Benjamin Levine Ebert, MD, PhD
President and CEO, Dana-Farber Cancer Institute
Richard and Susan Smith Professor of Medicine, Harvard Medical School
For patients whose cancers lack effective targeted treatments—or whose tumors return after standard therapies—a new therapeutic strategy that originated at the Dana-Farber Cancer Institute may offer hope. Eric Fischer, PhD, and his colleagues have pioneered an approach that goes beyond blocking cancer-causing proteins by eliminating them altogether.
Fischer’s research centers on molecular glue degraders, a class of small molecules that prompt cells to dispose of harmful proteins. Rather than inhibiting a protein’s activity, these compounds trigger the cell’s natural cleanup machinery to remove the protein entirely. This strategy opens new possibilities for treating cancers driven by targets that have long resisted traditional drug development. This technology, developed by Fischer and coworkers, has been licensed to Neomorph, a biotechnology company formed via a collaboration between Dana-Farber’s Center for Protein Degradation and healthcare investment firm Deerfield Management, to advance the science towards new cancer therapies.
From Unexpected Insight to Deliberate Strategy
The origins of Fischer’s work trace back to thalidomide, a drug infamous for causing birth defects in the 1950s but later found to be effective in certain blood cancers. Years after its initial use, scientists discovered that thalidomide works in an unusual way: instead of simply blocking a protein’s function, it causes specific disease-related proteins to be eliminated. After uncovering the structural basis of how thalidomide interacts with the human waste disposal system, Fischer joined Dana-Farber in 2015, driven by the recognition that this unexpected behavior pointed to a much broader opportunity. Could this mechanism be intentionally harnessed—and systematically expanded—to target cancer-driving proteins that had long been considered “undruggable”?
Working closely with collaborators, including Benjamin Ebert, MD, PhD, now President and CEO of Dana-Farber, and Nathanael Gray, PhD, formerly of Dana-Farber, who now serves as Co-Director of Cancer Drug Discovery at Stanford Medicine, Fischer set out to turn this insight into a reliable drug discovery approach. Their goal was not to pursue a single target, but to understand the underlying rules that govern how molecular glues work.
Establishing a Scientific Foundation for Protein Degradation
Foundational studies led by Fischer and collaborators revealed the basic principles of how small molecules can redirect the cell’s natural waste disposal system. Early work featured in Nature in 2014 showed that thalidomide-like compounds could make an E3 ligase (part of the machinery that tags proteins for destruction) recognize entirely new targets. Building on this early insight, later structural studies, including one in Elife in 2018 and another in Natural Chemical Biology in 2021, explained how this occurs: molecular glues act like connectors, stabilizing an interaction between a harmful protein and an E3 ligase that would not normally pair up. These discoveries demonstrated that protein degradation triggered by small molecules is not a random phenomenon, but one governed by understandable rules of shape, fit, and binding.
As the field advanced, the researchers also found that small chemical changes could strengthen or redirect these interactions (Cell, 2020), and that structural and computational tools could help map how different glues influence ligase–target pairing (Nature Communication, 2025).
Together, these studies established a clear scientific foundation: molecular glue degraders work through definable, adjustable principles. This growing understanding set the stage for Fischer and colleagues to begin building a systematic approach—one that could eventually be scaled, optimized, and translated beyond individual examples.
“Once we understood how [glue degraders] worked, our focus shifted from whether it was possible to how broadly and reliably it could be applied.”
Eric Fischer, PhD
Why This Matters for Cancer Treatment
Taken together, these discoveries raised an important question: what might they mean for cancer treatment? To find the answer, it’s important to understand that traditional cancer drugs are designed to interfere with a protein’s activity, often by binding to a specific site on its surface. While this approach has led to many successful therapies, it has clear limitations. Many cancer-driving proteins lack features that drugs can easily target, leaving critical disease mechanisms out of reach.
Molecular glue degraders take a different approach. By eliminating harmful proteins entirely, they offer a way to shut down cancer-promoting pathways at their source. This strategy may also help address one of the most persistent challenges in oncology: drug resistance. Cancer cells frequently adapt to therapies by mutating drug targets or activating alternative survival pathways. Removing a disease-driving protein altogether may make it harder for tumors to evade treatment.
“Once we understood how this mechanism worked, our focus shifted from whether it was possible to how broadly and reliably it could be applied,” Fischer says.
From Academic Discovery to Translation
As the science matured, Fischer and his colleagues worked to ensure the approach could move beyond the laboratory. In collaboration with Deerfield, they established the Center for Protein Degradation at Dana-Farber.
Through the Center, “we aimed to create a compelling avenue for academics and investors to come together and bring promising science through what is often called the ‘valley of death’ – the long, risky period where preclinical advancements very often fail to reach real-world patients,” says Cam Wheeler, Partner at Deerfield.
In order to further scale the technology and conduct the size and type of trials needed to develop the kind of therapies that could actually reach patients, the technology was licensed to Neomorph, a company that was formed as a spinout from the Center.
“Working closely with Eric and his collaborators, we were proud to spearhead the effort to spin this promising technology out of the academic lab and into what is today a thriving biotechnology company,” adds Wheeler.
Today Neomorph continues to train its focus on targeting the underlying drivers of disease rather than leveraging well-worn pathways.
“Molecular glues have already demonstrated incredible value in the clinic, and I believe this modality will continue to provide opportunities for genuinely transformational cancer therapies,” stresses Phil Chamberlain, Chief Executive Officer of Neomorph. “Co-founding Neomorph gave me an opportunity to work with world- leading academics in the space, who are also thoughtful partners and advisors.”
Looking Ahead
Neomorph’s programs are currently in early clinical or preclinical development, but the company’s long-term vision is clear: expand the druggable landscape, combine new protein-degradation strategies with existing therapies, and bring meaningful options to patients who urgently need them.
For Fischer, the work represents a shift in how cancer drugs can be conceived—not simply as inhibitors, but as tools to remove disease at its molecular roots. If successful, this approach could redefine what is possible in cancer therapy and extend the reach of precision medicine to patients who currently have few options.
Team Members: Benjamin Ebert, MD, PhD, Nathanael Gray, PhD, Eric Fischer, PhD
Team Members
Nathanael S. Gray, PhD
Professor of Chemical and Systems Biology, Co-Director of Cancer Drug Discovery, Stanford Medicine
Former Principal Investigator, Dana-Farber
Eric S. Fischer, PhD
Principal Investigator, Department of Cancer Biology, Dana-Farber
Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
