Ascendis Pharma (ASND) Investor Update summary

Trial design and patient population

• The pivotal, double-blind, placebo-controlled APPROACH trial enrolled 84 children aged 2–11 years with achondroplasia, randomized 2:1 to TransCon CNP or placebo, with an open-label extension period.

• Baseline demographics were well balanced, with an average age of 5.7 years and mean height of 88 cm.

• Genetic variants and diagnosis timing were representative of the broader achondroplasia population.

• Participants were stratified by age and sex across multiple countries.

Efficacy results

• TransCon CNP achieved a statistically significant increase in annualized growth velocity (AGV) of 1.49 cm/year over placebo at week 52 (p<0.0001).

• Children aged 5–11 years showed an AGV improvement of 1.78 cm/year (p<0.0001); ages 2–<5 years had a 1.02 cm/year increase (p=0.0084).

• Height Z-score improved by 0.3 for TransCon CNP, with a 0.28 advantage over placebo (ACH Z-score LS mean diff 0.28, CDC Z-score LS mean diff 0.30, p<0.0001).

• Children on TransCon CNP demonstrated catch-up growth, exceeding the growth rate of the general population without accelerated bone age.

Safety and tolerability

• Most adverse events were mild or moderate, with a safety profile comparable to placebo and no deaths, fractures, or bone-related safety events.

• Injection site reactions were mild and infrequent (0.41 events per patient year), with similar rates between treatment and placebo.

• No evidence of hypotension or discontinuations due to adverse events; no serious adverse events were related to TransCon CNP.