Brigham Research Institute (BRI) - Brigham and Women's Hospital

Parts A and B: - Male and female subjects in good health aged 18-55 years of age at Screening. - Body mass index (BMI) ≥30 kg/m2. - Subjects who are medically healthy with normal or clinically insignificant screening results. - Subjects must use a highly effective form of contraception and follow the study contraception requirements. - Ability to communicate well with the Investigator, understand and comply with the requirements of the trial, and understand English and sign the written informed consent. Part C: - Male and female patients with HO, aged 12-65 years of age at Screening. - Patient has documented evidence of acquired HO defined as: - Diagnosis of craniopharyngioma or other brain lesion affecting the hypothalamic region and has undergone surgery, or chemotherapy, or radiation therapy involving the hypothalamus at least 6 months before Screening, OR - Documented injury to the hypothalamus at least 6 months before Screening for which surgery/radiation is not indicated. - Weight gain associated with the hypothalamic injury either before or following therapy (surgery and/or following chemotherapy or radiotherapy), and a BMI of ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients 12 to <18 years of age. - Patients must use a highly effective form of contraception and follow the study contraception requirements. - Ability to communicate with the Investigator, understand and comply with the requirements of the trial, and understand and sign the written informed consent and assent (for patients aged <18 years), and informed consent for a parent or guardian of any patient <18.

Parts A and B - Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator. - Active or history of any significant medical condition such as and including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease. - Obesity due to genetic, syndromic, or endocrine etiologies. - History of renal transplant, end stage renal disease. - Diagnosis of severe psychiatric disorders. - Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results. - Cigarette smoking or dependence on caffeine, alcohol or drugs; unable or unwilling to abstain completely from caffeine, alcohol and related substances for 24 hours prior to and after study visits. - History of recent surgery (within 60 days of Screening). - Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose. - Pregnant and/or breastfeeding or desiring to become pregnant during this trial. Part C - Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET). - Weight loss >2% in the previous 3 months for patients aged ≥18 years or >2% reduction in BMI for patients aged 12 to <18 years and/or anti-obesity medications for the treatment of obesity. - Bariatric surgery or procedure within the last 2 years. - Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior. - Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results. - History of renal transplant, end stage renal disease. - Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose, or previous participation in a trial with setmelanotide. - Pregnant and/or breastfeeding or desiring to become pregnant during this trial. - Obesity attributable to other genetic or syndromic conditions (eg, PPL [pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), leptin receptor (LEPR), collectively], Bardet-Biedl syndrome [BBS]) prior to the hypothalamic injury. Other protocol defined Inclusion/Exclusion criteria may apply.