A Study of RM-718 in Healthy Subjects and in Patients With HO

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 screeningresults.

• Subjects must use a highly effective form of contraception and follow the studycontraception requirements.

• Ability to communicate well with the Investigator, understand and comply with therequirements of the trial, and understand English and sign the written informedconsent.

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 hypothalamicregion and has undergone surgery, or chemotherapy, or radiation therapyinvolving the hypothalamus at least 6 months before Screening, OR

• Documented injury to the hypothalamus at least 6 months before Screening forwhich surgery/radiation is not indicated.

• Weight gain associated with the hypothalamic injury either before or followingtherapy (surgery and/or following chemotherapy or radiotherapy), and a BMI of ≥30kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex forpatients 12 to <18 years of age.

• Patients must use a highly effective form of contraception and follow the studycontraception requirements.

• Ability to communicate with the Investigator, understand and comply with therequirements of the trial, and understand and sign the written informed consent andassent (for patients aged <18 years), and informed consent for a parent or guardianof any patient <18.

Key Exclusion Criteria:

Parts A and B

• Any clinically significant abnormalities on screening laboratories or physicalexamination 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 diseaseconsidered severe enough to interfere with the trial and/or confound the results.

• Cigarette smoking or dependence on caffeine, alcohol or drugs; unable or unwillingto abstain completely from caffeine, alcohol and related substances for 24 hoursprior 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 3months 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 withhypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumorsyndrome (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 medicationsfor the treatment of obesity.

• Bariatric surgery or procedure within the last 2 years.

• Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt orbehavior.

• Current, clinically significant pulmonary, cardiac, metabolic, or oncologic diseaseconsidered 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 3months or 5 half-lives, whichever is longer, prior to the first trial dose, orprevious 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 thehypothalamic injury.

Other protocol defined Inclusion/Exclusion criteria may apply.