NEW YORK, N.Y. | June 18, 2026
Cambrian Bio has presented positive Phase 1b clinical data for ATX-304, the first AMPK Network Activator to enter clinical development, at the American Diabetes Association (ADA) 86th Scientific Sessions. The investigational oral therapy demonstrated statistically significant improvements across multiple cardiometabolic markers in adults with obesity and prediabetes, including reductions in liver fat, visceral adipose tissue, and triglycerides, while increasing adiponectin levels and resting metabolic rate (RMR). The randomized, double-blind, placebo-controlled study also showed that ATX-304 was generally well tolerated, with an overall safety profile comparable to placebo and no adverse events related to core body temperature, heart rate, or flushing. The findings provide the first clinical evidence of successful human translation of an AMPK Network Activator, supporting continued development of the novel metabolic therapy.
Phase 1b Trial Demonstrates Broad Metabolic Benefits
The Phase 1b study enrolled 23 adults with obesity and prediabetes who received either ATX-304 (400 mg once daily) or placebo for eight weeks, followed by an optional eight-week open-label extension. Investigators reported statistically significant improvements in several metabolic endpoints. Plasma adiponectin, a hormone associated with improved insulin sensitivity, increased significantly (p<0.01), while plasma triglycerides decreased significantly (p<0.01). Imaging assessments further showed meaningful reductions in liver fat, measured by MRI-proton density fat fraction (MRI-PDFF), and visceral adipose tissue, both reaching statistical significance (p<0.05). In addition, resting metabolic rate increased by 8% (p<0.01), consistent with the therapy’s mechanism of enhancing mitochondrial activity and whole-body energy expenditure. Minimal weight loss was observed at the tested dose, aligning with preclinical predictions that greater metabolic effects may emerge at higher exposures planned for later-stage studies.
Novel AMPK Activation Mechanism Differentiates ATX-304
A companion mechanistic presentation demonstrated that ATX-304 activates AMP-activated protein kinase (AMPK) through a pathway independent of reductions in cellular ATP levels, distinguishing it from previous AMPK-targeting strategies that have often been associated with impaired cellular energy balance. Laboratory findings confirmed that ATP levels were preserved across all tested concentrations while simultaneously increasing cellular glucose uptake and mitochondrial respiration. This balanced enhancement of energy production and utilization is designed to mimic key biological effects associated with aerobic exercise, potentially offering therapeutic benefits across obesity and other cardiometabolic diseases. Importantly, the absence of safety signals commonly linked to excessive mitochondrial activation—including changes in core body temperature or 24-hour heart rate monitoring—further supports the differentiated safety profile of ATX-304.
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Phase 2 REWIRE Studies Planned
Building on these encouraging early clinical findings, Cambrian Bio plans to advance ATX-304 into two Phase 2 clinical trials. The REWIRE-1 study will evaluate higher drug exposures to assess improvements in muscle function and lipid metabolism, while REWIRE-2 will investigate the therapy’s ability to support muscle-sparing weight loss in individuals with obesity. The company believes that targeting the AMPK metabolic network may offer a novel therapeutic strategy capable of reversing metabolic decline associated with aging while addressing obesity and related cardiometabolic disorders. As the first AMPK Network Activator to demonstrate clinical activity in humans, ATX-304 represents a promising investigational candidate with the potential to reshape the treatment landscape for metabolic disease through its unique mechanism of increasing energy expenditure without compromising cellular energy balance.
Source: Cambrian Bio press release
