Chinook Therapeutics, Inc. announced a focused oral presentation on zigakibart (BION-1301) will be presented on Friday, June 16, 2023 at the 60th ERA Congress being held virtually and live in Milan, Italy. Updated Interim Results of a Phase 1/2 Study of Zigakibart (BION-1301) in Patients with IgA Nephropathy Zigakibart is a novel anti-APRIL monoclonal antibody currently in phase 2 clinical development for patients with IgAN. Blocking APRIL is a potentially disease-modifying approach to treating IgAN by reducing circulating levels of galactose-deficient IgA1 (Gd-IgA1).

Updated data from both Cohorts 1 and Cohort 2 will be presented from Part 3 of the ongoing phase 1/2 multi-center trial evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical responses of open-label zigakibart treatment in patients with IgAN. Key highlights from the presentation include the following: Patients in Cohort 1 initially received a 450mg intravenous (IV) dose of zigakibart every two weeks. After at least 24 weeks of IV dosing, patients in Cohort 1 transitioned to a 600 mg subcutaneous (SC) dose every two weeks for a total treatment duration of up to two years.

Cohort 1 enrolled 10 patients, of which two patients withdrew from the study for reasons unrelated to study drug, and eight patients continued receiving treatment. Patients in Cohort 2 are receiving a SC dose of 600 mg of zigakibart every two weeks for a total treatment duration of up to two years. Cohort 2 enrolled 30 patients, of which three patients were discontinued for not meeting the eligibility criterion of having biopsy-confirmed IgAN, and 27 patients continued receiving treatment.

Baseline 24-hour Urine Protein Excretion (g/day) 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. Safety and Tolerability As of the May 8, 2023 data cutoff, zigakibart has been well tolerated, with no deaths or treatment discontinuations due to adverse events.

Of all 40 patients enrolled in both Cohorts 1 and 2: All infections have been Grade 1 or 2 in severity and only one subject had infections deemed treatment-related (Grade 1 viral upper respiratory tract infection and influenza). There were no anti-drug antibodies observed in any patients. Two patients had IgG levels that fell below 3 g/L. One patient in Cohort 1 required protocol-mandated withholding of study drug.

The patient reached end-of-treatment prior to re-initiation of study drug. One patient in Cohort 2 had IgG levels below 3g/L at their week 12 follow-up after permanent discontinuation due to not meeting eligibility criteria for having biopsy-confirmed IgAN. No infections were reported in either patient while their IgG levels were below 3g/L. There were 16 injection site reactions (ISRs) reported from a total of 875 SC doses administered (<2%).

All ISRs were Grade 1 or Grade 2. One serious adverse event occurred (amnesia) that was not treatment-related and did not result in interruption of study drug. Mechanistic Biomarkers Zigakibart treatment resulted in rapid and sustained reductions in IgA, pathogenic Gd-IgA1, IgM and to a lesser extent IgG, in patients with IgAN. Zigakibart's effects on mechanistic biomarkers were highly consistent between Cohorts 1 and 2. 24-hour UPCR Zigakibart treatment resulted in sustained, clinically meaningful proteinuria reductions in patients with IgAN across a wide range of baseline proteinuria levels.

In the combined Cohorts 1 and 2, zigakibart demonstrated mean reductions in 24-hour urine protein creatinine ratio (UPCR) of 20% in 33 patients at 12 weeks of treatment, 39% in 33 patients at 24 weeks of treatment, 67% in 17 patients at 52 weeks of treatment, 67% in seven patients at 76 weeks of treatment and 72% in five patients at 100 weeks of treatment. 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. A moderated oral presentation (6-slide presentation) on research regarding the impact of maladaptive tubular epithelial cells on disease progression in chronic kidney diseases will be presented on Friday, and a free communication presentation (10-minute live oral presentation) on initial data from the phase 1 study of CHK-336 in healthy volunteers will be presented Saturday, June 17, 2023.