Speakers

A critical step in developing a quality drug product is the understanding of its in vivo, clinical, performance. Quantitative biopharmaceutics aims to understand the relationship between drug compound physicochemical and dosage form properties and it's behavior in the clinic, typically assessed by its pharmacokinetic profile. Given the complexity of this relationship, it's often difficult to capture it based on a single test. Thus integration of data from different scientific disciplines is key to achieving this goal. Rich datasets can be used to develop both general formulation strategies or to provide answers to compound specific questions, often by incorporating them into a structured model such as physiologically based pharmacokinetic modeling. The presentation will discuss how this integration of data facilitates formulation development with examples both for oral and parenteral modalities.

Advances in high throughput DNA sequencing, and more recently Next Generation Sequencing, have enabled researchers to develop DNA-recorded combinatorial synthesis schemes that generate DNA-Encoded Libraries (DELs) that exceed 1 Trillion members. Library compounds that bind to a target of interest are isolated from these DELs through affinity selection experiments in a manner similar to those used to evolve high affinity peptide ligand sequences with phage display. However, DEL technology differs from the phage display in that there is no library amplification step in the procedure. Thus, the design of these affinity selection experiments is of critical importance to ensure that we isolate library members that represent good starting points for drug discovery. This seminar will describe our internal DEL platform, investigations into the fundamental biochemical principles that govern DEL selection and the application of this technology for small molecule ligand discovery at Pfizer.

Link to Dr. Foley's Biography

Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. Taking advantage of recent clinical development advances and rapid growth in GWAS datasets, we extend the original work using updated data, test whether genetic evidence predicts future successes and introduce statistical models adjusting for target and indication-level properties. We present an extensible framework that lends itself to future developments and refinements with low barrier to entry.

Link to J. Wade Davis Biography

Mesenchymal Stromal Cells are living cell pharmaceuticals that have been the subject of clinical trials for more than a generation. The outcomes of advanced clinical trials have fallen short of expectations raised by encouraging pre-clinical animal data in a wide array of disease models. Important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted and analysis of clinical trial failures and successes provide a rational pathway to FDA regulatory approval.

Link to Jacques Galipeau's Biography