<br>        Inclusion Criteria:<br><br>          1. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each<br>             allele) genetic status for either the POMC or PCSK1 genes, with the loss-of-function<br>             (LOF) variant for each allele conferring a severe obesity phenotype.<br><br>          2. Age 6 years and above. 6+: US, Canada, UK, Germany, Spain, Belgium 12+:France<br><br>          3. If adult age =18 years, obesity with body mass index (BMI) = 30 kg/m2; if child or<br>             adolescent, obesity with weight > 97th percentile for age on growth chart assessment.<br><br>          4. Study participant and/or parent or guardian is able to communicate well with the<br>             investigator, to understand and comply with the requirements of the study, and be able<br>             to understand and sign the written informed consent/assent.<br><br>          5. Female participants of child-bearing potential must agree to use contraception as<br>             outlined in the protocol. Female participants of non-childbearing potential, defined<br>             as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral<br>             tubal ligation) or post-menopausal for at least 12 months (and confirmed with a<br>             screening FSH level in the post-menopausal lab range), do not require contraception<br>             during the study.<br><br>          6. Male participants with female partners of childbearing potential must agree to a<br>             double barrier method if they become sexually active during the study. Male patients<br>             must not donate sperm during and for 90 days following their participation in the<br>             study.<br><br>        Exclusion Criteria:<br><br>          1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the<br>             use of weight loss agents including herbal medications, that has resulted in weight<br>             loss or weight stabilization. Patients may be reconsidered approximately 1 month after<br>             cessation of such intensive regimens.<br><br>          2. Prior gastric bypass surgery resulting in >10% weight loss durably maintained from the<br>             baseline pre-operative weight with no evidence of weight regain. Specifically,<br>             patients may be considered if surgery was not successful, or resulted in <10% weight<br>             loss compared to pre-operative baseline weight or clear evidence of weight regain<br>             after an initial response to bariatric surgery. All patients with a history of<br>             bariatric surgery must be discussed with, and receive approval from Rhythm prior to<br>             enrollment.<br><br>          3. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic<br>             and Statistical Manual of Mental Disorders (DSM-III) disorders that the investigator<br>             believes will interfere significantly with study compliance.<br><br>          4. A Patient Health Questionnaire-9 (PHQ-9) score of = 15.<br><br>          5. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale<br>             (C-SSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the<br>             last month.<br><br>          6. Current, clinically significant pulmonary, cardiac, or oncologic disease, if these<br>             were severe enough to interfere with the study and/or would confound the results. Any<br>             such patients should be discussed with the sponsor prior to inclusion.<br><br>          7. History of significant liver disease or liver injury, or current liver assessment for<br>             a cause of abnormal liver tests [as indicated by abnormal liver function tests,<br>             alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, or<br>             serum bilirubin (> 2.0 x upper limit of normal (ULN) for any of these tests)] for an<br>             etiology other than non-alcoholic fatty liver disease (NAFLD). Thus, any underlying<br>             etiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH),<br>             other causes of hepatitis, or history of hepatic cirrhosis will be exclusionary, but<br>             the presence of NAFLD would not be exclusionary.<br><br>          8. History or presence of impaired renal function as indicated by clinically significant<br>             abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents (e.g.,<br>             albuminuria) or moderate to severe renal dysfunction as defined by the Cockcroft Gault<br>             equation < 30 mL/min (Appendix 11.10).<br><br>          9. History or close family history (parents or siblings) of skin cancer or melanoma, or<br>             patient history of ocular-cutaneous albinism.<br><br>         10. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions,<br>             determined as part of a screening comprehensive skin evaluation performed by a<br>             qualified dermatologist. Any concerning lesions identified during the screening period<br>             will be biopsied and results known to be benign prior to enrollment. If the<br>             pre-treatment biopsy results are of concern, the patient may need to be excluded from<br>             the study.<br><br>         11. Volunteer is, in the opinion of the Study Investigator, not suitable to participate in<br>             the study.<br><br>         12. Participation in any clinical study with an investigational drug/device within 3<br>             months prior to the first day of dosing.<br><br>         13. Significant hypersensitivity to study drug.<br><br>         14. Inability to comply with QD injection regimen.<br>