A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment

Key Inclusion Criteria: 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. Part D: * Confirmed diagnosis of PWS as determined by the Investigator at the time of Screening. * Age ≥12 to 65, inclusive, at the time of signing Informed Consent and/or Assent. * BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th Percentile for age and sex for patients \<18 years of age based on the US CDC criteria. * Able to meet contraception requirements. Key Exclusion Criteria: 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 use of 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. Part D * 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 or therapies for the treatment of obesity or hyperphagia. * Metabolic and bariatric surgery (MBS) or procedure within last 6 months. * 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. * Pregnant and/or breastfeeding or desiring to become pregnant during this trial. * 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 use of setmelanotide. Other protocol defined Inclusion/Exclusion criteria may apply.