Chief Scientific Officer, Ascendis Pharma
Peptide and protein drug candidates often suffer from suboptimal properties such as poor bioavailability and inadequate circulation half-life due to rapid renal clearance and/or receptor- mediated clearance. The TransCon technology enables transient conjugation of a parent drug to a carrier through a linker to create a polymeric prodrug. Following injection, the proprietary linker autohydrolyzes in an enzyme-independent process based on pH and temperature, and unmodified parent drug is released at a rate fine-tuned through the design of the TransCon linker. Since drug is released in its native form, its original pharmacology is retained, with the same biodistribution, receptor affinity, and mode-of-action as the parent drug. Linkers have been developed with release rates that allow for the development of prodrugs that can deliver proteins, peptides, and small molecules with dosing frequencies ranging from days to several months. Soluble as well as insoluble carrier systems can be used to enable systemic or localized delivery. The TransCon technology has been used to develop a pipeline of rare endocrinology disease programs: TransCon Growth Hormone (in phase 3 for pediatric growth hormone deficiency), a long-acting prodrug of parathyroid hormone, TransCon PTH (in phase 1 for hypoparathyroidism), and a long-acting prodrug of C-type natriuretic peptide, TransCon CNP, (filed for initiation of clinical development in Australia for achondroplasia).