Problem Statement: Although the volume of Proteolysis Targeting Chimeras (PROTAC) and targeted protein degrader-based therapeutic development programs has grown over the past several years, there is limited public discussion or scientific consensus on the application of rigorous, consistent, and effective methods for assessment of their clinical safety. As a result, the progress of these programs and their ability to support critical patient populations safely and efficiently has opportunity to be enhanced.
Null Hypothesis: To aid with ensuring the clear outcome of the workshop we will structure the meeting around a null hypothesis. The null hypothesis we will be testing is “the nonclinical safety evaluation of PROTAC/Molecular Glue based therapeutics does not differ from that of small molecules in any systematic way (for oncology and/or non-oncology indications)”.
Meeting Goal: The goal of this workshop is to discuss the preclinical and translational safety assessment of proteolysis targeting chimeras (PROTACs) and molecular glues, focusing on 6 topics as described based on sessions below. To this end, we have recruited speakers and attendees from institutions working actively in the area of PROTACs and molecular glues. The participants who have thus far agreed to help develop each of these sessions are listed here although the actual speaker list is not yet confirmed. It is anticipated that most of the session will be reserved for discussion rather than presentation.
Anticipated Attendance: This think-tank style meeting will be invitational and will engage representatives from the organizations sponsoring the event, those academic, clinical, and government scientists involved in the event design and other invited experts and stakeholders. At present there are approximately 40 scientists (from academia, government, and industry) involved in the planning and design of this event. Total attendance is anticipated to be approximately 250 attendees.
Workshop Outputs: The event will be summarized in a short summary white paper and/or other communication materials for the participants. If feasible, a manuscript highlighting key workshop recommendations, gaps and opportunities will be developed and submitted for peer-review. This workshop may be a single time event or could result in the recommendation to create an ongoing forum for discussion and scientific resolution of the issues that are raised during the event.
Regulatory Panel: In the last session we will have a panel of regulators familiar with the assessment of PROTACs and Molecular Glues. Panelists will provide their opinion (not necessarily that of their organizations) on key questions and challenges that have arisen in the meeting.
Point of Contact: For more information about the event please contact the program lead, Connie Mitchell (email@example.com), HESI Scientific Program Manager or Dr. Syril Pettit, HESI Executive Director (firstname.lastname@example.org)