Study of BMF-219 in Healthy Adult Subjects and in Adult Subjects With Type 2 Diabetes Mellitus (T2D)

Exclusion Criteria

• •1. Evidence or history of any clinically significant disease or malignancy.
• •2. Mean QTcF ≥ 440 msec on triplicate ECGs. Use of medications known to significantly prolong the QT or QTcF interval.
• •3. History of hypertension or untreated hypertension (sitting systolic blood pressure (BP) ≥140 and diastolic BP ≥90 mm Hg).
• •4. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
• •5. History of stomach or intestinal surgery or resection (except appendectomy, hernia repair, and/or cholecystectomy).
• •6. A history or evidence of HIV, HCV, or HBV infection at screening or active COVID-19 infection on screening.
• •7. Receiving an investigational intervention or having participated in another clinical trial within 30 days.
• •8. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
• •9. Received prior menin inhibitor treatment.
• •1. Type 1 Diabetes Mellitus or a secondary form of diabetes or any prior history of diabetic ketoacidosis.
• •2. Have had recurrence (≥2 episodes) of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms as judged by the Investigator.
• •3. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
• •4. Use of anti-diabetes medications (sulfonylureas, insulin, dipeptidyl peptidase-IV inhibitor \[DPP-4I\] \[linagliptin and saxagliptin only\] thiazolidinediones) within last 2 months prior to screening.
• •5. Fasting plasma glucose ≥255 mg/dL, fasting C-peptide \<0.8 ng/mL, fasting insulin \>55 μIU/mL.
• •6. Mean QTcF ≥450 ms. Use of medications known to significantly prolong the QT or QTc interval.
• •7. Fasting triglyceride ≥500 mg/dL.
• •8. Have an eGFR \<60 mL/min/1.73 Equation at screening.
• •9. AST or ALT \> 1.5 × ULN, bilirubin \> 1.5 × ULN. Isolated GGT elevation \>2.5 ULN without \> 1.5 x ULN AST, ALT and/or total bilirubin but with a history of abnormal LFTs in the last 6 months or a medical history of a liver disorder should be excluded.
• •10. History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
• •11. Active HBV or active HCV at screening. Known positive test, if any, prior to screening or history of HIV. An active COVID-19 infection at screening.
• •12. TSH \>6 mIU/L or \<0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
• •13. Severe uncontrolled treated or untreated hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg).
• •14. History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed).
• •15. History of cirrhosis.
• •16. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
• •1. Type 1 Diabetes Mellitus or a secondary form of diabetes.
• •2. Prior history of diabetic ketoacidosis or hyperosmolar coma.
• •3. History of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness.
• •4. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1 (MEN1).
• •5. Use of any of the following anti-diabetes medications within 2 months prior to screening: sulfonylureas, insulin, and the dipeptidyl peptidase-4 inhibitors (DPP4i) linagliptin and saxagliptin (sitagliptin and other DPP4i allowed) thiazolidinones \[TZD\]) within last 2 months prior to screening.
• •6. Fasting plasma glucose ≥255 mg/dL, fasting C-peptide \<0.8 ng/mL, fasting insulin \>55 μIU/mL.
• •7. Mean QTcF interval \>450 ms on triplicate ECGs. Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.
• •8. Fasting triglyceride ≥500 mg/dL.
• •9. eGFR\<60 mL/min/1.73.
• •10. AST or ALT \>1.5 × ULN, Total bilirubin \>1.5 × ULN at screening.
• •11. History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
• •12. Active HBV or active HCV at screening. Known positive test or history of HIV. An active COVID-19 infection at screening.
• •13. TSH \>6 mIU/L or \<0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
• •14. Severe uncontrolled treated or untreated hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg).
• •15. History of stomach or intestinal surgery or resection and/or gastroparesis.
• •16. History of cirrhosis.
• •17. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.