Introduction
The PREDICT-Meso Accelerator Network (35 institutions, 8 countries) aims to define the biology driving malignant pleural mesothelioma (MPM) evolution and develop targeted therapies. We provide an update on Meso-ORIGINS (MO), the primary vehicle for prospective tissue collection and risk prediction.

Aims
MO will generate a longitudinal cohort of patients with asbestos associated pleural inflammation (AAPI). The primary objective is to generate ? 63 benign-MPM tissue pairs (projected evolution rate 14% (95% CI 10.5-19.2) based on a prior feasibility trial). Secondary objectives are (a) generation of a multiomic risk prediction model (b) characterisation of intra-patient heterogeneity using multi-region thoracoscopic biopsies.

Methods
Arm A will recruit 500 AAPI patients and perform 6-monthly surveillance for 2 yrs. Suspicion of MPM evolution will prompt repeat pleural biopsy and banking. Arm A includes baseline risk profiling via serum proteomics, exhaled breath metabolomics +/- perfusion MRI. Arm B will address heterogeneity by recruiting patients with suspected MPM undergoing thoracoscopy (n=39)

Results
MO opened in July 2022 (planned 3.5yr recruitment). At submission, 17 UK centres are open (9 in setup). 37/500 and 26/39 patients have been recruited to Arms A and B, respectively. 2/30 Arm A cases with ? 1-month follow-up have evolved into MPM, making the current evolution rate 6.7% (95% CI 0.7-22.4). 5/26 Arm B cases have a confirmed MPM diagnosis with a mean (SD) of 5.2 (0.8) multi-region biopsies collected.

Conclusions
MO is collecting paired tissues that are critical for downstream PREDICT-Meso work packages focused on target identification, pre-clinical models and drug development.