POS1351 A PHASE 2, 104-WEEK STUDY OF REPEAT LORECIVIVINT INJECTIONS EVALUATING SAFETY, EFFICACY, AND BONE HEALTH UTILIZING QUANTITATIVE COMPUTED TOMOGRAPHY (QCT) IN KNEE OSTEOARTHRITIS (OA-06)

Background Knee osteoarthritis (OA) is a common joint disorder associated with pain, disability, and damage. There unmet need for safe efficacious treatments symptoms structural modification. Lorecivivint (LOR), an intra-articular (IA) CLK/DYRK inhibitor thought to modulate Wnt inflammatory pathways, in development as potential knee OA treatment. Objectives To assess the safety tolerability of repeated 6-month dosing LOR 104-week trial (OA-06, NCT03727022 ). Additionally, characterize juxta-articular bone health quantitative computed tomography (qCT) regional via dual energy x-ray absorptiometry (DXA). Methods Participants ACR-defined clinical radiographic OA, aged 40-80, Kellgren-Lawrence (KL) grades 2-3 were randomized 1:1 receive IA injections 2 mL 0.07 mg or vehicle PBO at baseline, 24, 52, 72 weeks. The was conducted two 52-week phases, part A (baseline week 52) B (week 53 104), completers invited into B. Safety assessed by collection adverse events (AEs), serious AEs (SAEs). Bone assessments included qCT target non-target BMD, DXA spine hip BMD bone/ cartilage biomarkers. Exploratory efficacy patient-reported outcomes (PROs). For imaging endpoints, change from baseline estimated using baseline-adjusted ANCOVA. Results 101 participants (mean age 60.9±9.1 years, BMI 28.6±3.7 kg/m , female 59.4%, KL2 52.5%) enrolled. 77 completed AE rates similar between LOR, no SAEs deemed treatment related. signals (no fractures, accelerated osteoporosis) observed LOR. Observed BMDs (Figure 1). Change Week 104 -7.08 (12.34) mg/cm 3 -2.95 (8.65) PBO, (estimated difference -4.05 [95% CI -11.21, 3.11], not significant). Trends those higher risk decreasing (female 65-80), showed meaningful differences PBO. significant total Potential confounding factors imbalances sex (PBO 68.0% vs. 51.0% female), KL grade 62.0% vs 42.1% 2), site randomization. PRO changes groups. conduct limitation small number qCT-enabled sites available US. Conclusion incidence groups affected Multiple over years did appear lead any effects locally around regionally hip. Table 1A 1B. Phase #Events/#Subjects Reporting (n=50) Adverse 52/25 52/24 5/2 3/2 Target-knee 7/6 4/3 Figure 1. Total Target weeks REFERENCES: NIL. Acknowledgements: Disclosure Interests Yusuf Yazici Shareholder of: Biosplice Therapeutics, Employee Christopher Swearingen Heli Ghandehari Jon Britt Sarah Kennedy Jeymi Tambiah Nancy Lane Consultant Therapeutics.