EUROPEAN REGIMEN ACCELERATOR FOR TUBERCULOSIS

Project Information

ERA4TB

Grant agreement ID: 853989

DOI

10.3030/853989

EC signature date 12 December 2019

Start date 1 January 2020

End date 31 December 2026

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 207 963 891,00

EU contribution

€ 89 815 600,00

Coordinated by

UNIVERSIDAD CARLOS III DE MADRID
Spain

Periodic Reporting for period 5 - ERA4TB (EUROPEAN REGIMEN ACCELERATOR FOR TUBERCULOSIS)

Reporting period: 2024-01-01 to 2024-12-31

Summary of the context and overall objectives of the project

After a brief hiatus due to Covid-19, tuberculosis (TB) has regained its position as the world’s leading infectious killer, with 10.8 million cases and 1.25 million deaths reported in 2023. Drug-resistant TB remains a significant threat, impeding global efforts to end the epidemic by 2030. Current treatment regimens are lengthy and challenging due to side effects, particularly in patients with co-morbidities such as HIV/AIDS or diabetes. Poor adherence has fuelled antimicrobial resistance (AMR), highlighting the urgent need for new, effective anti-TB drugs.

ERA4TB unites pharmaceutical companies, NGOs, SMEs, and academic institutions to accelerate TB treatment development. The initiative aims to create and test novel drug combinations with minimal resistance, establishing a preclinical pipeline to advance new treatments through Phase I trials.
The project also integrates a Knowledge Generation Pathway (KGP), leveraging in vitro, in vivo, and imaging studies with modelling activities to optimize drug development. Data management is a priority, ensuring research findings remain accessible for future studies through platforms like TB-PACTS (clinical data) and TB-APEX (preclinical data).

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

By its fifth year, ERA4TB has reached significant milestones:

• Eleven anti-TB compounds are in preclinical development, with nine progressing towards clinical trials.

• One compound completed its clinical trial ahead of schedule due to effective industry-academia collaboration.

• The Drug Development Information Management System (DDIM) has expanded, incorporating advanced imaging data from techniques like time-lapse microscopy, MALDI, CT, and PET.

• TB-PACTS and TB-APEX have grown to 33 and 68 data sources, respectively, with TB-APEX now publicly available.

• The Host-Pathogen Interaction (HPI) platform is fully operational, and seven partner laboratories have adopted the EUCAST reference method for drug activity assessment.

• Magnetic resonance imaging (MRI) is being introduced to enhance biomarker identification for clinical translation.

• A new single-cell transcriptomics initiative (Task 4.6) aims to improve TB lesion analysis and treatment evaluation.

• AI and in silico modelling are optimizing data integration, leading to better biomarker identification and experimental design.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

ERA4TB has established a European Open Platform with advanced experimental capabilities to accelerate anti-TB drug development. The project manages the most extensive anti-TB compound pipeline in antibacterial research, having completed two clinical trials.

Key advancements include:

• A robust preclinical development network and Clinical Trials Units (CTUs) for high-quality FTIH trials.

• Introduction of the first BSL-3 Hollow Fibre System in Europe, recognized as a key innovation by the European Commission’s Innovation Radar.

• Standardization efforts, such as EUCAST adoption for MIC determination, improving regulatory in vitro studies.

• Cutting-edge in vivo platforms, including Non-Human Primate (NHP) studies, enhancing translational research.

• AI-assisted imaging techniques, including MRI, to improve infection tracking and biomarker identification.

• Model-guided in vitro and in vivo experimental designs, integrating pharmacometric modelling and AI for optimized data analysis.

Ensuring long-term knowledge accessibility, ERA4TB continues expanding its data repositories. TB-PACTS and TB-APEX now include 101 data sources, supporting external researchers via the Access Review Committee. This initiative ensures ERA4TB’s impact extends beyond its duration, benefiting the global TB research community and contributing to worldwide efforts against TB and AMR.

Figure 1. Global TB milestones and targets: latest status (who TB Report, 2024)