TransCon CNP is a C-type natriuretic peptide (CNP-38) conjugated via a cleavable 
linker to a polyethylene glycol carrier molecule, designed to provide sustained 
systemic CNP levels upon weekly subcutaneous administration. TransCon CNP is in 
clinical development for the treatment of comorbidities associated with 
achondroplasia. In both mice and cynomolgus monkeys, sustained exposure to CNP 
via TransCon CNP was more efficacious in stimulating bone growth than 
intermittent CNP exposure. TransCon CNP was well tolerated with no adverse 
cardiovascular effects observed at exposure levels exceeding the expected 
clinical therapeutic exposure. At equivalent dose levels, reductions in blood 
pressure and/or an increase in heart rate were seen following single 
subcutaneous injections of the unconjugated CNP-38 molecule or a daily CNP-39 
molecule (same amino acid sequence as Vosoritide, USAN:INN). The half-life of 
the daily CNP-39 molecule in cynomolgus monkey was estimated to be 20 minutes, 
compared with 90 hours for CNP-38, released from TransCon CNP. C max for the 
CNP-39 molecule (20 µg/kg) was approximately 100-fold higher, compared with the 
peak CNP level associated with administration of 100 µg/kg CNP as TransCon CNP. 
Furthermore, CNP exposure for the daily CNP-39 molecule was only evident for up 
to 2 hours postdose (lower limit of quantification 37 pmol/l), whereas TransCon 
CNP gave rise to systemic exposure to CNP-38 for at least 7 days postdose. The 
prolonged CNP exposure and associated hemodynamically safe peak serum 
concentrations associated with TransCon CNP administration are suggested to 
improve efficacy, compared with short-lived CNP molecules, due to better 
therapeutic drug coverage and decreased risk of hypotension. SIGNIFICANCE 
STATEMENT: The hormone C-type natriuretic peptide (CNP) is in clinical 
development for the treatment of comorbidities associated with achondroplasia, 
the most common form of human dwarfism. The TransCon Technology was used to 
design TransCon CNP, a prodrug that slowly releases active CNP in the body over 
several days. Preclinical data show great promise for TransCon CNP to be an 
effective and well-tolerated drug that provides sustained levels of CNP in a 
convenient once-weekly dose, while avoiding high systemic CNP bolus 
concentrations that can induce cardiovascular side effects.