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Goldfinch Bio Presents Clinical Data from Phase 1 Trial Supporting Advancement of GFB-887 as a Precision Medicine for Patients with Kidney Diseases

October 22, 2020 Off By BusinessWire

— GFB-887, a first-in-class highly potent and selective inhibitor of the TRPC5-Rac1 pathway, was well-tolerated in single ascending doses —

— GFB-887 induced dose-dependent reductions in urinary Rac1, demonstrating target engagement —

— TRPC5-Rac1 pathway overactivation is key cause of disease in substantial portion of patients with focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) —

— Phase 2 clinical study of GFB-887 (TRACTION-2) underway; initial data expected in the first quarter of 2021 —

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Goldfinch Bio, a clinical stage biotechnology company focused on discovering and developing precision medicines for the treatment of kidney diseases, today announced for the first time results from its Phase 1 clinical trial evaluating GFB-887, a first-in-class highly potent and selective inhibitor of Transient Receptor Potential Canonical Channel 5 (TRPC5), in healthy volunteers. The data are being presented today at the virtual American Society of Nephrology (ASN) Kidney Week 2020 Annual Meeting.

Goldfinch Bio is developing GFB-887 as a precision medicine for patients with kidney diseases characterized by overactivation of the TRPC5-Rac1 pathway, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN). Overactivation of the TRPC5-Rac1 pathway leads to injury of podocytes, which are cells lining the kidney that, in their healthy state, prevent essential protein loss (proteinuria). Injury to podocytes causes podocyte loss, proteinuria and, eventually, kidney failure. TRPC5-Rac1 pathway overactivation is the key cause of disease in a substantial portion of FSGS and DN patients, and there are currently no approved drugs that specifically target the TRPC5-Rac1 pathway in these diseases.

“We are excited to share these first-in-human data, which demonstrate that GFB-887 is well-tolerated and suggest a dose-dependent reduction in urinary Rac1, confirming GFB-887 target engagement in the podocyte,” said Anthony Johnson, M.D., President and Chief Executive Officer of Goldfinch Bio. “Suppressing the TRPC5-Rac1 pathway has the potential to deliver clinically meaningful benefit to patients by reducing proteinuria and, as a result, preserving native kidney function. Supported by the Phase 1 data, we are now underway with our Phase 2 TRACTION-2 study of GFB-887 in FSGS and DN, as we continue to advance our mission of protecting patients from the inevitability of dialysis and kidney transplant by delivering precision medicines for subsets of kidney disease.”

Data from the Phase 1 Clinical Trial

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The primary objective of the randomized, double-blinded, placebo-controlled trial was to assess the safety, tolerability, pharmacokinetic (PK) profile and pharmacodynamics (PD) of GFB-887 in healthy volunteers. A key exploratory objective was to characterize changes in urinary Rac1. Urinary Rac1 concentration may predict therapeutic response to TRPC5 inhibition.

The study enrolled 70 subjects, who were randomized four to one to receive GFB-887 at seven dose levels (ranging from 5 mg to 900 mg) or placebo.

Primary Objective: Safety, Tolerability and PK Data

GFB-887 was observed to be well-tolerated at all doses. There were no dose-limiting toxicities, severe adverse events (AEs) or abnormalities in laboratory or clinical assessments. In total, 38 percent of subjects who received GFB-887 reported AEs, compared to 21 percent of subjects treated with placebo. GFB-887-treated subjects reported headache more frequently than placebo-treated subjects (28.6% versus 7.2% respectively). The only other AE that was reported in two or more GFB-887-treated subjects was nausea (3.6%). Slight, asymptomatic reductions in blood pressure were observed in subjects treated at the highest doses.

The PK profile of GFB-887 is consistent with once-daily dosing, with a half-life ranging from 55 to 68 hours. A single 40 mg dose was also shown to exceed the preclinical efficacious range in FSGS and DN models.

Exploratory Objective: PD Data

Dose dependent and sustained reductions in urinary Rac1 concentrations were observed, confirming GFB-887 target engagement and suppression of the TRPC5-Rac1 pathway. Significant Rac1 lowering was observed at the 5 mg dose, with increasing reductions observed with increasing dose levels. Single doses of GFB-887 at 40 mg and 80 mg resulted in 46 percent and 59 percent peak reductions in absolute urinary Rac1 concentration, respectively.

Additional Goldfinch Bio Kidney Week 2020 Presentations

In addition to the Phase 1 data presentation, Goldfinch Bio presented two additional poster presentations at Kidney Week 2020 related to the GFB-887 program, including new preclinical data supporting urinary Rac1 as a novel predictive biomarker of response, and the detailed design of TRACTION-2.

Goldfinch also gave a fourth poster presentation at the meeting highlighting its proprietary human kidney organoid models, a core component of its Integrated Precision Kidney Platform. Through the use of its high-throughput organoid platform, Goldfinch is harnessing the latest advances in patient-derived induced pluripotent stem cell, or iPSC, science to develop innovative human organoid models, which help the company validate novel targets and advance drug discovery in a more efficient and more cost effective manner.

About the TRACTION-2 Trial

Goldfinch Bio is currently enrolling patients in TRACTION-2, a multicenter, double-blind, randomized, placebo-controlled Phase 2 trial evaluating the safety, tolerability, PK and PD of GFB-887 in approximately 125 patients with FSGS and DN.¹ The primary endpoint of TRACTION-2 is to assess the clinical activity of multiple doses of GFB-887 over 12 weeks, as measured by percentage change from baseline in proteinuria. In addition to safety and efficacy, TRACTION-2 will also characterize on-treatment changes in urinary Rac1 and the association between urinary Rac1 and patient outcomes.

Goldfinch expects to report initial clinical data in the first quarter of 2021, and final 12-week data in mid-2021, subject to the impact of COVID-19.

About Goldfinch Bio

Goldfinch Bio, Inc. is a clinical stage biotechnology company that leverages a genomics-based, precision medicine approach to discovering and developing kidney disease treatments. Its Kidney Genome Atlas (KGA™) is a proprietary biology platform that drives candidate discovery, biomarker development and patient selection. The Company’s lead candidate, GFB-887, is a TRPC5 ion channel inhibitor, in Phase 2 development for the treatment of kidney diseases. Goldfinch Bio is also developing GFB-024, a peripherally-restricted cannabinoid receptor 1 (CB1) inverse agonist monoclonal antibody, for the treatment of rare and metabolic kidney diseases and expects to submit an investigational new drug (IND) application in 2021. Goldfinch Bio, headquartered in Cambridge, Massachusetts, was launched in 2016 by Third Rock Ventures and named in 2020 as one of FierceBiotech’s “Fierce 15.” Goldfinch Bio has an established strategic collaboration with Gilead Sciences, Inc. For more information, visit www.goldfinchbio.com.

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¹ Patients diagnosed with treatment resistant minimal change disease, which is considered a subset of FSGS, will also be allowed into the Phase 2 clinical.