PROJECT SUMMARY/ABSTRACT DISCOVERY & DEVELOPMENTAL THERAPEUTICS PROGRAM The Discovery and Developmental Therapeutics (DDT) Program accelerates discoveries that drive cancer diagnosis, detection, drug delivery, and therapeutic approaches with the premise that multidisciplinary interactions among DDT members will advance highly innovative anti-cancer strategies. The program includes three scientific themes: (1) Discovery, the discovery and evaluation of therapeutic targets and novel small molecules; (2) Cancer Imaging, the development and/or utilization of in vivo imaging agents and technologies for non-invasive diagnostic/therapeutic cancer applications; and (3) Developmental Therapeutics, human interventional cancer trials using novel therapies and individualized treatment options by functioning as a convergence point for translation of targets, imaging, therapeutic agents, and immunotherapies. The productive bench to bedside research of DDT members furnishes a rich training environment for the next generation of cancer researchers with integrated activities to promote biomedical science careers of under-represented groups. Strong engagement with Community Outreach and Engagement (COE) drives prioritization of catchment area needs in DDT programming and member research. The three scientific themes with COE priorities guide the program’s activities and intra- and inter-programmatic research. Under the leadership of Haian Fu, PhD (leader) and Kelly Goldsmith, MD (co-leader) the DDT Program includes 55 core members from 13 different Emory departments who published a total of 1,272 cancer-relevant scientific articles during the current funding period. Of these, 420(33%) were intra- and 373(29%) were inter-programmatic collaborations; 898 (71%) involved a collaboration with another cancer center or academic organization and 354(28%) were published in journals with an impact factor ≥10. As of December 31, 2021, DDT members held $20.4 million (direct) in annual cancer-relevant research funding, of which $6.9 million is peer-reviewed with $4.5 million (65%) from the NCI. Notable new team science funding includes the NCI P50 Lung SPORE (MPI: Ramalingam, Fu), successful renewal of NCTN Lead Academic Participation Site Award (UG1CA233247) in 2019 (MPI: Higgins, Saba, Staley), one of twelve NCI/VA Navigate awards (Harris) to promote clinical trials accruals at the Atlanta VA medical center, and NCI Cancer Target Discovery and Development (CTD2) network award (U01CA217875). Impactful DDT scientific contributions over the past funding cycle include: i) Discovery and development of MER-TK inhibitor MRX-2843 into a first in human Phase I clinical trial, ii) DDT discovery to FDA approval of radiopharmaceutical fluciclovine for recurrent prostate cancer, iii) FDA approval of Abatacept for acute graft versus host disease prevention and iv) leadership of multiple NCTN trials including Phase III trials that ushered in new treatment paradigms for cancer. Built on Wins...