ProMIS Neurosciences (PMN) Study result summary

Study design and patient demographics

• The Phase 1b PRECISE-AD trial enrolled 144 patients with mild cognitive impairment or early Alzheimer's disease, using a 3:1 randomization to drug versus placebo and multiple ascending dose cohorts (350 mg, 700 mg, 1,400 mg or 5, 10, 20 mg/kg) over 12 monthly IV infusions.

• 136 patients were included in the safety analysis, with all patients amyloid positive by PET imaging and positive tau-based biomarkers.

• Patient demographics matched real-world AD populations, with 61% APOE4 carriers and 11% homozygotes.

• 78% of patients had received at least nine months of dosing, and 49% completed the full 12-month trial at interim analysis.

• The trial is designed to assess safety, pharmacokinetics, biomarker effects, and clinical outcomes.

Safety findings

• No ARIA-E events were observed; total ARIA incidence was 4.4%, all mild, asymptomatic ARIA-H, with no treatment-related serious adverse events or discontinuations.

• Minimal infusion reactions occurred, with only one non-serious event reported.

• Safety profile was consistent across all genotypes, including high-risk APOE4 homozygotes.

• ARIA rates were lower than those reported for approved anti-amyloid therapies and tracked with placebo rates from literature.

• Frequent MRI scans were used for ARIA monitoring, ensuring high detection probability.

Biomarker results

• Plasma p-tau217 declined by 15% and CSF MTBR-tau243 by 13.3% at six months, with 68.5% and 62.5% of patients, respectively, showing improvement.

• Both biomarkers typically increase in untreated AD; observed declines suggest target engagement and potential disease modification.

• Biomarker changes tracked the 3:1 randomization, supporting a drug effect.

• Both p-tau217 and MTBR-tau243 are validated indicators of AD progression.

• Early movement in p-tau217 is correlated with later clinical outcomes.