Slide 1: Clene
> cLene NASDAQ: CLNN: clene.com Lar |
Slide 2: Forward Looking Statements
Forward Looking Statements ‘This presentation contin “forward ooking statements within the meaning f Secon 24E ofthe Secures Exchange Act of 1934, as amended, and Seton 27Af he Secures At of 1833, 94 amended, which are tensed oe covered bythe “tafe arbor” provslon reste by hate laws, lene’ toward oo
Slide 3: The Problem / A New Approach
THE PROBLEM + The World Heath Organization predicts ‘neurodegenerative diseases will become the second: ‘most prevalent cause of death within the next 20 * therapeutic breakthrough i urgently needed. + Inneurodegenerative diseases, impaired mitochondrial activity and compromised eellular metabolism
Slide 4: Building the Clinical Case for Neuroprotection & Remyelination
Building the Clinical Case for Neuroprotection & Remyelination Platform Trial HEALEY ALS ( ) MS RESCUE!| pcvene —_ +
Slide 5: What is CNM-Au8?
What is CNM-Au8*" ? (CNM Aus Nanoerystl Suspension ‘60 mL perbotle (once dally) 100 Tilion Nanocrystals per 60 mt dose (at 30 ma) CNM-Au8 Attributes: Y Nanocrystal suspension Y Orally administered (or by feeding tube) v Targets energy metabolism and oxidative stress Y Blood-brain-barrier penetrant >
Slide 6: CNM-Au8 | Surface Catalysis Supports Mitochondrial Function
CNM-Au8" | Surface Catalysis Supports Mitochondrial Function Mitochondrial Neuronal Survival Function And Function —* Quen NAD+ Species ( R a \ CNM-Aug Nanocrystal Catalysis Acts as an electron donor/receiver > cLene —e
Slide 7: Safety Review
Safety Review * Over 1000 participant-years of exposure to CNM-AUB * CNM-Au8 long-term treatment duration up to 6.0 years + TEAEs (treatment-emergent adverse events) predominantly assessed as mild- to-moderate severity, and transient * No related SAEs (serious adverse events) related to CNM-Au8 acro
Slide 8: Despite Missed Primary Endpoints, Concordant Survival Outcomes with CNM-Au8 Treatment in ALS are Promising
Despite Missed Primary Endpoints, Concordant Survival Outcomes with CNM-Au8 Treatment in ALS are Promising tS RESCUE HEALY as ALS. Expanded Acce Protocols As Partpat ExlytoMdStage Early tod Stage Midtointestoge MdoLateStage Real World Experence Demerrahis (ont) 6) (r=t6t Regen) (ress) ‘oso Duration
Slide 9: Time to Event | Survival During the Double-Blind Period
Time to Event | Survival During the Double-Blind Period Bistioem Nal HEALEY ALS Platform Trial CNM-Au8 30 mg (Full Analysis Set | All Shared Placebo) Time to Death or PAV* Time to Death HEALEY ALS Piatfonn Tal | Double-Blind Perio | Kaplan Moir Estimator HEALEY ALS Platform Tal | Double-Bind Period
Slide 10: Time to Event | Improved Survival During the OLE to Month 12
Time to Event | Improved Survival During the OLE to Month 12 Bistioem Nal HEALEY ALS Platform Trial CNM-Au8 30 mg, Time to Death or PAV Time to Death HEALEY ALS Pltorn Tel Kopan Maer Estimator | Open Label Extension HEALEY ALS Pato Tal | Kaplan Meter Ester] Open Label Extension Prespeciod Cova Ajste
Slide 11: CNM-Au8 | Delayed Time to Clinical Worsening Events
CNM-Au8 | Delayed Time to Clinical Worsening Events Concordant HEALEY ALS Platform Tal in Double-Blind Periods of Two Independent Phase 2 Trials fh RESCUE Delayed Time to Clinical Worsening respec Eporstr incl Compote Enon ‘Time to ALS Clinical Worsening | CNM-AuB 309 Delayed Time to Clinical Worsen
Slide 12: NfL is a Key Biomarker of Disease Progression in ALS Patients
NfL is a Key Biomarker of Disease Progression in ALS Patients Neurofilament Light Chain (NfL) Protein >< cLtene Nevrofiament ght (NAL — Sila aectasnaeaaaontonaemmeee
Slide 13: Plasma NfL Decline During Double-Blind & Long-Term Treatment
Plasma NfL Decline During Double-Blind & Long-Term Treatment Bistorm tat HEALEY ALS Platform Trial Double-Blind & Open Label Extension Double-Blind Period ‘Open Label Extension Plasma Neurofilament Light Chain (NIL) ‘CNM. 30mg Plasma NU Geometric Maan Change ‘Regimen C Within Rogimen Analys | Quarte
Slide 14: Evidence Linking Plasma NfL with CNM-Au8 Clinical Benefit
Evidence Linking Plasma NfL with CNM-Au8 Clinical Benefit Decline Time to Death or PAV to Month 12 ‘Week 52 post baseline wasa prespecified time point for OLE analyses et. pctene
Slide 15: Greatest Benefit in Participants with Highest Baseline NfL Burden
Greatest Benefit in Participants with Highest Baseline NfL Burden | Death or PAV HEALEY ALS Platform (Through Month 12) | Upper Tertile & > Median HEALEY | Upper Nit Tertile By Baseline Plasma NL “Time to Death or PAV (Through Month 12) In Partcipans withthe Highest Baselino Plasma NIL (Upper Tero)
Slide 16: Evidence Linking Plasma NfL with CNM-Au8 Clinical Benefit
Evidence Linking Plasma NfL with CNM-Au8 Clinical Benefit Plasma nf Decline 4 Time to Death or PAV to Month 12 Week 52 post baseline was a prespecified time point for OLE analyses >» cLene
Slide 17: Mats
Mats 3 . i "i ir | RE _CNM-AuB 30 mg WN poseaicog wm ; 7: ne pctene —
Slide 18: Long-Term Survival Benefit in Participants with Any NfL Decline at 24-Weeks
Long-Term Survival Benefit in Participants with Any NfL Decline at 24-Weeks HEALEY ALS Platform (Through Month 12) | Time to Death or PAV Hazard Ratio for Death or PAV ‘At 12 Months Post-Baseline ‘Hazard Ratio for Time to Death or PAV Through Month 12 by Pla NI Change rom Basline Threshold pi) and M
Slide 19: Evidence Supporting Long-Term Survival Benefit
Evidence Supporting Long-Term Survival Benefit Propensity Matched Controls PRO-ACT, ALS Natural History Consortium (ALS NHC), ANSWER-ALS pctene
Slide 20: Improved Long-Term Survival | HEALEY ALS Platform & Pooled ALS Trials
Improved Long-Term Survival | HEALEY ALS Platform & Pooled ALS Trials CNM-Au8 30 mg Original Randomization vs. Propensity Matched Controls Mess, HEALEY | Optimal Variable Ratio Matching oa Prespeciied Matching Methodology ‘Original CNM-Au6 30 Randomized mg vs. Propensity Matched Controls, HEALEY ALS
Slide 21: Long-Term Survival | Real-World Expanded Access Protocols
Long-Term Survival | Real-World Expanded Access Protocols CNM-Au8 30 mg vs. Propensity Matched Controls (Pooled PRO-ACT, ALS NHC, ANSWER-ALS) EAP Matching | Optimal Variable Ratio (respected) CCNM-Aus 30 mg EAP Participants vs. Propensity Matched Controls (CNMv-AuB 90 mg (EAPOI & EAPO2) All Evaluabl
Slide 22: Improved CNM-Au8 30 mg Long Term Survival vs. Regimen A Concurrent Controls
HEALEY ALS Improved CNM-Au8 30 mg Long Term Survival Platform Trial vs. Regimen A Concurrent Controls Post hoc analyses compared survival in participants who received CNM-Au8 30 mg (Regimen C) to those of Regimen A, a large concurrent control group vs. CNM-Aus treatment using the sam sablished withi
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) Screening DO “g* = f "6 12 O+f-0-0 @ Dey * Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMTs + 9296
Slide 24: CNM-Au8 Demonstrated Vision and Global Neurological Improvement in Stable MS patients on DMTs
CNM-Au8 Demonstrated Vision and Global @VISIONARY-MS Neurological Improvement in Stable MS patients on DMTs Significantly Improved Vision Change in Low Contrast Letter Acuity (LCLA) LLCLA Change inthe Affected Eye INTT-US Mean = SEM ‘Wook 48.eanOitererco= 3.13, os%cis 00810659, {Stan change from Baz
Slide 25: Long-Term LCLA Improvement in LTE Participants
Long-Term LCLA Improvement in LTE Participants QVISIONARYMS Low Contrast Letter Acuity Original Active (CNM-Au8) Original Placebo Longitudinal LCLA | Change fom Baseline (Total Correct, Both Eyes) | Al Active Longitudinal LCLA | Change from Baseline (Total Correct, Both Eyes) In LTE Partspants Orgin
Slide 26: CNM-Au8 Improved Information Signal Strength & Speed in the Visual Pathway
CNM-Au8 Improved Information Signal Strength & Speed in the Visual Pathway al Evoked Pot Improved Amplitude VE Angie Longin Pacer) Change serene sate ete Nea en = = A = Amplitude = Signal Strength Latency = Signal Speed From the Eye to Visual Cortex @VISIONARY-MS Improved Latency mctene
Slide 27: Long-Term SDMT Improvement in LTE Participants
Long-Term SDMT Improvement in LTE Participants @VISIONARY-MS ‘Symbol Digit Modality Test | Working Memory & Cognition Original Active (CNM-Au8) ‘Dyreiial etecabo Longitudinal SOMT | Change from Baseline (otal Score) |All Active Longitudinal SOMT | Change from Baseline (Total Score) In Te Partciparts
Slide 28: CNM-Au8 Treatment Demonstrated MS Lesion Repair and Promoted Remyelination
CNM-Au8 Treatment Demonstrated MS Lesion Repair and Promoted Remyelination Advanced 72 Lesion Myelin Water Fraction (Remyelination) T2 Lesion Axial Diffusivity (Axonal integrity) @VISIONARY-MS.
Slide 29: Clinical LTE Changes Correlated with mf-VEP & MRI DTI Improvement
Clinical LTE Changes Correlated with mf-VEP & MRI DTI Improvement mf-VEP Latency Correlations (Post Hoc) MTR DTI Correlations (Post Hoc) ‘tinea Correlations with mEVEP Latency & Amplitude Improvement ‘nical Conlatons with MOT Inproverent ‘Pearson Golan Coefeant for VEP Mates esson Corelstion Couteen
Slide 30: Clene | CNM-Au8 Path to Regulatory Approval
Clene | CNM-Au8 Path to Regulatory Approval 2025 MID-2025 i L (ats) > cLene
Slide 31: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases CNM-Au8” [evisionary-ns) sta el a gold nanocrystal Strong IP: development othe fs alae 150+ HEALEY ALS. Platform Trial J ifs RESCUE >» cLene
Slide 32: Clene Nanomedicine
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