMBARC with over 19,000 patients enrolled to provide comprehensive data on the epidemiology, natural history and management of BE in Europe to support the development of treatment http://www.iabcproject.com/EMBARCRegistry/.
• Drug discovery and development platform set up and overall pipeline in the antibacterial area increased with the delivery of 6 Lead declarations; 3 Candidates declarations; 2 compounds into preclinical studies; 1 compound into Phase I studies http://nd4bb-enable.eu.
• Recommendations to incentivise drug discovery and development ‘Revitalizing the antibiotic pipeline: Stimulating innovation while driving sustainable use and global access’ http://drive-ab.eu/drive-ab-outputs/drive-ab-reports/.

Although the projects from the AMR Accelerator have been launched more recently under IMI2 they are already generating important results notably for the development of potential new TB drugs/combinations. Further diagnostic tools are critical to ensure a better use of antibiotics and Value-DX is contributing by validating diagnostics https://www.value-dx.eu/.

Last month, IHI outlined seven draft topic texts for the next calls for proposals. Which of these do you think can have the greatest potential impact on infectious diseases and AMR-driven research?

Under IHI compared to IMI we have topics with a broader scope not necessarily focusing on a disease area, that are launched under a single stage call (i.e., Private Members apply simultaneously with Public Members in mixed consortia). This is aligned with the IHI Strategic Research and Innovation Agenda.  Therefore none of the 7 draft topics specifically address AMR, however topics like T1  Screening platform and biomarkers for prediction and prevention of diseases of unmet public health need and T2 Patient generated evidence to improve outcomes, support decision making, and accelerate innovation could have potential impact on infectious diseases and AMR-driven research.

At the end of the year, almost all the IMI1 projects will have closed. In your opinion, what are the most important lessons learnt from IMI1 which can best help design future IHI project calls?

A couple of lessons learnt:

• The public and private collaboration has been essential to build a high quality clinical and lab network that can conduct clinical trials for registration purposes and companies outside the consortium are now approaching the network.
• Business development models for antibiotic development remains a key development.
• Despite the success of our projects, managing these projects that focus on the development of innovative compounds against AMR is very challenging. While there is a real need for collaboration to support the development of innovative approaches against AMR, this support through a research project may not optimal and may not fully serve the purpose of a real accompaniment of the companies throughout the development cycle till licensing considering the constraints of the applicable legal framework/funding rules, administrative burden and timelines. A more appropriate scheme with the necessary legal and financial flexibility would be warranted to facilitate clinical development of innovative approaches against AMR.
• While there is a focus to ensure patients-centricity, patient and public involvement in antimicrobial medicines development research is not common and there is a lack of a strong AMR patients’ voice/organisation at EU level like there are in other diseases areas playing a key role in providing the patient perspective into the projects, driving changes, advising on research priorities, etc. The COMBACTE-MAGNET project has developed a toolkit to provide systematic and evidence-based guidance on how and when to involve the public in medicines development research, in particular antimicrobials: https://www.combacte.com/news/combacte-magnet-patient-and-public-involvement-ppi-toolkit-completed/. However there is a need for strengthening much more patient input at all levels of AMR research.