A Phase 1 Randomized, Double-blind, Placebo-controlled Single-ascending Dose and Multiple-ascending Dose (SAD and MAD) Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Isoform-specific AMPK Activator BLX-0871 in Healthy Adults With a Body Mass Index (BMI) of 20 - 35 kg/m2

This is a Phase 1, single-center, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and the effect of food on the PK of BLX-0871, a novel oral small-molecule AMPK activator, in healthy adult volunteers. The study consists of three parts: single ascending dose (SAD), food effect (FE), and multiple ascending dose (MAD) assessments.

Study Rationale and Objectives BLX-0871 is being developed as an oral small-molecule activator of AMP-activated protein kinase (AMPK), a central regulator of energy metabolism. AMPK activation promotes glucose uptake and fatty acid oxidation, supporting potential use in metabolic diseases such as type 2 diabetes and obesity. This first-in-human study is designed to characterize the initial safety profile, define the PK properties of BLX-0871, evaluate preliminary PD biomarkers of metabolic activity, and determine the impact of a high-fat meal on oral absorption.

Study Design Overview The study will enroll approximately 76 healthy adults across three sequential parts.

Part 1: Single Ascending Dose (SAD) This is a randomized, double-blind, placebo-controlled, sequential SAD study in up to four cohorts (approximately 8 participants per cohort; 6 active, 2 placebo). Doses will escalate sequentially following review of blinded safety, tolerability, PK, and PD data by a Safety Review Committee (SRC). A sentinel dosing approach will be used for each cohort (1 active, 1 placebo) prior to dosing the remainder of the cohort. Participants will be confined in the clinical research unit (CRU) for approximately 4 days for safety monitoring and PK/PD blood sampling, with an end-of-study (EOS) visit on Day 8. SAD data will inform dose selection for the FE and MAD parts of the study.

Part 2: Food Effect (FE) This is an open-label, randomized, 2-period, 2-sequence crossover study designed to evaluate the effect of a high-fat, high-calorie meal on the PK of a single oral dose of BLX-0871. A single cohort of 12 participants will receive BLX-0871 under both fasted and fed conditions, with a 7-day washout between doses. Participants will be confined for approximately 4 days in each period, with safety, PK, and PD assessments performed throughout. The SRC may adjust the washout interval or timing of assessments based on PK results from the SAD cohorts to ensure adequate elimination between periods.