KAR-2618 / Goldfinch Bio, BMS - LARVOL DELTA

Discovery of pyridazinone derivatives bearing tetrahydroimidazo[1,2-a]pyrazine scaffold as potent inhibitors of transient receptor potential canonical 5 to ameliorate hypertension-induced renal injury in rats. (PubMed, Eur J Med Chem) - "Recently, GFB-887, an investigational pyridazinone TRPC5 inhibitor, demonstrated significant therapeutic potential in a Phase II clinical trial for focal segmental glomerulosclerosis (FSGS), a rare and severe form of chronic kidney disease (CKD)...More importantly, in a rat model of hypertension-induced renal injury, oral administration of compound 12 (10 mg/kg, BID) efficaciously reduced mean blood pressure, inhibited proteinuria, and protected podocyte damage. These findings further confirmed the potential of TRPC5 inhibitors on the CKD treatment and provided compound 12 to be a valuable tool for exploring TRPC4/5 pathophysiology."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hypertension • Nephrology • Renal Disease • TRPC3 • TRPC5

A Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease (clinicaltrials.gov) - P2a | N=96 | Terminated | Sponsor: Goldfinch Bio, Inc. | Trial completion date: Aug 2022 ➔ Nov 2022 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2022 ➔ Nov 2022; Business reasons

Trial completion date • Trial primary completion date • Trial termination • Diabetes • Diabetic Nephropathy • Endocrine Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease • Urology

An Open-Label, Long-term Study of GFB-887 in Patients With Glomerular Kidney Diseases (clinicaltrials.gov) - P2 | N=31 | Terminated | Sponsor: Goldfinch Bio, Inc. | Trial completion date: Sep 2025 ➔ Nov 2022 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Nov 2022; Business reasons

Trial completion date • Trial primary completion date • Trial termination • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease • Urology

TRACTION-2: Efficacy and Safety of TRPC5 Channel Inhibitor GFB-887 in Patients With Inadequately Controlled Focal Segmental Glomerulosclerosis (FSGS) (KIDNEY WEEK 2022) - "WITHDRAWN"

Clinical • Late-breaking abstract • Focal Segmental Glomerulosclerosis • Glomerulonephritis

Transplanted organoids empower human preclinical assessment of drug candidate for the clinic. (PubMed, Sci Adv) - "We established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates feasibility of using transplanted human organoids in preclinical PD studies with an investigational new drug, empowering organoids to revolutionize drug discovery."

Journal • Preclinical • Nephrology • Renal Disease • Transplantation

[VIRTUAL] TRACTION-2 Study: Safety and Efficacy Evaluation of GFB-887, a TRPC5 Channel Inhibitor, in Patients With DN, FSGS, or TR-MCD (KIDNEY WEEK 2021) - P2a | "These measures included alternative methods to conduct study visits, including assessments at the patient’s home using a home healthcare nurse, via telephone, or using other telemedicine options; and use of a symptom-directed physical examination for visits conducted via home nursing or telemedicine. Results from this study will provide evidence that blockade of TRPC5-Rac1 pathway with GFB-887 is an effective strategy to treat patients with podocytopathies and guide the next phase of clinical development of GFB-887."

Clinical • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease

Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design. (PubMed, Kidney Int Rep) - P2a | "The projected sample size has 80% power to detect a treatment difference in proteinuria of 54% (FSGS/TR-MCD) or 44% (DN) compared to placebo. TRACTION-2 will explore whether targeted blockade of the TRPC5-Rac1 pathway with GFB-887 is an efficacious and safe treatment strategy for patients with FSGS, TR-MCD, and DN and the potential value of urinary Rac1 as a predictive biomarker of treatment response."

Clinical • Journal • Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease

A Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease (clinicaltrials.gov) - P2a; N=125; Recruiting; Sponsor: Goldfinch Bio, Inc.; Trial completion date: Dec 2021 ➔ Aug 2022; Trial primary completion date: Aug 2021 ➔ Aug 2022

Trial completion date • Trial primary completion date • Diabetes • Diabetic Nephropathy • Endocrine Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease • Urology

An Open-Label, Long-term Study of GFB-887 in Patients With Glomerular Kidney Diseases (clinicaltrials.gov) - P2; N=35; Recruiting; Sponsor: Goldfinch Bio, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease • Urology

An Open-Label, Long-term Study of GFB-887 in Patients With Glomerular Kidney Diseases (clinicaltrials.gov) - P2; N=35; Not yet recruiting; Sponsor: Goldfinch Bio, Inc.

New P2 trial • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease • Urology

GFB-887: “Single doses of GFB-887 were well-tolerated with a favorable PK profile in healthy subjects”; Focal segmental glomerulosis (Goldfinch Bio) - ASN Kidney Week 2020: “38% GFB-887-treated subjects reported AEs vs. 21% of placebo-treated subjects”

P1 data • Focal Segmental Glomerulosclerosis

[VIRTUAL] Urinary Rac1, a Novel Predictive Biomarker, Is Elevated in FSGS and Diabetic Nephropathy Patients and Reduced by TRPC5 Inhibition with GFB-887 in a Rat FSGS Model (KIDNEY WEEK 2020) - "The TRPC5 inhibitor, GFB-887, targets the TRPC5-Rac1 pathway and suppresses urinary Rac1 associated with its therapeutic action in a rat model of FSGS. Urinary Rac1 concentrations are markedly higher in FSGS and DN compared to healthy subjects, but not elevated in Alport. GFB-887 is efficacious in rodent models of FSGS and DN, but not of Alport, suggesting that elevated urinary Rac1 is predictive of response."

Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease • RAC1

[VIRTUAL] Safety and Efficacy Evaluation of GFB-887, a TRPC5 Channel Inhibitor, in Patients with DN, FSGS, or TR-MCD: Phase 2 Study Design (TRACTION Program) (KIDNEY WEEK 2020) - P2a | " Results from this study will provide evidence that blockade of TRPC5-Rac1 pathway with GFB-887 is an effective strategy to treat patients with podocytopathies and guide the next phase of clinical development of GFB-887. Funding: Goldfinch Bio"

Clinical • P2 data • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease

[VIRTUAL] GFB-887, a TRPC5 Inhibitor, Is Safe and Well Tolerated and Engages the TRPC5 Target, Leading to Reductions in Urinary Rac1 in Healthy Subjects (KIDNEY WEEK 2020) - P2a | "Single doses of GFB-887 were well tolerated with a favorable PK profile in healthy subjects. GFB-887 exhibits dose-dependent reduction in urinary Rac1, a regulator of podocyte cytoskeletal structure and motility, indicating that GFB-887 engages and inhibits the TRPC5-Rac1 pathway. The safety and efficacy of GFB-887 is currently being evaluated in patients with FSGS, MCD, and DN (NCT04387448)."

Clinical • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Pain • Renal Disease • RAC1

Goldfinch Bio Presents Clinical Data from Phase 1 Trial Supporting Advancement of GFB-887 as a Precision Medicine for Patients with Kidney Diseases (Businesswire) - P1, N=70; NCT03970122; Sponsor: Goldfinch Bio, Inc.; "Goldfinch Bio...today announced for the first time results from its Phase 1 clinical trial evaluating GFB-887...in healthy volunteers....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 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...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."

Biomarker • Clinical protocol • Enrollment status • P1 data • P2 data • Preclinical • Focal Segmental Glomerulosclerosis

Goldfinch Bio Announces Upcoming Presentation of Phase 1 Clinical Data for Lead Precision Kidney Therapeutic Candidate, GFB-887, and Expansion of Scientific Leadership Team (Businesswire) - P1, N=70; NCT03970122; Sponsor: Goldfinch Bio, Inc.; "Goldfinch Bio...today announced that it will present clinical data from a Phase 1 study of...GFB-887, at the American Society of Nephrology (ASN) Kidney Week 2020 Annual Meeting, taking place virtually October 22-25, 2020....The Phase 1 safety, tolerability and TRPC5-Rac1-pathway target engagement data to be presented support the advancement of its Phase 2 study of GFB-887 (TRACTION-2), which is now underway. Goldfinch Bio will present additional posters at Kidney Week 2020 showcasing GFB-887’s novel urinary Rac1 predictive biomarker strategy as well as the company’s proprietary platform."

P1 data • Preclinical • Focal Segmental Glomerulosclerosis

Academic and Industry Collaborative Study, including Goldfinch Bio, Demonstrates Benefit of Proteinuria Reduction on Kidney Survival in Patients with Focal Segmental Glomerulosclerosis (FSGS) (Businesswire) - P=NA, N=138; "Goldfinch Bio...today announced the publication of data demonstrating the benefit of continuous proteinuria reduction on kidney survival in patients with focal segmental glomerulosclerosis (FSGS) and underscoring the utility of proteinuria as a clinically meaningful endpoint in FSGS. The new findings...were published electronically in the American Journal of Kidney Diseases (AJKD)...Goldfinch Bio is currently advancing GFB-887, a first-in-class highly potent and selective inhibitor of Transient Receptor Potential Canonical Channel 5 (TRPC5)....TRPC5-Rac1 pathway overactivation is the key cause of disease in a substantial proportion of FSGS and DN patients."

Retrospective data • Trial status • Focal Segmental Glomerulosclerosis

Goldfinch Bio Initiates Phase 2 Clinical Trial Evaluating Novel Drug Candidate GFB-887 as a Precision Medicine for Patients with Kidney Diseases (Businesswire) - "Goldfinch Bio...today announced that it dosed the first patients in TRACTION-2, a Phase 2 clinical trial evaluating GFB-887 for the treatment of focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN)....Goldfinch expects to report initial clinical data at the end of 2020 or early in 2021, and final 12-week data in mid-2021, subject to the impact of COVID-19."

P2 data • Trial status • Focal Segmental Glomerulosclerosis

A Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease (clinicaltrials.gov) - P2a; N=125; Recruiting; Sponsor: Goldfinch Bio, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus • Metabolic Disorders • Nephrology • Renal Disease

After its $2B Gilead pact, Goldfinch Bio nabs a cool $100M series B (FierceBiotech) - "Today, it got off an oversubscribed series B financing worth $100 million...Goldfinch is now pushing two programs through development: GFB-887, a first-in-class selective inhibitor of transient receptor potential canonical channel 5 (TRPC5), and GFB-024, a peripherally restricted cannabinoid receptor 1 (CB1) inverse agonist. A phase 2 of GFB-887 in patients with FSGS and diabetic nephropathy (DN)...are slated for mid-20201, with an IND for GFB-024, licensed from Takeda, to treat CB1-mediated DN on the cards for 2021. The $100 million will go toward these efforts."

Financing • IND • New P2 trial • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Neuralgia • Pain • Peripheral Neuropathic Pain • Renal Disease

FIH Ph 1 Study of TRPC5 Channel Inhibitor GFB-887 in Healthy Subjects (clinicaltrials.gov) - P1; N=70; Completed; Sponsor: Goldfinch Bio, Inc.; Recruiting ➔ Completed

Clinical • Trial completion

Phase 2a Study of TRPC5 Channel Inhibitor in Patients With Diabetic Nephropathy, Focal Segmental Glomerulosclerosis, and Treatment-Resistant Minimal Change Disease (clinicaltrials.gov) - P2a; N=125; Not yet recruiting; Sponsor: Goldfinch Bio, Inc.

Clinical • New P2a trial • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Lupus • Metabolic Disorders • Nephrology • Renal Disease

Goldfinch Bio to present at the UBS Virtual Global Healthcare Conference (Businesswire) - "Goldfinch Bio....today announced that Anthony Johnson, M.D., President and Chief Executive Officer of Goldfinch Bio, will present a company overview at the UBS Virtual Global Healthcare Conference on Tuesday, May 19, 2020 at 2:10 p.m. ET. The presentation will include additional details on Goldfinch’s Phase 2 program with lead product candidate GFB-887, a transient receptor potential canonical 5 (TRPC5) ion channel inhibitor, for the treatment of patients with kidney diseases characterized by Rac1 overactivation, including focal segmental glomerulosclerosis (FSGS), treatment-resistant minimal change disease (TR-MCD) and diabetic nephropathy (DN)."

Clinical • Focal Segmental Glomerulosclerosis • Renal Disease

Goldfinch Bio to present oral and poster presentations at the American Society of Nephrology Kidney Week 2019 Annual Meeting (Businesswire) - "Goldfinch Bio...today announced it will present one oral and two poster presentations at the American Society of Nephrology (ASN) Kidney Week 2019 Annual Meeting, taking place November 5-10, 2019, in Washington, D.C."

Preclinical

An iPSC platform for Human Preclinical Evaluation of Kidney Disease Targeting Compounds (KIDNEY WEEK 2019) - "Results Here, we report three examples supporting the use of these models by – a) providing a mechanistic basis for the antiproteinuric effects of cyclosporine A via protective effects on podocytes from Rac1-mediated cytoskeletal injury in vitro, b) exploring of the effects of disease-causing genetic mutations, and c) demonstrating the protective effect of a novel TRPC5 channel blocker, GFB-887. In vivo transplantation resulted in vascularization of human iPSC derived kidney organoids, with functional perfusion confirmed by pharmacokinetic measurement of GFB-887 in the organoid after dosing by oral gavage. Conclusion Our kidney disease-targeted human iPSC platform provides a valuable complement to pre-clinical models for target validation and assessment of drug efficacy."

Preclinical