Optimizing Radiosynthetic Yield of [18F]FTT For Wide-Spread Distribution

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ABSTRACT: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi’s) have emerged as important new therapeutic agents targeting a broadening class of gene mutations present in breast, ovarian, prostate and a host of other cancers. These drugs have been targeted to patients and/or tumors with BRCA-related gene mutations, but not all patients whose tumors have these mutations respond to PARPi. Equally important, this approach misses patients who may benefit from PARPi since tumors without BRCA-related genes may respond. Trevarx Biomedical Inc.’s (Trevarx) first licensed product, [18F]fluorthanatrace ([18F]FTT), is a PET-labeled analog of the PARPi rucaparib, and provides quantitative images of regional PARP expression. Early clinical trial data in ovarian and breast cancer carried out at the University of Pennsylvania (Penn), Washington University in St. Louis (WU) and MD Anderson Cancer Center (MDACC) support the accuracy of [18F]FTT tumor uptake as an in-vivo measure of regional PARP1 drug binding and indicate its potential as a more effective PARPi imaging predictive biomarker. [18F]FTT has an established body of published academic research and a 2-3 year lead over other competitive PET PARPi imaging agents that have only recently completed first-in-human studies. Trevarx has the goal of making [18F]FTT widely available for clinical use as a companion diagnostic for PARPi therapy. Partnering with MDACC, Penn, and WU, Trevarx is developing a Phase 2 multi-center clinical trial in breast cancer that will lead to a subsequent Phase 3 trial to support an [18F]FTT NDA. To support this goal, Trevarx must develop the validated GMP synthesis and testing for [18F]FTT that is required to support eventual commercial production for Phase 3 trials and NDA submission. This Phase 1 STTR proposal by Trevarx and Penn will determine the best method for synthesizing [18F]FTT for widespread distribution by maximizing product consistency and production yield with the following aims: (1) Evaluate the synthesis yield and production robustness of [18F]FTT using two common GMP-compliant chemistry modules via two different synthesis routes; and (2) test the feasibility of simplifying [18F]FTT purification using solid-phase extraction methods. Completion of these aims will result in an optimized synthesis platform that will lead to a Phase 2 STTR effort to roll out a training and compliance program to sites that will participate in Phase 2 clinical trials and develop [18F]FTT for production with a commercial PET radiopharmaceutical supply partner to assure broadly available tracer supply for Phase 3 multi-center trials and prompt clinical rollout after drug approval.