The targeted-degrader pioneer Nurix Therapeutics and the antibody-drug conjugate (ADC) powerhouse Seagen expect that their two modalities can bring out the shine in each other. In a multiyear deal that could be worth up to $3.4 billion for Nurix, the partners will develop an emerging class of therapeutics called degrader-antibody conjugates (DACs).
“It’s very exciting to be the first to move these types of agents forward. DACs are a fundamentally different class of drugs to watch,” says Arthur T. Sands, Nurix’s CEO.
Targeted protein degraders, up-and-comers in the biopharmaceutical sector, harness the cell’s trash disposal system to tag unwanted proteins for degradation. Nurix’s drug candidate, NX-2127, for example, is intended to treat blood cancers by degrading the protein BTK.
But while the degrader drug pipeline is expanding quickly, the molecules tend to be bulky and hard to optimize for oral delivery and cellular penetration. When targeted at essential drivers of cancer cell survival, the potent molecules can also kill healthy cells.
By attaching degraders to antibodies, Nurix and Seagen hope to sidestep these limitations. The idea is that an injected antibody will deliver its degrader payload with missile-like precision to cells carrying a cancer-associated target. After the antibody binds its quarry, the cells engulf the therapeutic and release the degrader to destroy its intracellular target.
The DAC field is still in its infancy. A paper by researchers at Genentech introduced the modality in 2019. Last year, Orum Therapeutics advanced its ORM-5029—a GSPT1 degrader attached to an antibody that targets breast cancer cells—into the clinic.
Many questions remain for the field, including how to best link a degrader to an antibody and how many copies of a degrader are needed per antibody to achieve the best therapeutic effect. But Seagen’s decades of ADC know-how should help, says Gwenn M. Hansen, Nurix’s chief scientific officer. “I think they feel very comfortable that they can apply all of their past experience to this,” she says.
Nurix, meanwhile, expects to innovate on the degrader side of the equation. “It’s going to help us learn a lot about the degrader design,” Hansen says. To date, the field has prioritized degraders that can be taken orally, but this approach constrains the chemical space that can be tapped, she explains. DACs, by contrast, are injected therapeutics. “We’re going to screen with a much wider array of chemical entities, because now we just don’t have that limitation of having to think about oral bioavailability,” Hansen says.
Nurix and Seagen will focus on cancer, though they have yet to disclose targets. Once suitable degraders have been identified, they can be attached to different antibodies to take on different cancer types, Sands adds. “The product potential here is really quite large, because the system is very modular.”
Pfizer, which has an active interest in degraders, is in the process of acquiring Seagen for $43 billion.