Key insights from @raffcolo’s plenary talk on next-gen #ADCs from #AACR26.
👉The paradigm shift – we have been optimizing ADCs for the <1% that reaches the tumor. Next-gen design must account for ADC disposition - drug-like payloads, less over-stabilized linkers, antibodies optimized for tumor penetration. 💊
👉Developing novel ADC payloads is hard. Most are discontinued, including ISACs (TLR, STING), BCL-2 family (BCL-XL, MCL1), degraders (GSPT1, BET), and KSP inhibitors. Only 9 payload classes are currently approved. 🎯
👉Dual-payload ADCs are entering the clinic fast. 6 already in clinical development and nearly all pair TOPO1i with a second payload (Triptolide, MMAE, ATR, or STING). 37 abstracts on dual payloads at #AACR26 alone. 🏥
👉Outside-the-box approaches gaining traction: pre-targeting strategies (chemically released drugs, click-activated prodrugs), sequential cleavage linkers, and alternative targeting moieties 🔬
Themes for the future: improve efficacy, improve safety, overcome resistance. #ADC #lcsm