Dana-Farber’s Dr. Eric Fischer and Deerfield’s Frank Nestle on breakthroughs in targeted protein degradation
Deerfield Partner and 3DC CEO Frank Nestle, MD, PhD, sat down with Dana-Farber’s Eric Fischer, PhD, to discuss one of oncology’s most exciting new modalities: targeted protein degradation.
Eric Fischer is a professor at Dana-Farber Cancer Institute and Harvard Medical School, where he directs the Chemical Biology Program and leads a translational research lab focused on the mechanistic foundations of protein homeostasis and drug discovery.
From the seminal discovery of thalidomide’s mechanism of action all the way to Deerfield and Dana-Farber founding a dedicated Center for Protein Degradation in Boston, learn how Eric’s question-driven approach to basic science informs how he thinks about targets, translational potential, and time management.
✨ Key Insights ✨
🔬 A puzzle solved, piece by piece
Despite evidence for clinical proof of concept around targeted protein degradation, the field was missing a thorough understanding of what was going on at a mechanistic level. Several labs worked in parallel on key pieces of the puzzle, and in 2014, Eric and collaborators helped complete it, proving that thalidomide and its derivatives work by reprogramming ubiquitin ligases to degrade disease-driving transcription factors.
🔓 Drugging the undruggable
Unlike traditional small molecules, molecular glue degraders don't require a well-defined binding pocket on their target protein - they can engage surfaces that would have been entirely off-limits to classical medicinal chemistry.
In Eric’s words: “This unlocked targets like Ikaros and Aiolos that no way you could have convinced a chemist beforehand to think about making a molecule."
🏗 A new model for academic drug discovery
Eric built a thoughtfully composed lab at Dana-Farber to merge rigorous basic science with early drug discovery execution. He credits this (and the Center for Protein Degradation, a Deerfield-funded laboratory that was embedded within Dana-Farber), with allowing him to scale his impact in ways a traditional academic lab could not.
🧬 From center to clinic
One company born from the Center for Protein Degradation is Neomorph, a molecular glue-focused biotech whose first-in-class ARNT degrader targeting clear cell renal cell carcinoma recently entered the clinic, allowing Eric to draw a direct line from his academic work to a therapy under evaluation in the real world.
☎ Advice for the next generation
Eric’s guidance for aspiring drug hunters? Surround yourself with people who've done it before, pick partners who understand the science, and never stop asking whether the questions you're pursuing are still the right ones.
Deerfield's current collaboration with Dana-Farber, Riverway Discoveries, is designed to pair scientific rigor with creative funding structures that aim to carry early discoveries across the translational gap and into the hands of patients.
This edition of the Discovery @ Deerfield newsletter and the interview herein (collectively, the “Content”) are provided for informational purposes only and do not constitute an offer to sell or a solicitation of an offer to buy any security or to participate in any investment strategy with any funds, vehicles, or accounts sponsored or managed by Deerfield Management Company, L.P. (“Deerfield”) or its portfolio companies. Nothing herein constitutes investment, legal, or tax advice. The Content is not directed to prospective investors and is not intended as marketing of any Deerfield fund, vehicle, or account. The views expressed are those of the interviewee and do not necessarily reflect those of Deerfield. Eric Fischer, Ph.D. is not a client of Deerfield or an investor in any Deerfield investment vehicle, and no direct or indirect compensation has been provided in exchange for his statements. Dr. Fischer serves on the board of directors of, and in other executive or advisory capacities for, certain Deerfield portfolio companies and has personal financial interests in such companies. As a result, Dr. Fischer has an incentive to make positive statements about Deerfield, its investment vehicles, and affiliates, and his views may be influenced by these relationships. Deerfield makes no representation or warranty as to the accuracy or completeness of the Content, which is subject to change without notice. Past performance is not indicative of future results, and no assurance can be given that any investment will be profitable.