Chinook Therapeutics Presents Data During the ISN World Congress of Nephrology 2021 - Seite 2

WCN21-0706: A Phase 1, Open Label, Randomized, Single Dose, Parallel Group Safety and Bioavailability Study of BION-1301 Administered by Intravenous (IV) and Subcutaneous (SC) Routes

BION-1301 is a novel anti-APRIL monoclonal antibody currently in phase 1 clinical development for IgAN. Blocking APRIL is a potential disease-modifying approach to treating IgAN by reducing circulating levels of Gd-IgA1 to prevent the formation of immune complexes that deposit in the glomeruli of the kidney, causing damage.

The ongoing phase 1 multi-center trial (see www.clinicaltrials.gov, identifier NCT03945318) evaluated the safety and tolerability of BION-1301 in 63 healthy volunteers in double-blinded, placebo-controlled single-ascending dose (SAD) and multiple-ascending dose (MAD) settings. Healthy volunteers in the SAD portion of the study received placebo or a single intravenous (IV) dose of BION-1301 ranging from 10 mg to 1350 mg on day 1. Healthy volunteers in the MAD portion of the study received placebo or IV doses of BION-1301 ranging from 50 mg to 450 mg on days 1, 15 and 29 (three doses total).

As previously presented, BION-1301 was well-tolerated with no serious adverse events (SAEs), a pharmacokinetic (PK) half-life of approximately 33 days and demonstrated dose-dependent pharmacodynamic (PD) effects characterized by durable reductions in serum levels of IgA and IgM, with a lesser reduction in IgG. Recently analyzed data from this study in healthy volunteers also demonstrated that BION-1301 produced dose-dependent reductions in serum Gd-IgA1 levels that were greater in magnitude than previously reported for total IgA concentrations. In the MAD cohort, BION-1301 reduced Gd-IgA1 levels by 39%, 51% and 55% on Day 29 following the first two doses but prior to the third dose of BION-1301 at 50 mg, 150 mg and 450 mg, respectively, compared to a mean 6% increase in Gd-IgA1 in the placebo group. Upon further follow-up on Day 85, which was 56 days after the third and final dose of BION-1301, Gd-IgA1 reductions were sustained, with mean reductions of 24%, 48% and 70%, at 50 mg, 150 mg and 450 mg, respectively, compared to a mean 4% increase in Gd-IgA1 in the placebo group. Data figures from Day 85 were not included in the poster presentation, but can be found in Chinook’s corporate presentation located on the Events and Presentations section of Chinook’s website.