Clene Inc. · NASDAQ:CLNN
Clene — Investor Presentation (December 2023)
32 slides from Clene's investor presentation, Dec 21, 2023
Slide 1: Clene
> cLene clene.com NASDAQ: CLNN
Slide 2: Forward Looking Statements
Forward Looking Statements ‘This preentation contains “forward looking statement” within the meaning of Section 22€ ofthe Securities Exchange Act of 1934, as amended and Section 27A of the Secures Act of 1933, a5 amended, which are Intended to be covered by the “safe harbor” prowslons created by tho
Slide 3: Improving Mitochondrial Health and Protecting Neurons in Neurodegenerative Diseases
sed on Improving Mitochondrial Health and Protecting tion leurodegenerative Diseases aN THE PROBLEM 0) A NEW APPROACH * A therapeutic breakthrough is urgently needed, + Inneurodegenerative diseases, impaired mitochondrial activity and compromised cellular metabolism can lead to neuronal death, >» cL
Slide 4: Building the Clinical Case for Neuroprotection & Remyelination
Building the Clinical Case for Neuroprotection & Remyelination ( ) | A rescuesis | / Ge RepairPD | HEALEY ALS / Platform Trial | VISIONARY-MS Growing Body of Clinical Evidence Across ALS and MS Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases Proprietary Nanotherapeutic Man
Slide 5: All Neurodegenerative Diseases Involve Neuronal Death
All Neurodegenerative Diseases Involve Neuronal Death AMYOTROPHIC LATERAL SCLEROSIS DEATH, INDEPENDENT OF SUBTYPE —— Motor Neurons FRONTOTEMPORAL DEMENTIA Spindle Neurons HUNTINGTON'S DISEASE ‘Medium Spiny Neurons NEURONAL DEGENERATION, MULTIPLE SCLEROSIS ‘Axonal Degeneration —( 5 } sia pctene Tc fe
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 Dying neurons exhibit hallmarks that ‘Converging pathways in neurodegeneration, {from genetics to mechanisms sent i et eo ‘Geeeet Creams ieroy on ree MO ot [ iTocHONORIAL " Bh HYPERENCITABIUTY NAD+ PATHWAY DE
Slide 7: CNM-Au8 | Surface Catalysis Improves Mitochondrial Function
CNM-Au8?® | Surface Catalysis Improves Mitochondrial Function MITOCHONDRIAL NEURONAL SURVIVAL FUNCTION ‘AND FUNCTION NAD+ => => = \ CNM-Au8 Nanocrystal Catalysis pctene Sikeston stare
Slide 8: Years of Subject Exposure Without Identified Safety Signals Across ALS, MS, and PD
Over 500 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 Studi Resulted in as Predominantly Mild-to =r 500 Years of Subject Exposure Witho
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 demonstrated a potentially meaningful 10% improvement in NADH ratio, an essential molecule for energy production’ Study Objective: Demonstrate target engagement & for CNM-Au8 on
Slide 10: 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 — 0 ET seins maconeagn te sien thagte napenrsoe sianess WAMU OAR ! MEALEY ALS ts RESCUE BEARER AAS RESCUEALS IEALEY ALS Platform cw § a Real-World AALS Pati
Slide 11: CNM-Au8 | Clinical Worsening Concordant in Two Phase 2 Trials
CNM-Au8 | Clinical Worsening Concordant in Two Phase 2 Trials Evidence for Decreased Clinical Worsening Events Across Two Phase 2 Studies Time to ALS Clinical Worsening {Timo to Clinical Worsening | CNM-Au8 30mg First Occurence of Death Tracheostomy, Assistod Vontaton, or Fooding Tubo First Occurenc
Slide 12: CNM-Au8 | ALS Survival at 30mg Concordant in Two Phase 2 Trials
CNM-Au8 | ALS Survival at 30mg Concordant in Two Phase 2 Trials 8% RESCUE Bator tal ath through 168 weeks onion deatiiat Unadjusted Survival Cross-Over Adjusted Survival resaxe Deere rt ene man resources onan th "toto asaow se "RS Peon fen aie an pctene
Slide 13: RESCUE-ALS Improved Exploratory Endpoints: Function, QOL, Slowed Clinical Worsening
RESCUE! Improved 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=45 enrolled with early AS Proportion with <6 AALS Specific QOL [ALS Clinical Worsening * point
Slide 14: RESCUE-ALS OLE | 52% Reduced Risk of ALS Clinical Worsening
8% RESCUE! OLE | 52% Reduced Risk of ALS Clinical Worsening ALS Clinical Worsening Events ‘Time to Death, Tracheostomy, Assisted Ventiation, or Feeding Tube RESCUE-ALS Double-Blind & OLE Periods (24-month LPLY data cut) Proportion Event Free, Kaplan-Meier Analyses. (@ ( ) AW s . ( ( } Tracheostomy (
Slide 15: RESCUE-ALS Up to 19.3 Month Survival Benefit vs. Original Placebo
% 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 (l-Cause Moray) ‘Cross-Over Adjusted Analysis of Survival FRESCUE-ALS [24-month LPLV data cut ITT Population f=) [RES
Slide 16: RESCUE-ALS Long-Term Survival Benefit Compared to Historical Matched PRO-ACT Placebo Controls
6 RESCUE Long-Term Survival Benefit Compared to Historical Matched PRO-ACT = Placebo Controls CNM-Au8 treatment demonstrated a significant survival benefit: = 70% decreased risk of death + Follow-up of active compared to matched placebo from PRO-ACT fe ues "RO-ACT onan approximately 12,00 pte record
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 HEALEY ALS
Survival Signal | >90% Reduced Risk of Death HEALEY ALS with CNM-Au8 30mg Shared Placebo Across Regimens CNM-Au8 Regimen Only (Regimen C) (CNM-AuB 30mg Survival | Adjusted Cox Proportional Hazard (CNM-Au8 30mg Survival | Adjusted Cox Proportional Hazard Ful Analysis Sot (Al/Sharod Piacabo, Rogimans
Slide 19: Delayed Time to ALS Clinical Worsening HEALEY ALS
i ini i HEALEY ALS Delayed Time to ALS Clinical Worsening HEALEY CNM-Au8 30mg | Within Regimen Analysis (Primary Model) Time to Clinical Worsening | CNM-Au8 30mg First Occurence of Death, PAV, Tracheostomy or Feeding Tube HEALEY ALS Piatform Trial | Kaplan-Meier Estimate Regimen C Population, Effica
Slide 20: Significant Biomarker Plasma NfL Difference Platform Trial
Significant Biomarker Plasma NfL Difference Platiorm “ial CNM-Au8 vs. Placebo | All RGC Participants During Double-Blind Period Plasma NIL Plasma NIL IRGC Within Regimen Anais | Quant 4NPA Baseline Nit > Median All RCG (n=161); Difference of LS Means on Ln Scale (SE) RGC Within Regimen Analyis | Qua
Slide 21: Continued Long Term Plasma NfL Decline in the OLE
Continued Long Term Plasma NfL Decline in the OLE 76-Weeks post baseline MMRM (CNM-Au8 30mg) — 2 LS Geometric Mean Ratio “Change rom Baseline CNM-Au8 30mg Plasma NfL Geometric Mean Change GC Within Regimen Analyis | Long Term Extension | Quanterix 4NPA ‘Al Evaluable with Baseline, n=99; LS Geometric
Slide 22: Validation of NfL Association with Clinical Outcomes
Validation of NfL Association with Clinical Outcomes Post Hoc | Clinical Worsening Event (Average Events per Patient per Group) Clinical Worsening Events Frequency is Associated with Higher Baseline INfL Responder Analyses in Participants with a NfL Decline of 25% (Post- NfL Levels (by Quartile) Bas
Slide 23: Long-Term Survival | Propensity Matched Placebo
Long-Term Survival | Propensity Matched Placebo PRO-ACT Placebo Matching vs. Regimen C CNM-Au8 30mg ‘Baseline Values Mean (SD) or Percent (%) HEALEY Regimen C CNM-Aus 30mg 55.4 (10.4) 5955 (11.0) 55.4 (11.2) ‘Onset Age ‘Sex (Male, %) 56% 62% 56% BMI (kg/m?) 27.4 (5.3) 26.5 (4.9) 27.2 (5.2) [ALSERS-R
Slide 24: Long-Term Survival | Propensity Matched Placebo
Long-Term Survival | Propensity Matched Placebo PRO-ACT Placebo vs. CNM-Au8 30mg CNM-Au8 30mg HEALEY HEALEY-ALS Platform Long-Torm Survival (CNM-Au8 30mg Observed Survival vs. PRO-ACT Matched Placebo Controls, vans: Ate 2080 vs, Poet 67022 Laprank praive = 0.15 CNM-Au8 30mg Integrated Meta-Analysis
Slide 25: HEALEY Platform Long-Term Survival
Phase 2 HEALEY Platform Long-Term Survival Betton tral Unadjusted Survival (Delayed Start) RPSFTM Cross-Over Adjusted Survival (-903 cross-over to active at Week 24) LUnasted Overt Sunival| HEALEY Within Regnen ‘rose ver Aste Anes of Sura MEALEY Within Regimen Hea. geen tong em Foto, CAM ALE 0 We Pa
Slide 26: 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 “gS KE O40 0 @ 0 @ 0 @ * Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMs O8 e + 92% tre
Slide 27: 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 ‘Change in Low Contras Letter Acuity (UCLA) Change in modified MS Functional Composite (mMSFC) oka chiaige Wi Ev LA acon doit art,
Slide 28: CNM-Au8 Improved Information Signal in the Visual Pathway
CNM-Au8 Improved Information Signal in the Visual Pathway mf-VEP Mean Amplitude Percent (%) Change QVISIONARY ITT Population, LS Mean = SEM, Segments Nest by Partipant EP Afectd Eye VEP Fellow Eye Wike#8.\S-MeanDiference 61 __ Wk 4B LS-Mean Difrence =9.7 95% Cl=.0610 127 95% C1=3.110163 Increased Am
Slide 29: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity @VISIONARY-MS Throughout the Brain Preserved Whole Brain White Matter Integrity Consistent Effect Across All Brain Regions Dituon Tensor imaging Fractional Aisotopy (A) Change Chm Ter np cnt Attn A Webs (Cerebrum) oy Week 48 Change from Baseline irr Popa S ha
Slide 30: Clene | CNM-Au8 Path to Regulatory Approval
Clene | CNM-Au8 Path to Regulatory Approval 2024 MID-2024 2028 i L pctene
Slide 31: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases CNM-Au8° a gold nanocrys pension, in (dfs rescue — 3 ‘ > cLene
Slide 32: Clene Nanomedicine
® CLene \ 4 NANOMEDICINE