A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia

Inclusion Criteria:

1. Written, signed informed consent and/or assent (if applicable) by the parent(s) orlegal representative(s) of the participant, and as required by the IRB/HREC/IEC.

2. Male or female between 2 to 11 years of age (inclusive) at the time of Visit 1.

3. Clinical diagnosis of ACH with genetic confirmation of heterozygote genotype presentat Visit 1. Documentation of historic test results are acceptable for proof ofdiagnosis.

4. Able to stand without assistance.

5. Parent(s)/caregiver(s)/legal guardian(s) willing and able to administer weekly SCinjections of IMP and comply with all protocol requirements.

6. At least 6 months of growth and disease history from TCC-NHS-01 or TCC-201 orcomparable growth and disease history available from medical records.

7. No intracranial pathology as confirmed by brain MRI (historical MRI obtained within 2 years prior to screening allowable).

Exclusion Criteria:

1. Participation in any interventional clinical trial within three months prior toscreening (except TCC-201 or ASND0039).

2. Closed epiphysis at screening.

3. History of or suspected hypersensitivity to the IMP or related products.

4. Findings on fundoscopy at screening consistent with intracranial hypertension,papilledema, or evidence of any other retinal disease for which GH therapy iscontraindicated.

5. Have a growth disorder or medical condition other than ACH that results in shortstature or abnormal growth such as severe ACH with developmental delay andacanthosis nigricans (SADDAN), hypochondroplasia, GHD, Turner syndrome,pseudoachondroplasia, inflammatory bowel disease, celiac disease, hypothyroidism,hyperthyroidism, pre-diabetes, or diabetes mellitus.

6. Have received any dose of prescription and/or investigational medications or deviceintended to affect stature, growth, or body proportionality at any time prior toscreening.

7. Receiving concurrent treatment with any agent that might influence growth orinterfere with GH secretion or action:

8. Inhaled corticosteroid therapy at a dose of >400 µg/day of inhaled budesonideor equivalent for more than 28 consecutive days total over the course of 12months prior to screening.

9. Require, or anticipated to require, chronic (>4 weeks) or repeated treatment (more than twice/year and >3 weeks/year) with systemic corticosteroids duringparticipation in the trial.

10. Currently using or have used within 12 months prior to screening any sexsteroids (for example estrogen), non-steroidal anabolic agents (for example,oxandrolone) or gonadotropin-releasing hormone (GnRH) analogues treatment.

11. Treatment for attention-deficit hyperactive disorder (ADHD) such asmethylphenidate.

12. Known history or presence of injury or disease of the growth plate(s), other thanACH, that affects growth potential of long bones.

13. Known history of any bone-related surgery affecting growth potential of long bones,such as Orthopaedic reconstructive surgery for bone lengthening (procedures for legbowing such as 8-plate are not exclusionary).

14. Cervicomedullary decompression surgery within 6 months prior to Screening or withanticipated need for repeat decompression surgery during the time of the trial.

15. Evidence at screening consistent with severe cervicomedullary junction compressionbased on clinical and/or radiologic findings that indicate immediate surgicalintervention is required.

16. Ventriculoperitoneal shunt and laminectomy with full recovery within 6 months priorto Screening.

17. Salter-Harris fracture within 6 months prior to screening (within 2 months forfracture of digits and buckle fractures).

18. Clinically significant musculoskeletal disease, such as Salter-Harris fractures orclinical and/or radiographic evidence of severe hip pathology.

19. Planned or expected surgical intervention during trial participation that maysignificantly affect trial parameters (confounding of safety events) or wouldprevent the participant from performing trial procedures. Minimally invasivesurgeries such as insertion of grommets, adenoidectomy, tonsillectomy, ormyringotomy tube placement, are permitted during the trial.

20. Severe untreated sleep apnoea or newly initiated sleep apnoea treatment (e.g.,Continuous Positive Airway Pressure [CPAP] in the previous 2 months prior toscreening).

21. Clinically significant finding or arrhythmia as determined by the investigator thatindicates abnormal cardiac function or conduction that includes, but is notexclusive to:

22. Repaired or unrepaired coarctation.

23. Moderate or greater complexity congenital heart disease including tetralogy ofFallot, Atrioventricular septal defects, truncus arteriosus, total anomalouspulmonary venous return, double outlet right ventricle, or single ventricleheart disease.

24. QT corrected using Fridericia's correction (QTcF) ≥ 450 msec at screening.

25. Known history or presence of condition that impacts haemodynamic stability (such asautonomic dysfunction and orthostatic intolerance).

26. Known history or presence at screening of the following:

27. Chronic anaemia (iron deficiency anaemia that is resolved or consideredadequately treated in the Investigator's opinion is allowed).

28. Chronic renal insufficiency defined as estimated glomerular filtration rate (eGFR) according to the revised bedside Schwartz equation less than <60mL/min/1.73 m2 for >3 months.

29. Chronic or recurrent illness that can affect hydration or volume status,including conditions associated with decreased nutritional intake or increasedvolume loss.

30. Known history or presence of malignant disease.

31. Hepatic transaminases (aspartate aminotransferase (AST) or alanine transferase (ALT)) greater than 3x upper limit of normal (ULN) at screening.

32. Serum 25-hydroxy-vitamin D (25OHD) level of <30 nmol/L (<12 ng/mL) at screening. Participants with 25OHD levels between 30-50 nmol/L (12-20 ng/mL) may be enrolledprovided treatment with Vitamin D supplementation is initiated.

33. Any disease or condition that, in the opinion of the Investigator, may make theparticipant unlikely to fully complete the trial, may confound interpretation oftrial results, or may present undue risk from receiving trial treatment. This couldinclude family situations, complications or manifestations, or medications thatmight impact safety or be considered confounding.

34. Sexually active male and female participants who are unwilling or unable to use ahighly effective form of contraception for the entire trial period and for 90 daysafter last dose of trial treatment.

35. Female participants who are pregnant, lactating or breastfeeding.