navepegritide (TransCon CNP) / Ascendis, Teijin, Specialised Therap - LARVOL DELTA

Effects of Navepegritide on Growth in Children With Achondroplasia: 52-Week Results from the ApproaCH Clinical Trial (ESPE-ESE 2025) - "Statistically significant improvements in ACH-specific height Z-scores in children treated with navepegritide compared with placebo were also observed. These findings suggest that the design of navepegritide – to provide continuous exposure to active CNP – improves growth in children with ACH while maintaining a safety and tolerability profile comparable to placebo."

Clinical • Genetic Disorders • FGFR3

Effects of Navepegritide on Bone Morphometry in Children With Achondroplasia: 52-Week Results from the ApproaCH Clinical Trial (ESPE-ESE 2025) - "Conclusion In the ApproaCH trial, weekly administration of navepegritide demonstrated superiority over placebo in AGV and improved aspects of bone morphometry in children with ACH. These findings highlight that the design of navepegritide, which provides continuous exposure to active CNP, may deliver benefits that go beyond promoting linear growth – actively targeting and addressing critical aspects of skeletal dysplasia in ACH, which are key contributors to health-related complications."

Clinical • Genetic Disorders • Orthopedics • Pain • FGFR3

Safety and Tolerability of Navepegritide Treatment in Children With Achondroplasia: 52-Week Results From the Pivotal ApproaCH Trial (ENDO 2025) - "These results suggest that the design of once-weekly navepegritide as a prodrug with a low CNP Cmax contributes to a favorable safety and tolerability profile, and may address limitations of existing ACH therapies and support improved treatment adherence.*. .*"

Clinical • Genetic Disorders • Hypotension • FGFR3

teACH: A Clinical Trial to Evaluate Efficacy and Safety of Navepegritide in Adolescents (12 - 18 Years of Age) With Achondroplasia. (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Ascendis Pharma A/S

New P2 trial • Genetic Disorders

COACH: A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Genetic Disorders

A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of TransCon CNP Administered Once Weekly in Prepubertal Children With Achondroplasia (clinicaltrials.gov) - P2 | N=57 | Completed | Sponsor: Ascendis Pharma A/S | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders

Progress in managing children with achondroplasia. (PubMed, Expert Rev Endocrinol Metab) - "This review discusses key advances in the therapeutic management of children with achondroplasia, including vosoritide, the first approved drug, and other emerging precision therapies. These include navepegritide, a long-acting form of C-type natriuretic peptide, and infigratinib, a tyrosine kinase receptor inhibitor, summarizing trial outcomes to date...These new treatment options highlight the importance of prompt prenatal identification and subsequent testing of a suspected fetus with achondroplasia and counseling of families. It is hoped that, in the near future, families will have the option to consider a range of effective targeted therapies that best suit their child with achondroplasia, starting from birth should they choose."

Journal • Review • Genetic Disorders

COACH: A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Genetic Disorders

COACH: A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S

Combination therapy • New P2 trial • Genetic Disorders

A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of TransCon CNP Administered Once Weekly in Prepubertal Children With Achondroplasia (clinicaltrials.gov) - P2 | N=57 | Active, not recruiting | Sponsor: Ascendis Pharma A/S

Trial completion date • Genetic Disorders

A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Infants (0 to <2 Years of Age) With Achondroplasia (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

ApproaCH: A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Children With Achondroplasia (clinicaltrials.gov) - P2/3 | N=84 | Active, not recruiting | Sponsor: Ascendis Pharma Growth Disorders A/S | Phase classification: P2b ➔ P2/3

Phase classification • Genetic Disorders

Once-Weekly TransCon CNP Achieved Primary Efficacy Objective in ACcomplisH China Phase 2 Trial (PRNewswire) - P2 | N=57 | ACcomplisH (NCT04085523) | Sponsor: Ascendis Pharma A/S | "VISEN Pharmaceuticals...is pleased to announce the topline results from the ACcomplisH China Phase 2 Trial in children with achondroplasia (ACH) aged 2 to 10 years. In the trial, patients dosed with TransCon CNP at the 100 μg CNP/kg/week showed significantly higher annualized growth velocity (AGV) than placebo (1.180 cm/year, P=0.018) at Week 52...The ACcomplisH China Phase 2 Trial was a randomized, double-blind, placebo-controlled clinical trial conducted across 6 investigational sites in China. The study aimed to evaluate the safety and efficacy of once-weekly TransCon CNP compared to placebo in children with ACH aged 2 to 10 years old.

P2 data • Genetic Disorders