Characterizing MOA for MPN targeted therapy (INCA033989) using single cell multi-omits in the clinic

In myeloproliferative neoplasms (MPN), many cells carry the disease mutation without driving disease. That makes it hard to show a targeted therapy’s mechanism of action with standard bulk assays.

In this 18-minute webinar from World Single Cell Day, Dr. Erin Crowgey, Director of Translational Medicine at Incyte, explains how her team used single-cell multiomics in clinical trials. They applied it to INCA033989, a monoclonal antibody that targets the complex formed by mutant CALR and the thrombopoietin receptor. Working with Mission Bio, the team built a custom assay on the Tapestri® platform covering 46 cell surface proteins and 37 genes. They then used it on patient samples from phase 1 trials in essential thrombocythemia (ET) and myelofibrosis (MF).

Topics include:

• Why many CALR-mutant cells are “silent carriers,” and what that means for measuring response
• An MPN cell atlas, built from protein expression, for consistent cell annotation as trial samples arrive
• Depletion of CALR-mutant myeloid cells and a return of wild-type cells in ET patients after treatment
• Loss of mutant stem and progenitor cells and erythroid progenitors from circulation in MF
• Clone-level tracking showing CALR-mutant clones responding regardless of co-occurring mutations
• How single-cell findings line up with molecular and clinical response measures

This session is for translational and clinical researchers who want to see how single-cell readouts can support mechanism-of-action work in clinical trials.