A decision was made to halt development on a high value target due to mechanism related safety challenges. Subsequent to that decision, two competitor molecules showed a modest therapeutic window in the clinic, despite not showing any selectivity in vitro and in cellular assays. It was unclear which properties to optimize to produce a differentiated best-in-class molecule with an improved therapeutic window.
- Built a systems pharmacology model of competitor compounds
- Identified potential contributors to therapeutic window
- Worked with the team to identify compounds and experiments to validate the mechanism
- Determined the best-in-class compound profile
- A molecule matching the best-in-class profile has been advanced to preclinical development
- Convinced management to support a program despite being years behind the frontrunners
- Accelerated timelines to deliver a truly differentiated best-in-class compound