Innovation: Molecular glue degrader.
Targeted Cancer(s): Colorectal cancer, hepatocellular carcinoma, and other solid tumors.
Scientific Leadership/Leadership:  Yong Cang, Ph.D., Co-founder, Chairman & CSO
Lily Zou, Ph.D., MBA, Co-founder, CEO
Xiaobing Qian, MD, Ph.D., Chief Development Officer
Stage of Business: Clinical development stage

Degron Therapeutics is developing a new class of small molecule molecular glue degrader (MGD) drugs using GlueXplorer®, a proprietary molecular glue-based targeted protein degradation drug discovery platform. The company has created a rapidly-expanding structurally differentiated compound library and screening and validation system to develop novel MGDs that target previously undruggable disease targets.

The company’s lead program, DEG6498, is a first-in-class MGD targeting HuR (Human antigen R), a previously undruggable RNA-binding protein playing critical roles in driving cancer, inflammation and metabolic diseases. The company has received clearance from the US FDA for its IND to start Phase 1/2 study to evaluate its safety, tolerability and anti-tumor activity in multiple solid tumors. Patient enrollment of a Phase I trial is expected to start in early 2025.

• Many disease targets are “undruggable” by conventional drug modalities (e.g. small molecule inhibitors, monoclonal antibodies, etc.) due to the lack of druggable binding pockets or intracellular location.
• In the past, MGDs have been discovered serendipitously. The rational design of MGDs has been extremely challenging due to the complexity of ternary structure formed by E3 ligase-MGD-target.
• Most MGD development efforts are based on IMiDs’ core chemical structure, which leads to limited number of MGD targets and poor IP protection.

• MGDs recruit disease-causing proteins to ubiquitin ligase enzymes, which attach ubiquitins that tag the target proteins for disposal by targeted protein degradation.
• Degron’s GlueXplorer® platform includes more than 10,000 structurally differentiated MGD compounds with associated compound-induced proximity and degradation data. This biology-backed library, combined with the company’s comprehensive screening and validation systems, enables the discovery of novel targets and the optimization of new MGDs.

Degron has generated large chemical-induced degradation and proximity data sets. In addition to producing first-in-class pipeline programs, this proprietary data broadens our understanding of potential MGD targets and supports MGD discovery collaborations with industry partners.

Potency: HuR (Human antigen R) is a previously undruggable RNA-binding protein playing critical roles in driving cancer, inflammatory and metabolic disorders. HuR is over-expressed or cytoplasmic enriched in many cancers particularly in response to stresses including oncogenic mutations and chemo or targeted therapies. HuR is also a well-studied target in inflammatory and metabolic diseases such as pancreatitis, rheumatoid arthritis, and neuroinflammation.

Proof of Concept: HuR is considered “undruggable” by conventional approaches. Multiple modalities (RNAi, small molecule inhibitors of translocation, dimerization or RNA binding) have been investigated to target this protein but none has advanced beyond preclinical stage due to various technical challenges.

Safety and Tolerability: The Investigational New Drug (IND) application for DEG6498, Degron’s first-in-class HuR MGD, to be studied in multiple solid tumors, has been cleared by the FDA. Patient enrollment of a Phase I trial is expected in early 2025.