Are We Ready for the Next Wave of Proximity Degraders?

Why It Matters

These advances turn previously undruggable targets into tractable therapeutic opportunities, potentially reshaping oncology, neurology and immunology pipelines. The scale of investment signals a market shift toward protein‑degradation strategies as a core pillar of future drug discovery.

Key Takeaways

• Proximity glue market attracted over $15 billion in deals this year
• Proxygen secured $2.55 billion Merck partnership for next‑gen glues
• New platforms enable systematic screening of ~600 E3 ligases
• RIPTACs offer oral “hold‑and‑kill” mechanism similar to ADCs
• Glue‑DACs aim to replace toxic ADC payloads with degraders

Pulse Analysis

The surge in molecular glue degraders reflects a broader industry pivot toward induced‑proximity therapeutics, a class that can target proteins once deemed "undruggable." Unlike traditional PROTACs, glues are compact enough to cross the blood‑brain barrier and do not require a linker, enabling them to engage intracellular targets with high efficiency. Companies such as Proxygen are leveraging high‑throughput platforms to map the human repertoire of roughly 600 E3 ligases, selecting the optimal ligase‑target pair before screening for glue candidates. This systematic approach reduces reliance on serendipitous discovery and accelerates IND‑enabling timelines for programs like the p300 and CDK12 covalent glues, which promise durable tumor suppression with infrequent dosing.

Beyond pure degradation, next‑generation proximity modalities are expanding the therapeutic toolbox. Regulated Induced Proximity Targeted Chimeras (RIPTACs) pioneered by Halda Therapeutics employ a "hold‑and‑kill" strategy, binding a target protein and an essential pan‑protein to trigger selective cell death, while remaining orally bioavailable. Meanwhile, Fortitude Biomedicines’ Glue‑DACs aim to replace the cytotoxic payloads of antibody‑drug conjugates with small‑molecule degraders, addressing the growing problem of ADC resistance. These innovations illustrate how proximity chemistry can merge the targeting precision of biologics with the manufacturing simplicity of small molecules.

The financial momentum underscores the strategic importance of this technology. In the past year, more than $15 billion in agreements have been signed, involving major pharma players such as AbbVie, Novartis, Takeda and Merck. This capital influx fuels both discovery platforms and clinical programs, suggesting that molecular glues and related proximity agents will soon move from niche research tools to mainstream drug pipelines. For investors and biotech executives, the message is clear: mastering induced proximity could be the key to unlocking a new wave of high‑value therapeutics across oncology, neuroscience and immunology.