Fibrosis
SRK-373 for fibrosis
We have discovered novel, highly differentiated inhibitors of latent TGFβ1 activation that selectively target proTGFβ1 associated with the extracellular matrix, but not with immune cells. The aim of our approach is to target only the disease-causing pool of TGFβ1, and not the pool of TGFβ1 that is protective against inflammation. This approach is referred to as “context-dependent” or “context-specific” inhibition.” We envisage that this ability to differentially inhibit a subset of TGFβ1 signaling in fibrotic tissues, while maintaining normal immunosuppressive function intact, will be most suitable for the treatment of fibrotic diseases that accompany disease-driving inflammation.
Our preclinical studies have demonstrated that preventing TGFβ1 activation can offer a powerful new approach to treating fibrosis in multiple organs. We’re advancing preclinical research with the goal of developing new medicines for patients with fibrotic diseases.
Our selective approach could offer a novel way to suppress pro-fibrotic signaling in multiple organs, while minimizing adverse effects. TGFβ1 has historically proved to be a challenging therapeutic target since it acts in multiple biological pathways. Non-selective approaches risk inhibiting the signaling of two other forms of TGFβ (TGFβ2 and TGFβ3), resulting in unintended effects and treatment challenges. And in the context of fibrosis, selectively targeting TGFβ1 requires even greater selectivity. We believe our approach of targeting latent TGFβ1 in the extracellular matrix (where fibrosis occurs) offers the greatest level of selectivity in treating this chronic disease.
We are researching a highly potent, anti-latent TGFβ1 antibody that selectively inhibits TGFβ1 activation within the extracellular matrix by targeting latent TGFβ1 associated with latent TGFβ-binding proteins (LTBPs), which enables specific inhibition of TGFβ1 in fibrotic tissue. This is a unique strategy that specifically blocks latent TGFβ1 activation within the extracellular matrix, the primary location of fibrosis, but has no effect on latent TGFβ1 present on the surface of immune cells. This allows the targeting of the disease-associated TGFβ1 in fibrosis without interfering with immune-suppressing activities that provide protective effects in inflammatory conditions.
We are advancing our fibrosis program towards investigational new drug (IND)-enabling studies.
