Phase 1/1b Study of TLC-6740 in Healthy Subjects and Subjects with Obesity, with or Without Diabetes

Inclusion Criteria:

• Non-smoking, healthy male or female subject between 18 and 55 years of age,inclusive (Parts A-E); male or female subject between 18 and 70 years of age,inclusive (Parts F, G)

• Body mass index (BMI) from 19 to 35 kg/m2, inclusive (Parts A-E); BMI ≥ 30 kg/m2 and ≤ 50 kg/m2 (Parts F, G)

• Estimated glomerular filtration rate (eGFR) ≥ 80 mL/min (Parts A-E); eGFR ≥ 60mL/min/1.73m2 or eGFR ≥ 45 mL/min/1.73m2, depending on cohort (Parts F, G)

• ALT/AST/ALP ≤ 1 x ULN (Parts A-E); ALT/AST < 3 x ULN, ALP < 1.5 x ULN (Parts F, G)

• Screening laboratory evaluations (hematology, chemistry, and urinalysis) must fallwithin the normal range of the local laboratory's reference ranges unless theresults have been determined by the investigator to have no clinical significance (Parts A-E)

• Subject must have either a normal 12-lead electrocardiogram (ECG) or one withabnormalities that are considered clinically insignificant by the investigator

• Females of childbearing potential must have a negative pregnancy test at Screeningand clinic admission

• Male subjects and female subjects of childbearing potential who engage inheterosexual intercourse must agree to use protocol-specified method(s) ofcontraception

• Must, in the opinion of the investigator, be in good health based upon medicalhistory and physical examination, including vital signs

Exclusion Criteria:

• Pregnant or lactating subjects

• Unstable type 2 diabetes (as defined as: HbA1c > 10.0%; treatment with insulinand/or pioglitazone within 90 days prior to Screening; any history of diabeticketoacidosis, hyperosmolar state, and/or acutely decompensated blood glucosecontrol; hypoglycemia unawareness, hospitalization due to hypoglycemia, or historyof severe hypoglycemia [requiring outside assistance to regain normal neurologicstatus]) (Part F)

• History of type 2 diabetes diagnosed prior

• Medical history of type 1 diabetes or latent autoimmune diabetes of adults (LADA)

• Obesity induced by other endocrinologic disorders (e.g., Cushing syndrome) ordiagnosed monogenetic or syndromic forms of obesity (e.g., melanocortin 4 receptordeficiency or Prader-Willi syndrome)

• Known serious hypersensitivity to tirzepatide or any of the excipients intirzepatide (Part G)

• Subjects who have any serious or active medical or psychiatric illness (includingdepression) that, in the opinion of the investigator, would interfere with thesubject's treatment, assessment, or compliance with the protocol

• Subjects who have received any investigational compound within 30 days or 5half-lives, whichever is longer, prior to study drug dosing

• Current alcohol abuse that is judged by the investigator to potentially interferewith the subject's compliance or safety

• Current substance abuse that is judged by the investigator to potentially interferewith the subject's compliance or safety

• A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitisB (HBV) surface antigen, or hepatitis C (HCV) antibody

• Medical history of drug sensitivity or drug allergy (such as anaphylaxis orhepatoxicity)

• Presence or history of cardiovascular disease, including significant cardiovasculardisease (including a history of myocardial infarction based on ECG and/or clinicalhistory), history of cardiac conduction abnormalities (including any history ofventricular tachycardia), congestive heart failure, cardiomyopathy with leftventricular ejection fraction < 40%, a family history of Long QT Syndrome, orunexplained death in an otherwise healthy individual between the ages of 1 and 30years

• Syncope, palpitations, or unexplained dizziness

• Implanted defibrillator or pacemaker

• Medical history of liver disease, including but not limited to alcoholic liverdisease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosingcholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease,clinically significant iron overload, or alpha-1-antitrypsin deficiency)

• Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acidhypersecretory conditions

• History of medical or surgical treatment that permanently alters intestinalabsorption (e.g., gastric or intestinal surgery)

• Subjects who have received vaccination for COVID-19 within 14 days of Admission

Note: Other protocol defined Inclusion/Exclusion criteria may apply.