Phase 3 Randomized Double-Blind Placebo-Controlled Study of KAI-9531 in Adults With Obesity or Overweight and Diabetes

The primary objective of this study is to evaluate the efficacy of KAI-9531 administered via subcutaneous injection once weekly compared to placebo in participants with obesity or overweight and diabetes. Specifically, the study seeks to demonstrate superiority in terms of the percent change in body weight and the change in hemoglobin A1c (HbA1c).

Secondary objectives include:

• Demonstration of superiority regarding percent change in body weight and change in HbA1c.
• Assessment of changes in waist circumference, fasting blood glucose, systolic blood pressure, and lipid parameters.
• Evaluation of the impact of weight on the quality of life using the IWQOL-Lite-CT questionnaire.
• Analysis of efficacy in a subgroup of participants with a body mass index (BMI) ≥35 kg/m2.
• Evaluation of maintenance dose effects on body mass index, diastolic blood pressure, and participant-reported outcomes including the COEQ and FNQ.
• Assessment of safety, tolerability, and immunogenicity of maintenance doses.
• Characterization of population pharmacokinetics and the relationship between drug concentration and clinical outcomes.

This clinical trial involves a total of 1074 participants diagnosed with type 2 diabetes mellitus. The study population includes both male and female individuals, including vulnerable groups, within the age ranges of 3 and 4. Participants are characterized by the presence of obesity and a body mass index of at least 27 kg/m2. Eligible subjects must have maintained stable therapy for their condition for three months prior to screening, which may consist of lifestyle modifications or specific oral medications. The exclusion criteria for stable therapy include the use of glucagon-like peptide-1 receptor agonist, glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor dual agonist, or dipeptidyl peptidase-4 inhibitor. Additionally, participants must have a documented history of at least one unsuccessful attempt at weight reduction through diet and exercise within the preceding six months. The primary objectives are to evaluate the effects of the investigational product on percent change in body weight and changes in hemoglobin A1c.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of KAI-9531 compared to a placebo in participants living with obesity and type 2 diabetes mellitus. The investigational product is administered via subcutaneous injection once weekly. The primary objectives are to demonstrate superiority in the percent change in body weight and the change in hemoglobin A1c from baseline at Week 76. The research methodology includes a screening visit to confirm eligibility based on criteria such as a body mass index of $\ge$27 kg/m2 and stable therapy for diabetes. Participants will undergo periodic study visits to monitor efficacy and safety endpoints, including changes in fasting blood glucose, blood pressure, and lipid profiles, through to the end-of-study assessment. The total duration of the trial is estimated to span from June 2026 to April 2028.

KAI-9531 is an experimental solution for injection containing the active substance TYROSYL-2-AMINOISOBUTYRYL-GLUTAMYL-GLYCYL-THREONYL-PHENYLALANYLTHREONYL-SERYL-ASPARTATE-TYROSYL-SERYL-ISOLEUCYL-TYROSYL-LYSYL([2-[2- AMINOETHOXY]ETHOXY]ACETYL-[2-[2-AMINOETHOXY]ETHOXY]ACETYL-GAMMA-GLUTAMYL-EICOSANOYL)-GLUTAMYL-LYSYL-ISOLEUCYL-ALANYL-ALANYL-GLUTAMINE-GLUTAMYL-PHENYLALANYL-VALYL-ASPARAGINE-CHROMYL-LEUCYL-LEUCYL-ALANYL-GLYCYL-GLYCYL-PROLYL-SERYL-SERYL-GLYCYL-ALANYL-PROLYL-PROLYL-PROLYL-SERYL AMIDE. The medication is administered via subcutaneous injection on a once weekly dosing schedule.

The placebo is a solution for injection that is identical to the KAI-9531 solution but contains no active drug.

The efficacy of KAI-9531 will be evaluated in participants living with obesity or overweight and diabetes. The primary endpoints consist of the percent change in body weight (kg) from baseline and the change in hemoglobin A1c (%) from baseline, both measured at Week 76.

Secondary efficacy assessments include several parameters measured at Week 76, such as:

• The percentage of participants achieving specific weight reduction thresholds of ≥5%, ≥10%, ≥15%, ≥20%, and ≥25%.
• Changes in waist circumference (cm), absolute weight (kg), and body mass index (kg/m2).
• The percentage of participants achieving HbA1c levels <7%, ≤6.5%, or <5.7%.
• Changes in fasting blood glucose (mg/dL), systolic blood pressure (mm Hg), and diastolic blood pressure (mm Hg).
• Percent changes in fasting triglycerides (mg/dL), HDL-cholesterol (mg/dL), non-HDL-cholesterol (mg/dL), total cholesterol (mg/dL), LDL-cholesterol (mg/dL), VLDL-cholesterol (mg/dL), and insulin (mIU/L).
• The percentage of participants with a ≥30% reduction in body weight.
• Changes in the IWQOL-Lite-CT physical function composite score, the Control of Eating Questionnaire (COEQ), and the Food Noise Questionnaire (FNQ) score.
• The percent change in body weight at Week 76 within a subgroup of participants with a BMI ≥35 kg/m2.