Metabolic Disease

Metabolic syndrome — the cluster of central obesity, insulin resistance, dyslipidemia, and hypertension — affects roughly a quarter of adults worldwide. Its unifying biology is inflammation of adipose tissue.

Adipose tissue as an immune organ

In lean individuals, adipose tissue contains a small population of anti-inflammatory M2 macrophages and regulatory T cells that maintain insulin sensitivity. In obesity, this balance inverts: macrophages shift to a pro-inflammatory M1 phenotype, T cells skew toward Th1 and Th17, and the tissue becomes a source of TNF, IL-6, and free fatty acids.

This inflammatory state directly causes insulin resistance by interfering with insulin signaling in adipocytes, muscle, and liver. It also drives ectopic fat deposition and the progression from simple steatosis to steatohepatitis and fibrosis.

The gap in current treatment

GLP-1 receptor agonists have transformed obesity treatment, producing substantial weight loss and improving metabolic markers. But weight loss alone does not resolve adipose inflammation in all patients, and a significant fraction do not achieve durable metabolic benefit. There is a clear opportunity for therapies that target the inflammatory component directly — either alone or in combination with incretin-based therapy.

Our approach

Our metabolic program targets a chemokine axis that recruits pro-inflammatory monocytes into adipose tissue. By blocking recruitment rather than systemic cytokine signaling, we aim to restore insulin sensitivity without broad immunosuppression. The program is in lead optimization, with candidate selection targeted for next year.