Abstract Number: Esoc2026lb16 Birch: A Phase Iia Proof-of-Concept Study of Biox-101 in Spontaneous Intracerebral Haemorrhage

Abstract Background and aims Secondary brain injury following spontaneous intracerebral haemorrhage (ICH) is driven by thromboinflammatory mechanisms, including neutrophil activation, neutrophil extracellular traps (NETs) and microthrombi. BIOX-101 is a recombinant FXIa/FXIIa inhibitor with anti-inflammatory properties that showed favourable safety and neuroprotective effects in a preclinical ICH model, supporting clinical evaluation in acute ICH. The primary aim was to assess the safety and tolerability of BIOX-101 added to standard of care (SoC), compared with SoC alone, in adults with spontaneous ICH. Secondary aims were to obtain preliminary estimates of biological activity using imaging, pharmacokinetics/pharmacodynamics (PK/PD), biomarkers and exploratory assessment of clinical outcomes. Methods BIRCH (NCT05970224) is a multicentre, randomized, open-label Phase IIa proof-of-concept trial conducted in Belgium. Adults with first-ever spontaneous supratentorial ICH (5-60 mL) were randomized 3:1 within 24 hours of symptom onset to BIOX-101 plus SoC or SoC alone, using minimization balanced for age, NIHSS and systolic blood pressure. BIOX-101 was administered as a 1-hour loading dose followed by a 47-hour infusion (38.7 mg/kg total). Imaging included serial CT and DW-MRI with blinded central review. PK/PD and biomarkers (coagulation, neutrophil-to-lymphocyte ratio) were collected up to 168 hours. NIHSS was assessed to Day 7 and modified Rankin Scale (mRS) to Day 360. Analyses were descriptive. Results Safety outcomes included evolution in haemorrhage volume and perihaematomal oedema. PK/PD characterisation, inflammatory biomarker progression, radiological detection of ischaemic lesions and functional outcome (mRS) were assessed. Conclusions Enrolment is complete (N=23); final results will be presented. Conflict of interest