Goldfinch Bio Presents Data on TRPC5 Inhibition as a Target for Proteinuric Kidney Disease and Announces GFB-887 as Lead Drug Program to Treat FSGS

Preclinical data presented at 12^th International Podocyte Conference demonstrate selective targeting of TRPC5 that prevents podocyte injury and reverses proteinuric disease

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Goldfinch Bio, a company focused on discovering and developing precision medicines for the treatment of genetically-informed kidney diseases, today announced GFB-887, a selective inhibitor of transient receptor potential canonical 5 (TRPC5), as the company’s lead drug development candidate. The company plans to initiate clinical studies of GFB-887 in 2019 for the treatment of focal segmental glomerulosclerosis (FSGS), a rare kidney disorder, with the potential to expand into other kidney disease indications. The announcement of this program coincides with the presentation of data demonstrating that potent and selective targeting of TRPC5 prevented podocyte injury and reduced proteinuria in a preclinical model of FSGS. The data were presented at the 12^th International Podocyte Conference taking place on May 30 - June 2, 2018 in Montreal, Canada.

“Since its inception, Goldfinch has embarked on a fundamentally new approach to treating kidney diseases that couples the Kidney Genome Atlas (disease-specific genomic and clinical information) with inducible pluripotent stem cell-derived organoids (human models of kidney diseases). We are thrilled to share our data about TRPC5 therapeutic mechanisms with leaders in the kidney field and announce GFB-887 as the first development candidate to emerge from our product engine,” said Anthony Johnson, M.D., President and Chief Executive Officer of Goldfinch Bio. “We look forward to advancing GFB-887 for the treatment of FSGS and other kidney diseases that have the appropriate molecular rationale.”

In further details of the poster presentation entitled, “A small molecule inhibitor of TRPC5 protects against podocyte injury and proteinuria in hypertensive FSGS,” Goldfinch reported for the first time that:

• Goldfinch TRPC5 inhibitor binds selectively with nanomolar affinity to TRPC5, with no significant binding observed to TRPC6.
• TRPC5 inhibition protects against protamine sulfate-induced loss of stress fibers, restores stress fibers in podocytes after synaptopodin depletion, and suppresses pathogenic podocyte motility.
• Inhibition of TRPC5 suppresses proteinuria in hypertension-induced FSGS in uninephrectomized, DOCA (deoxycorticosterone acetate) salt-treated rats without altering blood pressure.

About FSGS
FSGS (focal segmental glomerulosclerosis) is a rare kidney disorder and histopathologic diagnosis characterized by severe scarring of the kidney's filtering units, or glomeruli, leading to proteinuria, an excess of essential proteins spilling into the urine. FSGS is associated with the injury and loss of podocytes, terminally differentiated cells of the kidney glomeruli essential for filtration and proper kidney function. Recent research into the genetics of kidney disease has identified over 30 genes associated with FSGS, and implicates the podocyte as a central player in the pathogenesis of FSGS. There are currently no FDA approved treatments for FSGS.

About TRPC5
TRPC5 is a calcium-permeable ion channel that has been implicated in the pathogenesis of FSGS by triggering a Rac1-TRPC5 disease pathway. Recent evidence has demonstrated that TRPC5 and Rac1, a critical regulator of cellular motility, form a vicious cycle that drives pathogenic remodeling of the actin cytoskeleton in podocytes. This causes podocyte loss and breach of the filtration barrier, which leads to proteinuria, the hallmark of progressive kidney diseases such as FSGS. Inhibition of TRPC5 offers a potential point of therapeutic intervention to halt progression of FSGS to kidney failure¹. TRPC5 represents a target for therapeutic intervention to halt progression of FSGS to kidney failure.

About Goldfinch Bio
Goldfinch Bio is a biotechnology company that is singularly focused on discovering and developing precision therapies for patients with kidney diseases. Just as the goldfinch has long been a symbol of healing and renewal and was a prominent figure of the Renaissance, Goldfinch Bio is leading a new age of therapeutic discovery to transform the treatment paradigm for patients with kidney diseases. Goldfinch was launched in 2016 by Third Rock Ventures, and is headquartered in Cambridge, Mass. For more information, please visit www.goldfinchbio.com.

1. Y. Zhou et al., Science 358, 1332 (2017).