Goldfinch Bio Announces Positive Preliminary Data from Phase 2 Clinical Trial Evaluating GFB-887 as a Precision Medicine for Patients with Focal Segmental Glomerular Sclerosis (FSGS)

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 positive preliminary data from its ongoing Phase 2 clinical trial evaluating GFB-887, a podocyte-targeting small molecule inhibitor of Transient Receptor Potential Canonical Channel 5 (TRPC5), for the treatment of FSGS and diabetic nephropathy (DN).

Preliminary results of the ongoing Phase 2 trial showed:

• Patients treated with GFB-887 experienced a statistically significant and clinically meaningful 32% placebo-adjusted mean reduction in UPCR, a measure of proteinuria, at the end of 12 weeks of treatment (p=0.04).
• Nine of the ten evaluable GFB-887-treated patients (90%) experienced a reduction in UPCR; four of seven patients treated with placebo had an increase in UPCR (57%).
• Preliminary exploratory biomarker and genetic data suggest an emerging patient selection strategy for GFB-887:
  • In a subset of patients identified by a threshold reduction in a TRPC5-Rac1 pathway biomarker, uRac1, at week 2 of treatment, patients treated with GFB-887 showed a 48% placebo-adjusted mean reduction in UPCR at the end of the 12-week treatment period.
  • In addition, an analysis of the whole exome sequencing of eight of the ten treated patients showed that patients with mutations in the TRPC5-Rac1 pathway, other genes associated with monogenic causes of FSGS, and other podocytopathies experienced the greatest responses to GFB-887, whereas the one patient non-responsive to GFB-887 had a mutation in a tubular gene associated with another form of kidney disease.
• No treatment effect was observed in the initial cohort of 44 treated DN patients.
• GFB-887 was generally safe and well-tolerated in patients with FSGS or DN. There were no serious adverse events (SAEs) related to trial drug.

“These preliminary results contribute to my belief that we are on the threshold of an exciting new era in the treatment of FSGS and other kidney diseases, which will be defined by targeted, patient subset-driven therapies, with potentially limited systemic side effects, and long-awaited hope for patients,” said Katherine Tuttle, M.D., FASN, FACP, FNKF, Executive Director for Research at Providence Health Care and Professor of Medicine at the University of Washington and an investigator in the Phase 2 clinical trial. “Data suggest that incremental reductions in proteinuria can lead to clinically meaningful differences in the rate of disease progression, which may offer FSGS patients years of preserved native kidney function, delaying kidney failure and the need for dialysis or transplant. I am excited to watch the continued progress of GFB-887 and the potential impact on the kidney health of FSGS patients.”

Anthony Johnson, M.D., President and Chief Executive Officer of Goldfinch Bio, commented, “We are pleased with the initial findings of clinical activity in our Phase 2 trial of GFB-887. These data provide important early evidence supporting GFB-887’s potential as a disease-modifying precision medicine that can reduce proteinuria and potentially stop disease progression, with a favorable safety and tolerability profile. The clear delineation between high and low responders signals a potentially compelling biomarker and genetics-driven strategy for patient selection, furthering our goal to bring the promise of precision medicine to people with FSGS and other kidney diseases. We look forward to the planned interim analysis of this trial mid-year, which will provide additional key insights and inform our next steps to advance clinical development of GFB-887 as quickly as possible.”

Phase 2 Clinical Trial Design
The primary objective of the multicenter, double-blind, randomized, placebo-controlled Phase 2 (TRACTION-2) trial is to assess the clinical activity of multiple doses of GFB-887 for 12 weeks, as measured by percent change from baseline in UPCR in patients with FSGS, or percent change in urine albumin to creatine ratio (UACR) in patients with DN.¹ The trial is anticipated to enroll up to 125 patients in total. Secondary outcome measures include safety and tolerability and pharmacokinetics of multiple doses of GFB-887, as well as remission status in FSGS patients. Key exploratory endpoints include an assessment of the association between uRac1 and TRPC5-Rac1 pathway mutational burden – a potential patient selection biomarker – and efficacy, as well as changes in health-related quality of life scores and the nephrotic syndrome edema-clinician rating scale.

As of the February 2022 administrative assessment, 17 response-evaluable FSGS patients had been randomized 2:1 and dosed for 12 weeks at therapeutic doses of either 120 or 360 mg daily (n=10) or placebo (n=7). Two patients were excluded from the assessment as they did not complete the 12-week study period due to adverse events, which were not trial drug related. All enrolled patients had a diagnosis of FSGS confirmed by biopsy, as well as a UPCR ≥1.0 g/g and an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² at screening, and consenting patients underwent whole exome sequencing.

As of the February 2022 administrative assessment, 44 DN patients had been randomized 1:1 and dosed for 12 weeks at therapeutic doses of either 120 or 180 mg daily (n=22), or placebo (n=22). No treatment effect was observed in either DN cohort.

As previously guided, Goldfinch Bio plans to conduct and report an interim analysis in mid-2022 after approximately 70% of evaluable FSGS or DN patients have completed treatment for 12 weeks at the highest dose cohorts.

About FSGS
FSGS is a progressive glomerular disorder, which causes podocyte injury and podocyte loss, severe proteinuria, and eventually loss of kidney function and often kidney failure. Currently there are no approved treatments for FSGS. FSGS is characterized by an overactivation of the TRPC5-Rac1 pathway. By inhibiting the TRPC5-Rac1 pathway, GFB-887 is designed to protect podocytes, reduce proteinuria, and slow or halt disease progression.

About Goldfinch Bio
Goldfinch Bio, Inc. is a clinical stage biotechnology company focused on delivering disease-modifying precision medicines that bring hope and renewed quality of life to people living with kidney diseases. We aspire to save kidneys and end dialysis. Our precision medicine product engine allows us to discover, validate and drug novel targets that may allow us to better treat subsets of patients, within a heterogeneous kidney disease, based on common characteristics. We have a robust pipeline of novel, precision medicine product candidates targeting kidney diseases with significant unmet need, including two clinical-stage assets. Visit us at www.goldfinchbio.com to learn more.

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.

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