Lead Optimization: Robust and Thoughtful Early Safety Involvement Is Needed

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On Sunday March 12, 2018, I attended the very informative Continuing Education (CE) course "Lead Optimization of Therapeutic Small Molecules: From Drug Target to Clinical Candidate Selection—Strategies and Decision Making," endorsed by SOT Drug Discovery Toxicology, Cardiovascular Toxicology, and In Vitro and Alternative Methods Specialty Sections.

The course was very well-received and had a room full of attendees. It provided an extensive overview of the strategies and approaches leading from drug target selection to lead identification, optimization, and selection of clinical candidates for first-in-human studies. The main message is that robust and thoughtful early safety involvement would reduce attrition in later phases of drug development. Six different topics were covered during the course.

  • Rebecca Erikson, Denali Therapeutics, Inc., addressed safety considerations in target selection.
  • Zoe Zhong, Genentech, Inc., focused on increasing selectivity and minimizing off-target effects.
  • Derek Leishman, a cardiovascular expert from Eli Lilly and Company, outlined strategies for assessment of cardiovascular safety during lead optimization.
  • Maik Schuler, Pfizer, Inc., discussed strategies for early mechanistic genetic toxicology screening.
  • William Proctor, Genentech, Inc., talked about assessing hepatotoxicity risk in drug discovery.
  • Mark Fielden, Amgen Inc., talked about an integrated assessment of in vitro and in vivo toxicology studies for the rapid identification of clinical candidates.

All presentations focused on the practical aspects of implementing de-risking strategies, and the presenters provided relevant examples to illustrate these approaches. Overall, the audience was left with a good understanding of how to address safety for small molecules from the inception of a program to candidate selection into investigational new drug (IND)-enabling studies.

Editor's Note: This Continuing Education course was recorded and will be available as part of CEd-Tox, the SOT online Continuing Education program, in May 2018.

This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email SOT Communications Director Michelle Werts.

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