Our Science

Fibrosis and fibro-inflammation: why it matters

Fibrosis is an aberrant response to tissue injury that can become chronic and self-perpetuating, resulting in progressive scarring and loss of organ function. It may be triggered by inflammation, infection, cell injury, trauma or cancer, among other causes. In normal physiology, scarring is self-limited; in chronic disease, the process can become prolonged and excessive, producing fibrotic remodeling that interferes with organ function.  

Immune cells are the main source of TGFβ and play a central role in initiating a fibrotic response. In turn, the presence of fibrosis further enhances immune activation and impairs the efficacy of anti-inflammatory therapies. Crucially, current treatments fail to address the fibrotic component of fibro-inflammatory diseases. Targeting both fibrosis and inflammation has the potential to allow better control of inflammation and address fibrotic remodeling, in a wide range of difficult-to-treat fibro-inflammatory disorders. 

Targeting the TGFẞ / ALK5 pathway with organ-restricted approach 

TGFβ is a key regulator of tissue repair and immune responses, helping to control inflammation under normal conditions but, when dysregulated, contributing to chronic inflammation, impaired healing, and ultimately fibrosis. As such, the TGFβ/ALK5 pathway is an attractive target for direct anti-fibrotic drug development. However, systemic inhibition of TGFβ/ALK5 has historically been limited by safety concerns, including cardiovascular toxicity. Therefore, there is a need for approaches that can act locally in the affected organ while limiting systemic exposure.  

Our concept is to develop organ-restricted ALK5 inhibitors designed to deliver direct anti-fibrotic activity in the target tissue. In Fibrostenosing Crohn’s Disease, a GI-restricted direct anti-fibrotic approach may complement established and emerging anti-inflammatory therapies by addressing the fibrotic component of fibro-inflammatory disease. In Idiopathic Pulmonary Fibrosis, where fibrosis is the primary driver of disease progression, a lung-restricted direct anti-fibrotic approach may have potential either as monotherapy or in combination with other anti-fibrotic therapies.  

View our pipeline

Broader discovery engine

Beyond our clinical-stage programs, we are advancing multiple small molecule and antibody candidates against validated and potentially disease-modifying targets for fibro-inflammatory indications. To date, we retain exclusive, worldwide development and commercialization rights to our product candidates and preclinical programs.