Formulation and Delivery
Robert Abel, PhD (he/him/his)
Chief Scientific Officer, Platform
Schrödinger
BROOKLYN, New York
Naveen Thakral, PhD
Senior Director, Pharmaceutical Sciences
Schrodinger, Inc. USA
New York, New York
The efficient discovery and development of high-quality clinical candidates remain hampered by late-stage failures, often arising from unforeseen toxicity or suboptimal physicochemical properties. To address these persistent challenges, we are developing and deploying an integrated suite of advanced computational tools designed to accelerate the design-make-test-analyze cycle and increase the probability of success. This presentation will detail several new and emerging scientific advances that are transforming the path from initial hit to a viable development candidate. Central to our strategy is the development of predictive, structure-based in silico ADMET panels, conceived as computational analogues to standard experimental assays. These models allow for the critical assessment of off-target liabilities and other key properties early in the discovery process. We then leverage these predictive models within an ultra-large-scale de novo design platform to generate and prioritize novel molecular structures optimized against multiple objectives simultaneously. A case study on Wee1 kinase will be presented to highlight how this integrated approach was used to successfully ideate novel matter and resolve a challenging kinome-wide selectivity issue. Finally, we demonstrate the extension of these technologies beyond candidate selection to address critical drug development challenges. We will present cutting-edge methods for prospectively predicting small molecule crystal structure polymorphs and their relative stabilities, along with techniques for accurately estimating polymorph-specific aqueous solubility. Collectively, these integrated computational strategies provide a powerful, holistic approach for accelerating the design, optimization, and successful development of promising new medicines.