Goldfinch starts phase 1 trial of GFB-024 for diabetic nephropathy

Goldfinch starts phase 1 trial of GFB-024 for diabetic nephropathy

The biotechnology company Goldfinch Bio has initiated the phase 1 clinical trial of its GFB-024, a novel precision medicine product candidate for patients with severe insulin-resistant diabetic nephropathy (DN).

GFB-024 is a peripherally restricted cannabinoid 1 (CB1) inverse agonist monoclonal antibody intended to treat patients with severe insulin-resistant DN and CB1 pathway overactivation. The company has dosed the first subjects in its phase 1 clinical trial of its new product candidate.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.

Many people with type 2 diabetes, such as those classified with severe insulin-resistant diabetes (SIRD), have metabolic syndrome characterised 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.

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.

“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.” 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.

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, randomised, 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 de-risking. Goldfinch expects to report initial data in 2022.

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.