Cambrian Bio Presents Positive Human Translational Data for ATX-304, the First AMPK Network Activator, at the American Diabetes Association's 86th Scientific Sessions

• Phase 1b data establish first clinical evidence of human translation of an AMPK Network Activator, with statistically significant improvements in liver fat, visceral adipose tissue, triglycerides, adiponectin, and resting metabolic rate in adults with obesity and prediabetes
• Overall tolerability profile comparable to placebo. No adverse events related to core body temperature, flushing, or heart rate
• Companion mechanistic poster confirms ATX-304 activates AMPK without decreasing cellular ATP levels, distinguishing it from prior AMPK-targeting approaches
• Phase 2 studies REWIRE-1 and REWIRE-2 planned to assess exercise mimetic effects and muscle-sparing weight loss

NEW YORK--(BUSINESS WIRE)--Cambrian Bio, a clinical-stage drug development company with pipeline therapies targeting critical metabolic pathways that decline with age, today announced the presentation of first human clinical data for ATX-304, an AMP-activated protein kinase (AMPK) Network Activator in clinical development for obesity and other forms of cardiometabolic disease. The data were presented in two poster sessions at the American Diabetes Association’s (ADA) 86th Scientific Sessions that took place June 5–8, 2026, in New Orleans, Louisiana.

ATX-304 is the first AMPK Network Activator to enter clinical development. Its mechanism targets two complementary cellular processes that drive metabolic decline. ATX-304 increases both cellular glucose uptake and mitochondrial respiration, resulting in a balanced increase of energetic supply and demand – which drives an increase in whole-body metabolic rate. The Phase 1b results confirm that ATX-304's preclinical promise translated to humans, with statistically significant improvements observed across multiple measures of lipid metabolism, body composition, and energy expenditure.

The Phase 1b study (Abstract #1782-P) enrolled 23 adults with obesity and prediabetes in a randomized, double-blind, placebo-controlled design with an optional open-label extension (OLE). Participants received ATX-304 400 mg once daily or placebo for 8 weeks, followed by an 8-week OLE.

ATX-304 produced statistically significant, time-dependent improvements in lipid metabolism and body composition. Plasma adiponectin increased significantly (p<0.01), and plasma triglycerides decreased significantly (p<0.01). Liver fat, measured by MRI-PDFF, decreased significantly (p<0.05), as did visceral adipose tissue (p<0.05).

ATX-304 also increased resting metabolic rate (RMR) by 8% (p<0.01), consistent with the drug's mechanism of increasing energy expenditure through mitochondrial activation. Minimal weight loss was observed at this exposure level, consistent with preclinical predictions.

Treatment-emergent adverse events (TEAEs) were predominantly mild and occurred at a similar frequency to placebo. Critically, no adverse events indicative of mitochondrial failure were observed, including no increase in continuously monitored core body temperature or 24-hour heart rate. No new safety signals were observed during the OLE.

Pharmacokinetic data confirmed that ATX-304 exposure in this study reached the threshold predicted to translate the metabolic effects observed in preclinical models.

“Unlocking the potential of AMPK activation has been a major drug development goal for almost 30 years, and for the first time, we have demonstrated activity of an AMPK activator in humans,” said James Peyer, PhD, CEO and Founder of Cambrian Bio. “The full AMPK Network Activation of ATX-304 elevates overall metabolic activity in a cell, driving up both substrate availability and use, increasing energy expenditure in a manner that closely resembles aerobic exercise training.”

"The Phase 1b data for ATX-304 demonstrate statistically significant improvements across multiple metabolic parameters, including liver fat, visceral adipose tissue, triglycerides, adiponectin, and resting metabolic rate," said Ruth Thieroff-Ekerdt, MD, Chief Medical Officer of Cambrian Bio and corresponding author of the Phase 1b poster. "The absence of any adverse events indicative of mitochondrial uncoupling, including no increase in continuously monitored core body temperature or 24-hour heart rate, is a particularly important finding for a drug that increases energy expenditure. We look forward to advancing ATX-304 into Phase 2 studies to further explore its applications in reversing metabolic decline and treating obesity."

Cambrian has plans for two Phase 2 clinical studies: REWIRE-1, which aims to evaluate the effect of higher exposures of ATX-304 on muscle function and lipid metabolism, and REWIRE-2, which aims to demonstrate proof of concept in weight loss for people with obesity.

Mechanistic Data Confirm Differentiated AMPK Activation (Abstract #1788-P)

A companion poster presented at ADA 2026 characterized ATX-304's mechanism of action at the cellular and mitochondrial level. The data demonstrate that ATX-304 activates AMPK through a mechanism independent of changes in cellular ATP levels, and that ATX-304 preserved ATP levels at all tested concentrations.

Next Steps

Based on these results, Cambrian Bio plans to advance ATX-304 into Phase 2 studies at higher exposures to evaluate its utility in reducing body weight through mobilization of lipids from adipose and ectopic fat tissue and increasing energy expenditure.

Poster Presentation Details

Abstract #1782-P: Phase 1b Study Results of AMPK/Mitochondrial Activator ATX-304 in Prediabetic Obese Participants | American Diabetes Association 86th Scientific Sessions, June 5–8, 2026, New Orleans, LA

Abstract #1788-P: AMPK Activation by ATX-304 Is Not Secondary to Changes in ATP Levels | American Diabetes Association 86th Scientific Sessions, June 5–8, 2026, New Orleans, LA

About ATX-304

ATX-304 is an AMPK Network Activator that increases both energy supply and metabolic demand. The drug is a peripherally restricted, oral small molecule entering Phase 2 clinical trials in obesity and other cardiometabolic diseases. In a human study in adults with obesity and prediabetes, ATX-304 produced statistically significant improvements in lipid metabolism, body composition, and resting metabolic rate. In preclinical studies, ATX-304 demonstrated muscle-sparing weight loss in obese animals, reversal of multiple cardiometabolic diseases, and major improvements in exercise endurance. ATX-304 is an investigational drug agent that is not available for human use outside a clinical trial setting.

About Cambrian Bio

Cambrian Bio (Cambrian BioPharma Inc.) is a clinical-stage drug development company focused on building therapeutics to treat and prevent today’s most debilitating chronic diseases, with programs targeting critical metabolic sensing functions that decline with age, including AMPK and mTOR. To learn more, visit www.CambrianBio.com and follow us on LinkedIn and X.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of applicable securities laws, including statements regarding the planned clinical development of ATX-304, anticipated Phase 2 studies, and the potential therapeutic benefits of ATX-304. Forward-looking statements are generally identified by words such as 'plan,' 'expect,' 'anticipate,' 'intend,' 'believe,' and similar expressions. These statements are based on management's current expectations and assumptions and are subject to a number of known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially, including the inherent uncertainty of clinical development, regulatory requirements, and the availability of funding. Cambrian Bio undertakes no obligation to update or revise any forward-looking statements as a result of new information, future events, or otherwise, except as required by law.