The goal of this study is to determine how well LB54640 works and how safe it is in patients with Hypothalamic Obesity (HO). The study will evaluate the effect of LB54640 on safety, weight reduction, hunger, and quality of life in patients 12 years of age and older with HO. Patients will take an oral daily dose of either LB54640 (low, middle, or high dose) or placebo through Week 14. Eligible patients who consent to continue in the study after Week 14 will take an oral daily dose of LB54640 through Week 56.

Key Inclusion Criteria:

• Documented evidence of acquired hypothalamic obesity (HO)
• Age 12 years and older
• Weight gain associated with the hypothalamic injury and a BMI of ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients <18 years of age
• Male and female participants agree to follow study contraception requirements and use a highly effective form of contraception throughout the study and for 90 days after the study

Key Exclusion Criteria:

• Weight loss >2% in the previous 3 months for patients ≥18 years of age or >2% reduction in BMI for patients <18 years of age
• History of major surgical procedure within 30 days
• HbA1c >10.9%
• Fasting glucose level >270 mg/dL
• Previous use of MC4R agonists
• Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET).
• Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior
• History or close family history of skin cancer or melanoma
• Current clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results

Other protocol defined Inclusion/Exclusion criteria may apply.