Dueling glue degraders take on sickle cell disease

The targeted protein degrader BMS-986470 from Bristol Myers Squibb (BMS) boosts levels of fetal hemoglobin in cells, mice, and monkeys, the company reported this weekend at the American Society of Hematology (ASH) meeting. The dual Wiz and ZBTB7A degrader entered into a first Phase 1/2 sickle cell disease trial in July, 1 month ahead of a similar compound from Novartis. “It’s a super exciting molecule and a fantastic exemplar of what we think is possible with targeted protein degraders,” Neil Bence, head of oncology discovery at BMS and who worked on the BMS-986470 program, tells C&EN. Molecular glue -based degraders, small molecules that shunt proteins of interest to the cell’s garbage disposal system, have been making waves in oncology. The advancing sickle cell disease candidates showcase their potential in other diseases as well, Bence says. Sickle cell disease affects around 8 million people worldwide . It is caused by mutations