Research Project
9674882
Core C Summary The translational core (Core C), will provide operational support and strategic scientific, regulatory, preclinical, and clinical guidance to all Center Projects. Core C will assist projects in establishing Target Product Profiles and Development Plans for advancing their compounds toward the clinic. The Core will provide support to Projects 1?3 in executing these Development Plans, for example in conducting non-GMP and cGMP active pharmaceutical ingredient (API) generation, drug substance stability testing, advanced in vivo pharmacokinetics (PK) dose ranging studies, and studies of absorption, distribution, metabolism, and excretion (ADME), human dose projection, and non-GLP and GLP (Good laboratory practice) preclinical toxicity and safety assessments, with the ultimate delivery of two Investigational New Drugs (IND). Activity 1 focuses on preclinical candidate selection with dose escalation PK studies and metabolite identification. These studies will identify animal species which show similar metabolite profiling to the human metabolite profile, select appropriate doses for the non-GLP safety evaluations, and determine efficacious exposures and pharmacodynamic drivers of efficacy in in vitro and animal studies to perform an initial human dose and exposure projection. Activity 2 The appropriate project and core teams may nominate an evaluated compound for entry into preclinical development (IND-enabling studies). The Center Scientific Advisory Committee (SAC), in consultation with experts from the leadership of Cores A, B, and C, as well as the project leaders and Center PI, will evaluate the nominated compound against the criteria of the Preclinical Development Candidate described in the Overall CETR description. Should the nomination be endorsed, a program of IND-enabling activities will be initiated, followed by the preparation of the IND and electronic submission to the FDA. During this phase, in collaboration with Core B and Project 4, the human dose projection will be optimized. As in Activity 1, all IND-enabling activities will be conducted through Core C with direction by Core C leadership in collaboration with the appropriate project leader.
