A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMF-650 in Otherwise Healthy Overweight or Obese Participants.

This is a single center, double-blind, randomized, placebo-controlled, first-in-human (FIH) study of BMF-650, an oral non-peptide GLP-1 receptor agonist administered to otherwise healthy overweight or obese participants. Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study.

Inclusion Criteria:

1. Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures.
2. Must be willing and able to comply with all study requirements
3. Healthy males or non-pregnant, non-lactating healthy females with obesity or overweight.
4. For Part 1 (SAD cohorts), BMI of 25.0 to 40.0 kg/m2 as measured at screening, with no chronic health conditions.
5. For Part 2 (MAD cohorts), BMI of 30.0 to 45.0 kg/m2, as measured at screening with no chronic health conditions.
6. Have a stable body weight (less than or equal to 5% body weight gain or loss) for 3 months prior to screening.
7. HbA1c ≤ 6.5%

Exclusion Criteria:

Medical/Surgical History and Mental Health

1. Known self or family history (first-degree relative) of medullary thyroid cancer and/or multiple endocrine neoplasia Type 2 (MEN2).

2. History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy and/or hernia repair will be allowed).

3. Significant history of or currently have major depressive disorder or psychiatric disorder or suicidal ideation within the last 2 years.

4. Severe uncontrolled treated or untreated hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP >90 mmHg).

5. Mean QTcF interval greater than 450 msec on triplicate ECGs.

   Diagnostic Assessments

6. Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator

7. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.

8. eGFR of <60 mL/min/1.73 m2

9. AST, ALT or total bilirubin > ULN

10. Lipase and/or amylase > ULN

11. Calcitonin ≥20 ng/L

    Prior Study Participation

12. Participants who have received any IMP in a clinical research study within 5 half -lives or within 30 days prior to first dose

    Prior and Concomitant Medication

13. Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than HRT/hormonal contraception) in the 14 days before first IMP administration

14. Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.

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

16. Participants who have previously used GLP-1 receptor agonist, or GIP/GLP-1 dual receptor agonists, or any investigational medicine containing a GLP-1 and/or GIP receptor agonist in the 6 months prior to first IMP administration

This is a double-blind study. Treatment assignment will not be known to the participants, the sponsor or the staff who are involved in the clinical evaluation of the participants and the analysis of data as indicated in the blinding plan. If appearance matching of the placebo is not possible then use of masking and/or unblinded dosing teams will be used to preserve the study blind.