A Phase 1, Multiple Ascending Dose Study to Evaluate HMS1005 in Participants With Type 2 Diabetes

Inclusion Criteria: 1. Males or females, of any race, between 18 and 65 years of age, inclusive. 2. Body mass index between 18 and 38.0 kg/m2, inclusive. 3. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix 3. 4. T2DM, as determined by the ADA Standard Care Diagnostic Criteria 2025, and * are drug naïve, treated with diet and exercise, or * have been on a stable dose of ≤2000 mg metformin for ≥1 month, and/or * have been on a stable dose of other antidiabetic medications for ≥90 days. 5. Except for findings consistent with T2DM, in good health, determined from medical history, 12-lead electrocardiogram (ECG), vital signs measurements, clinical laboratory evaluations, and physical examinations at screening and/or check in, as assessed by the Investigator (or designee). 6. Doses of antihypertensive and lipid-lowering therapies must be stable for 30 days prior to screening and remain unchanged during the study unless necessary to protect participant safety on an emergency basis (e.g., hypertensive crisis). 7. Glycated hemoglobin between 7.0% and 10.5%, inclusive. 8. Fasting plasma glucose between 126 and 240 mg/dL, inclusive. Testing may be repeated once, at the discretion of the Investigator (or designee). 9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Exclusion Criteria: 1. Type 1 diabetes mellitus, maturity onset diabetes of the young, or diabetes mellitus caused by damage to the pancreas or any other condition (eg, acromegaly or Cushing's syndrome). 2. Diabetic neuropathy, retinopathy, or nephropathy. 3. History of acute diabetic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, lactic acidosis, or hyperosmolar nonketotic coma within the 6 months prior to screening, or chronic metabolic acidosis. 4. History of severe hypoglycemia, defined as severe cognitive impairment requiring external assistance for recovery within 3 months prior to dosing; or recurrent hypoglycemia (Level 2), defined as ≥2 episodes within 3 months prior to dosing; or ADA Level 3 hypoglycemia within 6 months prior to dosing. 5. Hypoglycemia unawareness or asymptomatic hypoglycemia. 6. Clinically significant history of liver disease (eg, hepatitis and cirrhosis) within 1 year prior to screening. 7. Clinically significant history of renal disease. Mild to moderate chronic kidney disease is permitted. 8. Clinically significant history of cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, or congestive heart disease within 1 year prior to screening. Managed hypertension is permitted (defined as systolic blood pressure \<160 mmHg and/or diastolic blood pressure \<100 mmHg). 9. Clinically significant history of any central nervous system or psychiatric disease, including transient ischemic attack, stroke, seizure disorder, depression, or behavioral disturbances within 1 year prior to screening. 10. Clinically significant gastric emptying abnormality (eg, severe diabetic gastroparesis or gastric outlet obstruction) or have had gastric bypass surgery. 11. Clinically significant or unstable history of any hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, endocrine, or psychiatric disorder, as determined by the Investigator (or designee). 12. Known or active malignancy, except basal cell carcinoma and cutaneous squamous cell carcinoma. 13. Any hospital admission or major surgery within 90 days prior to screening. 14. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the Investigator (or designee). 15. Fasting C peptide \< 0.81 ng/mL. 16. Alanine aminotransferase, aspartate aminotransferase, or gamma glutamyl transferase \>2 × the upper limit of normal (ULN); or total bilirubin \>1.5× ULN. Testing may be repeated once, at the discretion of the Investigator (or designee). 17. Uncontrolled hypertriglyceridemia \> 500 mg/dL. 18. Estimated glomerular filtration rate ≤ 45 mL/minutes/1.73 m2, as calculated using the 2021 Chronic Kidney Disease Epidemiology equation. 19. Hemoglobin ≤120 g/L (male) or ≤110 g/L (female). 20. QT interval corrected for heart rate using Fridericia's method \> 450 msec. 21. Positive hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency (HIV 1 and HIV 2) antibodies and p24 antigen. 22. Positive pregnancy test. 23. Use of insulin, sulfonylureas, GLP-1 agonists, DPP-4 inhibitors, SGLT2 inhibitor and glinides (eg, repaglinide and nateglinide). 24. Use of any strong or moderate cytochrome P450 (CYP) 3A4 inducers within 28 days prior to dosing or any strong or moderate CYP3A4 inhibitors within 7 days or 5 half-lives, whichever is longer, prior to dosing (Appendix 5). 25. Use of any P glycoprotein inducers within 14 days prior to dosing or any P glycoprotein inhibitors within 5 days or 5 half-lives, whichever is longer, prior to dosing (Appendix 6). 26. Use of any carboxylesterase 2 inhibitors within 5 days or 5 half-lives, whichever is longer, prior to dosing (Appendix 7). 27. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days. 28. Positive alcohol test result, or positive urine drug screen (confirmed by repeat) at screening or check in. 29. Current drug abuse, defined as the use of any illegal substance or misuse or excessive used of over the counter or prescription drugs; or current alcohol abuse, defined as the inability to stop or control alcohol use, despite adverse social or health consequences. 30. Consumption of alcohol, or caffeine containing foods or beverages within 48 hours, or foods and beverages containing grapefruit or Seville oranges within 7 days prior to check in. 31. Use of tobacco or nicotine containing products within 1 month prior to screening. 32. Receipt or donation of \> 1 unit (approximately 450 mL) of blood products within 3 months prior to screening. 33. Poor peripheral venous access. 34. Participants who, in the opinion of the Investigator (or designee), should not participate in this study.