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.

Scientist in lab coat examining cell cultures through a microscope, representing biomedical research at DomainOne Therapeutics.

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.

In the News

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.

“As a scientist turned CEO and now director of a new commercialization engine at Southern Research, I’m thrilled about the launch of DomainOne Therapeutics. With three interconnected patent families licensed from UAB and SR, DomainOne is advancing promising TSP-1 inhibitors to treat fibrosis and sclerosis. This represents a major commercialization win for our Station 41 ecosystem.”

Dr. Erik Schwiebert
Director, Station 41

"For over 30 years, my research has focused on how TSP-1 activates TGF-β, driving fibrosis and immune suppression. It is incredibly gratifying to see DomainOne Therapeutics advancing this work into potential therapies. The team at Orange Grove Bio brings invaluable expertise in drug development, clinical trial design, and regulatory strategy, helping to translate these discoveries into first-in-class fibrosis treatments."

Headshot of Joanne Murphy-Ullrich, PhD
Dr. Joanne Murphy-Ullrich, PhD
Academic Founder, Professor Emerita, University of Alabama at Birmingham

Help Us Shape the Future of Fibrosis Therapy

Whether you’re a potential partner, investor, or advocate for advancing fibrosis research, we invite you to connect with us. Let’s bring life-changing treatments to patients in need.