Molecular glue degraders are gaining traction in the clinic as well as funding from Big Pharma, with their potential to treat previously “undruggable” cancers and immunological diseases. Here are five clinical programs worth keeping an eye on.
Molecular glue degraders, known for their ability to break down disease-causing proteins, are gaining traction in the clinic and driving sizable Big Pharma deals that reflect the modality’s market potential.
Pharma giants like Bristol Myers Squibb, Novartis, Eli Lilly and Roche have poured millions into acquiring assets and partnering with smaller biotechs to develop molecular glues into treatments in areas such as cancer and immunology.
The promise of molecular glues comes down to selectivity and an ability to hit novel targets, said Robert Driscoll, senior vice president of equities research at Wedbush Securities. For drugmakers seeking pipeline prospects to make up for ongoing patent losses, these glues could pave the way to novel targets with limited market competition, he said.
“When we look at the market potential of these molecular glues, the ability to potentially tackle undruggable targets unlocks some doors,” Driscoll told BioSpace. “If you have a novel target, you have a real advantage versus other folks out there who will be fast followers. The market potential there is huge.”
Molecular glues were discovered essentially by accident in the 1950s when the morning sickness drug thalidomide—infamous for causing birth defects—was found, along with related molecules, to spur immuno-modulating interactions by degrading disease-causing proteins.
One of those related molecules—lenalidomide—went on to become the blockbuster cancer drug Revlimid from Celgene, a company that was acquired by Bristol Myers Squibb in 2019 in one of the largest pharma deals in history.
Thalidomide and its analogs are the only molecular glues currently approved by the FDA, all of them manufactured by Bristol Myers Squibb as the multiple myeloma treatments Revlimid, Thalomid and Pomalyst.
Now, the molecular glue pipeline is brimming with potential, with Big Pharmas and smaller biotechs alike betting on the promise that these molecules can offer new approaches to difficult disease targets.
Here, BioSpace takes a deep dive into five standout programs leading the way in molecular glue R&D.
BMS’ multiple myeloma relapse renegade
As the only drugmaker to have successfully developed and marketed a molecular glue protein degrader for multiple myeloma, BMS is ahead of the curve with its CELMoD program of oral therapies for blood cancers.
Among the key molecules in the company’s pipeline is CC-92480, or mezigdomide. In a Phase 3 trial, the asset, when combined with Amgen’s Kyprolis and a corticosteroid, showed improvement in progression-free survival (PFS) in patients with multiple myeloma that has returned following previous treatment.
The combination, nicknamed MeziKd, is “a follow-on from approved early-generation molecular glues” that offers an oral option for patients with multiple myeloma with potential to be best in class, according to Driscoll.
Paul Richardson, director of clinical research and clinical program leader at Dana-Farber’s Jerome Lipper Multiple Myeloma Center, in a March press release touted the drug combination as an important new regimen for patients whose cancer doesn’t respond to treatments like Darzalex or BMS’s own Revlimid.
“While treatment advances have been meaningful, far too many patients with multiple myeloma still relapse or stop responding—making the need for new options urgent,” Richardson said in a prepared statement. MeziKd “could address a key unmet need” for relapsing patients, he added.
Monte Rosa’s AI-propelled assets caught Novartis’ notice
Monte Rosa Therapeutics is among the smaller companies making a splash in this space, securing two deals with Novartis to develop molecular glues derived from the biotech’s AI discovery engine.
Novartis paid $150 million up front with the potential for $2.1 billion in milestones in a licensing agreement with Monte Rosa in 2024 to advance the latter’s molecular glues targeting the VAV1 protein. The Swiss behemoth followed that up last year with another $120 million in upfront payments and milestones that could bring deal’s total to $5.7 billion.
In clinical trials for immune-mediated and autoimmune conditions, MRT-6160 in a first-in-human trial showed VAV1 degradation greater than 90%, as well as T cell, B cell and cytokine inhibition.
Monte Rosa has also demonstrated clinical effectiveness with another molecule called MRT-2359 in patients with metastatic castration-resistant prostate cancer via a Phase 1/2 study with interim results released in December 2025. MRT-2359 is being combined in this trial with the anti-androgen medicine enzalutamide.
Monte Rosa’s AI discovery platform has allowed the company to work more quickly than basic screening approaches normally allow, Driscoll said.
“The discovery of novel targets is expanding the target space here and allowing Monte Rosa to come up with new targets and apply that to selectivity challenges, adding efficiency to the process,” he continued.
C4 touts ‘best in class’ potential for DACs
C4 Therapeutics has also caught Big Pharma’s attention with its molecular glue-based degrader-antibody conjugates (DACs)
C4 pulled in a $73 million series A financing round almost a decade ago along with a strategic collaboration with Roche. The partners followed that up in April with another licensing deal worth $20 million upfront and up to $1 billion in milestones down the road.
Together, the companies are developing cemsidomide, formerly known as CFT-7455, a molecular glue degrader that targets the proteins IKZF1 and IKZF3 to treat multiple myeloma. The drug candidate is in a Phase 2 trial following a successful early-stage study in which C4 touted high overall response rates.
“C4 is claiming best-in-class potential, and that’s very exciting for the multiple myeloma space, which doesn’t have too many oral drugs,” Driscoll said.
Neomorph and numerous partners target HIF
Another biotech with deep Big Pharma connections, Neomorph is currently running a Phase 1/2 trial of its molecular glue degrader NEO-811 in patients with locally advanced or metastatic non-resectable clear cell renal cell carcinoma.
The San Diego–based company calls the HIF signaling pathway inhibited by NEO-811 the “Achilles heel” of clear cell renal cell carcinoma, and the program has attracted collaborations with industry giants AbbVie, Biogen and Novo Nordisk, each with more than $1 billion in potential milestone payments.
Similar to Monte Rosa, Neomorph has “gone all-in on molecular glues” and a platform that allows the company to discover novel signals in proteins that make them an ideal target for degradation, Driscoll said. Neomorph’s library of molecular glues is based on “rational design rather than random chance,” according to the company, which allows for more intentional targeting of disease as early as the discovery stage.
Degron, Takeda aim to stick it to solid tumors
Degron Therapeutics’ lead molecular glue degrader DEG6498 entered the clinic late last year to treat advanced solid tumors using an RNA-binding protein that was considered “previously undruggable,” according to a May press release announcing the company’s $40 million series A extension.
And the company, like many of its molecular glue peers, has picked up critical Big Pharma funding, this time from Takeda, which in 2024 signed a deal with Degron worth up to $1.2 billion. Most importantly, Takeda gained access to Degron’s discovery platform, called GlueXplorer, which uses AI to predict novel targets.
Takeda CSO Chris Arendt at the time lauded the ability of molecular glues to aim at targets that had previously been undruggable and inaccessible by other treatments.
AI’s application in finding new targets for molecular glues allows the field to advance at a faster clip than would otherwise be possible, Driscoll said. This strategy, he said, “is where the magic is happening.”
