Ascendis Pharma (ASND) Investor Update summary

Trial design and patient population

• The double-blind, placebo-controlled APPROACH trial enrolled 84 children aged 2–11 with achondroplasia, randomized 2:1 to TransCon CNP or placebo, with an open-label extension period and primary analysis at week 52 focused on annualized growth velocity (AGV).

• Baseline demographics were well balanced, with an average age of 5.7 years and mean height of 88 cm; genetic variants were representative of the achondroplasia population.

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

Efficacy results

• TransCon CNP achieved a statistically significant increase in AGV of 1.49 cm/year over placebo at week 52 (5.89 vs. 4.41 cm/year; p<0.0001), with early and sustained growth benefit.

• In children aged 5–11, the LS mean AGV difference was 1.78 cm/year (p<0.0001); for ages 2–<5, the difference was 1.02 cm/year (p=0.0084).

• Statistically significant improvements in height Z-scores were observed versus placebo (ACH Z-score LS mean diff 0.28, CDC Z-score LS mean diff 0.30, both p<0.0004), indicating catch-up growth.

• Children treated with TransCon CNP exceeded the growth rate of the general population, with no accelerated bone age.

Safety and tolerability

• Most adverse events were mild or moderate and typical for the age group; serious adverse events were not related to the study drug.

• Injection site reactions were infrequent (0.41 events per patient year), all mild, and no hypotensive effects were observed.

• No adverse events led to discontinuation or withdrawal from the trial.

• No deaths, fractures, or bone-related safety events occurred.