Goldfinch Bio Initiates Phase 1 Clinical Trial of GFB-024, a Novel Precision Medicine Product Candidate for Patients with Severe Insulin Resistant Diabetic Nephropathy (DN)
CAMBRIDGE, Mass. – May 13, 2021 – Goldfinch Bio, a clinical stage biotechnology company focused on discovering and developing precision medicines for the treatment of kidney diseases, today announced that it dosed the first subjects in its Phase 1 clinical trial of its product candidate, GFB-024. GFB-024 is a peripherally restricted cannabinoid 1 (CB1) inverse agonist monoclonal antibody intended to treat patients with severe insulin resistant diabetic nephropathy (DN) and CB1 pathway overactivation. GFB-024 is Goldfinch Bio’s second kidney precision medicine candidate to advance to clinical trials. The company’s most advanced precision medicine product candidate, GFB-887, a small molecule inhibitor of TRPC5, is currently in Phase 2 study (TRACTION-2 Clinical Trial) for the treatment of focal segmental glomerular disease (FSGS) and DN.
“At Goldfinch Bio, we recognize the tremendous heterogeneity in kidney disease, and we are committed to delivering disease-modifying medicines that are tailored specifically to distinct, genetically or phenotypically defined patient subsets. Our strategy with GFB-024 exemplifies this approach,” said Anthony Johnson, M.D., President and Chief Executive Officer of Goldfinch Bio. “We are advancing GFB-024 for people with a rapidly progressive form of DN who present with the distinct clinical phenotype of severe insulin-resistant diabetes (SIRD) and whose disease is strongly linked to overactivation of the CB1 pathway. We are pleased to initiate clinical development of GFB-024 and look forward to reporting initial data in 2022.”
“Many people with type 2 diabetes, such as those classified with SIRD, have metabolic syndrome characterized by obesity, high triglycerides, and insulin resistance. This group is at particularly high risk of developing diabetic kidney disease and progression to kidney failure. Despite this high risk, these patients are currently treated the same way as other people with diabetic kidney disease,” 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. “Identification of biomarkers related to the CB1 pathway, and a medicine designed specifically to inhibit this pathway, could be a key advancement toward the aspiration of precision medicine in kidney disease to ‘deliver the right treatment to the right patient at the right time’ for these individuals.”
Patients with SIRD are characterized by obesity, marked insulin resistance, macroalbuminuria, and a fivefold greater risk of end stage kidney disease. Preclinical data generated by Goldfinch Bio demonstrate that elevated levels of circulating endocannabinoids, such as those observed in patients with insulin resistance, activate the CB1 pathway in podocytes, tubular cells and peripheral metabolic organs. This, in turn, can lead to mitochondrial dysfunction, resulting in podocyte cell death, proteinuria and tubular cellular injury, and ultimately serious harm to the kidneys.
In preclinical studies, Goldfinch Bio observed that treatment with GFB-024 resulted in inhibition of CB1 receptor signaling, protecting against both podocyte and tubular cell injury, with negligible exposure in the brain and no central nervous system physiological effect. Currently, there are no approved peripherally restricted CB1 inhibitors.
The Phase 1 trial is a double-blind, randomized, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single-ascending doses of GFB-024 in up to 56 overweight and obese healthy volunteers. The trial will also evaluate repeat dosing of GFB-024 in one cohort of subjects with type 2 diabetes mellitus to assess immunogenicity, multiple dose PK and safety. In addition, the trial will explore candidate predictive biomarkers to confirm peripheral CB1 target engagement to identify patients most likely to respond to GFB-024 and provide early central nervous system (CNS) safety derisking. Goldfinch expects to report initial data in 2022. For more information about the clinical trial design, please visit: www.clinicaltrials.gov (NCT04880291).
GFB-024 is a peripherally-restricted cannabinoid 1 (CB1) inverse agonist monoclonal antibody intended to treat patients with severe insulin resistance diabetic nephropathy and CB1 pathway overactivation. GFB-024 has the potential to provide disease-modifying effects in the kidney while treating the underlying metabolic dysfunction in obese patients without the CNS side-effects seen by prior small molecule CB1 antagonists. GFB-024 has demonstrated podocyte protective effects in preclinical models, while clinical data from first generation CB1 antagonists have demonstrated metabolic benefits, such as reduced cholesterol, glucose, and HbA1c, in third-party clinical trials, which may also lead to additional beneficial kidney effects.
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 and validate novel targets aimed at understanding the molecular and phenotypic heterogeneity in diverse kidney disease patient populations to identify subsets most likely to respond to our treatments. We have a robust pipeline of novel, precision medicine product candidates targeting kidney diseases with significant unmet need, including two clinical-stage assets. In 2020, Goldfinch Bio was named one of Fierce Biotech’s “Fierce 15” companies. Visit us at www.goldfinchbio.com to learn more.
 Patients diagnosed with treatment resistant minimal change disease, which is considered a subset of FSGS, are also being enrolled in the Phase 2 clinical trial.