image: Anders Karlén, Professor of Computer-Aided Drug Design, Uppsala University & project coordinator, COMBINE. E-mail: anders.karlen@ilk.uu.se
Credit: David Naylor/Uppsala University
New antibiotics are crucial in the fight against antimicrobial resistance. Assessing the effectiveness of new antibiotics requires standardised high-quality infection models, readily available to stakeholders developing new antibacterial treatments. The Innovative Medicines Initiative project COMBINE is developing a standardised in vivo pneumonia model to test small molecule antibiotics. This model is now being evaluated through a unique collaboration with some of the main actors in the field: CARB-X & CAIRD, iiCON and Pharmacology Discovery Services.
Through this collaboration, key stakeholders will be able to share expertise and data, strengthening the validation studies of the COMBINE pneumonia model through testing by multiple organisations. This is part of an ongoing effort to develop a standardised protocol for the in vivo pneumonia model. Data from the model will also support the establishment of a reference strain bank of clinically relevant, well-characterized Gram-negative strains. COMBINE is also providing a framework to bridge the gap between preclinical data and clinical outcomes using mathematical modeling approaches.
The pneumonia model will support harmonisation, and the collaboration between COMBINE, CARB-X, CAIRD, iiCON and Pharmacology Discovery Services will improve quality through input and advice on the general strategy and standardisation parameters. The collaboration has been consolidated through agreements that enable the sharing of data and expertise, and exchange of ideas on study design for validation and benchmarking studies. The work on the pneumonia model is led by a team at Statens Serum Institut in Denmark, with COMBINE in vivo experiments will be performed at three different project partner sites: Statens Serum Institut, Paul-Ehrlich-Institut and GSK in order to test reproducibility between different laboratories.
“I am pleased that the protocol that COMBINE has developed for the standard pneumonia model works well with the isolates and antibiotics tested so far. Further studies are now in progress to fully characterise the model, and we look forward to making the protocol available to the AMR community,“ said Lena Friberg, Professor of Pharmacokinetics and Pharmacodynamics at Uppsala University, who is leading the COMBINE efforts on translation.
CARB-X will play an important role in this work by supporting the validation of the pneumonia model with approved antibiotics used in clinical settings, with CAIRD leading the work to provide a benchmark for new experimental antibiotics through back-translation of clinical data from human plasma and lungs. iiCON is another strategic partner, working with the Antimicrobial Pharmacodynamics and Therapeutics (APT) group at the University of Liverpool and Infex Therapeutics to support the development of experimental models of invasive bacterial and fungal diseases and mathematical modelling to ensure optimal dose selection. Another important part of the work will be facilitated by Pharmacology Discovery Services, supplying data on the efficacy of standard antibiotics in mouse lung infection models.
COMBINE has a coordinating role in the AMR Accelerator, a cluster of public-private partnership projects funded by the Innovative Medicines Initiative (IMI). The initiative brings together academia, pharma industry, patient organisations, non-profits and small and medium sized companies to develop a robust pipeline of antibiotics. “We are excited to bring standardised tools to those working to fill the pipeline with new antibiotics, and proud to be part of a community of stakeholders working together to combat antimicrobial resistance”, said Anders Karlén, Professor of Computer-Aided Drug Design & project coordinator.
More information & Contact
Scientists interested in joining COMBINE efforts (by sharing preclinical or clinical pneumonia data, conducting validation studies in their labs or sharing bacterial isolates) are welcome to contact us at IMI-COMBINE@pei.de
COMBINE
The COMBINE project (Collaboration for prevention and treatment of MDR bacterial infections) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No 853967. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA companies’ in kind contribution.https://amr-accelerator.eu/project/combine/
X: @AMR_Combine, LinkedIn: https://www.linkedin.com/showcase/amr-accelerator/
CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator)
CARB-X is a global non-profit partnership dedicated to supporting early-stage antibacterial research and development to address the rising threat of drug-resistant bacteria. CARB-X supports innovative therapeutics, preventatives and rapid diagnostics. CARB-X is led by Boston University and funded by a consortium of governments and foundations. CARB-X funds only projects that target drug-resistant bacteria highlighted on the CDC’s Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO, with a priority on those pathogens deemed Serious or Urgent on the CDC list or Critical or High on the WHO list. https://carb-x.org/
X: @CARB_X, LinkedIn: https://www.linkedin.com/company/16219870
iiCON
iiCON’s mission is to accelerate and support the discovery and development of innovative new anti-infectives, diagnostics, and preventative products. The Antimicrobial Pharmacodynamics and Therapeutics (APT) group at the University of Liverpool and Infex Therapeutics are key partners in iiCON. APT develop experimental models of invasive bacterial and fungal diseases along with mathematical modelling to ensure optimal dose selection. Infex Therapeutics is an anti-infective specialist company translating research into novel therapeutics. www.infectioninnovation.com
iiCON contact: Shampa Das, shampa.das@liverpool.ac.uk
Pharmacology Discovery Service
Pharmacology Discovery Service is a Eurofins Discovery partner lab and CRO with extensive experience in preclinical antibacterial development, and providers of in vivo pneumonia efficacy studies to the NIH preclinical service, offering consultative guidance from 15+ years of experience performing lung infection models for the AMR drug discovery community. http://www.pharmacologydiscoveryservices.com/efficacy-models/antimicrobials/in-vivo-antimicrobials
CAIRD (Center for Anti-Infective Research and Development)
CAIRDs mission is to advance anti-infective pharmacology and create optimal antibiotic utilization strategies that are safe and effective, while educating the clinical and scientific community for the purpose of benefiting the care of patients with infectious diseases both within and outside Hartford Healthcare. https://hartfordhealthcare.org/health-professionals/research/medical-professionals/center-for-anti-infective-research-development
CAIRD media contact: Liz Roper, Director of Research, lizabeth.roper@hhchealth.org
Innovative Medicines Initiative (IMI)
COMBINE and the AMR Accelerator are funded by the Innovative Medicines Initiative 2 Joint undertaking, an EU public private partnership. The funding scheme is followed by the Innovative Health Initiative (IHI), that aims to translate health research and innovation into tangible benefits for patients and society, and ensure that Europe remains at the cutting edge of interdisciplinary, sustainable, patient-centric health research. https://www.ihi.europa.eu/
IMI/IHI media contact: communications@ihi.europa.eu
Method of Research
Experimental study
Subject of Research
Animals