Validation of a microrna panel to pre-symptomatically predict the risk of radiation-induced fibrosis

Chromologic LLC received a $533,384 Cooperative Agreement from the National Institutes of Health (NIH) Office of the Director under the Trans-NIH Research Support program (CFDA 93.310), awarded September 2, 2025, with completion targeted for August 31, 2030. The company, in collaboration with Dr. Diana Gage, M.D. at the Greater Los Angeles Veterans Administration Medical Center and UCLA, is developing and validating the MIDOS assay—a microRNA (miRNA)-based predictive diagnostic tool designed to identify individuals at risk for radiation-induced lung injury prior to symptom onset. The assay analyzes a panel of four circulating miRNA sequences from plasma samples collected 15-30 days post-radiation exposure and leverages profibrotic signaling pathways (TGF-β and BMP) associated with pulmonary fibrosis development.

The funded research activities include validation of the MIDOS assay in a larger patient population (N=100) of lung and breast cancer patients undergoing radiotherapy, with an initial validation cohort demonstrating strong performance (area under ROC curve = 0.85). Additionally, the project will assess cancer's impact on baseline miRNA levels, evaluate longitudinal miRNA dynamics following radiation treatment, identify potential confounders affecting panel miRNA, and determine whether an expanded miRNA panel improves assay specificity and sensitivity. These deliverables are intended to advance the clinical development pathway of this diagnostic technology following preliminary FDA feedback from a pre-submission meeting in April 2022.

Abstract

Chromologic has identified a small panel of four circulating microrna (mirna) sequences that can be used to predict the onset of radiation-induced lung injury from plasma samples taken approximately 15-30 days post- exposure. These mirnas are linked to genes associated with profibrotic signaling pathways (e.g., TGF-β and BMP signaling) that are differentially regulated in fibrotic lung tissue following radiation exposure. A bayesian predictive model (the midos assay) was developed using this panel through the analysis of mouse (n = 128), non-human primate (n = 67), and human (n = 303) mirna responses to irradiation and longitudinal assessment of pneumonitis and fibrosis. An initial assessment of the midos assay in human patients (n = 21) was performed at the greater LOS angeles veteran's administration medical center (VA) in lung and breast cancer patients that received radiotherapy (RT) suggested the midos assay had good performance in this patient population (area under the ROC curve = 0.85). Based on feedback from the FDA following a pre- submission meeting (april 2022 Q230171) discussing the midos assay, chromologic and DR. Diana gage, M.D. (VA/ucla) propose to advance the development of this mirna-based predictive assay for radiation- induced lung injury by (i) validating the performance of the assay in a larger patient population (n = 100); (II) assessing the impact of cancer on baseline mirna levels; (III) assessing the longitudinal dynamics of mirna abundance following radiation treatment; (IV) evaluating the impact of potential confounders on panel mirna; and (v) evaluating the impact of an expanded mirna panel on the specificity and sensitivity of the assay.