POS1143 URINARY CD163 PREDICTS COMPLETE RENAL RESPONSE WITH ZETOMIPZOMIB TREATMENT IN THE OPEN-LABEL MISSION PHASE 2 STUDY IN PATIENTS WITH LUPUS NEPHRITIS

Background Complete renal response (CRR) defined by ACR/EULAR guidelines is a desirable clinical outcome associated with long-term preservation of kidney function in patients lupus nephritis (LN) as demonstrated trials when achieved after 1-2 years. Urinary CD163 (uCD163), biomarker that correlates LN histologic inflammation, has been observed to predict therapy [1] . Results previously reported on MISSION, Phase 2 open-label study evaluating the safety and tolerability zetomipzomib active, proliferative LN, clinically meaningful responses along reductions uCD163 strong correlation UPCR [2] Decrease at early timepoints its prediction proteinuria may increase probability achieving treatment effect. Objectives Data from MISSION was used evaluate potential predictor complete for LN. Methods In MISSON study, active (Class III or IV ± V) received 60 mg subcutaneously once weekly (first dose 30 mg) addition stable background 24 weeks. End-of-treatment (EOT) Week (W) 25, end-of-study (EOS) occurred W37. data W13 W25 were model predictive association CRR* & W37, respectively. A logistic regression Youden Index generate Receiver Operating Characteristics (ROC) curves help accuracy identify optimal cut-off points differentiate responders non-responders. *Complete Renal Response: ≤0.5, eGFR ≥60 mL/min/1.73m no worsening baseline ≥25%, prednisone (or equivalent) ≤10 use prohibited medication. Of 21 enrolled 17 reached EOT EOS. CRR 35% 41% Anti-inflammatory reduction uCD163, which strongly correlated improvement W13, W37 (Figure 1). For thirteen who consented urine analysis, 24-hour was: mean=2.8 mg/mg, median=1.8 SD=3.3, range 0.93-13.4; uCD163: mean=1.7 mg/mmol, median=0.97 SD=2.3, 0.28, 8.9. ROC analysis results suggests values ≤0.13 ≤0.09 are more likely achieve following (Table Conclusion This post-hoc generated Ph2 levels might up 3 months later could therefore potentially guide therapy. Further evidence needed larger randomized confirm utility limits biomarker. Reference [1]Mejia Vilet et al, JASN 2020; Parikh SV ASN 2022. Figure 1. Correlation Plots Table Summary Analysis based Logistic Regression Model Predictor Outcome N Cutpoint AUC (max=1) Sensitivity (0-1) Specificity Predictive non-CRR 13 (p=0.3615) 25 (4 CRR) 12 (1 missing) =0.13 1.0 100% (p=0.1218) 37 (5 =0.09 0.8 0.6 80% =0.56* 0.75 67% 86% *based criterion smallest Δ=Sensitivity – Specificity. Acknowledgements: NIL. Disclosure Interests Joan T Merrill Consultant of: AbbVie, Alexion, Alumis, Amgen, Astra Zeneca, Aurinia, Bristol Myers Squibb, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Lilly, Merck, Pfizer, Provention, Remegen, Sanofi, UCB, Zenas, Grant/research support from: Richard Leff Shareholder Kezar Life Sciences, Andrea Fan Employee Full time employee Kiruthi Palaniswamy Noreen Henig Chief Medical Officer Steven Hua Sciences.