Our Scientific Approach

At DomainOne Therapeutics, our research is driven by a commitment to precision and innovation in fibrosis treatment.

We are pioneering small molecule antagonists that modulate TGF-β activation specifically at sites of inflammation. Unlike traditional fibrosis treatment strategies that focus on underlying comorbidities or broad immunosuppression, our approach selectively blocks TSP-1-mediated activation of TGF-β, to prevent excessive fibrotic signaling and promote healthy tissue repair.

By targeting the upstream, disease-specific activator of TGF-β, we aim to develop safer, more effective treatments for fibrosis-related diseases, including kidney, liver, lung, and cardiac fibrosis.

The Power of TSP-1 Modulation

At the core of DomainOne Therapeutics’ platform is a first-in-class approach to selectively block TGF-β activation by TSP-1. TSP-1 is a key regulator of TGF-β, controlling its conversion from an inactive to an active state, with highly regulated expression triggered by tissue damage or disease stimuli. By blocking TSP-1-mediated TGF-β activation at sites of inflammation, DomainOne Therapeutics’ small molecules prevent excessive pathogenic TGF-β activation, a major driver of fibrosis, inflammation, and cancer progression.
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This unique mechanism of action provides a highly targeted approach to stop fibrosis while leaving critical homeostatic TGF-β signaling intact. This will allow us to achieve efficacy without the systemic toxicities observed with previous systemic TGF-β-targeting therapies.

Scientist conducting microscopy research in a dimly lit laboratory, highlighting the precision and focus behind therapeutic discovery at DomainOne Therapeutics.

Team of scientists collaborating and sketching molecular structures on glass, illustrating innovative drug development at DomainOne Therapeutics.

How It Works

Fibrosis results from excessive TGF-β activation, which leads to uncontrolled tissue scarring and organ dysfunction. Our TSP-1 antagonists intervene by:

Preventing Pathologic TGF-β Activation – Selectively blocking TSP-1 halts the fibrotic signaling cascade in disease-relevant tissues.

Targeting Organ-Specific Fibrosis – Designed to treat kidney, liver, lung, and cardiac fibrosis with minimal off-target or on-target adverse effects.

Orally Available Therapy – Unlike monoclonal antibodies or complex biologics, our small molecule approach is patient-friendly and accessible.

Innovative R&D and Strategic Collaborations

DomainOne Therapeutics’ technology is built on decades of research into TSP-1 and TGF-β biology, providing a highly validated therapeutic strategy.

Founded on breakthrough research from the University of Alabama at Birmingham and Southern Research.

Supported by Orange Grove Bio, ensuring a strong translational pipeline from academic discovery to clinical development.

Extensive preclinical validation of MOA demonstrates efficacy in kidney, liver, lung, and cardiovascular fibrosis models.

Scientist analyzing CF gene therapy data in a modern research lab.

Group of scientists analyzing test tube samples and data under laboratory lighting, demonstrating collaborative discovery at DomainOne Therapeutics.

Our Pipeline

DomainOne Therapeutics’ lead program is focused on preventing kidney damage associated with acute kidney injury (AKI) and subsequent progression to chronic kidney disease (CKD), with potential expansion into other fibrotic disease, including liver fibrosis, cardiac fibrosis, systemic sclerosis, and Duchenne muscular dystrophy.

First-in-class TSP-1 antagonists designed to prevent fibrosis progression.

Strong preclinical efficacy across multiple fibrosis models.