CAMBRIDGE, Mass.–(BUSINESS WIRE)–February 28, 2022–
Goldfinch Bio, a clinical-stage biotechnology company focused on the discovery and development of precision drugs for the treatment of kidney disease, today announced positive preliminary data from its ongoing Phase 2 clinical trial evaluating GFB- 887, a small molecule transient receptor potential inhibitor targeting Canonical Channel 5 (TRPC5) podocytes, for the treatment of FSGS and diabetic nephropathy (DN).
Preliminary results from the ongoing phase 2 trial have shown:
- Patients treated with GFB-887 had a statistically significant and clinically significant placebo-adjusted mean reduction of 32% in UPCR, a measure of proteinuria, at the end of 12 weeks of treatment (p=0.04) .
- Nine of ten evaluable GFB-887-treated patients (90%) had a reduction in UPCR; four of seven placebo-treated patients showed an increase in UPCR (57%).
- Preliminary exploratory biomarkers and genetic data suggest an emerging patient selection strategy for GFB-887:
- In a subset of patients identified by a reduction in the threshold of a TRPC5-Rac1 pathway biomarker, uRac1, at week 2 of treatment, patients treated with GFB-887 showed a mean placebo-adjusted reduction of 48 % of UPCR at the end of the 12- week treatment period.
- Additionally, a whole exome sequencing analysis of eight out of ten treated patients showed that patients with mutations in the TRPC5-Rac1 pathway, other genes associated with monogenic causes of FSGS and other podocytopathies showed the greatest responses to GFB-887, while the only patient who did not respond 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 the test 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 therapies, focused on patient subgroups, with potentially limited systemic side effects, and long-awaited hope for patients,” said Katherine Tuttle, MD, FASN, FACP, FNKF, executive director of research at Providence Health Care and University of Washington professor of medicine and researcher in the Phase 2 clinical trial. “The data suggest that progressive reductions in proteinuria may lead to clinically meaningful differences in the rate of disease progression, which may provide FSGS patients with years of preserved native kidney function, delaying kidney failure and the need for dialysis or transplantation. I am excited to see the continued progress of GFB-887 and the potential impact on the kidney health of FSGS patients.
Anthony Johnson, MD, President and CEO of Goldfinch Bio, said, “We are pleased with the initial results of clinical activity in our Phase 2 trial of GFB-887. These data provide important preliminary evidence supporting the potential of GFB-887 as a disease-modifying precision drug that can reduce proteinuria and potentially arrest 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 of bringing the promise of precision medicine to people with FSGS and others. 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 the 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 trial (TRACTION-2) is to evaluate the clinical activity of multiple doses of GFB-887 over 12 weeks, as measured by percent change from baseline in UPCR in patients with FSGS, or percent change in urinary albumin to creatine ratio (UACR) in patients with DN. 1 The trial is expected to enroll up to 125 patients in total. Secondary outcomes include safety, 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 the mutational load of the uRac1 pathway and TRPC5-Rac1 – a potential patient selection biomarker – and efficacy, as well as changes in quality scores of Life-Related Health and Nephrotic Syndrome Clinician-Edema Rating Scale.
At the time of the February 2022 administrative review, 17 response-evaluable FSGS patients had been randomized 2:1 and treated for 12 weeks with therapeutic doses of 120 or 360 mg daily (n=10) or placebo ( n = 7). Two patients were excluded from the evaluation because they did not complete the 12-week study period due to adverse events, which were unrelated to the test drug. All enrolled patients had a biopsy-confirmed diagnosis of FSGS, as well as an 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.
At the time of the February 2022 administrative review, 44 DN patients had been randomized 1:1 and treated for 12 weeks with therapeutic doses of 120 or 180 mg daily (n=22) or placebo (n=22 ). No treatment effect was observed in either DN cohort.
As previously reported, 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.
FSGS is a progressive glomerular disorder, which causes damage and loss of podocytes, severe proteinuria, and eventually loss of renal function and often renal failure. There are currently 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 arrest disease progression.
About Organic Goldfinch
Goldfinch Bio, Inc. is a clinical-stage biotechnology company focused on providing precision disease-modifying drugs that bring hope and renewed quality of life to people with kidney disease. We aspire to save the kidneys and end dialysis. Our precision medicine product engine enables us to discover, validate and treat novel targets that may allow us to better treat subsets of patients, within heterogeneous kidney disease, based on common characteristics . We have a strong pipeline of new precision medicine product candidates targeting kidney disease with high 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 eligible to participate in the Phase 2 clinical.
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KEYWORD: UNITED STATES NORTH AMERICA MASSACHUSETTS
INDUSTRY KEYWORD: BIOTECHNOLOGY PHARMACEUTICAL HEALTH CLINICAL TRIALS
SOURCE: Organic Goldfinch, Inc.
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PUBLISHED: 02/28/2022 07:00 / DISK: 02/28/2022 07:02