Oligomer-Targeting Agent PMN310 Shows Safety, Target Engagement in Early-Stage Study
The positive data from this Phase 1a trial will inform the dosing for the upcoming Phase 1b portion in patients with AD, expected to commence in the second half of 2024.
Neil Warma, chief executive officer at ProMIS
Newly announced findings from a phase 1a trial (NCT06105528) of healthy volunteers showed that treatment with investigational PMN310 (ProMIS Neurosciences) was safe and well tolerated across 4 dose levels, with dose-dependent impacts on cerebrospinal fluid (CSF) indicative of target engagement. The full dataset is expected to be presented at an upcoming medical meeting in the second half of 2024.1
PMN310, a humanized monoclonal antibody designed and developed based on its selectivity for soluble amyloid-ß oligomers (AßOs), was generally well tolerated through the first 4 single-ascending dose (SAD) cohorts (2.5, 5, 10, and 20 mg/kg). The study, which comprised of 40 individuals across 2 sites in the United States, showed no treatment-emergent serious adverse events (AEs) with PMN310.
Additional data showed that at both days 3 and 29, investigators observed 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. Overall, the concentrations documented after treatment suggested target engagement that may be sufficient in the planned follow-up trial of patients with Alzheimer disease (AD).
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"Today's announcement marks a pivotal moment for ProMIS and the Alzheimer's community that underscores our progress advancing PMN310 as a potentially transformative therapeutic option for early Alzheimer disease,” Neil Warma, chief executive officer at ProMIS, said in a statement.1 "These data are a positive first step in evaluating the potential of our antibody therapeutic candidates, which are designed to selectively target toxic misfolded proteins in neurodegenerative diseases. We are looking forward to advancing PMN310 into the Phase 1b portion of the clinical study in patients with Alzheimer, which we expect to initiate in the coming months."
PMN310 is designed to selectively target the toxic oligomers of amyloid-ß, with a possibly more favorable clinical safety and efficacy profile over other amyloid-directed therapeutics currently in development. The agent does not bind monomers, plaque, or vascular deposits, potentially lowering the risk for amyloid-related imaging abnormalities (ARIA), an issue seen in AD drug development. Additionally, doses of PMN310 may not be limited by off-target binding or AEs.
"These encouraging data from the first four cohorts of our first-in-human Phase 1a clinical trial of PMN310 in healthy volunteers support the safety and tolerability profile of PMN310, and the levels of PMN310 in the CSF suggest its potential for target engagement," Larry Altstiel, MD, PhD, chief medical officer at ProMIS, said in a statement.1 "Importantly, these results will inform the dosing of our Phase 1b clinical trial in patients with Alzheimer disease, which is on track to initiate in the second half of 2024."
The phase 1a portion of the study featured healthy volunteers, aged 18 to 65 years old whose body mass index were between 18 and 32 kg/m2. Those with a current or relevant history of physical or psychiatric illness, a history of alcohol abuse and/or illicit drug abuse, or experiences of significant systemic illness within 30 days of first dose of study drug were excluded from the study. Patients were included if deemed medically healthy with no clinically significant or relevant abnormalities in medical history, physical exams, vital signs, electrocardiogram, or laboratory evaluations.
