Drug Discovery in Translational and Clinical Research Programs of the University of Michigan Comprehensive Cancer Center (UMCCC) & Centers for Discovery of New Medicine & Chemical Genomics

Baker L, Tewari M, Groppi V, Wang S, Leopold J

UMCCC launched a new joint project between its developmental therapeutics program and its translational and clinical research programs. The aim is to advance novel UMCCC clinical candidates into early phase I, IB and II trials.  Our first-in-human trials will seek a safe and effective dose/schedule and increase pharmacologic and biologic understanding along the dose -escalating schema.  Importantly, our clinicians who were part of the preclinical team will be advocates for the drug in its clinical development.  Features of this program include genomic interrogation using MIOncoSeq, a 1700  gene deep sequencing program developed at Michigan; target engagement and and precision imaging will be used for initial  efficacy. We will also use monitoring of cell-free tumor DNA in plasma as a liquid biopsy approach to monitor response to treatment over time.  The developmental therapeutics program includes several successful discovery labs.  Until now the model used is to seek a partnering relationship with preclinical data.  The alternative new model seeks to partner with a drug company after the successful phase 1 trial.  Currently 8 compounds are undergoing lead optimization while 6 are in preclinical development (MTX211-EGFR/PI3K; UM164-SRC/P38; SC144gp130; ZBC11-BETi; QCA570-BET degrader; CJ-2575-BCL2.) Six drugs from these discovery labs are currently in the clinic (ATR101-ACAT; SM406 cIAP;Mi773-MDM2; SM1387-cIAP/XIAP;AA115-MDM2 and BM1252-BCL2/XL.)  Our center has a dedicated phase 1 research unit with capabilities including: timed blood, urine, PK/PD sampling; investigational drug accountability/compliance; and clinical trials bank processing, storage and shipping.  Our team-based strategy addresses the care of the patient and the science of the drug.