Phase 1b PRECISE-AD Trial of Oligomer-Targeting Agent PMN310 Gets Underway

Neil Warma, chief executive officer at ProMIS

ProMIS Neurosciences’ phase 1b PRECISE-AD trial (NCT06750432), a randomized, double-blind, placebo-controlled trial of PMN310, a monoclonal antibody in development for patients with Alzheimer disease (AD), is now underway. PMN310, a humanized IgG1 treatment targeting toxic amyloid-ß (Aß) oligomers, aims to reduce AD pathology while minimizing risk of amyloid-related imaging abnormalities (ARIA) linked with existing approved therapies.¹

The study, which will enroll 100 patients across 22 sites in the United States, tests the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple intravenous infusions of PMN310 in patients with early-stage AD. PRECISE-AD will evaluate 3 dose levels (350 mg, 700 mg, and 1400 mg), with patients randomly assigned in a 3:1 fashion for a 12-month period. Notably, patients will undergo frequent MRI scans throughout the study to monitor for the emergence of ARIA.

"The initiation of the PRECISE-AD trial is a major milestone in our journey to develop PMN310 as a potential treatment for AD. Current AD treatments offer only modest efficacy, often accompanied by significant side effect challenges such as ARIA, leaving a substantial unmet need for new options. We believe PMN310 has the potential to deliver on this need through its selective targeting mechanism," Neil Warma, chief executive officer at ProMIS, said in a statement.

This study includes ambulatory male or female participants aged 50 or older with adequate visual and auditory abilities to complete cognitive and functional assessments. Eligible individuals must meet criteria for mild cognitive impairment (MCI) or mild AD dementia, including a Global Clinical Dementia Rating of 0.5-1.0, objective episodic memory impairment, and a Mini Mental State Exam (MMSE) score between 20-28. Participants must have a positive amyloid PET scan or meet specific diagnostic criteria for AD. Additional criteria include a BMI of 18.5-35 kg/m², willingness to use contraception (if of childbearing potential), reliable caregiver support, and acceptable venous access for blood collection. Patients on stable doses of approved AD medications may also be included.

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Exclusion criteria include individuals living in long-term care facilities, those with conditions (e.g., Parkinson’s disease, uncontrolled diabetes) that could affect cognitive function or study outcomes, and those with significant lab or ECG abnormalities (e.g., QTc > 450 msec in males, liver or kidney dysfunction). Participants with unstable diseases, recent stroke, seizures, or systemic illness within 30 days are excluded. Also excluded are those with contraindications to PET/MRI, a negative amyloid PET scan, or recent anti-amyloid treatments. Pregnant or breastfeeding individuals, those with substance abuse history, HIV, or recent COVID-19 are not eligible.

"We have partnered with some of the best AD treatment centers in the U.S. for this trial and they are actively screening and enrolling patients,” Warma said in a statement.¹ "The PRECISE-AD trial has been carefully designed to generate robust clinical data, including biomarker insights and efficacy signals that will guide the next phase of development. We are excited about the opportunity to deliver real innovation to patients and look forward to sharing updates as we progress, with certain interim data anticipated in the first half of 2026."

PMN310 previously completed a successful phase 1a trial (NCT06105528) of healthy volunteers, with findings first announced in August 2024. The study comprised of 40 individuals aged 18 to 65 years old across 2 sites in the United States. All told, treatment with the agent was considered well tolerated through the first 4 single-ascending dose (SAD) cohorts (2.5, 5, 10, and 20 mg/kg), with dose-dependent impacts on cerebrospinal fluid (CSF) indicative of target engagement.²

At both days 3 and 29, study results showed a dose proportionality of PMN310 levels in CSF, with the lowest dose reaching a greater than 100-fold molar excess compared with expected levels of oligomers in the CSF. Notably, the half-life of the treatment was approximately 25 days, further supporting once-per-month dosing. All told, observed concentrations after treatment suggested target engagement that may be sufficient in the planned PRECISE-AD trial of patients with AD.

REFERENCES
1. ProMIS Neurosciences Initiates Phase 1b Clinical Trial (PRECISE-AD) in Alzheimer’s Disease. News release. ProMIS Neuroscience. January 10, 2025. Accessed January 10, 2025. https://www.globenewswire.com/news-release/2025/01/10/3007552/0/en/ProMIS-Neurosciences-Initiates-Phase-1b-Clinical-Trial-PRECISE-AD-in-Alzheimer-s-Disease.html
2. ProMIS Neurosciences reports positive top-line data from its phase 1a Alzheimer’s trial. July 26, 2024. Accessed January 10, 2025. https://www.globenewswire.com/news-release/2024/07/26/2919566/0/en/ProMIS-Neurosciences-Reports-Positive-Top-Line-Data-from-its-Phase-1a-Alzheimer-s-Trial.html