BTK degraders work despite most kinase inhibitor resistance mutations. However, resistance to degraders themselves alters the BTK binding pocket so significantly that subsequent targeting with any BTK kinase inhibitor is unlikely to be effective, positioning them as a potential end-of-line therapy.

Step Pharma's synthetic lethality approach targets two redundant enzymes in the same pathway. Deleting one makes cancer cells entirely dependent on the other. This direct dependency is harder for biology to circumvent compared to approaches targeting different, interconnected pathways, creating a "cleaner" kill mechanism.

The degradation mechanism is fundamentally superior to inhibition because it removes the entire protein, addressing both its enzymatic and scaffolding functions. This allows degraders to hit targets harder and more completely, suggesting they could become the dominant modality across oncology and other therapeutic areas.

T-cell receptor (TCR) therapies offer a significant advantage over monoclonal antibodies by targeting intracellular proteins. They recognize peptides presented on the cell surface, effectively unlocking 90% of the proteome and requiring far fewer target molecules (5-10 copies vs. 1000+) to kill a cancer cell.

To overcome on-target, off-tumor toxicity, LabGenius designs antibodies that act like biological computers. These molecules "sample" the density of target receptors on a cell's surface and are engineered to activate and kill only when a specific threshold is met, distinguishing high-expression cancer cells from low-expression healthy cells.

Pathways like integrins have long been of interest but lacked effective therapeutic approaches. The advent of new technologies, such as antibody-drug conjugates and checkpoint inhibitors, has created opportunities to re-explore these older targets with potent, modern drugs, breathing new life into decades-old research.

After several tau-targeting antibodies failed, including J&J's pazdenimab, confidence in blocking extracellular tau is waning. The field's new hope is Biogen’s Biv80, an antisense drug that prevents tau protein production at the mRNA level, a mechanism that has shown potential to reverse pathology in early data.

A single degrader molecule can destroy thousands of target proteins per hour, a massive improvement over the 1-to-1 stoichiometry of traditional inhibitors. This extreme potency makes them ideal payloads for Degrader-Antibody Conjugates (DACs), combining the precision of antibodies with the power of catalytic degradation.

While China is known for licensing novel assets, its researchers are also becoming leaders in a more fundamental area: drug delivery and formulation. This is particularly evident in the targeted protein degradation space, where Chinese publications dominate innovations related to improving drug-like properties.