Clene Inc. · NASDAQ:CLNN
Clene — Investor Presentation (June 2023)
37 slides from Clene's investor presentation, Jun 15, 2023
Slide 1: Clene
® cLene NASDAQ: CLNN clene.com
Slide 2: RESCUE-ALS OLE | Preserved ALSFRS-R Functional Decline
6% 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 ALS Spe Chanaeo Wea an Sapte he OLE hae ELE ek ALSERS- tof
Slide 3: OLE | Decreased ALS Time to Clinical Worsening
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 400 i i i i 78 The risk of ALS clinical worsening was decreased ~50% for CNM-Au8 compared to placebo in OLE up-to-120 weeks Clin
Slide 4: RESCUE-ALS Demonstrated Significant Impact on Long-Term Survival
a RESCUE\|¢ Demonstrated Significant Impact on Long-Term Survival 60% Decreased Risk of Death through 120 weeks Long-Term Survival (All-Cause Mortality): Originally Randomized Active vs. Placebo Interim Analysis (14-July-2022), ITT Population, All Subjects from Randomization {Long-term vital status
Slide 5: 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 6: Survival Signal | >90% Reduced Risk of Death with 30mg
Survival Signal | >90% Reduced Risk of Death with 30mg Shared Placebo Across Regimens (CNM-Au8 30mg Survival | Adjusted Gox Proportional Hazard Full Analysis Set (All Saved Placebo, Regimens A, B,C, D) ‘etazar Reducton a Week 2 (1 Hoard Rao, 95% Gomndoe era a beat or Death a nanan a | es, beatn woes
Slide 7: Time to Clinical Worsening Events
Time to Clinical Worsening Events Biatiorm ‘ial Death Permanent Assisted Hospitalization Feeding Tube Assisted Ventilation ie and All Placement Ventilation use 40 (A. ‘+ Time to clinical worsening events were prespecified in the protocol and analysis plan * p-values provided are uncorrected for mult
Slide 8: Delayed Time to ALS Clinical Worsening (Composite)
Delayed Time to ALS Clinical Worsening (Composite) Reduction in Time to ALS Clinical Worsening (Composite) frst nstenoe of Dee, Tracheostomy, PAV or Fee dng Toe Clinical Worsening Composite Fk Adjust GoxProportana Hazard Model (inary Covera Mod (Time to First Instance) ‘% Hazard Reduction to Week 24
Slide 9: Delayed Time to Clinical Event Summary
Delayed Time to Clinical Event Summary CNM-Au8 30mg | Within Regimen Analysis (Primary Model) CNM-Au8 30mg delayed time to clinical worsening at 6 months eombhoodp (CNM-Aus 30mg | Clinical Event Risk Reduction ‘Within Regimen Analysis (Eficay Regimen Only) Fisk Acusted Cox Proportional Hazard Model
Slide 10: Plasma NfL Difference | CNM-Au8 vs. Placebo
Plasma NfL Difference | CNM-Au8 vs. Placebo AIL RGC Participants —s 115: 1.10; 1.05: 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) 10 (0.048); p= 0.040 47.9% 0.95: LS Geometric Mean Ratio to Bas
Slide 11: Consistent Plasma NfL Effects in Higher Risk Patients
Consistent Plasma NfL Effects in Higher Risk Patients Grea Sensitivity Analyses | In Definite and Probable ALS; Higher Baseline NfL Levels, and Fast Progressors (Post Hoc) Definite & Probable ALS Baseline Nfl > Median Fast Progressors Plasma Nf Plasma Nf Plasma Nf. |nE Escar iaqooed Cincy Desi ALS &
Slide 12: Forward Looking Statements
Forward Looking Statements ‘This presentation contains Narwor-lookingstetements" within the meaning ef Section 21€ ofthe Secures Exchange Act of 1934, as amended, and Section 27A ofthe Securities Act of 1933, amended, which are intended tobe covered bythe “safe harbor” provisions created by thse law
Slide 13: CNM-Au8 | ALS Clinical Worsening Summary
— CNM-Au8 | ALS Clinical Worsening Summary Evidence for Decreased Clinical Worsening Events Across Two Phase 2 Studies Phase 2 RESCUE-ALS CNM-Au8 30mg, Decreased Time to Clinical Worsening ALS Clinical Worsening 1T Pepaton, At Randontzd ‘CNN. Aus 20mg! Reduction in Tne to ALS Ctnical Worsen Koplan e
Slide 14: CNM-Au8 Has Demonstrated ALS Survival Benefit in Two Phase 2 Studies
CNM-Au8 Has Demonstrated ALS Survival Benefit at 30 mg Dose in Two Phase 2 Studies 60% decreased risk of HEALEY ALS >90% risk reduction of RESCUE death through 120 tae death at 30mg at 24 weeks - weeks Long-Term Survival (AI-Cause Mrtaiy Orignaly Randomized Active ve Pacabo ‘CNM-AuB 30mg Adjusted Co
Slide 15: 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 m Treatment Emergent 2 Pl : : : Adverse Events (TEAEs) Participants with Any TEAE | 90% 93% 92% 93% Participants with Related TEAEs 39% 34% 29% 43% Partici
Slide 16: ALS Summary | Survival Benefit and Delayed Clinical Worsening
ALS Summary | CNM-Au8 Has Demonstrated Survival Benefit and Delayed Time to Clinical Worsening and Functional Decline Significant + ALS remains a devastating and fatal disease within ~3 to 5 years of diagnosis—a Opportunity significant unmet need ? * Demonstrated significant ALS survival benefit at
Slide 17: 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 “SY EEE O-++-0O—O—@—__0-—_@—_0-_@ 0 oe id * Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background D
Slide 18: Baseline Demographics and Study Analysis VISIONARY-MS
Baseline Demographics and Study Analysis @VISIONARY-MS * Allparticipants 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 CNM-Au8 15 mg, 38.4 15 23 78.0 1.
Slide 19: CNM-Au8 Demonstrated Vision and Global Neurological Improvement
CNM-Au8 Demonstrated Vision and Global Neurological Improvement in Stable MS patients on DMTs 9. Global Neurological an Improvement o. ‘Change in modified MS Functional Composite (mMSFC) @VISIONARY-MS nificantly Improved ‘Change in Low Contrast Letter Acuity (LCLA) LLCLA Change in the Affected Eye L
Slide 20: VISIONARY-MS Measures of Axonal Integrity
@VISIONARY-MS VISIONARY-MS Measures of Axonal Integrity Visual Evoked Potentials (VEP) Advanced MRI Techniques Multi-focal Amplitude and Latency Changes Diffusion Tensor Imaging (DTI) changes Fractional Anisotropy Brain Diffusivity What Happens in the Visual System Happens Throughout the MS Brain >
Slide 21: CNM-Au8 Improved Information Signal in the Visual Pathway
@VISIONARY-MS CNM-Au8 Improved Information Signal in the Visual Pathway mf-VEP Mean Amplitude Percent (%) Change ITT Popuiation, LS Mean « SEM, Segments Nested by Participant VEP Affected Eye VEP Follow Eye 16 10 Increased Amplitude A : ds. . (Signal Strength) te Sones From the Eye to the Brain’s $8
Slide 22: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity Throughout the Brain Preserved Whole Brain White Matter Integrity Diffuion Tensor Imaging | Fractional Anisotropy (FA) Change hole Bran (Gerobrm) ITT Population, LS Mean + SEM Change from Basatine ‘Uae! Square Mean) Wieok 48 LS Mean Diference = 0.0029 95% C1=
Slide 23: Clinical Case for Neuroprotection & Remyelination
Clinical Case fo Neuropro ha RESCUE CNM-Au8 demonstrated statistically significant survival benefit of 60% decreased risk of death through 120 wks Potentic Prop tec tion & Remyelination CNM-Au8 demonstrated global 1 neurological improvement in stable relapsing MS as an adjunct to immunomodulatory DM
Slide 24: Summary | Consistent Paraclinical Evidence of Neuroprotective Effects
Summary | Consistent Paraclinical Evidence of Neuroprotective Effects Favoring CNM-Au8 Treatment linical Paraclini Endpoint jlean Chan FA within the whole bran (cerebrum) Diffusion Tensor Imaging (OT) measure of Fractional ‘Anisotropy (FA) within total Cerebral White Matter FA within total Cerebral
Slide 25: VISIONARY-MS Safety Summary
VISIONARY-MS Safety Summary QVISIONARY-MS. 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 A ame ‘Subjects with any TEAE 22 (92%) 21 (88%)
Slide 26: 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 * MS patients continue to progress with increasing cognitive and functional deficits accumulating even while receiving disease-modifying therapies—a significant unmet medical need
Slide 27: Over 450 Years of Subject Exposure Without Identified Safety Signals
Over 450 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 ulted in as Predominantly Mild-to- Over 450 Years of Subject Exp
Slide 28: Growing Body of Evidence for CNM-Au8
— x Growing Body of Evidence for CNM-Au8° Disease 200 2022 2023 Key Findings RESCUEALS rent ‘Amyotrophic Lateral Sclerosis (ALS) Parkinsons Disease (PD) eabheeabainagst gsgement ley MS act Y Sonia Multiple Sclerosis (MS) MS; Pe net Dumont gobsinewolgea! mpravenerto oS patemeon ance eeageent &stety e
Slide 29: Clene | Anticipated Catalysts Over the Next Year
Clene | Anticipated Catalysts Over the Next Year MID-2023 2024 MID-2024 1 1 i = + UrinaryP75 Clinical Data up-to-18 months + Serum Creatinine | ALSFRS, Clinical Worsening) Long Term Survival Data ‘Survival & Clinical data up- to-3yrs BEE vec tate sero (a5) Bb ste srs . oo pciene —
Slide 30: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases CNM-Aug” Povisionary-nsy a gold nanocrystal Strong IP: 150+ patent therapeutic Bs RESCUE +: jctene
Slide 31: Clene Nanomedicine
® CLene \ NANOMEDICINE
Slide 32: 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 Dopaminergic Neurons MULTIPLE SCLEROSIS FRONTOTEMPORAL ‘Axon
Slide 33: 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-Au8 Machenlucetoas Improved Energy Production and Nanocrystals Utilization Clean surfaced, Highly Faceted _ Shapes Increased NAD y Increased ATP Decreased reactive B EI } oxygen species Nace Increased pr
Slide 34: 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 ¢ 4 Sclerosis (MS) Disease (PD) MOUS MOOD. NE COS target ‘treatments available, only immunomodulation symptom-targeted options YEARS’ =< EMERGING EVIDENCE Of. ce noranmencic fe
Slide 35: Two REPAIR Trials Demonstrated Target Brain Engagement
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 36: RESCUE-ALS Encouraging Efficacy Signals in Phase 2 Endpoints
iB RESCUE! § Encouraging Efficacy Signals in Phase 2 Trial 1° & 2° Endpoints Study Objective: taint oeueal ry 8 Secrday Enis Detect preservation of “ou motor neuron function in | isnabenta tL“ usm cng ‘nn so © ringette Samay ee peopl ith early ALS measured by MUNIX tna st A fm wwrocsines cree “a ———
Slide 37: RESCUE-ALS CNM-Au8 Improved Patient Function, QOL, and Slowed Clinical Worsening
— >} — (6 RESCUE! ¢ 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=45 enrolled with early als Proportion with <6 ALS Specific QOL ALS Clinical Worsening point decli