Mark Kelley

My studies have focused on the enzyme apurinic/apyrimidinic endonuclease 1/ Redox effector factor-1 (APE1/Ref-1)—mechanistically as well as a therapeutic target in cancers and other diseases such as eye (DR, DME, AMD), Inflammatory Bowel Disease (Ulcerative Colitis and Crohn’s) and Necrotizing Enterocolitis (NEC). APE1/Ref-1 is unique to the Base Excision Repair Pathway (BER), with dual repair and redox signaling functions that are crucial to cellular viability. I have concentrated on teasing apart these functions and in the process, we have discovered and have been developing redox-specific inhibitors of Ref-1. This original work was the impetus for becoming Chief Scientific Founder and Officer of Apexian Pharmaceutical targeting Ref-1 to produce new therapeutics for some of the deadliest and hardest-to-treat cancers, as well as other indications. Apexian completed a phase I clinical trial using oral APX3330 in solid tumor patients (NCT03375086). This trial established safety, expected PK, target engagement, and responses in patients in the trial. Also, a phase II trial using a APX drug we developed and licensed to Ocuphire Pharma for DR completed in 2023 (NCT04692688). Further trials with that drug are planned in retinal disease. The FDA has approved a SPA for a Phase III trial in DR. In broader terms, all the academic chairs I’ve held and the program leader and director positions I currently hold are dedicated to fast-tracking collaboration and translational research to find more effective treatments for cancer, IBD and retinal disease. I am co-directing the Cancer Drug Discovery and Development Accelerator (C3DA) program in the IU Simon Comprehensive Cancer Center (IUSCCC) and am a member of the CTSA drug discovery Drug Development to Commercialization at IUSM. In my leadership positions, I also help equip the next generation of researchers by training and mentoring graduate students, MD and MSTP students, junior faculty, postdoctorates, fellows, and post-baccalaureate students. I am co-PI of a NCI T32 Pediatric and Adult Translational Cancer Drug Discovery and Development Training Program (PACT-D3) which focuses on grooming the next generation of diverse, basic, and translational researchers with interests in cancer drug discovery and development. I am the PI of the IUSCCC ACS Institutional training grant in its 38th year. I am also a recent AAAS Science Fellow. I have been consistently funded by NIH/NCI for over 32 consecutive years.

Additionally, we are in the process of launching a new clinical stage spinout startup to advance APX3330 forward for inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis) as an oral pill. Preclinical data in multiple accepted models confirms our approach along with the compounds safety profile in humans.