Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 639 |
| INN | Zigakibart |
| Status | Clinical |
| Drug code(s) | FUB523, BION-1301 |
| Brand name | None |
| mAb sequence source | mAb humanized |
| General Molecular Category | Naked monospecific |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG4 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | None |
| Target(s) | APRIL |
| Indications of clinical studies | IgA nephropathy, Multiple myeloma (terminated) |
| Primary therapeutic area | Immune-mediated / inflammatory disorders |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | November 15, 2017 |
| Start of Phase 2 | |
| Start of Phase 3 | July 15, 2023 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | Novartis Pharmaceuticals |
| Licensee/Partner | None |
| Comments about company or candidate | Jan 2024: SanReno Therapeutics, a clinical-stage company specializing in the discovery, development, and commercialization of innovative therapies for kidney diseases, today announces its acquisition by Novartis, a global medicines company. Following the acquisition's closure, SanReno becomes an indirect, wholly-owned subsidiary of Novartis. Established in late 2021 as a joint venture between the investor consortium and Chinook Therapeutics (now part of Novartis), SanReno holds exclusive rights in Greater China and Singapore for two late-stage assets targeting Immunoglobulin A Nephropathy (IgAN): atrasentan and zigakibart. July 28, 2023: Chinook Therapeutics, Inc. announced that the first patient with IgA nephropathy (IgAN) has been enrolled in the NCT05852938 BEYOND study, a pivotal phase 3 clinical trial evaluating the safety and efficacy of zigakibart (BION-1301), a potentially disease-modifying anti-APRIL monoclonal antibody. June 12, 2023 — Novartis announced that it has entered into an agreement to acquire Chinook Therapeutics, Listed as Phase 2 asset in company pipeline accessed Mar 2023; Feb 2023 press release: Chinook has finalized trial design, is conducting site and country feasibility and completing global regulatory interactions to enable initiation of a phase 3 trial of BION-1301 in mid-2023. Oct. 05, 2020 - Chinook Therapeutics, Inc. announced the closing of its merger with Aduro Biotech, Inc. and $115 million private placement financing. June 24, 2020 I Aduro Biotech, Inc. (NASDAQ: ADRO), a clinical-stage biopharmaceutical company focused on developing therapies targeting the Stimulator of Interferon Genes (STING) and A Proliferation Inducing Ligand (APRIL) pathways for the treatment of cancer, autoimmune and inflammatory diseases, today announced that the first patient with IgA nephropathy has been dosed in a Phase 1 clinical trial of BION-1301, an investigational humanized IgG4 monoclonal antibody that blocks APRIL binding to both the BCMA and TACI receptors. NCT03945318 Phase 1 study in IgA nephropathy started in April 2019 active not recruiting as of last update in Jan 2023. NCT03340883 Phase 1/2 study started in Nov 2017 terminated in July 2019 (No objective responses observed following completion of Phase 1 dose-escalation) BION-1301 is Aduro’s proprietary monoclonal antibody targeting APRIL, which the company intends to evaluate in patients with multiple myeloma. Preclinical studies demonstrated that BION-1301 halts tumor growth, overcomes drug resistance to standard-of-care agents such as lenalidomide and bortezomib, and relieves immunosuppression. The team at Aduro Biotech Europe, in collaboration with Jan Paul Medema, Ph.D. of the Amsterdam Medical Center, developed BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, using Aduro’s B-select monoclonal antibody platform. |
| Full address of company | Basel, Switzerland Europe Switzerland https://www.novartis.com/contacts |
B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. BION-131 is a novel humanized high-affinity anti-APRIL antibody (KD 0.4 ± 0.15 nM, EC50 0.29 ± 0.05 nM). Its epitope was mapped to the BCMA and TACI binding site conferring fully blocking capacity to BION-1301. Blocking potency (IC50) was 1.61± 0.78 nM (BCMA) and 1.29 ± 0.89 nM (TACI) respectively. The mouse anti-human parental antibody hAPRIL.01A inhibited APRIL-dependent B-cell proliferation and IgA production in vitro and in vivo (Guadagnoli et al. Blood Jun 23;117, 2011). In B-cell cultures, hAPRIL.01A reduced IgM, IgA and IgG-secreting cells after CpG pulse and APRIL stimulation. Following administration of a single-dose of BION-1301 to NHP, PK parameters typical for human IgG4 antibodies were observed, and confirmed a lack of tolerability issues. In a 4-week repeat dose NHP study BION-1301 demonstrated a favorable safety profile (No Observed Adverse Event Level was 100 mg/kg). Chronic exposure to BION-1301 led to a significantly reduced IgA level vs baseline of -50±14, -52±14, -59±7 % at 10, 30 and 100 mg/kg respectively. (ASN Kidney Week 2018, Abstract: FR-PO114)
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |