After years of momentum behind antibody–drug conjugates (ADCs) and targeted protein degraders, the biotech industry is beginning to wonder: what happens when you try to combine them? The answer may lie in degrader-antibody conjugates, an emerging modality that is drawing increasing interest from next-generation biotech companies. Although still in its infancy, the field is evolving quickly, and competition is already taking shape as big pharma tentatively dips its toes into the space.
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What are degrader-antibody conjugates?
So, what exactly are degrader–antibody conjugates?
They are ultimately a class of therapies designed to bring together two powerful drug discovery strategies: the cell-targeting precision of ADCs and the catalytic mechanism of targeted protein degraders. Like ADCs, in a degrader-antibody conjugate, an antibody is used to selectively bind to a cell-surface antigen and deliver a payload into the cell – but instead of a traditional cytotoxic agent, that payload is a degrader molecule capable of recruiting the cell’s own protein disposal machinery. Once inside, the degrader can then tag a specific intracellular protein for destruction, rather than simply inhibiting its activity.
This distinction is important because conventional small molecule inhibitors typically need sustained, high levels of target engagement to be effective, whereas degraders act catalytically, removing the target protein altogether and potentially achieving longer-lasting effects at lower exposures.
So, by combining this mechanism with antibody-guided delivery, degrader-antibody conjugates aim to extend protein degradation into a more targeted, cell-specific context. In theory, this could allow drug developers to tackle difficult or previously “undruggable” targets with greater precision, while limiting systemic exposure to the degrader payload.
The key players in the degrader-antibody conjugate space
There are currently several companies working in the degrader-antibody conjugate space; while a couple have recently attracted headlines, others are working more quietly, away from the spotlight, to progress their technologies. Below are some of the main players.
C4 Therapeutics expands partnership with Roche to focus on degrader-antibody conjugates
Earlier this month, Roche joined the small list of big pharmas taking a leap of faith on degrader-antibody conjugates by expanding its existing long-term partnership with C4 Therapeutics (C4T) to specifically focus on advancing degrader-antibody conjugates.
Under the new joint research plan, the two companies are collaborating on two programs to develop degrader-antibody conjugates against undisclosed oncology targets exclusive to the collaboration. C4T will use its TORPEDO platform to design degrader payload candidates, while Roche will select and design the antibody, as well as conjugate the antibody to the degrader payload. The big pharma will also be responsible for advancing the candidates through preclinical and clinical development, as well as commercialization.
C4T’s platform allows the company to create a new generation of small molecule medicines centered around heterobivalent degraders, molecular glue degraders, and degrader-antibody conjugates. According to the company, the platform integrates DNA-encoded library technology, a Cereblon toolkit, diverse chemical libraries, degrader design assisted by artificial intelligence (AI)-driven ternary complex models, and proteomics to selectively target disease-causing proteins.
This is not the first time that C4T has made a degrader-antibody conjugate deal with a big pharma. Merck also entered into a $610 million partnership with C4T in 2023, securing exclusive rights to degrader-antibody conjugates against one target, as well as options on three more targets. However, Merck ended the collaboration agreement in November 2025.
The new partnership with Roche is another opportunity to progress the development of degrader-antibody conjugates, and eventually prove the worth of this emerging drug class.
Orum Therapeutics raises $100 million to progress degrader-antibody conjugate programs toward the clinic
South Korean company Orum Therapeutics is most definitely a leader in the field, as it secured approximately $100 million in December to help it advance its degrader-antibody conjugate programs toward the clinic, including its lead candidate ORM-1153.
In 2023, the company also struck a deal with Bristol Myers Squibb (BMS), in which the big pharma paid $100 million upfront to acquire ORM-6151 (now called BMS-986497), a degrader-antibody conjugate that uses an anti-CD33 antibody to deliver a GSPT1 degrader. BMS now has the candidate in a phase 1 trial in acute myeloid leukemia and myelodysplastic syndrome.
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Furthermore, in 2024, Orum’s technology attracted Vertex Pharmaceuticals as well, as the two companies signed a multi-target license and option agreement, whereby Orum granted Vertex the rights to conduct research using its dual-precision targeted protein degradation (TPD²) technology for the discovery of novel targeted conditioning agents for use with gene editing.
Nurix Therapeutics, Firefly Bio, and Prelude Therapeutics also working in the space
With two degrader-antibody conjugates listed in its pipeline – one under oncology and one under autoimmune diseases – Nurix Therapeutics is another company attempting to progress this modality. In 2023, it entered into a collaboration with Seagen to develop a portfolio of degrader-antibody conjugates for cancer indications. Since Pfizer subsequently acquired Seagen, the big pharma has retained this partnership, and Nurix lists Pfizer as a partner for its oncology-focused degrader-antibody conjugate.
There is also Firefly Bio, which emerged from stealth in February 2024 with a $94 million series A financing. The company has developed a platform to treat cancer using degrader antibody conjugates. In the press release regarding its emergence from stealth, the company said that in preclinical studies in both solid and liquid tumors, a single administration of its degrader-antibody conjugates showed significant reductions in tumor volume at very low doses. However, there has been no real news of the company and its progress since.
Prelude Therapeutics is another company dabbling in degrader-antibody conjugates. It says on its website that it has developed highly potent SMARCA2/4 and CDK9 degrader payloads optimized for efficacy, tolerability, and developability when coupled to a wide range of different antibodies, and that its payloads and corresponding payload-linkers are available for licensing to partners to expand the reach of this new technology.
What does the future hold for this emerging field?
Given that the degrader-antibody conjugate space is only in its very early stages, it is too soon to say whether the modality will live up to expectations.
What seems likely, however, is that progress will hinge on solving practical constraints like payload size, stability, linker design, and efficient intracellular release. Additionally, one of the most important shifts to watch will be the evolution of degrader payloads themselves, potentially toward smaller, more drug-like structures that are better suited for conjugation.
At the same time, the field will probably move toward greater biological precision. First-generation degrader-antibody conjugates are likely to follow the familiar ADC playbook, targeting well-validated oncology antigens. But in the longer term, there is scope to expand into immunology indications too.
If successful, these drugs could enable selective degradation of proteins in defined cell populations – something that neither traditional degraders nor ADCs can fully achieve on their own today. Such success will depend heavily on identifying the right surface targets and ensuring that intracellular delivery is both efficient and reproducible.
Ultimately, the future of degrader-antibody conjugates will depend on whether they can demonstrate a clear advantage over existing therapies in the clinic. If they can deliver on their promise, they could represent a meaningful step forward in targeted therapeutics.
