A Multi-Peptide Hybrid LC-MS/MS Assay For The Determination Of CTI-1601 In Monkey Tissues Provides Insight Into Its Disposition And Processing

By Jean-Nicholas Mess, Kevork Mekhssian, David Bettoun, Jennifer Johansson, and Anahita Keyhani

Friedreich’s Ataxia (FRDA) is a rare genetic disorder caused by a deficiency of the mitochondrial protein Frataxin (FXN). CTI-1601, a 24.9kDa fusion protein, is being investigated as a protein replacement therapy to restore functional FXN levels in mitochondria. It consists of the transactivator of transcription (TAT) transduction domain linked to the N-terminus of the full-length human FXN protein, leveraging the TAT peptide’s cell-penetrating ability for mitochondrial translocation and processing into mature FXN.

To evaluate the disposition and processing of CTI-1601, a multi-peptide hybrid LC-MS/MS assay was developed to quantify CTI-1601 in cynomolgus monkey buccal cells, skin biopsies, and platelets following a 14-day repeated administration regimen.