Study of Subcutaneously Administered ENT-03 for the Treatment of Obesity and Diabetes

Prior treatment

• Bariatric surgery within the past five years.
• Patients on anti-diabetic medications other than metformin.
• History of major depressive disorder within the previous two years, a lifetime history of suicide attempt, suicidal behavior within the previous month, or history of other severe psychiatric disorders.
• Use of medications affecting body weight within the past three months:
  • Drugs approved for the treatment of obesity
  • Cyproheptadine or medroxyprogesterone
  • Atypical anti-psychotic drugs
  • Tricyclic antidepressants
  • Lithium, MAO's, glucocorticoids
  • SSRI's or SNRI's
  • Antiepileptic drugs
• Participation in an investigational drug trial within the month prior to dosing in the present study.

Other illness

• History of excessive alcohol use (defined as \>21 drinks per week for males and \>14 drinks per week for females), recreational drug use within the past three months, or failure on urinary drug screen.
• Evidence of eating disorders.
• Diseases interfering with metabolism and/or ingestive behavior (e.g., myxedema, Cushing's disease, schizophrenia, major psychoses).

Lab values

• Significant renal impairment (eGFR \<60 mg/mL/1.73m2).
• Liver function tests (i.e., ALT, AST, alkaline phosphatase) greater than twice the upper limit of normal upon repeated measurements.
• Any clinically significant abnormality following the Investigator's review of the physical examination and clinical laboratory tests.
• A baseline prolongation of QT/QTc interval after repeated measurements of \>450 ms; a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).

Other

• Pregnant or breastfeeding within six months of screening assessment.
• Substantial changes in eating habits or exercise routine within the preceding three months.
• \>5% weight change in the past three months.
• Patients with gastroparesis.
• Score of \>15 on the Columbia Suicide Severity Rating Scale (C-SSRS).

• Subjects aged 18-70 years, both genders.
• Healthy as determined by a physician, based on history, medical examination, vital signs, and laboratory tests.
• Males that agree to use condoms for the duration of participation in the study.
• Females of non-child-bearing potential (i.e., tubal ligation, hysterectomy, or postmenopausal).
• Female patients of child-bearing potential with negative serum pregnancy tests and who agree to use double-barrier contraception during the study.
• Subjects must be able to read, speak, and understand English and/or Spanish and provide written informed consent, and be willing and able to comply with study procedures.
• Subjects must have a BMI 30-35 kg/m2 inclusive assessed immediately prior to screening.
• Fasting insulin level ≥11 mIU/L.
• HbA1c \< 8.5% (diabetic subjects only).
• Subjects with Type 2 diabetes on no anti-diabetic medication or on stable doses of metformin for 4 weeks or more (diabetic cohorts only).
• No history of active or chronic disease other than that allowed by study: hypertension, hyperlipidemia, hyperglycemia, GERD, heartburn, or Type 2 diabetes (cohorts 6 and 7 only).