Ascendis Pharma (ASND) Study Update summary

Study design and patient population

• The COACH trial is a phase 2 study evaluating once-weekly TransCon CNP and TransCon Growth Hormone (hGH), alone and in combination, in children with achondroplasia aged 2–11 years.

• The trial included two cohorts: 12 treatment-naive (mean age 4.67 years) and 9 previously treated with TransCon CNP monotherapy (mean age 7.89 years).

• The primary efficacy objective is to assess the effect on linear growth compared to TransCon CNP alone, with annualized growth velocity (AGV) at Week 52 as the primary endpoint.

• Secondary endpoints include changes in height Z-score and body proportionality; safety endpoints focus on treatment-emergent adverse events.

Efficacy results at week 26

• Treatment-naive children on combination therapy achieved a mean AGV of 9.14 cm/year, a 4.23 cm/year increase from baseline, and a +0.53 improvement in mean ACH height Z-score over 26 weeks.

• Previously treated cohort had mean AGV of 8.25 cm/year, a 3.10 cm/year increase from baseline, and a +0.44 improvement in mean ACH height Z-score.

• Growth velocity exceeded the 97th percentile for average-stature children in both cohorts.

• Combination therapy led to accelerated improvement in body proportionality, aligning with increased linear growth.

• Bone age advanced in line with chronological age.

Safety and tolerability

• Safety profile of the combination was similar to each agent alone; adverse events were generally mild or moderate.

• No symptomatic hypotension, fractures, or bone-related safety events were observed.

• Injection site reactions were mild and consistent with monotherapy experience.

• No TEAEs led to discontinuation or withdrawal, and no deaths were reported.

• One serious adverse event (respiratory tract infection) occurred but was not related to study drugs.