ATX-304

Target Indication: Obesity and Obesity Associated Diseases

Phase: Phase 2

ATX-304 is a full-spectrum AMPK activator that increases both energy supply and metabolic demand. The drug is a peripherallyrestricted, oral small molecule entering Phase 2 clinical trials in obesity and other cardiometabolic diseases.

Understanding the mechanism

AMPK: the master regulator of cellular energy balance

AMPK governs a signaling network that controls how cells sense and respond to energy demand. Full-spectrum activation of this network drives glucose and fatty acid uptake while increasing mitochondrial proton conductance, elevating whole-body energy expenditure in a manner that closely resembles aerobic exercise training. When this network declines with age, or chronic nutrient excess, the consequences ripple across metabolism.

AMPK signaling declines with age and obesity

As AMPK activity declines with aging or chronic nutrient excess, cells lose the ability to adapt to shifts in energy demand, limiting fat oxidation, glucose uptake, and mitochondrial energy production.

This loss of metabolic flexibility is a primary driver of insulin resistance, excess fat accumulation, and the progression of cardiometabolic disease.

Li, M., et. al. Mech. Aging. Dev. 2012. 133(11-12). 655-64. DOI: 10.1016/j.mad.2012.09.001.
Mortensen, B., et. al. Am. J. Physiol. Endocrinol. Metab. 2009. 297. E956-64. DOI: 10.1152/ajpendo.00058.2009.

ATX-304 is designed to restore balance through targeted activation

ATX-304 activates the AMPK network through a mechanism independent of cellular ATP levels, increasing mitochondrial proton conductance and driving glucose and fatty acid uptake simultaneously. In a Phase 1b study in adults with obesity and prediabetes, this translated to statistically significant improvements in liver fat, visceral adipose tissue, triglycerides, adiponectin, and resting metabolic rate.

ATX-304 has broader
implications for metabolic health

Amplifier’s approach builds on decades of research, translating discoveries about metabolic aging into new medicines that can safely restore healthy metabolism.

By improving the cellular processes that regulate energy balance, we aim to advance how metabolic health can be maintained and sustained across metabolic diseases and during natural aging.