Slide 1: Clene
®cLene ] 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 Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the “safe harbor" provisions created
Slide 3: The Problem and A New Approach
* A therapeutic breakthrough is urgently THE PROBLEM * ‘The World Health Organization predicts neurodegenerative diseases will become the second- most prevalent cause of death within the next 20 years. ded, * In neurodegenerative diseases, impaired mitochondrial activity and compromised cellular met
Slide 4: Building the Clinical Case for Neuroprotection & Remyelination
Building the Clinical Case for Neuroprotection & Remyelination | HEALEY ALS Platform Trial | We RepairPD @VISIONARY-MS | 2? RepairMS Body of Clinical Evidence Across ALS and MS Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases Growing Proprietary Nanotherapeutic Manufacturin
Slide 5: All Neurodegenerative Diseases Involve Neuronal Death
All Neurodegenerative Diseases Involve Neuronal Death AMYOTROPHIC LATERAL SCLEROSIS DEATH, INDEPENDENT OF SUBTYPE = ae ‘Motor Neurons FRONTOTEMPORAL DEMENTIA Spindle Neurons HUNTINGTON'S DISEASE Medium Spiny Neurons NEURONAL DEGENERATION MULTIPLE SCLEROSIS ‘Axonal Degeneration is PB ccens I aes edd
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 <_ MITOCHONDRIAL DYSFUNCTION Bh. NAD+ PATHWAY DEFICITS AGGREGATED PROTEINS. AUTOPHAGY INFLAMMATION NA
Slide 7: CNM-Au8 | Surface Catalysis Improves Mitochondrial Function
CNM-Au8® | Surface Catalysis Improves Mitochondrial Function MITOCHONDRIAL NEURONAL SURVIVAL FUNCTION AND FUNCTION Reactive ‘Oxygen NAD+ Species ( CNM-Au8 Nanocrystal Catalysis pciene
Slide 8: 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 Results demonstrated a potentially meaningful 10% improvement in NAD+/NADH ratio, an essential molecule for energy production? Study Objective: Demonstrate target es te CNM-Au8 o
Slide 9: Over 650 Years of Subject Exposure Without Identified Safety Signals
Over 650 Years of Subject Exposure Without Identified Safety Signals Across ALS, MS, and PD Clean Toxicology Well Tolerated Findings Adverse Event (AE) Profile All Animal Toxicology Studies Assessed Resulted in as Predominantly Mild-to No-Adverse Effect Level (NOAEL) Moderate Severity Findings and T
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 6 RESCUE Becton a RESCUE-ALS RESCUE-OLE | HEALEY ALS Platform | HEALEY OLE Real-World ALS Patient Early-to-Mid-Stage Sonia Mid-to-Late-Stage Se paropanis ie
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 Phase 2 RESCUE-ALS CNM-Aué Decreased Time to Clini ‘Time to ALS Clinical Worsening First Occurence of Death, Tracheostomy, Assisted Ventiation, or Feeding Tube IT
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 ft RESCUE Patton tal Up t ed risk of death through 168 week Unadjusted Survival Cross-Over Adjusted Survival 110.1 Months Survival Difference {Upto 19.3 Month Survival Benefit vs. Original Pbo Survival During Blinded Period peg rt Cae M
Slide 13: RESCUE-ALS Encouraging Efficacy Signals in Phase 2 Trial
és RESCUEA|S Encouraging Efficacy Signals in Phase 2 Trial Study Objective: Detect preservation of motor neuron function in people with early ALS as measured by MUNIX Study Design: 36-week blinded treatment with ongoing long-term open-label follow-up Spinaicors [RUN Sum e (eestor) Line Onset (spina
Slide 14: RESCUE-ALS OLE
6% RESCUE! OLE ras W ) Death ( a 0) Tracheostomy \ \*%) Ventilation 52% Reduced Risk of ALS Clinical Worsening ALS Clinical Worsening Events ‘Time to Death, Tracheostomy, Assisted Ventilation, or Feeding Tube RESCUE-ALS Double-Biind & OLE Periods (24-month LPLV data cut) Proportion Event Free, Kapla
Slide 15: CNM-Au8 30mg Treatment Improved Long-Term Survival
CNM-Au8 30mg Treatment Improved Long-Term Survival vs. Propedpitypcue Matched PRO-ACT & MiNDAUS (Australian) Controls 3 j 4 bas 757) | cow A HR: 0.31 (95% CE 0.142-0682) | !—b m= Logrank, pe 0.0145 al 0 6 2 © @ © © «@ 4 Months (Post-Basoine) — — CNM-AUB 90mg pony ~~ PRO-ACT Matched Contos CMA: 39 «3
Slide 16: 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 17: Survival Signal | >90% Reduced Risk of Death
Survival Signal | >90% Reduced Risk of Death with CNM-Au8 30mg — v7 } Shared Placebo Across Regimens ‘CNM-Au8 30mg Survival | Adjusted Cox Proportional Hazard Full Analysis Set (All Shared Placebo, Regimens A, 8, C, D) 9% Hazard Reduction at Week 24 (1--Hazard Ratio, 95% Confidence Interval) ae cme
Slide 18: Delayed Time to ALS Clinical Worsening
Delayed Time to ALS Clinical Worsening CNM-Au8 30mg | Within Regimen Analysis (Primary Model) — is Probability Event Free 100 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,
Slide 19: CNM-Au8 Target Engagement | NAD+ Improvement
HEALEY ALS. CNM-Au8 Target Engagement | NAD+ Improvement Platform Trial Original CNM-Au8 30mg. Ex-Placebo to CNM-Au8, Nicotinamide Adenine Dinucleotide Oxidized Form (NAD#) Nicotinamide Adenine Dinucleotide Oxidized Form (NAD#) oomere Mean Chege rom Bastin (ole Bia) ‘Georc Hean Changs tan Sasi (Woe
Slide 20: CNM-Au8 Target Engagement | Glutathione Ratio Improvement
CNM-Au8 Target Engagement | Glutathione Ratio Improvement GSH/GSSG Ratio Original CNM-Au8 30mg Glutathione Ratio (GSHIGSSG) ‘Geametc Mean Change om Baseline (Whole Boos) ‘CHAS 0g. Al Evahate Partipats (=53) MMM, LS Mean 2 SEM CGeometri Mean Change "rom Bacelne ato). & 000 Wook (Post Baseine) ons < e
Slide 21: Significant Biomarker Plasma NfL Difference
Significant Biomarker Plasma NfL Difference CNM-Au8 vs. Placebo | All RGC Participants During Double-Blind Period MMRM log NfL by group, contrast model; prespecified covariates included: (i) pre-treatment ALSFRS-R slope (delta-F5), (i) months from symptom onset, i) use of riluzole, (iv) use of edara
Slide 22: Continued Long Term Plasma NfL Decline in the OLE
HEALEY ALS: Continued Long Term Plasma NfL Decline in the OLE weseey ats 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 Difference = SEM
Slide 23: 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 NfL Responder Analyses in Participants with a NfL Decline of 25% (Post- 'NfL Levels (by Quartile) Bas
Slide 24: CNM-Au8 NfL Responders Demonstrated Robust NfL Declines
HEALEY ALS. CNM-Au8 NfL Responders Demonstrated Robust NfL Declines Piston Trial NfL Decline by Participant Nfl Decline Across Responders CCNM-Au® NIL Responder Subset CCNM-Au® NIL Responder Subset HEALEY ALS Platform Thal Open Label Extension HEALEY ALS Piatform Tal Open Label Extension Within Regi
Slide 25: CNM-Au8 NfL Responders Showed Slowed ALSFRS-R Decline
HEALEY ALS. CNM-Au8 NfL Responders Showed Slowed ALSFRS-R Decline Platform Trial NfL Responders vs. NfL Non-Responders ALSFRS-R Decline ALSFRS-R Respiratory Subdomain Long-Term ALSFRS-R Respiratory Subscore Change by NfL Status Long-Term ALSFRS-R Total Score Change by Nfl Responder Status Responder
Slide 26: CNM-Au8 NfL Responders Demonstrated Improved Survival
CNM-Au8 NfL Responders Demonstrated Improved Survival HEALEY ALS. Platform Trial NfL Responders vs. NfL Non-Responders and vs. PRO-ACT Matched Controls NfL Responders vs. Nfl. Non-Responders ‘CNM-Au8 Long-Term Survival by Plasma NfL Responder Status 'AICNM-AUB with Basaine Covariates (1-116 of 120)
Slide 27: CNM-Au8 30mg Treatment Improved Long-Term Survival vs. Matched Controls
CNM-Au8 30mg Treatment Improved Long-Term Survival vs. Propgisteptey ts Matched PRO-ACT & NHC Controls PRO-ACT Controls Natural History Consortium Controls (CNM-Au8 30 mg Long Term Survival | HEALEY ALS Platform Trial (CNM-AuB 30 mg Long Term Survival | HEALEY ALS Platform Trial ‘Orginal GNM-AuB (t=
Slide 28: EAP Participant Enrollment
EAP Participant Enrollment * AIL EAP participants (CNM-Au8 30mg) enrolled through 15-December-2023 with EDC data entry * Survival updated through the 14-January-2024 data cut EAPOL in collaboration with the EAPO1 EAPO2 Healey Center (MGH) (US, 16 sites) Former HEALEY Regimen C The Healey center cove
Slide 29: EAP Survival vs. ALS Natural History and PRO-ACT
EAP Survival vs. ALS Natural History and PRO-ACT Matched Controls | Ccontrol-Matched EAP and All EAP ALS Natural History Study | EAP Matched (n=220) PRO-ACT | EAP Matched (n=220) EAP Long-Term Survival EAP Long-Term Survival ALS Natural istry Stuy Propnay Matched Contls PRO-ACT Propel Matched Contos
Slide 30: 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 “EX Ea O4/-0-0- 80 _@__0- 8-0-8 * Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMTS + 92%
Slide 31: 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 Global Neurological Improvement ignificantly Improved Change in Low Contrast Letter Acuity (LCLA) Change in modified MS Functional Composite (mMSFC) LOLA atfectedtelow, SHPT dominantinon-domin
Slide 32: Long-Term LCLA Improvement in LTE Participants
Long-Term LCLA Improvement in LTE Participants QUISIONARY NS Low Contrast Letter Acuity Original Active (CNM-Au8) Original Placebo Longitudinal LCLA | Change from Baseline (Total Correct, Both Eyes) |All Active Longitudinal LCLA | Change from Baseline (Total Correct, Both Eyes) INTE Paricipants Orig
Slide 33: CNM-Au8 Improved Information Signal Strength & Speed in the Visual Pathway
CNM-Au8 Improved Information Signal Strength & Speed @VISIONARY-MS in the Visual Pathway Visual Evoked Potential Improved Amplitude Improved Latency {VE Amite |Longtudina Percent) Change YEP Average Latency | Longitudinal Percent (1) Change In LTE Parcipants (edz; 90 active, 12 explaceo), AllEvaluab
Slide 34: Long-Term SDMT Improvement in LTE Participants
@VISIONARY-MS Long-Term SDMT Improvement in LTE Participants Symbol Digit Modality Test | Working Memory & Cognition Original Active (CNM-Au8) gir naebe Longitudinal SOMT | Change from Baseline (Total Score) | All Active Longitudinal SDMT | Chi from Baseli Total Score) In LTE Participants Originally
Slide 35: CNM-Au8 Treatment Demonstrated MS Lesion Repair and Promoted Remyelination
CNM-Au8 Treatment Demonstrated MS Lesion Repair @VISIONARY-MS and Promoted Remyelination Advanced M hniqu T2 Lesion Myelin Water Fraction (Remyelination) T2 Lesion Axial Diffusivity (Axonal integrity) ‘2 Lesion Axial Diftusivity inthe Corebrur [MRI Longtail Analyses (7-60), Al Evaluabla, TT Populati
Slide 36: Clene | CNM-Au8 Path to Regulatory Approval
Clene | CNM-Au8 Path to Regulatory Approval 2024 MID-2024 2025 N | >= instar up 4-30 months ‘Amyotrophic Lateral Sclerosis (ALS) Data Readouts / Phase 3 Planning Bib Pere tegutory BBE tit serous nial data opto. yr pctene — x
Slide 37: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases CNM-Aus°” Favisionany-usy d nanocrystal development cellular energetic catalyst to remyelinate® & protect neurological function B59 RESCUE HEALEY ALS Platform Trial Strong IP: 150+ nts on nanothi mctene
Slide 38: Clene Nanomedicine
\_s CLene NANOMEDICINE