zigakibart (FUB523) / Novartis - LARVOL DELTA

BEYOND: A Study of Zigakibart in Adults With IgA Nephropathy (clinicaltrials.gov) - P3 | N=350 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • IgA Nephropathy • Renal Disease

Results from ongoing trials and other highlights (Novartis Press Release) - P1/2 | N=103 | NCT04684745 | Sponsor: Novartis Pharmaceuticals | "Updated results from the Phase I/II study for zigakibart in IgAN showed a robust and clinically meaningful reduction in proteinuria of 60.4% from baseline and eGFR stabilization over 100 weeks of treatment. To date, this is the longest duration of treatment reported for an anti-APRIL agent, demonstrating long-term safety and efficacy. Data presented at ERA. The Phase III BEYOND trial is ongoing with anticipated readout in 2026."

P1/2 data • P3 data • IgA Nephropathy

Changes in proteinuria and kidney function in subgroups of patients with IgAN defined by baseline Gd-IgA1 levels in a Phase 1/2 study of zigakibart (ERA 2025) - P1/2 | "Following 76 weeks of zigakibart treatment patients achieved 74.4% mean percent reduction of Gd-IgA1. Zigakibart provides clinically meaningful treatment benefits in terms of proteinuria reduction and eGFR stabilisation in patients with IgAN, independent of their baseline Gd-IgA1 levels."

Clinical • P1/2 data • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Renal Disease

Sustained long term efficacy and safety of zigakibart over 100 weeks in patients with IgAN (ERA 2025) - P1/2, P3 | "Zigakibart was well tolerated and led to robust, clinically meaningful reductions in proteinuria and eGFR stabilisation in patients, which were sustained up to 100 weeks of treatment. To date, this is the longest duration of treatment reported for an anti-APRIL agent, demonstrating long-term efficacy and safety. Clinically meaningful proteinuria remission rates were maintained for the duration of treatment and sustained eGFR stabilisation was observed independent of the proteinuria remission status."

Clinical • Late-breaking abstract • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Inflammation • Lupus Nephritis

Zigakibart-treated patients with IgAN achieved high rates of proteinuria remission and stable eGFR over 76 weeks in a Phase 1/2 study (ERA 2025) - P1/2 | "Following 76 weeks of zigakibart treatment, 29% and 45% of patients achieved UPE reductions below stringent thresholds of <300 and <500 mg/24 h, demonstrating robust, clinically meaningful proteinuria remission. Sustained eGFR stabilisation was observed independent of the achieved UPE remission thresholds. Taken together, these findings support the disease- modifying effect of zigakibart in IgAN."

Clinical • P1/2 data • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Renal Disease

Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy. (PubMed, Kidney Int) - P1/2, P3 | "Overall, zigakibart demonstrated robust pharmacological activity, and clinical evidence shows an acceptable safety profile with clinically meaningful proteinuria reduction and sustained estimated glomerular filtration rate stabilization in patients with IgAN, providing a potentially disease-modifying approach for the treatment of IgAN. The effects of zigakibart on proteinuria and long-term kidney function in adults with IgAN are being evaluated in the ongoing Phase 3 BEYOND study (NCT05852938)."

Journal • P1/2 data • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • TNFSF13

A Phase 3, Randomized, Double-blind, Placebo-controlled Study of BION-1301 in Adults with IgA Nephropathy(The BEYOND Study) (ChiCTR) - P3 | N=292 | Recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

New P3 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Open-label Extension Study of Zigakibart in Adults With IgA Nephropathy. (clinicaltrials.gov) - P3 | N=220 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P3 trial • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • Urology

A Phase 1/2 Trial of Zigakibart in IgA Nephropathy (IgAN) (ISN-WCN 2025) - No abstract available

P1/2 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

A Phase 1/2 Trial of Zigakibart in IgA Nephropathy (IgAN) (ISN-WCN 2025) - P1/2, P3 | "The global Phase 3 BEYOND study (NCT05852938) is also evaluating the efficacy and safety of zigakibart in adults with IgAN. This abstract was also submitted for the ASNKidney Week 2024: Barratt J, et al.: A Phase 1/2 Trial of Zigakibart in IgA Nephropathy (IgAN) [Abstract FR-PO856]."

Late-breaking abstract • P1/2 data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Inflammation • Lupus Nephritis • Renal Disease

A Phase 1/2 Trial of Zigakibart in IgA Nephropathy (KIDNEY WEEK 2024) - P1/2, P3 | "Zigakibart was well tolerated and led to sustained, clinically meaningful reductions in proteinuria and eGFR stabilization in patients. The global Phase 3 BEYOND study (NCT05852938) is also evaluating the efficacy and safety of zigakibart in adults with IgAN."

P1/2 data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Inflammation • Lupus Nephritis • Renal Disease

Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN) (clinicaltrials.gov) - P1/2 | N=103 | Active, not recruiting | Sponsor: Chinook Therapeutics, Inc. | Trial completion date: Oct 2026 ➔ Apr 2026

Trial completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

One year of zigakibart treatment shows clinically meaningful proteinuria reduction and good tolerability in a Phase 1/2 study of IgA nephropathy (ERA-EDTA 2024) - P1/2, P3 | "Zigakibart resulted in clinically meaningful reductions in proteinuria over 52 weeks of treatment in patients with IgAN and was well tolerated. The global phase 3 BEYOND registrational study (NCT05852938) is also evaluating the effect of zigakibart on proteinuria and long-term kidney function in adult patients with IgAN."

Clinical • Late-breaking abstract • P1/2 data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Renal Disease

Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN) (clinicaltrials.gov) - P1/2 | N=103 | Active, not recruiting | Sponsor: Chinook Therapeutics, Inc. | Trial completion date: Apr 2026 ➔ Oct 2026

Trial completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

BEYOND: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED TRIAL OF ZIGAKIBART IN ADULTS WITH IGA NEPHROPATHY (ISN-WCN 2024) - P1/2 | "Zigakibart provides a potentially disease-modifying approach for the treatment of IgAN by directly targeting the disease pathogenesis. The Phase 3 trial will evaluate the effect of zigakibart vs. placebo on proteinuria, eGFR and composite clinical endpoints and key safety measures in adult patients with IgAN at risk of progressive kidney function loss."

Clinical • P3 data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Renal Disease • Transplantation

The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy. (PubMed, Clin Kidney J) - "Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart and sibeprenlimab, are currently under investigation as potential therapies in IgAN. Preliminary results suggest that these agents are well-tolerated, and reduce levels of Gd-IgA1, with corresponding improvement in proteinuria. Further studies are ongoing to confirm the safety and efficacy of anti-APRIL approaches as an effective therapeutic strategy in IgAN."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease • TNFRSF13B • TNFRSF1B • TNFSF13

Novartis upgrades mid-term sales growth guidance, showcases its differentiated innovative medicines strategy and robust pipeline at R&D Day (Novartis Press Release) - "Submissions planned by 2027 include iptacopan, atrasentan and zigakibart for treatment of IgAN, iptacopan for the treatment of C3G, pelacarsen to lower Lp(a) for CV risk reduction and Leqvio for pediatric hyperlipidemia."

Regulatory • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia • IgA Nephropathy • Immunology • Metabolic Disorders

A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP). (PubMed, Clin Rheumatol) - "Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Inflammation • Nephrology • Renal Disease • Vasculitis

The BEYOND Trial: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Zigakibart in Adults with IgA Nephropathy (KIDNEY WEEK 2023) - P3 | "Safety endpoints include type, incidence, severity, and relatedness of adverse events (AEs) and serious AEs. Exploratory endpoints include impact of zigakibart on disease biomarkers and health-related quality of life as well as analysis of zigakibart pharmacokinetics and immunogenicity."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • Transplantation

Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN) (clinicaltrials.gov) - P1/2 | N=103 | Active, not recruiting | Sponsor: Chinook Therapeutics, Inc. | Trial completion date: Jan 2026 ➔ Apr 2026

Trial completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

BEYOND: A Study of BION-1301 in Adults With IgA Nephropathy (clinicaltrials.gov) - P3 | N=292 | Recruiting | Sponsor: Chinook Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jul 2026 ➔ Dec 2025

Enrollment open • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF BION-1301 IN ADULTS WITH IGA NEPHROPATHY (ERA-EDTA 2023) - P1/2 | "BION-1301 provides a potentially disease-modifying approach for the treatment of IgAN by directly targeting the disease pathogenesis. Interim results of the Phase 1/2 open-label trial demonstrated proof-of-concept for BION-1301 to reduce pathogenic Gd-IgA1 and provide sustained, clinically meaningful reductions in proteinuria while supporting SC dosing at 600 mg The Phase 3 trial will evaluate the effect of BION-1301 vs. placebo on proteinuria, eGFR and composite clinical endpoints and key safety measures in adult patients with IgAN at risk of progressive kidney function loss."

Clinical • P3 data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Renal Disease • Transplantation • CHEK2

UPDATED INTERIM RESULTS OF A PHASE 1/2 STUDY OF BION-1301 IN PATIENTS WITH IGA NEPHROPATHY (ERA-EDTA 2023) - "BION-1301 offers disease-modifying potential by directly target ing the initiating pathogenesis of IgAN. Interim biomarker and clinical activity responses support advancement of BION-1301 into later-stage development for patients with IgAN."

Clinical • P1/2 data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Renal Disease

Chinook Therapeutics to Present Updated Data from Zigakibart (BION-1301) Phase 1/2 Trial in Patients with IgA Nephropathy (IgAN) at the 60th European Renal Association (ERA) Congress (GlobeNewswire) - P1/2 | N=103 | NCT03945318 | Sponsor: Chinook Therapeutics, Inc. | "Chinook Therapeutics...announced a focused oral presentation on zigakibart (BION-1301) will be presented on Friday, June 16, 2023 at the 60th ERA Congress....The median baseline 24-hour urine protein excretion for patients enrolled in Cohort 1 was 1.2 g/day, with a range of 0.7 – 6.5 g/day, and the median baseline 24-hour urine protein excretion for patients enrolled in Cohort 2 was 1.1 g/day, with a range of 0.3 – 7.0 g/day. With a median baseline 24-hour urine protein excretion for patients enrolled in both Cohorts 1 and 2 of 1.1 g/day, this population represents patients with IgAN at high risk of kidney disease progression....Overviews of the phase 3 BEYOND and phase 2 ASSIST trials are also being presented as focused oral presentations (digital poster with 3-minute presentation) on Friday, June 16, 2023."

P1/2 data • Trial status • IgA Nephropathy • Renal Disease

Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN) (clinicaltrials.gov) - P1/2 | N=103 | Active, not recruiting | Sponsor: Chinook Therapeutics, Inc. | Trial completion date: Apr 2024 ➔ Jan 2026 | Trial primary completion date: Oct 2023 ➔ Nov 2025

Trial completion date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease