CNM-Au8 / Clene - LARVOL DELTA

CNM-Au8 Strengthens Overall Survival Signal in the HEALEY ALS Platform Trial Open-Label Extension Period (GlobeNewswire) - "CNM-Au8 30 mg treatment demonstrated statistically significant improved survival across both the FAS and CRS populations based on a Cox proportional hazard model and restricted mean survival time (RMST) analyses...In the FAS population: 1-year Cox proportional hazard ratio: 0.2723, 95% CI: 0.0961 – 0.7719, p=0.0144 → 73% reduction in risk of death...In the CRS population: 1-year Cox proportional hazard ratio: 0.229, 95% CI: 0.07 – 0.752, p = 0.0151 → 77% reduction in risk of death."

Biomarker • Clinical data • Amyotrophic Lateral Sclerosis

Among placebo-treated participants who transitioned to CNM-Au8 in the HEALEY ALS Platform Trial OLE, NfL trajectories generally showed decline or stabilization compared to increases observed during the double-blind period. (GlobeNewswire) - "With only relatively few ex-placebo participants (n=31), these analyses had limited power, but the relative decline compared to the double-blind period showed comparable GMR differences (OLE Week 28 GMR: 0.885, 95% CI: 0.737 – 1.063, p=0.185). These findings are consistent with the NfL effects previously published for CNM-Au8 vs. placebo during the 24-week double-blind period (Week 24 GMR difference: 0.905, 95% CI: 0.822 – 0.996, p=0.040)."

Biomarker • Clinical data • Amyotrophic Lateral Sclerosis

Additional disease-relevant biomarker effects on GFAP were identified with statistically significant declines observed during the double-blind period in the HEALEY ALS Platform Trial… (GlobeNewswire) - "GFAP increase in ALS is a marker of harmful reactive astrogliosis, astrocytic injury, and degenerative processes that contribute to motor neuron loss. High GFAP levels are associated with a statistically significant increase in mortality risk in ALS patients. In comparison, placebo participants demonstrated increases across both NfL and GFAP biomarkers during the 24-week double-blind period. Consistent with these findings, in the matched NIH-EAP population, the magnitude and timing of NfL and GFAP reduction were closely correlated (Pearson’s r >0.85....demonstrating concordant effects for NfL and GFAP in the HEALEY ALS Platform Trial and NIH-EAP participants."

Biomarker • P2/3 data • Amyotrophic Lateral Sclerosis

Statistically significant decrease in NfL levels compared to matched ALS controls across the full analysis set (all evaluable matched participants) in the NIH-EAP (GlobeNewswire) - "The Week 36 AUC (area under curve) difference (SEM) of NfL (Ln(pg/mL)*Week) was: –0.0899 (0.0430), p = 0.0373, equivalent to a geometric mean ratio (GMR) difference of 0.914, 95% CI: 0.840 – 0.995. The effect size was similar to the NfL decline observed in the original double-blind phase of the HEALEY ALS Platform Trial: HEALEY W24 AUC GMR of 0.901, 95% CI: 0.845 – 0.959, p=0.0013 compared to the NIH-EAP W24 AUC GMR of 0.911, 95% CI: 0.836 – 0.993, p=0.0339. Multiple pre-specified supportive analyses in the NIH-EAP across the full analysis set at Week 24 and Week 48 confirmed the of the findings (p<0.05). Pre-specified subgroups showed significant effects in participants including those with an age younger than the median, on background riluzole treatment, and in participants with bulbar onset (p<0.05). In the primary analysis population in non-bulbar onset participants (i.e., predominantly limb onset), the Week 36 AUC NfL change was not significant (p=0.2085)."

Biomarker • Retrospective data • Amyotrophic Lateral Sclerosis

NfL and GFAP biomarker decline is associated with improved survival. (GlobeNewswire) - "Among participants treated in the HEALEY ALS Platform Trial with CNM-Au8 30 mg, participants with the greatest declines across both NfL and GFAP biomarkers during the double-blind period had the largest long-term overall survival improvement relative to all participants treated with CNM-Au8 30 mg (NfL and GFAP average AUC decline"

Biomarker • P2/3 data • Amyotrophic Lateral Sclerosis

Clene…announced it plans provide an update on its CNM-Au8 program in ALS, and to host an investor call and webcast at 8:30 am ET on Wednesday, December 3, 2025 (GlobeNewswire)

Clinical data • Amyotrophic Lateral Sclerosis

A comparison of baseline characteristics of decentralized and In-clinic participants enrolled in the CNM-Au8 EAP04 study (ALS-MND 2025) - "There were no clinically meaningful differences in baseline disease severity or progression risk between institutionally and remotely enrolled participants. These findings support the feasibility of decentralized models in ALS research and validate the integration of data from both enrollment pathways in future analyses. Expanding access through telehealth does not compromise clinical comparability, strengthening the case for broader DCT adoption in ALS trials."

Clene Reports…Recent Operating Highlights (GlobeNewswire) - "...As recommended by the FDA, Clene plans to request a Type C meeting with the FDA to review its data from these analyses, which meeting is expected to occur in the first quarter of 2026....The Company plans to submit a New Drug Application (NDA) in the first quarter of 2026 under an accelerated approval pathway. The Company expects to have the first patient dosed in the confirmatory Phase 3 RESTORE-ALS trial of CNM-Au8 in the first half of 2026."

FDA event • FDA filing • New P3 trial • Amyotrophic Lateral Sclerosis

A Phase 2, Open Label, Sequential Group, Investigator Blinded Study ofMagnetic Resonance Spectroscopy (to Assess the Effects ofCNM-Au8 for the Bioenergetic Improvement of Impaired Neuronal RedoxState in Multiple Sclerosis (REPAIR-MS) - Results (ECTRIMS 2025) - " REPAIR-MS cohort 1 included relapsing remitting MS, stable on natalizumab...Sguigna received personal compensation for consulting services from Genentech, EMD Serono, Horizon Therapeutics, Amgen, and Bristol Myers Squibb and has received research support from Genentech, Clene Nanomedicine, Zenas Biopharma, IPMSA through the NMSS, PCORI, DOD/CDMRP, and NIH/NIA through his institution... CNM-Au8 showed evidence of improved brain bioenergetics improvement in MS participants with an average percent increase in the NAD+/NADH ratio of 9.5% (p=0.0275). CNM-Au8 treatment was safe and well-tolerated with treatment emergent adverse events predominantly assessed as mild-to-moderate severity, and transient. This data buttresses the theory that bioenergetic failure contributes to neurodegeneration in MS."

Clinical • Late-breaking abstract • P2 data • CNS Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease

Clene Presents New Clinical Data at ECTRIMS 2025 Meeting Demonstrating CNM-Au8 Improves Brain Energy Metabolism in Multiple Sclerosis Patients (GlobeNewswire) - "The mean NAD+/NADH ratio in the brain was significantly increased following 12 weeks of treatment with CNM-Au8 in the full REPAIR population (+0.449 units, 95% CI: 0.093 to 0.805, p=0.0148; percent change: 8.65%, 95% CI: 2.6% to 14.7%, p=0.0006)...Baseline measures of working memory and cognitive processing speed, measured by the Symbol Digit Modalities Test, were significantly associated with average brain ATP levels (peak signal area average for α-ATP, β-ATP, γ-ATP; Pearson Correlation: ρ=0.542, p=0.0009)....CNM-Au8 treatment was safe and well tolerated with treatment emergent adverse events characterized as transient and predominantly mild-to-moderate in severity."

Late-breaking abstract • P2 data • Multiple Sclerosis

Clene Presents Preclinical Data Supporting CNM-Au8 for the Treatment of Parkinson’s Disease (GlobeNewswire) - "Improved mitochondrial health in familial PD: CNM-Au8 increased mitochondrial health (membrane potential) and mitochondrial volume, while reducing harmful reactive oxygen species (ROS) in fPD neurons. Similar, relatively milder effects were observed in sPD neurons. Reduced inflammation in sporadic PD: CNM-Au8 lowered levels of senescence-related inflammatory proteins, including CD40 and CXCL10, in sPD neurons, helping to reduce neuroinflammation that exacerbates PD progression."

Preclinical • Parkinson's Disease

Clene Inc. Advances Toward ALS Drug Approval… (City Buzz) - "The biopharmaceutical company plans to submit a New Drug Application for CNM-Au8 in ALS treatment by the end of 2025, representing a significant milestone for patients suffering from the progressive neurodegenerative disease."

FDA filing • Amyotrophic Lateral Sclerosis

CNM-Au8 for the treatment of MS (GlobeNewswire) - "The Company plans to hold an end-of-Phase 2 Type B meeting with the FDA in the third quarter of 2025. This meeting will review results from the Phase 2 VISIONARY-MS trial and discuss the planned Phase 3 study focusing on cognition improvement as an adjunct to standard-of-care MS therapies."

FDA event • New P3 trial • Multiple Sclerosis

CNM-Au8 for the treatment of ALS (GlobeNewswire) - "NfL change will be analyzed following 9 months of treatment (primary NfL analysis) and after 6 months of treatment (supportive NfL analysis). These analyses are intended to provide supportive data of the NfL change previously demonstrated in the HEALEY ALS Platform Trial double-blind period following 6 months of treatment with CNM-Au8. Clene expects to conduct the analysis of this NfL biomarker data early in the fourth quarter of 2025."

Trial status • Amyotrophic Lateral Sclerosis

Clene Provides Regulatory Update Following Constructive FDA Type-C Meeting on Neurofilament Biomarker Analysis Plan and Confirms Two Additional FDA Meetings (GlobeNewswire) - "Clene, Inc...and its subsidiary, Clene Nanomedicine, Inc...provided a regulatory update following a Type C meeting with the U.S. Food and Drug Administration (FDA), and announced two additional meetings scheduled with the FDA in the 3rd quarter of 2025...In the recently concluded Type C meeting, Clene discussed its proposed statistical analysis plan (SAP) for comparing neurofilament light (NfL) biomarker data from its ongoing NIH-sponsored Expanded Access Protocol (EAP), supporting nearly 200 people living with ALS treated with compassionate use of CNM-Au8, to matched ALS controls. The FDA provided constructive feedback on Clene’s proposed analysis methodology for assessing NfL change...The NfL analyses will be conducted early in the 4th quarter of 2025. If the findings demonstrate a clinically meaningful decline in NfL, they may support a new drug application (NDA) submission under the accelerated approval pathway, planned for the end of 2025."

FDA event • FDA filing • Amyotrophic Lateral Sclerosis • Multiple Sclerosis

CNM-Au8 in Amyotrophic Lateral Sclerosis. (PubMed, JAMA) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

CNM-Au8 in Amyotrophic Lateral Sclerosis-Reply. (PubMed, JAMA) - No abstract available

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

Clene Reports First Quarter 2025 Financial Results and Recent Operating Highlights (GlobeNewswire) - "Cash and cash equivalents of $9.8 million as of March 31, 2025, providing cash runway into the third quarter of 2025....Clene plans to discuss the entire VISIONARY-MS trial, including this recently presented data at an end-of-Phase 2 meeting with the FDA in the third quarter of 2025."

Commercial • FDA event • P2 data • Amyotrophic Lateral Sclerosis • Multiple Sclerosis

AAN 2025: Gains from CNM-Au8 in RRMS linked to nerve cell repair (Multiple Sclerosis News Today) - "The findings come from the Phase 2 VISIONARY-MS clinical trial (NCT03536559) and its long-term extension study VISIONMS-LTE (NCT04626921)....The data were discussed in a late-breaking presentation...at the American Academy of Neurology (AAN) Annual Meeting....The newly presented data, consistent with previous reports, showed that CNM-Au8 continued to be associated with clinical improvements and indicators of improved nerve health in the extension study. In particular, improvements were observed in the latency and amplitude of visual evoked potentials, known as VEPs. These measures are indicators of the speed and strength of electrical signals being sent from the eyes to the brain, with an improvement reflecting possible optic nerve repair. MRI data also indicated improvements in the brain’s neuronal structure suggestive of remyelination."

Retrospective data • Multiple Sclerosis

Physiologic and Anatomical Evidence of Neuronal Repair and Remyelination from the Long-Term Open Label Extension of the Phase 2 VISIONARY-MS Trial (AAN 2025) - "Background CNM-Au8 is an investigational drug that catalytically enhances cellular energy metabolism...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."

Clinical • Late-breaking abstract • P2 data

Clene Reports Full Year 2024 Financial Results and Recent Operating Highlights (GlobeNewswire) - "Clene will meet with the FDA in the second quarter of 2025 to review and finalize its statistical analysis plan for the EAP NfL biomarker analyses followed by the actual NfL biomarker collection and analyses in the third quarter to support NDA submission. NDA submission is anticipated to occur in the second half of 2025....Clene plans to commence the confirmatory Phase 3 RESTORE-ALS trial with participant enrollment beginning in mid-2025 which is prior to the submission of the NDA."

FDA event • FDA filing • Trial status • Amyotrophic Lateral Sclerosis

CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. (PubMed, JAMA) - P2/3 | "No benefit of CNM-Au8 on ALS disease progression was observed at 24 weeks. ClinicalTrials.gov Identifiers: NCT04297683, NCT04414345."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Fatigue

Clene Demonstrates Strengthened ALS Survival Benefit with CNM-Au8 Treatment (GlobeNewswire) - P2/3 | N=161 | HEALEY ALS (NCT04414345) | "Median Survival: CNM-Au8 30 mg group (Regimen C, n=59) achieved 951 days versus 753 days in the Regimen A comparator group (n=162) – a gain of 198 days (6.5 months); Restricted Mean Survival Time (RMST) Benefit: covariate-adjusted RMST improvement of 124 days (4.1 months) was observed (95% CI: 3 to 245 days, p=0.045). RMST is a metric that estimates the average time a group survives relative to a comparator...In participants with baseline serum NfL > 33 pg/mL and TRICALS risk score range between –6.5 and –2.5 (i.e., filtering slow progressors where there was an imbalance between groups), median survival improved from 589 days (Regimen A, n=120) to 951 days (CNM-Au8 30 mg, n=51), representing an 11.9 month gain."

P2/3 data • Amyotrophic Lateral Sclerosis

Clene and APST Enter Into an Agreement to Support FDA’s Recommendation for Long-Term NfL Biomarker Analyses of CNM-Au8’s Impact on NfL Reduction (GlobeNewswire) - "Clene Inc...and its wholly owned subsidiary Clene Nanomedicine Inc....today announced that it has entered into an agreement with German-based APST Research GmbH (APST) to utilize its extensive NfL database to support the FDA-recommended analyses of CNM-Au8’s effect on NfL decline in participants in ongoing Expanded Access Protocols (EAPs)...The database in the repository comprises extensive sNfL data from over 4,300 ALS patients as well as self-reported ALSFRS-R....Analyses of NIH-sponsored EAP NfL reduction, if positive, will support the planned NDA submission for potential Accelerated Approval of CNM-Au8 in ALS, planned in the second half of 2025."

Commercial • FDA filing • Amyotrophic Lateral Sclerosis

REPAIR-MS: 31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Multiple Sclerosis. (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Clene Nanomedicine | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis