What it is
ATX-304, formerly called O304, is an investigational oral small molecule rather than a peptide, stimulant, or anabolic agent. It is described as a peripherally restricted AMPK network activator in development for obesity and obesity-associated cardiometabolic disease.
The mechanism is broader than AMPK alone
The original research found that O304 increased AMPK activity by suppressing dephosphorylation of activated AMPK. Later work showed increased mitochondrial respiration through proton leak. In practical terms, ATX-304 can increase both fuel availability and metabolic demand: cells take up and oxidize more substrate while some of the mitochondrial gradient is dissipated rather than captured through ATP synthase.
The early human metabolic signal
A small randomized Phase 1b study enrolled 23 adults with obesity and prediabetes. Participants received a 400 mg ATX-304 sodium-salt tablet once daily or placebo for eight weeks, followed by an optional open-label extension. The conference report described higher adiponectin, lower triglycerides, reduced liver and visceral fat, and an increase in resting metabolic rate. Minimal weight loss occurred at that exposure. The study remains a small sponsor-affiliated conference report rather than a full peer-reviewed outcomes paper.
The older diabetes trial was less decisive
The earlier TELLUS study administered 1,000 mg/day of an O304 oral suspension for 28 days to 65 people with type 2 diabetes taking metformin. The prespecified between-group fasting-glucose endpoint was not significant. Favorable glucose and insulin-resistance findings came from within-group and post-hoc analyses. Adverse events were similar between groups, with no serious adverse event in the O304 arm.
What the preclinical work adds
Mouse studies reported improved glucose handling, exercise capacity, cardiac function, body fat, cholesterol, liver steatosis, and fibrosis. ATX-304 shifted liver metabolism toward greater fatty-acid oxidation and less lipid synthesis. Those findings make body composition, liver fat, lipids, and training performance relevant observations, but they do not establish the result in a healthy trained person.
Exposure and safety context
The current personal total of 400 mg/day matches the nominal daily amount used in the Phase 1b study, but the schedule and product are not equivalent: the clinical study used one daily dose of a specifically formulated sodium-salt tablet. Short human studies were reasonably reassuring, and the Phase 1b report described no increase in continuously monitored core temperature or 24-hour heart rate. They do not establish long-term safety, athletic performance, muscle preservation, or the effects of combining ATX-304 with other metabolic research compounds.
Sources
- Thieroff-Ekerdt et al., Diabetes 2026 abstract 1782-P — Phase 1b design and initial human metabolic findings.
- Cambrian Bio Phase 1b report — reported effect details, tolerability, and planned next studies.
- EU Clinical Trials Register: TELLUS — official O304 Phase 2a design, endpoints, pharmacokinetics, and adverse events.
- Steneberg et al., JCI Insight 2018 — AMPK mechanism, preclinical metabolic work, and the TELLUS report.
- Norlin et al., Communications Biology 2023 — mitochondrial proton leak, glucose utilization, and diabetic mouse models.
- Holm et al., JCI Insight 2025 — body-fat, cholesterol, liver-fat, fibrosis, and metabolic-switching findings in mice.