Novel BXOS110 promising neuroprotective agent in acute ischaemic stroke

BXOS110, a novel PSD-95* protein inhibitor, has shown potential for improving functional outcomes in patients with acute ischaemic stroke, according to the BEST** trial presented at ISC 2025.

“Consistent with the findings of FRONTIER, BXOS110 administration within 3 hours after stroke onset showed a tendency toward better functional outcomes at 3 months compared with placebo, combined with reperfusion therapy,” said Dr Zixiao Li from Beijing Tiantan Hospital, Capital Medical University in Beijing, China.

In the BEST phase II trial, 299 patients (mean age 63.5 years, 29 percent female) presenting within 3 hours of stroke onset were randomized to receive BXOS110 at high dose (3 mg/kg, with a maximum dose of 300 mg; n=102) or low dose (2 mg/kg, with a maximum dose of 200 mg; n=99) or placebo (n=98) once daily. More than 90 percent of the participants also received intravenous thrombolysis.

At 90 days following stroke onset, BXOS110-treated patients were nine times more likely to achieve a modified Rankin Scale (mRS) score of 0–2 than placebo-treated patients. [ISC 2025, abstract LB45]

Results showed that 85.3 percent in the high-dose and 78.8 percent in the low-dose BXOS110 groups had mRS scores of 0–2 at 90 days after stroke compared with 77.6 percent in the placebo group. High-dose BXOS110 showed a relative risk ratio of 9.06 (p=0.055) compared with placebo.

A higher percentage of patients treated with high-dose BXOS110 also achieved an NIHSS*** score of ≤1 on day 10 (or at discharge) or a ≥4-point reduction from baseline than those treated with placebo (84 percent vs 77.9 percent).

In terms of safety, serious adverse events (SAEs) occurred at a higher rate in the high-dose BXOS110 arm vs the low-dose BXOS110 and placebo arms (15.7 percent vs 5.1 percent and 4.1 percent, respectively; p=0.006), but no AEs led to study drug discontinuation.

The high-dose group also had a higher mortality rate compared with the low-dose or placebo groups (4.9 percent vs 0 percent and 2 percent, respectively; p=0.064).

“BXOS110 showed a favourable trend in improving 90-day functional outcomes, particularly at high dose, though safety concerns at high dose warrant careful consideration,” said Li. “These findings highlight the potential of BXOS110 as a neuroprotective agent in ischemic stroke and provide valuable insight for the design of phase III studies.

“We hope to expand the sample size in the design of our phase III clinical study based on the effective doses explored in the current phase II study to further investigate the neuroprotective effect in patients with acute ischemic stroke,” Li added. “We need to focus on whether any serious AEs related to the drug [will] occur during the phase III study.”