Slide 1: Clene
® cLlene clene.com NASDAQ: CLNN.
Slide 2: Forward Looking Statements
Forward Looking Statements ‘This presentation contains “forward looking statements” within the meaning of Section 21€ ofthe Secrtles Exchange Act of 1924, a¢ amended, and Secon 27A ofthe Secures Act of 1933, a5 amended, which ae intended tobe covered by the “safe hrbor” provisions erated by those la
Slide 3: CNM-Au8 demonstrated survival benefit and neurological improvement
CNM-Au8 demonstrated statistically significant survival benefit of 60% decreased risk of death through 120 wks CNM-Au8 demonstrated global neurological improvement in stable relapsing MS as an adjunet to immunomodulatory DMTs
Slide 4: Neurodegenerative Diseases Share A Common Mechanism
Neurodegenerative Diseases Share A Common Mechanism: A Decline In The Brain’s Ability To Produce Energy Brain Energy Potential Specific Neuronal Populations Are Vulnerable to Energetic Failure Declines With Normal Aging PARKINSON'S DISEASE 205 DEMENTIA ie ramon Eos : a Sclenos's Spindle Neurons 310
Slide 5: CNM-Au8 Pioneering A New Drug Class To Improve Cellular Energy
CNM-Au8°® | Pioneering A New Drug Class To Improve Cellular Energy Production And Utilization CNM-Aus Mechanistic Effects Improved Energy Production and Nanocrystals Utilization Clean surfaced, Highly Faceted Shopes Increased NAD Increased ATP | 7 EB F Decreased reactive oxygen species cunt aus : y
Slide 6: Significant Global Opportunity for Treatment in Combination with Standard of Care
Significant Global Opportunity for Treatment in Combination with Standard of Care Motor Neuron Multiple Parkinson’s Disease Sclerosis (MS) Disease (PD) La MOM a MOSM... oe YEARS oS EMERGING EVIDENCE Q/ or coraninercic WAT EARLY MS IS NEURONS ARE LOST. ureprtencr 2S SS NEURODEGENERATIVE 1D arourcnosi
Slide 7: Two REPAIR Trials Demonstrated Target Brain Engagement and Improved Energy Metabolism
Two REPAIR Trials Demonstrated Target Brain Engagement and Improved Energy Metabolism in Early Parkinson’s and Stable Relapsing MS Results demonstrated a potentially meaningful 10% improvement in NAD+/NADH ratio, an essential molecule for energy production! Study Objective: to demonstrate target eng
Slide 8: RESCUE-ALS Encouraging Efficacy Signals in Phase 2 Trial
Ex RESCUE Encouraging Efficacy Signals in Phase 2 Trial 1° & 2° Endpoints Lol Rescue-ALS Primary & Secondary Endpoints. = (Wk 36 LS Moan Change = 95% CI) tion motor neuron function in rebirctinnad +e © mun0x sum ¢% change) 3 tomate people with early ALS as ured by MUNIX tins 1 taxecsuncs cng as —+—
Slide 9: RESCUE-ALS CNM-Au8 Improved Patient Function, QOL, and Slowed Clinical Worsening
Ek RESCUE\s CNM-Au8 Improved 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 Als Proportion with <6 ALS Specific QOL ALS Clinical Worsening: pom dene an —_————
Slide 10: RESCUE OLE Preserved ALSFRS-R Functional Decline
8% RESCUE OLE | Preserved ALSFRS-R Functional Decline Early CNM-Au8 Treatment Impacts Long-Term Function Compared to Original Placebo ALSFRS-R Slope ALSFRS-R Slope ALSFRS-R Slope Baseline to Week 48 Week 60 [OLE Week 24] to Week 120 Summary rom sn Sar ot an en ee a9 session toc re Pee eels pment aes
Slide 11: RESCUE OLE Decreased ALS Time to Clinical Worsening
6 RESCUE OLE | Decreased ALS Time to Clinical Worsening Rescue-ALS OLE Disease Progression Events Proportion Event Free by Study Visit (14-July-2022 Data Cut) Kaplan-Meier Analyses 100 Hazard ratio= 0.478 The risk of ALS clinical worsening was 18 £ 1. 5% Wald C1= 0.25t0 4.018 loot decreased ~50% for
Slide 12: RESCUE OLE: Demonstrated Significant Impact on Long-Term Survival
as RESCUE\\: Demonstrated Significant Impact on Long-Term Survival 60% Decreased Risk of Death through 120 weeks ‘Long-Term Survival (Al-Cause Mortality): Originally Randomized Active vs. Placebo Interim Analysis (14-July-2022), ITT Population, All Subjects from Randomization (Cong-term vital status
Slide 13: 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 14: Survival Signal: >90% Reduced Risk of Death with 30mg
Survival Signal | >90% Reduced Risk of Death with 30mg Death or Desth Equivalent (PAV) iu Shared Placebo Across Regimens NMA mg Survival | Adjusted Cox Proportional Hard Full Analysis Set (All Shared Placebo, Regimens A, B, C, D). Stinson tou 24 (1 - Hazard Ratio, 95% Confidence Interval) SR ali ‘96
Slide 15: Time to Clinical Worsening Events
Time to Clinical Worsening Events Blatiorm ‘Mal eater as Death Permanent Assisted Hospitalization Feeding Tube Assisted Ventilation as oa Al Placement Ventilation Es NEY, day * Time to clinical worsening events were prespecified in the protocol and analysis plan * p-values provided are uncorrected f
Slide 16: Delayed Time to ALS Clinical Worsening (Composite)
Delayed Time to ALS Clinical Worsening (Composite) Reduction in Time to ALS Clinical Worsening (Composite) First Instance of Death, Trachoostomy, PAY, or Feoding Tube Clinical Worsening Composite risks Coe Peps sol nay Corns Nod) (Time to First Instance) ‘% Hazard Reduction to Week 24 (Double-Blind
Slide 17: Delayed Time to Clinical Event Summary
Delayed Time to Clinical Event Summary HEACEYACS CNM-Au8 30mg | Within Regimen Analysis (Primary Model) CNM-Au8 30mg delayed time to clinical worsening at 6 months ‘CNM-AuB 30mg Clinical Event Risk Reduction ‘Within Regimen Analysis Eticay Roginen iy) Fisk Agusted Cox Poporional Hazaré Model Percent
Slide 18: Plasma NfL Difference: CNM-Au8 vs. Placebo
Plasma NfL Difference | CNM-Au8 vs. Placebo All RGC Participants —« Plasma NfL RGC Within Regimen Analyis | Quanterix 4NPA. All RCG (n=161); Difference of LS Means on Ln Scale (SE) Difference of LS Means on Ln Scale (SE) = -0.010 (0.048); p= 0.040 2 47.9% 2 tos ii / dow a ° 3 2.3% - -O Placebo 0.90-
Slide 19: Consistent Plasma NfL Effect in Fast Progressors
Consistent Plasma NfL Effect in Fast Progressors eae Sensitivity Post Hoc | by Pretreatment delta-FS (ALSFRS-R Slope > 0.45) Plasma NAL te Pout resin Sp er In EL Exec Dagrono Dott ALS 8 Poste ALS Plasma NL ‘ ‘ayo P| "REC Win Regen An | Queer ¥PA seine Ns Mean ethene Deron cts wasn ee SE) Posto 6} Da
Slide 20: CNM-Au8 ALS Clinical Worsening Summary
CNM-Au8 | ALS Clinical Worsening Summary Evidence for Decreased Clinical Worsening Events Across Two Phase 2 Studies RESCUE-ALS CNM-Au8 30mg Phase 2 HEALEY A Time to Clinical Worsening Decreased Time Bitionm ta 2 poor ‘ vas oxme ae] + Tocheosomy - Ss 55%, pe 01063 ton an cata ng on) oman Pecteacten
Slide 21: CNM-Au8 Has Demonstrated ALS Survival Benefit at 30mg Dose
CNM-Au8 Has Demonstrated ALS Survival Benefit at 30 mg Dose in Two Phase 2 Studies 60% decreased risk of PINEANICEE >90% risk reduction of a RESCUE(\.S death through 120 PC MmITREE ‘death at 30mg at 24 weeks Long-Term Sura (A-Couse Mertaliy: Originally Randomized Active vs Placebo ‘M-Au8 30mg | Adjs
Slide 22: Promising Evidence from Two Phase 2 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 ‘ALS Patient Demographics Duration Survival Delayed Time to Worsening Preserved Function (ALSFRS-R) Progression Biomarkers * Consistent Ev Early-to-Mid-Stag
Slide 23: ALS Summary
— 2» ALS Summary | CNM-Au8 Has Demonstrated Survival Benefit and Delayed Time to Clinical Worsening and Functional Decline Significant Opportunity CNM-Au8* Clinical Results 6s RESCUE HEALEY ALS Platform Trial Global Phase 3 ALS Trial * ALS remains a devastating and fatal disease within ~3 to 5 years
Slide 24: HEALEY ALS Platform Safety Summary
HEALEY ALS Platform Safety Summary * Occurrence of TEAEs were balanced between CNM-Au8 and placebo . No SAEs were assessed as related to CNM-Au8 Treatment Emergent Adverse Events (TEAEs) | Participants with Any TEAE 90% | 93% 92% 93% | Participants with Related TEAEs 39% 34% 29% 43% Participants wit
Slide 25: 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) Sereening Do Ys “ge ge 9g SF weex weex wee 36 a3 ‘48 O+4-0-0 @ O- @ O- @ O- @ * Enrolled stable relapsing remitting MS participants with chronic optic neu
Slide 26: Baseline Demographics and Study Analysis
Baseline Demographics and Study Analysis QVISIONARYMS * All participants diagnosed with stable relapsing remitting MS with chronic optic neuropathy * 92% treated with background DMTs (inc 53% monoclonal antibodies, 32% oral) * Modified ITT (mITT) Analysis Population Baseline Value A (9 3 Weight mean
Slide 27: CNM-Au8 Demonstrated Vision and Global Neurological Improvement
CNM-Au8 Demonstrated Vision and Global @VISIONARY-MS Neurological Improvement in Stable MS patients on DMTs Significantly Improved Vision Global Neurological & Improvement or I rey ‘Change in Low Contrast Letter Acuity (LCLA) CChange in modified MS Functional Composite (mMSFC) {LOLA atecteaetow, HPT
Slide 28: VISIONARY-MS Measures of Axonal Integrity
VISIONARY-MS Measures of Axonal Integrity Visual Evoked Potentials (VEP) Multi-focal Amplitude and Latency Changes What Happens in the Visual System Happens ‘Throughout the MS Brain Advanced MRI Techniques @VISIONARY-MS Diffusion Tensor Imaging (DTI) changes Fractional Anisotropy Brain Diffusivity s
Slide 29: CNM-Au8 Improved Information Signal in the Visual Pathway
CNM-Au8 Improved Information Signal in the Visual Pathway Increased Amplitude (Signal Strength) Visual Cortex | is From the Eye to the Brain’s u ‘ ge mf-VEP Mean Amplitude Percent (%) Change ITT Population, LS Mean = SEM, Segments Nested by Participant EP Alfected Eye EP Fellow Eye Wk 48 LS-Mean Dif
Slide 30: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity Throughout the —@v!sionary-Ms Brain Preserved Whole Brain White Matter Integrity Consistent Effect Across All Brain Regions Difuion Tensor imaging | Fractional Anisotropy (FA) Change Ditsion Tensor aging | Fractional Anisotropy FA) ‘now Brin (Corebr Wook 48 C
Slide 31: Consistent Paraclinical Evidence of Neuroprotective Effects
Summary | Consistent Paraclinical Evidence of Neuroprotective Effects Favoring CNM-Au8 Treatment Paraclinical Paral Mean C FA within the whole bran (Cerebrum) p=00199 Diffusion Tensor GA) FA within total Cerebral White Matter p=0080s measure of Fractional Anisotropy FA) FA within total Cerebral Norm
Slide 32: VISIONARY-MS Safety Summary
VISIONARY-MS Safety Summary QVISIONARYMS CNM-Au8 treatment was safe and well-tolerated - Treatment emergent adverse events (TEAEs) were transient and predominantly mild-to-moderate - No dose limiting adverse events; no related serious adverse events ment Emergent Adverse Events CNM-Au8 CNM-Au8 15 mg
Slide 33: CNM-Au8 is Consistently Favored for Treatment of MS
CNM-Au8 is Consistently Favored for Treatment of MS @VISIONARY-MS Progression Independent of an Immunomodulatory Effect Significant Opportunity CNM-Au8° Clinical Results Global Phase 3 MS Trial * MS patients continue to progress with increasing cognitive and functional deficits accumulating even whi
Slide 34: Over 450 Years of Subject Exposure Without Identified Safety Signals
Over 400 Years of Subject Exposure Without Identified Safety Signals Across ALS, MS, and PD Clean Toxicology Well Tolerated Patient Exposure Across Findings Adverse Event (AE) Profile ALS, MS & PD All Animal Toxicology Studies Assessed ' ma a : F Over 450 Years of Subject Resulted in as Predominantl
Slide 35: Growing Body of Evidence for CNM-Au8
Growing Body of Evidence for CNM-Au8° Disease 2021 2022 2023 Key Findings RESCUELIS : ‘Amyotrophic Lateral Sclerosis (ALS) Demons sua beet sees Parkinsons Disease (PD) MS. he Multiple Sclerosis (MS) ad teabtiedbrintaet Denonsratedbei noone Imerovematin Sptntson adie ‘ate ongngtoeasbiontraet jclene
Slide 36: CNM-Au8 Path to Regulatory Approval
Clene | CNM-Au8 Path to Regulatory Approval MID 202? “ MID-s0ee —«} — — pctene
Slide 37: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases (@VISIONARY-MS Strong IP: 150+ patents on. therapeutic susper developmer cellular energeticcatal toremyelinate? & protect neurological function Eis RESCUE HEALEY ALS. Platform Trial —» - - wee pctene
Slide 38: Clene Nanomedicine
> cLene J=— + NANOMEDICINE