Ep187: Eric Fischer on Creating a New Class of Medicines

Episode Summary

Executive Summary: Eric Fisher traces his path from a curiosity-driven childhood in Germany to becoming a leading expert in targeted protein degradation at Dana-Farber. He explains how thalidomide’s mechanism, CRBN biology, and molecular glues transformed “undruggable” targets into viable therapeutic opportunities, while emphasizing that basic structural biology, industry collaboration, and the right people are essential to turning discoveries into medicines.

Main Topics: From Germany to structural biology (Priority: 5/5): Fisher describes a free-range childhood in Hamburg, early interests in biology, math, programming, and building things, and how a structural biology lab in Basel sparked his career path. Thalidomide as the proof-of-concept moment (Priority: 5/5): He recounts how studying thalidomide and cereblon led to the realization that the drug works by inducing degradation of transcription factors, helping establish targeted protein degradation as a real therapeutic class. The rise of targeted protein degradation and molecular glues (Priority: 5/5): The conversation explains PROTACs and molecular glues, how they differ, and why glues can reach previously inaccessible intracellular targets through composite binding surfaces. Academic discovery meets translational biotech (Priority: 4/5): Fisher outlines why some science can remain in academia while drug development needs biotech/pharma resources, and how that logic shaped the Dana-Farber/Deerfield Center for Protein Degradation. Building companies and selecting projects (Priority: 4/5): He discusses Neomorph and other spinouts, criteria for advancing a project, and how he decides whether a target belongs in an academic lab, startup, or pharma partnership. Broader therapeutic implications (Priority: 4/5): Fisher argues targeted protein degraders could expand druggable biology in oncology and autoimmunity, much like monoclonal antibodies expanded surface-targeting decades ago. People, mentorship, and philanthropy (Priority: 3/5): He credits mentors, collaborators, and organizations like Damon Runyon for enabling early work, and reflects on why he chose to join the Kilimanjaro traverse fundraiser.

Key Arguments: Basic discovery is the foundation of applied drug development; without understanding mechanism, intervention design is weak. Thalidomide and related molecules provided clinical proof that targeted protein degradation is feasible in humans, accelerating the whole field. PROTACs are powerful but chemically challenging because of size and drug-like property tradeoffs; molecular glues are smaller and may be more drug-like, but are less rule-based and often discovered serendipitously. Not every promising idea should stay in academia; manufacturing, optimization, and clinical development often require biotech/pharma infrastructure. The most important criterion for a project is whether a clear biological hypothesis predicts meaningful clinical benefit early enough to justify investment. Targeted protein degraders could be transformative beyond cancer, especially for autoimmune diseases where key pathways converge on transcription factors and transcriptional programs. Progress in the field depends as much on people and collaborative environments as on technology and funding.

Data Points: Dana-Farber / Deerfield Center funding: $80 million - Investment used to launch the Center for Protein Degradation in 2018. PhD timing: 2010-2014 era - Fisher describes the thalidomide mechanism work culminating in a series of papers in 2014. Early lab support: 1st attempt NIH R01 funded - He said he submitted an R01 expecting it not to get funded, but it was funded on the first attempt. Laboratory setup timeline: ~10 years - He notes it will be 10 years in October since arriving at Dana-Farber. Thalidomide tragedy: 10,000 children - He references the number of children born with severe birth defects linked to thalidomide. Civil service / alternative service: 14 months - In Germany, he spent a year working in a psychiatric hospital as alternative service. Center creation year: 2018 - The Dana-Farber/Deerfield Center for Protein Degradation was launched with Deerfield funding in 2018. Summer lab time: 1-2 weeks - He says he tries to spend one or two summer weeks with no meetings and just do experiments.

Pivotal Quotes: "We just have to try hard enough." — Eric Fisher: On how previously undruggable targets like KRAS and transcription factors became addressable. "It was the clinical proof of concept for an entirely new class of drugs." — Eric Fisher: Describing how thalidomide/lenalidomide’s mechanism changed the field of targeted protein degradation. "I think it has the potential to play a similar role to monoclonal antibodies." — Eric Fisher: On the future impact of targeted protein degraders in expanding druggable biology.

Implications: Targeted protein degradation is moving from conceptual breakthrough to clinical reality. For scientists and investors, the field rewards mechanistic depth, structural insight, and disciplined project selection. For patients, it could open treatment options for previously inaccessible disease drivers in cancer and autoimmunity.