GFB-887 is a precision-based, podocyte-targeting, small molecule inhibitor of TRPC5, designed specifically to treat individuals with kidney diseases associated with an over-activation of the TRPC5-Rac1 pathway. GFB-887 is designed to reduce proteinuria and maintain podocyte number without modulating blood pressure.
GFB-887’s differentiating attributes
Urinary Rac1 biomarker has the potential to predict a subset of patients most likely to respond to treatment
Mechanism of action is a clinically validated pathway shown to be implicated in kidney diseases
Once-daily, orally administered improving ease of use and patient compliance
Non-immunosuppressant unlike other therapies used by people with FSGS
Mechanism of GFB-887
TRPC5 is a calcium-permeable, nonselective cation channel. Under healthy conditions, the TRPC5 channel is present on intracellular vesicles of the podocyte with limited cell surface expression and activity. Overactivation of Rac1 signaling leads to TRPC5 insertion into the plasma membrane and channel activation. This leads to calcium influx, activation of calcineurin, and further Rac1 activation, and ultimately a pathological positive feedback loop. The activation of the TRCP5-Rac1 pathway disrupts the podocyte cytoskeleton, causing proteinuria, podocyte death, and glomerular sclerosis/scarring.
GFB-887 is designed to bind TRPC5 at the cell surface, to block the pathogenic TRPC5-Rac1 signaling, hence seeking to maintain podocyte integrity and reduce podocyte death.
We believe approximately 60-70% of individuals with FSGS can attribute their disease to activation of the TRPC5-Rac1 pathway leading to podocyte injury, podocyte loss, and kidney failure.
Data from our Phase 1 trial demonstrated that GFB-887 was well-tolerated and engaged its intended target as demonstrated by dose dependent reductions in our biomarker, urinary Rac1. These data supported the initiation of our ongoing Phase 2 trial, TRACTION-2, for which we are enrolling people with FSGS, treatment resistant minimal change disease and DN. Patients participating in TRACTION-2 may be eligible to participate in an open-label, long-term extension trial.