Targeting TGF-β Activation to Treat Fibrosis
Innovative small molecule antagonists designed to disrupt fibrosis at its source.
About DomainOne Therapeutics
DomainOne Therapeutics is pioneering first-in-class small molecule antagonists that modulate TGF-β activation, a key driver of fibrosis, inflammation, and cancer. Our approach focuses on blocking Thrombospondin-1 (TSP-1), a key activator of TGF-β specifically at sites of tissue damage and inflammation. This site-specific targeting prevents tissue scarring without the systemic toxicity associated with traditional TGF-β inhibition.
A subsidiary of Orange Grove Bio, DomainOne Therapeutics is built on groundbreaking research from the University of Alabama at Birmingham and Southern Research. Our lead program targets Acute Kidney Injury (AKI) and the progression to chronic Kidney Disease (CKD), each of which is a serious and significant medical condition with large patient populations and no effective treatment options.

Our Science
DomainOne Therapeutics is redefining the paradigm for targeting TGF-β, a key regulator of fibrosis, inflammation, and cancer by developing small molecule antagonists of Thrombospondin-1 (TSP-1) a disease-relevant regulator of TGF-β activation at sites of inflammation. Our first-in-class small molecule antagonists are designed to disrupt fibrosis at its source, to prevent excessive tissue scarring while maintaining the body’s healthy repair functions.
01
Selective TGF-β Modulation
Suppress pathologic TGF-β activation and signaling specifically at sites of inflammation to prevent fibrosis without disrupting homeostatic processes.
02
Orally Available Small Molecules
A more accessible and patient-friendly alternative to biologics.
03
Targeted Fibrosis Therapy
Designed to treat the cause of kidney, liver, lung, and cardiac fibrosis while homeostatic processes are maintained.
Investing in the Future of Fibrosis Treatment
The impacts of AKI and CKD in the US and around the globe are huge– approximately 22% of all hospitalized patients experience AKI while the global prevalence of CKD is approaching an estimated 1 billion people– yet current treatments only manage symptoms rather than addressing the root cause. DomainOne Therapeutics’ TSP-1-targeted small molecules offer a novel approach to halting fibrotic progression while avoiding the systemic toxicity seen with direct systemic TGF-β inhibition.
Backed by Orange Grove Bio, and built on decades of research from the University of Alabama at Birmingham and Southern Research, DomainOne Therapeutics is advancing toward clinical development with a transformative approach to fibrosis treatment.