Clene Nanomedicine Inc
Clinical Development

Author Of 2 Presentations

Clinical Trials Poster Presentation

P0206 - Effects of nanocatalysis on CNS bioenergetic markers in patients treated with CNM-Au8: Interim results from two Phase 2 31Phosphorous imaging studies (ID 1741)

Presentation Number
P0206
Presentation Topic
Clinical Trials

Abstract

Background

Multiple sclerosis (MS) and Parkinson’s Disease (PD) patients display marked bioenergetic deficits in the CNS. 31Phosphorous magnetic resonance spectroscopy (31P-MRS) is a non-invasive, quantitative imaging technique for monitoring bioenergetic metabolites, as well as phospholipid and myelin precursors. CNM-Au8 is a suspension of clean-surfaced, faceted, gold nanocrystals that catalyze NAD and ATP production and reduce oxidative stress, resulting in remyelination and neuroprotection. Two Phase 2 CNS imaging trials, REPAIR-MS and -PD, were initiated to determine the effects of orally delivered CNM-Au8 on 31P-MRS brain metabolites. An interim analysis of data from completers of these ongoing trials is presented.

Objectives

The objective of this study is to determine the effect of CNM-Au8 treatment on 31P brain bioenergetic metabolites in MS and PD patients.

Methods

7 Tesla 31P-MRS was conducted at baseline (BL) and after 12-16 weeks of CNM-Au8 treatment (30 mg/day, p.o.). A full volume coil was used to collect whole brain spectra in ~600 voxels with a spatial resolution of 2 cm3. Automated analyses of the integrated area of each 31P peak by voxel was normalized to phosphocreatine area and then averaged across voxels for each patient at BL and end of study (EOS). Linear regression determined r2 values for the percentage change from BL for each metabolite versus BL values.

Results

Results for 4 MS and 6 PD completers were analyzed. Percent change from BL at the EOS visit was highly correlated to BL levels for key bioenergetic markers. Patients with nicotinamide adenine dinucleotide (NAD) levels less than the BL mean significantly increased whole-brain NAD levels at the EOS visit, while patients with BL NAD levels greater than the mean normalized levels to the BL mean. Importantly, this relationship was observed for total NAD levels (r2 = 0.6384; p = 0.0056), β-ATP (r2 = 0.8723; p < 0.0001), and several other 31P metabolites, indicating a homeostatic effect of CNM-Au8 on brain bioenergetics. In the 4 MS patients, there were marked correlations for NAD (r2 = 0.9241; p = 0.039), β-ATP (r2 = 0.968; p=0.016), and several other 31P metabolites.

Conclusions

These preliminary results provide the first clinical evidence demonstrating the catalytic effects of CNM-Au8 on key bioenergetic metabolites in MS and PD brains. Full analyses will be conducted once the trials are completed. The brain metabolic homeostasis observed with CNM-Au8 treatment may be neuroprotective, a hypothesis currently being explored in the ongoing VISIONARY-MS study.

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Clinical Trials Poster Presentation

P0243 - VISIONARY-MS: A Phase 2 clinical trial of catalytic gold nanocrystals, CNM-Au8, for the treatment of chronic optic neuropathy (ID 431)

Abstract

Background

Therapies that promote neuroprotection and remyelination are a high priority for multiple sclerosis (MS). CNM-Au8 is an orally delivered suspension of clean-surfaced, faceted gold nanocrystals. CNM-Au8 acts as a nanocatalyst, enhancing cellular bioenergetics, with robust activity in multiple preclinical models of neuroprotection and remyelination. Phase 1 studies identified 15mg and 30 mg per day as well-tolerated doses, with human exposures exceeding those demonstrating preclinical efficacy. No safety issues emerged.

Objectives

To present the rationale for, and design of, the VISIONARY-MS study (NCT03536559), provide clinical trial baseline demographics and visual characteristics, and report interim, blinded efficacy data.

Methods

VISIONARY-MS is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and pharmacokinetics of CNM-Au8 (15 mg or 30 mg daily) versus placebo for 24 weeks in stable relapsing multiple sclerosis (RMS) patients with chronic optic neuropathy, currently receiving disease-modifying therapy (DMT). Key inclusion criteria: age 18-55 years, diagnosis of RMS, disease duration £ 15 years, no history of optic neuritis (ON) for 6 months prior to entry (+/- ON prior to that), clinically stable on an approved DMT, Best Corrected Low Contrast Letter Acuity (BC-LCLA) ≤ 20/40 in the affected eye and ≤ 20/32 in the unaffected eye [BC-LCLA ≤ Best Corrected High Contrast Letter Acuity (BC-HCVA) in both eyes], and mean retinal nerve fibre layer thickness ³ 70 mm in both eyes.

Primary endpoint: mean change in BC-LCLA, as measured by 2.5% Sloan letter chart, from baseline to week 24. Key secondary endpoint: mean change in average mf-VEP latency in the mf-VEP affected eye (greatest mf-VEP latency delay at Baseline) from baseline to Week 24.

Other exploratory outcomes: changes in mf-VEP amplitude and latency measures, retinal morphology, nerve fibre layer thickness, magnetic resonance imaging metrics [T1 Black Hole lesion volume, diffusion tensor imaging, magnetization transfer imaging (MTR) and myelin water imaging], EDSS, 25-Foot Timed Walk, Symbol Digit Modality Test, 9-Hole Peg Test and quality of life from baseline to Week 24.

Results

The study commenced in December 2018. Enrolment is ongoing at selected sites in Australia and North America. Baseline demographics and visual characteristics will be presented. Available interim, blinded efficacy data will be presented.

Conclusions

VISIONARY-MS represents the first efficacy study for a completely novel therapeutic catagory. CNM-Au8 is a nanotherapeutic agent providing bioenergetic, catalyitc support to neurons and oligodendroglia precursor cells, resultng in neuroprotection and improved remyelination in an MS population.

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