Report on clinical correlates to MRI diffusion tensor imaging (DTI) and visual evoked potential (VEP) results in participants in the long-term open-label extension (OLE) of the Phase 2 VISIONARY-MS trial.

CNM-Au8 is an investigational drug that catalytically enhances cellular energy metabolism. In VISIONARY-MS trial, primary and secondary outcomes demonstrated significant clinical efficacy for low contrast letter acuity (LCLA) and the modified MSFC during the 48-week double-blind period in the mITT population.

Longitudinal MRI and VEP scans were obtained in participants every 24-weeks post-baseline through Week 144. MRI DTI (e.g., magnetization transfer ratio (MTR), axonal diffusivity (AD), fractional anisotropy (FA)) change, and multi-focal VEP latency and amplitude core segment change were correlated with clinical outcomes including LCLA, a measure of vision, and the symbol digit modalities test (SDMT), a measure of cognition. Pearson correlation coefficients with p-values are reported.

mf-VEP latency (i.e., decreased values = improved conduction velocity) was correlated clinically with improved LCLA total (sum of correct letters across eyes; r= -0.35, p<0.05) and SDMT change (r= -0.34, p<0.05); and inversely correlated with MTR (r= -0.395, p=0.01) and AD (r= -0.41, p=0.002). mf-VEP amplitude (i.e., improved conduction signal strength) was correlated with improved AD (r= 0.45, p=0.003) and improved MTR (r=0.38, p<0.05). MTR was positively correlated with improved AD (r=0.746, p<0.0001).

Physiological VEP and anatomical MRI data indicate long-term treatment with CNM-Au8 30 mg resulted in improved neuronal function and remyelination evidenced by improved cerebral AD, improved MTR, and improved VEP latency within the same participants. VEP latency and MTR improvements were associated with improved clinical outcomes. The VISIONARY-MS trial is the first Phase 2 study to demonstrate clinical and physiological improvements consistent with improved neuronal cellular function and remyelination.