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

Inclusion Criteria:

Healthy Subject Inclusion Criteria:

1. Males or females, age ≥18 and ≤65 years.

2. BMI ≥18 and ≤35 kg/m2.

3. Subjects are healthy on the basis of their medical history, physical examination,ECG, and routine laboratory data.

4. All subjects must be willing and able to provide written, signed informed consentand be willing and able to comply with all study procedures and tests.

Subjects with T2D: (MAD Cohorts) Inclusion Criteria:

1. Males or females, age ≥18 and ≤65 years.

2. Diagnosed with T2D within the last 15 years.

3. Treated with lifestyle management with or without at the most 3 anti-diabeticmedications with a stable dose for at least 2 months prior to screening. If onmetformin, the stable dose should be at least 500mg/day.

4. HbA1c ≥7.0% and ≤10.5%.

5. BMI ≥25 and ≤40 kg/m2.

6. Females are to be not pregnant, non-lactating.

7. All Subjects must be willing and able to provide written, signed informed consentand be willing and able to comply with all study procedures and tests.

Subjects with T2D: (Expansion Cohort) Inclusion Criteria:

1. Males or females, age ≥18 and ≤65 years.

2. Diagnosed with T2D within the last 7 years.

3. Treated with lifestyle management with or without at the most 3 anti-diabeticmedications with a stable dose for at least 2 months prior to screening. If onmetformin, the stable dose should be at least 500mg/day.

4. HbA1c ≥7.0% and ≤10.5%.

5. BMI ≥25 and ≤40 kg/m2.

6. Females are to be not pregnant, non-lactating.

7. All Subjects must be willing and able to provide written, signed informed consentand be willing and able to comply with all study procedures and tests.

Exclusion Criteria:

Healthy Subject 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 significantlyprolong 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 neoplasiaType 1.

5. History of stomach or intestinal surgery or resection (except appendectomy, herniarepair, and/or cholecystectomy).

6. A history or evidence of HIV, HCV, or HBV infection at screening or active COVID-19infection on screening.

7. Receiving an investigational intervention or having participated in another clinicaltrial within 30 days.

8. Currently dieting (formal weight loss program) and/or are currently using or haveused within 2 months of screening any drugs for weight management.

9. Received prior menin inhibitor treatment.

Subjects with T2D (MAD Cohorts) Exclusion Criteria:

1. Type 1 Diabetes Mellitus or a secondary form of diabetes or any prior history ofdiabetic ketoacidosis.

2. Have had recurrence (≥2 episodes) of severe hypoglycemia (defined by the occurrenceof neuroglycopenic symptoms requiring the assistance of another person for recovery)within the last 6 months prior to screening or, has a history of hypoglycemiaunawareness or poor recognition of hypoglycemic symptoms as judged by theInvestigator.

3. Known self or family history (first-degree relative) of multiple endocrine neoplasiaType 1.

4. Use of anti-diabetes medications (sulfonylureas, insulin, dipeptidyl peptidase-IVinhibitor [DPP-4I] [linagliptin and saxagliptin only] thiazolidinediones) withinlast 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 QTcinterval.

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 ULNwithout > 1.5 x ULN AST, ALT and/or total bilirubin but with a history of abnormalLFTs in the last 6 months or a medical history of a liver disorder should beexcluded.

10. History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 xULN.

11. Active HBV or active HCV at screening. Known positive test, if any, prior toscreening 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 toscreening).

13. Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150mmHg or diastolic blood pressure >90 mmHg).

14. History of stomach or intestinal surgery or resection and/or gastroparesis (exceptthat 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 haveused within 2 months of screening any drugs for weight management.

Subjects with T2D (Expansion Cohort) Exclusion Criteria:

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 neuroglycopenicsymptoms requiring the assistance of another person for recovery) within the last 6months prior to screening or, has a history of hypoglycemia unawareness.

4. Known self or family history (first-degree relative) of multiple endocrine neoplasiaType 1 (MEN1).

5. Use of any of the following anti-diabetes medications within 2 months prior toscreening: 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 orover-the-counter medications known to significantly prolong the QT or QTc intervalis 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 xULN.

12. Active HBV or active HCV at screening. Known positive test or history of HIV. Anactive COVID-19 infection at screening.

13. TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior toscreening).

14. Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150mmHg 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 haveused within 2 months of screening any drugs for weight management.