Clene Inc. · NASDAQ:CLNN
Clene — Corporate Update (November 2023)
29 slides from Clene's corporate update, Nov 7, 2023
Slide 1: > cLene
> cLene NASDAQ: CLNN clene.com
Slide 2: Forward Looking Statements
Forward Looking Statements ‘This presentation contains “orward looking statement” within the meaning of Section 216 ofthe SeuritiesExchenge Act of 1934, as amended, and Section 27A of the Securities Act of 1933, 98 amended, which are intended tobe covered by the “safe harbor” provisions created by t
Slide 3: Neurodegenerative Diseases: The Problem and a New Approach
- Neurodegenerative Diseases \ By THE PROBLEM U A NEW APPROACH + The World Health Organization predicts LOL + Clene is pioneering catalyticnanotherapeutics to treat 7 neurodegenerative diseases will become the second neurodegenerative diseases, suchas amyotrophic lateral ‘most prevalent cause of dea
Slide 4: Building the Clinical Case for Neuroprotection & Remyelination
Building the Clinical Case for Neuroprotection & Remyelination HEALEY ALS i! Prttorm Trial \ he RESCUE ( u Ge RepairPD a) RepairMS Growing Body of Clinical Evidence Across ALS and MS Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases Proprietary Nanotherapeutic Manufacturing
Slide 5: All Neurodegenerative Diseases Involve Neuronal Death
All Neurodegenerative Diseases Involve Neuronal Death AMYOTROPHIC LATERAL SCLEROSIS Motor Neurons DEATH, INDEPENDENTOF SUBTYPE FRONTOTEMPORAL DEMENTIA Spindle Neurons HUNTINGTON'S DISEASE ‘Medium Spiny Neurons NEURONAL DEGENERATION MULTIPLE SCLEROSIS ‘Axonal Degeneration page errr
Slide 6: Hallmarks of Neuronal Death Converge on Mitochondrial Dysfunction and NAD+ Pathway Deficits
Hallmarks of Neuronal Death Converge on Mitochondrial Dysfunction and NAD+ Pathway Deficits SM ------<- otne neon xi atari that S @ | [MITOCHONDRIAL DYSFUNCTION. HYPEREXCTABIUTY [NAD+ PATHWAY DEFICITS CQUALACTVATION/ INLAWMATION pctene
Slide 7: CNM-Au8 | Surface Catalysis Improves Mito Function
CNM-Au8?® | Surface Catalysis Improves Mito Function MITOCHONDRIAL, NEURONAL SURVIVAL FUNCTION ‘AND FUNCTION Nanocrystal Catalysis > cLene 7}
Slide 8: Over 500 Years of Subject Exposure Without Identified Safety Signals
Over 500 Years of Subject Exposure Without Identified Safety Signals Across ALS, MS, and PD Clean Toxicology Well Tolerated Findings Adverse Event (AE) Profile All Animal Toxicology Studies Assessed Resulted in as Predominantly Mild-to- No-Adverse Effect Level (NOAEL) Moderate Severity Findings and
Slide 9: Two REPAIR Trials Demonstrated Target Brain Engagement and Improved Energy Metabolism
Two REPAIR Trials Demonstrated Target Brain Engagement and Improved Energy Metabolism in Early PD and Stable Relapsing MS Results demonstrated a potentially meaningful 10% improvement in NAD+/NADH ratio, an essential molecule for energy production’ Study Objective: Demonstrate target engagement & fo
Slide 10: Promising Evidence from Two Phase Trials and Long-Term Data
Promising Evidence from Two Phase 2 Trials and Long-Term Data CNM-Au8 Demonstrated Survival, Delayed Clinical Worsening, and Preserved Function HEALEY ALS Platform Trial 8% RESCUE ALS Patient Early-to-Mid-Stage ? Mid-to-Late-Stage 44, x Demographics (45) es (161 Regimen C) Sean Duration 36-weeks Up
Slide 11: CNM-Au8 | Clinical Worsening Concordant in Two Phase Trials
CNM-Au8 | Clinical Worsening Concordant in Two Phase 2 Trials Evidence for Decreased Clinical Worsening Events Across Two Phase 2 Studies Phase 2 RESCUE Phase 2 HEALEY ALS Platform CNM Decree cine Warerng Seo Time to Clinical Worsening | CNM-Au8 30mg Time to ALS cincl Worsening au Fret ssvenes cl Da
Slide 12: CNM-Au8 | ALS Survival at 30mg Concordant in Two Phase Trials
CNM-Au8 | ALS Survival at 30mg Concordant in Two Phase 2 Trials HEALEY ALS. Platform Tr Unadjusted Survival Cross-Over Adjusted Survival rat 20mp | Aue ox opr He Rao (0a aaa on 9 Cantos) saronetpreens nen mite rescuE RE atmo omen TH aon edith “SenrantetFon sassy ‘RESTIM, Poorer Ee Pe Rar een id > cL
Slide 13: RESCUE-ALS Improved Exploratory Endpoints: Function, QOL, Slowed Clinical Worsening
a RESCUE\|$ !mproved Exploratory Endpoints: Patient Function, QOL, and Slowed Time to ALS Clinical Worsening Phase 2 Study: 36-Week Placebo-Control Treatment Period 1:1 Randomization (Active 30 mg: Placebo); _N=4S enrolled with early As Proportion wth <6 AS Specie QOL INS Cina! Worsening pant deatne
Slide 14: RESCUE OLE | 52% Reduced Risk of ALS Clinical Worsening
6% RESCUE OLE | 52% Reduced Risk of ALS Clinical Worsening ALS Clinical Worsening Events Time to Death, Tracheostomy, Assisted Ventlation, or Feeding Tube RESCUE-ALS Double-Blind & OLE Periods (24-month LPLV data cut) Proporton Event Fee Keplan Meier Anaoes Death ‘100. . Hazadrabo= 0478 52% decrease
Slide 15: RESCUE-ALS Up to 19.3 Month Survival Benefit vs. Original Placebo
a RESCUE(\S Up to 19.3 Month Survival Benefit vs. Original Placebo Unadjusted Survival Difference: 10.1 Months Cross-Over Adjusted Survival Difference: 19.3 Months overall Survival (Al-Cause Mott) ‘cross-Over Adjusted Analysis of Survival RESOUE-ALS (2-month LPL Gta ct TT Popeation 8) FRESOUE-ALS 2
Slide 16: RESCUE Long-Term Survival Benefit Compared to Historical Matched PRO-ACT Placebo Controls
abe RESCUE Long-Term Survival Benefit Compared to Historical Matched PRO-ACT Placebo Controls RESCUE-ALS Long-Term Survival (CNM-Au8 Observed Survival vs. PRO-ACT Matched Placebo Controls CNM-Au8 treatment demonstrated a significant survival benefit: % decreased risk of death Follow-up of active com
Slide 17: HEALEY ALS Platform Trial Design
A Multi-center, Randomized Double-Blind, Placebo-Controlled HEALEY ALS Clinical Trial Assessing the Efficacy, Safety, Tolerability, Platform Trial Pharmacokinetics, and Pharmacodynamics of CNM-Au8 in Participants with Amyotrophic Lateral Sclerosis 24-Week Treatment Period (3:1 randomization, 120 act
Slide 18: Survival Signal | >90% Reduced Risk of Death with CNM-Au8 30mg
Survival Signal | >90% Reduced Risk of Death with CNM-Au8 30mg Shared Placebo Across Regimens ‘CNM-Au8 30mg Survival | Adjusted Cox Proportional Hazard FullAnaiysis Set (Al Shared Placebo, Regimens A,B,C, 0) HEALEY ALS. Platform Trial ‘CNM-Au8 Regimen Only (Regimen C) (CNM-Au8 30mg Survival | Adjust
Slide 19: HEALEY ALS: Delayed Time to ALS Clinical Worsening
HEALEY ALS. Delayed Time to ALS Clinical Worsening HEALEY CNM-Au8 30mg | Within Regimen Analysis (Primary Model) — 1004 Time to Clinical Worsening | CNM-Au8 30mg. First Occurence of Death, PAV, Tracheostomy or Feeding Tube HEALEY ALS Platform Trial | Kaplan-Meier Estimate Regimen C Population, Effic
Slide 20: Significant Biomarker Plasma NfL Difference
Significant Biomarker Plasma NfL Difference HEALEY ALS. Platform Trial CNM-Au8 vs. Placebo | All RGC Participants During Double-Blind Period 16 10: Plasma NfL. GC Within Regimen Analyis | Quanterix 4NPA [AIIRCG (n=161); Difference of LS Means on Ln Scale (SE) Ditfrence of LS Means on Ln Scale (SE) =
Slide 21: Long-Term Survival | Propensity Matched Placebo
Long-Term Survival | Propensity Matched Placebo PRO-ACT Placebo Matching vs. Regimen C CNM-Au8 30mg HEALEY Regimen C Baseline Values Mean (SO) or Percent (%) cNM-Au Onset Age ssa(ioa) | 55.5 (11.0) ‘Sex (Male, %) 56% | 62% BMI (kg/m) 274(53) | —_26.5(48) AALSFRS-R (Total Score) 345 (58) | 37.7155) D
Slide 22: Long-Term Survival | Propensity Matched Placebo
Long-Term Survival | Propensity Matched Placebo PRO-ACT Placebo vs. CNM-Au8 30mg CNM-Au8 30mg HEALEY CNM-Au8 30mg Integrated Meta-Analysis HEALEY-ALS Platform Long-Term Survival Integrated Meta-Analysis of CNM-Au8 30mg Long-Term Survival (CNM-Au8 30mg Observed Survival vs. PRO-ACT Matched Placebo Co
Slide 23: VISIONARY-MS Core Design Elements
VISIONARY-MS Core Design Elements STUDY Phase 2 Study: 48-Week Placebo-Control Treatment Period 2:1 Randomization (Active [15mg, 30 mg]: Placebo) cs oD er 2 a. ‘oa ‘30 ‘36 “a a8 O+fF-0-O @ O- @ O ° O @ 4 EOS + Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on backg
Slide 24: CNM-Au8 Demonstrated Vision and Global Neurological Improvement in VISIONARY-MS
CNM-Au8 Demonstrated Vision and Global @VISIONARY-MS Neurological Improvement in Stable MS patients on DMTs Significantly Improved Vision Global Neurological & Improvement Ta Be Change in Low Contrast Letter Acuity (LCLA) ‘Change in modified MS Functional Composite (mMSFC) LCLA Chango inthe Acted Ey
Slide 25: CNM-Au8 Improved Information Signal in the Visual Pathway
CNM-Au8 Improved Information Signal in the Visual Pathway ‘mf-VEP Mean Amplitude Percent (%) Change @VISIONARY-MS ITT Population, LS Mean = SEM, Segments Nested by Participant Visual Evoked Potentials (VEP) tay VEPAMectod Eye VEP Follow Eye 10: Increased Amplitude (Signal Strength) | . § - | From th
Slide 26: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity @VISIONARY-MS Throughout the Brain Advanced MRI Techniqu Preserved Whole Brain White Matter Integrity Consistent Effect Across All Brain Regions Dion Tensor inging| Fractional Anisotropy (FA) Chan Otsion Trsr maging Fractal Antony FA) ‘n\inola Brin (Creorun)
Slide 27: Clene | CNM-Au8 Path to Regulatory Approval
Clene | CNM-Au8 Path to Regulatory Approval MID-2023 2024 MID-2024 | 1 i = Amyotrophic Lateral Sclerosis (ALS) Data eadouts / Phase 391 lanned Regulatory > cLene
Slide 28: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases CNM-Au8" FAVISIONARY-MS Sic suspe caer platform, pt trade secret protection ib RESCUE HEALEY ALS Platform Trial — x - on pctene
Slide 29: m® CLene
m® CLene \_4 NANOMEDICINE