Clene Inc. · NASDAQ:CLNN
Clene — Investor Presentation (January 2024)
34 slides from Clene's investor presentation, Jan 8, 2024
Slide 1: Clene
> cLene NASDAQ: CLNN. clene.com ca |
Slide 2: Forward Looking Statements
Forward Looking Statements “Ths preenttion contains “frward-ooking statements” within the meaning of Section 21E of the Secrties Exchange Act of 934, mended, and Section 27A ofthe Secures Act of 1933, 5 “amended, which are intended tobe covered by the “sale harbor” provisions created by thse laws, C
Slide 3: Improving Mitochondrial Health and Protecting Neurons
sed on Improving Mitochondrial Health and Protecting reurod T \ B\ THE PROBLEM Y A NEW APPROACH ‘most prevalent cause of death within the next 20, impaired mitochondeiat activity and compromised pioneering anew lar metabolism can function lead to neuronal death > cLene
Slide 4: Building the Clinical Case for Neuroprotection & Remyelination
Building the Clinical Case for Neuroprotection & Remyelination / HEALEY ALS / Platform Trial | Ge RepairPD P) RepairMS | @VISIONARY-MS jody of Clinical Evidence A Treat Nanoth Strong IP: 150+ granted pater pm clene
Slide 5: All Neurodegenerative Diseases Involve Neuronal Death
All Neurodegenerative Diseases Involve Neuronal Death ANIvOTROPHIC LATERAL SCLEROSIS DEATH, INDEPENDENTOF SUBTYPE Pa Motor Neurons FRONTOTEMPORAL DEMENTIA Spindle Neurons HUNTINGTON'S DISEASE ‘Medium Spiny Neurons [NEURONAL DEGENERATION MULTIPLE SCLEROSIS ‘xonal Degeneration nn pm clene ee tere ee o
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 4 oe Dying neurons exhibit hallmarks that [= Converging pathways in neurodegeneration, {rom genetics to mechanisms ie Tae = ey NADs PATHWAY DEFICITS uacacrvaTion’ * = a5) NAD# nicotinamide adenine dinucleotid
Slide 7: CNM-Au8 | Surface Catalysis Improves Mitochondrial Function
CNM-Au8° | Surface Catalysis Improves Mitochondrial Function MITOCHONDRIAL NEURONAL SURVIVAL FUNCTION ‘AND FUNCTION Cc Ca CNM-Aus Nanocrystal Catalysis CO rere eee EEE j>ctene
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 Patient Exposure Across Findings Adverse Event (AE) Profile ALS, MS & PD Over 500 Years of Subject Exposure Without Identified Safety Signal: Resulted in as Predominantly Mild-
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 Study Objective: Demonstrate target eng CNM-Au8 on CNS biomarkers related to nt & for energetic effects in the brain using Magnetic Resonance Spectroscopy (#!P-MRS) Ge RepairPD E
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 i RESCUE SERS eal Word ss Patent caito-Mi sage a teres Ge | SERS | ety | Weer | eet =e ewer) Use7s yea rece UN se avec Ilva cues ete - a Ed ro-act iv] Delay
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-ALS CNM-Aua Decreased Time to Clinic : ‘eALS Cine! Worsening Tine to Cac Moen CAMAUB 9 ft Onc iO amen st tn rong Tita Fn cena fat Pa Tarot ting Tat
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 Trial Unadjusted Survival Cross-Over Adjusted Survival mean rymtammcum rin reas eae > cLene
Slide 13: RESCUE Improved Exploratory Endpoints: Patient Function, QOL, and Slowed Time to ALS Clinical Worsening
a 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 ALS Proportion with <6 ALS Specific QOL, AALS Clinical Worsening * poi
Slide 14: RESCUE OLE | 52% Reduced Risk of ALS Clinical Worsening
8% RESCUES 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) Proportion Event Fre, Keplan-Meler Analyses 1 Hararrato= 0478 0225101015 Log ran
Slide 15: RESCUE Up to 19.3 Month Survival Benefit vs. Original Placebo
it RESCUE Up to 19.3 Month Survival Benefit vs. Original Placebo Unadjusted Survival Difference: 10.1 Months Cross-Over Adjusted Survival Difference: 19.3 Months cio tr use it Sr ean pa Spun Sct ons Sasori 3 i : H * 95% Wald CI= 0.10600 0.597 ar srr DH = be tune meee ea we ew we dette > cLene
Slide 16: RESCUE 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 RESCUE-ALS Long-Term Survival Ln Query Simi Ws PCAC. Meehwes Pacsba Cools CNM-Au8 treatment demonstrated a significant rvival benefit: placebo from PRO: ACT conti spronimatly 12,000 pin ecards rm mip compe
Slide 17: HEALEY ALS Platform Trial Design and Results
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-Au® 30mg Survival | Adjusted Cox Proportional Hazard [CNM-Au8 30mg Survival | Adjusted Cox Proportional Hazard Ful Analysis Sot (Al Shared Placebo, Rogmens A
Slide 19: Delayed Time to ALS Clinical Worsening HEALEY ALS
Delayed Time to ALS Clinical Worsening HEALEY ALS 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 Platform Trial | Kaplan-Meier Estimate Regimen C Population, Efficacy Regimen Only
Slide 20: Significant Biomarker Plasma NfL Difference Between Groups
Significant Biomarker Plasma NfL Difference Beton tral CNM-Au8 vs. Placebo | All RGC Participants During Double-Blind Period Plasma NfL Plasma Nf IRGC vthin Regian Analy | Quarter 4NPA Baseline NL> Median A Roe nto; Dione ots Means on Ln Seat (SE) Rac within Ragimen Anaya] Quarter ANPA os Hoe 9} Onc
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) CNM-Au8 30mg Plasma NfL. Geometric Mean Change [RGC Within Regimen Analyis | Long Term Extension | Quanterix 4NPA ‘All Evaluable with Baseline, n=99; LS Geometric Mean Diference = SEM Week 76 Diference of LS
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 NNfL Responder Analyses in Participants with a NfL Decline of 25% (Post: NAL 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 | HEALEY Regimen C Baseline Values ‘Mean (S0) or Percent (36) ‘onset Age 55.4 (10.4) 5555 (11.0) 55.4 (11.1) ‘sex (Male, 56% 62% [ 56% BMI (kg/m) 274(5.3) 265 (49) 272 (52) |ALSFRS-R (Total Score) 345
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-Term Survival ‘CNM-AuB 30mg Observed Survival vs. PRO-ACT Matched Placebo Controls CNM-Au8 30mg Integrated Meta-Analysis Integrated Meta-Analysis of CNM-Au8 30mg Long-Term Su
Slide 25: HEALEY Platform Long-Term Survival
Phase 2 HEALEY Platform Long-Term Survival Si tioen a Unadjusted Survival (Delayed Start) RPSFTM Cross-Over Adjusted Survival (90% cross-over to active at Week 24) Unacusted Overall Sunval| HEALEY Within Regimen ‘ros- Over Acted Anyi ot Sura HEALEY Win Regimen ever hogan ong tam Flow Ups ENNIO ngs P
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 “@* not 2 cs ‘aa 30 3 a ‘48 Oo +f-0-0 @ oO @ Oo @ O- @ Day £08 + Enrolled stable relapsing remitting MS participants with chronic optic neuro
Slide 27: CNM-Au8 Demonstrated Vision and Global Neurological Improvement in Stable MS
CNM-Au8 Demonstrated Vision and Global @VISIONARY-MS Neurological Improvement in Stable MS patients on DMTs Improvement ae AS Change in Low Contrast Letter Acuity (LCLA) Change in modified MS Functional Composite (mMSFC) BAGormeb belieasise Leia atoata 9 mean mat SOM TE mI LS Mean = SEM Week 4 LS-Me
Slide 28: Long-Term LCLA Improvement in LTE Participants
Long-Term LCLA Improvement in LTE Participants CUSIONARY NS Low Contrast Letter Acuity Original Active Original Placebo Longitudinal LCLA| Change rom Bastin (tal Correct, oth Eyes) | AN Active Longitudinal LA | Change fom Bassline (Total Correct, Both Eyes) Tr LTE arkparts Only ReraomandoGNNALE 5) m
Slide 29: 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) Longitudinal SOMT | Change from Basoline (Total Score) |All Active In LTE Parcipants Originally Randomized to CNMAuB (n=35), ITT Population {US Mesn = SEM, C
Slide 30: CNM-Au8 Improved Information Signal in the Visual Pathway
CNM-Au8 Improved Information Signal in the Visual Pathway ‘m{-VEP Mean Amplitude Percent (28) Change @VISIONARY-MS ITT Poptation, LS Mean + SEM, Sagmonts Nested by Patina tay VEPAMoctod Eye VER Fotiow Eve Wr 48 LS-MeanDiferce=6.1 Wk 48 LS-Mean Difeence = 97 25% Cl=-0610 127 nay s it Increased Amplit
Slide 31: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity @VISIONARY-MS Throughout the Brain | Technique: Preserved Whole Brain White Matter Integrity Consistent Effect Across All Brain Regions Diuion Tensor imaging | Fractional Anisotropy (FA) Change Ditton Tensor maging | Faction Anistropy (A) ‘Whole Brain (Corebr
Slide 32: Clene | CNM-Au8 Path to Regulatory Approval
Clene | CNM-Au8 Path to Regulatory Approval 2024 MID-2024 2025 i n fi > cLene
Slide 33: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases F @VISIONARY-Ms } a - Strong IP: 150+ As RESCUE HEALEY ALS strorm Trial a - ais > cLene
Slide 34: Clene Nanomedicine
> cLene Js— + NANOMEDICINE