ABSTRACT: Poly (ADP-ribose) polymerase inhibitors (PARPi’s) have emerged as important therapeutic agents targeting a broadening class of gene mutations approved for treatment of breast, ovarian, prostate, and other cancers. Genomic assays of BRCA-related genes and tumor homologous repair deficiency are used as companion diagnostics for PARPi therapy but have imperfect predictive efficacy for PARPi response. Trevarx Biomedical Inc.’s (Trevarx) product, [18F]Fluorthanatrace ([18F]FTT), a PET-radiolabeled analog of the PARPi, rucaparib, provides quantitative images of regional PARP expression and drug engagement for all approved PARPi’s. It can thus serve as a PARPi companion diagnostic to identify those most likely to respond to PARPi therapy, and importantly, those unlikely to respond. Over 175 patients imaged in single center clinical trials support the accuracy of [18F]FTT tumor uptake as an in-vivo measure of regional PARPi drug binding, and as an effective imaging-based biomarker of PARP-1 protein levels. A pre-IND meeting with FDA suggested that approval would require: (1) a Phase 3 tissue correlating [18F]FTT uptake and PARP-1 protein expression in tumor samples and (2) multi-center Phase 2 studies of [18F]FTT’s accuracy in predicting PARPi response. A 3-center Phase 2 trial PET-tissue comparison study has been initiated as a pilot for the larger Phase 3 trial, and striking new single- center Phase 2 results on [18F]FTT predictive accuracy strongly support Phase 2 multi-center trials under development. The focus of this proposal is to establish wide-spread radiopharmaceutical supply to support the expanded multi-center trials needed for approval and subsequent clinical translation. With a 3 year competitive lead, [18F]FTT is projected to enter a Phase 3 tracer-tissue trial and multi-center Phase 2 predictive efficacy trials to support an NDA in 2025. The steps described in this project will reduce the extended timeline for FDA approval that has been observed with previous PET radiotracers. Building on the success of our Phase I STTR project (1R41CA2612590-01), this STTR Phase II proposal by Trevarx and Penn will minimize this timeline by establishing methods for unifying radiosynthesis, maximizing product consistency and production yield, and generating a database to manage a larger supply chain for [18F]FTT. We aim to establish a new paradigm for rapid commercialization of PET radiopharmaceuticals by providing a “best practice” template by combining efforts in academic centers and commercial radiopharmaceutical supplier prior to Phase 3 to efficiently bring a novel PET radiotracer to market. Our STTR Phase II proposal establishes a roadmap to move from a single center academic trial to Phase 3 multi-center trials to efficient cGMP commercial production upon NDA approval. In this revised application, we provide more details on [18F]FTT production ( i.e., synthesis kit development and product formulation) and our strategy for the combined aca...