ProMIS Neurosciences (PMN) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Platform and therapeutic hypothesis

• EpiSelect predicts protein misfolding and designs antibodies to a three-dimensional epitope present on a disease-specific misfolded form; PMN310 is intended to selectively target toxic amyloid-beta oligomers.

• The stated hypothesis is that toxic oligomers drive cognitive decline; management argues selectivity may avoid binding plaque and monomers that can divert antibodies from the oligomer target.

• Preclinical assays showed PMN310 did not bind monomers or plaque; comparator antibodies donanemab, aducanumab, lecanemab and ACU193 bound plaque in the cited tests.

• Phase I-A in healthy volunteers showed PMN310 was safe and well tolerated, crossed the blood-brain barrier and reached levels the speaker said were sufficient to fully engage the oligomer target.

• PMN310 uses an IgG1 backbone intended to trigger microglial activation, supporting oligomer neutralization and clearance.

PRECISE-AD interim findings

• Phase I-B PRECISE-AD is a randomized, double-blind, placebo-controlled 12-month study with 3:1 randomization, three active-dose levels and more than 100 participants; 144 subjects were enrolled.

• The July 28 interim analysis covered blinded six-month safety and biomarkers, not clinical outcomes; participants were assessed together without dose-level separation.

• At six months, interim results showed zero ARIA-E cases, ARIA-H rates in line with placebo, no treatment-related serious adverse events and no treatment-related dropouts.

• Blinded p-tau217 and MTBR-tau243 levels decreased from baseline, although natural-history data cited by the speaker indicate both biomarkers would generally increase; results were not presented by dose.

• Management described the biomarker results as encouraging but not necessarily predictive; clinical efficacy and complete-study findings remain to be assessed.

Competitive context and potential differentiation

• Management said marketed antibodies may derive some efficacy from oligomer binding, but also bind other amyloid-beta forms, including plaque and monomers; it linked off-target binding with ARIA risk.

• Management characterized ALTITUDE-AD results for sabirnetug as consistent with prior evidence of plaque binding and ARIA-E, and said they do not test the oligomer hypothesis because the antibody is not oligomer-selective.

• Management sees reduced ARIA and MRI-monitoring burden as potential advantages; if clean safety is demonstrated, MRI monitoring could be substantially reduced, subject to future evidence and clinical practice.