BIOX-101 Shows Early Safety, Exploratory Efficacy Signals in Phase 2a Intracerebral Hemorrhage Trial

Final data from the phase 2a BIRCH trial (NCT05970224) suggest that treatment with investigational BIOX-101 (Bioxodes) may reduce perihematomal edema growth and improve functional recovery in patients with spontaneous intracerebral hemorrhage (ICH), although the findings remain preliminary given the study’s small sample size and open-label design. The results were presented at the 2026 European Stroke Organization Conference (ESOC) and are expected to inform the development of a planned adaptive phase 2b/3 study.¹

In the randomized, multicenter, open-label BIRCH study, investigators evaluated BIOX-101 in 23 patients with first-ever spontaneous ICH treated within 24 hours of symptom onset. Patients were randomized in a 3:1 ratio to receive BIOX-101 plus standard of care or standard care alone. The investigational therapy was administered as a 48-hour intravenous infusion.¹

According to the company, hemorrhage volume decreased by 2.19 mL at day 3 in the BIOX-101 group, compared with an increase of 3.85 mL in the standard-of-care arm. Perihematomal edema growth at day 3 was also numerically lower with BIOX-101 (6.44 mL vs 10.46 mL). Investigators additionally reported fewer secondary ischemic lesions and a more stable neutrophil-to-lymphocyte ratio among treated patients. Functional outcomes favored the investigational therapy, although the trial was not powered for efficacy. By day 90, 7 of 16 evaluable patients treated with BIOX-101 achieved a modified Rankin Scale score of 0 to 2, compared with none of the 5 evaluable patients in the control arm.¹

Safety findings were also highlighted in the presentation. No mortality or microhemorrhages were reported by day 7 in either study arm. Serious adverse events occurred in 2 patients receiving BIOX-101 and 2 patients receiving standard care; investigators noted that the events in the treatment group were considered unlikely related or unrelated to therapy.¹

“These final BIRCH data are highly encouraging in a disease where there are no approved therapeutic options,” Robin Lemmens, MD, PhD, head of the stroke unit at University Hospitals Leuven and principal investigator of the BIRCH trial, said in a statement.¹ “The directional findings on hemorrhage volume, edema growth and functional recovery, together with a clean safety profile in patients who typically face very poor outcomes, provide a strong basis for advancing BIOX-101 into the planned pivotal adaptive Phase 2b/3 trial.”¹

Still, important limitations temper interpretation of the BIRCH findings. The study enrolled only 23 patients and used an open-label design, increasing susceptibility to bias and potential baseline imbalances between groups. Several efficacy outcomes were exploratory and descriptive rather than statistically powered confirmatory endpoints. In addition, the control cohort included only 6 patients, limiting confidence in between-group comparisons.

“These final clinical proof-of-concept results provide strong evidence supporting our biological therapeutic candidate’s mechanism of action as the first disease-modifying breakthrough therapy for ICH patients,” Marc Dechamps, chief executive officer at Bioxodes, in a statement.¹ “Recent discussions and feedback from regulators and our regulatory consultants in the U.S. and Europe have validated our new adaptive Phase 2b/3 pivotal trial design, which we will initiate upon accessing sufficient funding. We believe that positive Phase 2b data could enable us to register BIOX-101 for accelerated approval around the end of 2029 and launch this breakthrough therapy towards the end of 2030 in the U.S. and in 2031 in Europe.”¹

Bioxodes stated that regulatory discussions in the United States and Europe support advancement into a single adaptive phase 2b/3 trial enrolling up to 500 patients. The planned study is expected to use functional outcomes as the primary endpoint, with perihematomal edema serving as a key secondary endpoint.

BIOX-101 is a recombinant protein derived from a molecule identified in tick saliva and is designed to inhibit coagulation factors XIa and XIIa while also modulating inflammatory signaling pathways. Interest in factor XI inhibition has increased in recent years due to its potential to reduce thrombosis while maintaining a lower bleeding risk compared with conventional anticoagulants.² Several factor XI–targeting agents are currently in development across cardiovascular and cerebrovascular indications.

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The rationale for testing the therapy in ICH reflects growing recognition that secondary inflammatory injury contributes substantially to neurologic deterioration after hemorrhagic stroke. Expansion of perihematomal edema has been associated with worse neurologic outcomes and is increasingly being used as a biomarker endpoint in clinical trials.³

ICH remains one of the most lethal forms of stroke, accounting for a disproportionate share of stroke-related mortality and long-term disability. Despite advances in supportive care, blood pressure management, and neurosurgical approaches, no pharmacologic therapy has received regulatory approval specifically aimed at limiting secondary brain injury after spontaneous ICH.³

Whether reductions in edema growth or inflammatory biomarkers will translate into meaningful long-term neurologic benefit remains uncertain. Larger, blinded trials will be necessary to confirm reproducibility, better define safety—particularly bleeding risk—and determine whether BIOX-101 can improve disability or mortality outcomes after ICH.

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REFERENCES
1. Bioxodes presents positive final Phase 2a intracerebral hemorrhage results at ESOC affirming breakthrough potential of BIOX-101. Bioxodes. News Release. May 6, 2026. Accessed: May 7, 2026. https://www.globenewswire.com/news-release/2026/05/06/3288801/0/en/bioxodes-presents-positive-final-phase-2a-intracerebral-hemorrhage-results-at-esoc-affirming-breakthrough-potential-of-biox-101.html
2. Sprügel MI, Kuramatsu JB, Volbers B, et al. Perihemorrhagic edema: revisiting hematoma volume, location, and surface. Neurology. 2019;93(12):e1156-e1163. doi:10.1212/WNL.0000000000008084
3. Weitz JI, Strony J, Ageno W, et al. Milvexian for the prevention of venous thromboembolism. N Engl J Med. 2021;385(23):2161-2172. DOI:10.1056/NEJMoa2113194