Slide 1: Clene
> cLene NASDAQ: CLNN clene.com ar |
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of Section 21E ofthe Securities Exchange Act of 1934, as amended, and Section 27A ofthe Securities Act of 1933, a5 amended, which are intended tobe covered by the “safe harbor” provisions created by
Slide 3: Building the Clinical Case for Neuroprotection
Building the Clinical Case for Neuropro @VISIONARY-MS A RESCUE if CNM-Au8 demonstrated global neurological improvement in stable relapsing MS as an adjunct to immunomodulatory DMTs CNM-Au8 demonstrated ed brain statistically signifi survival benefit o' decreased risk of death through 120 wks \cross
Slide 4: 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 ‘Axonal Degeneration
Slide 5: 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-Aus Mechanistic Effects Improved Energy Production and Nanocrystals Utilization Increased NAD Ps NS \ Increased ATP Decreased reactive | EI ] ‘oxygen species / \ 4 Ctend Increased proteostasis Ss 4 Nanoc
Slide 6: 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 s322%%0 Sclerosis (MS) Disease (PD) ee 4KOURS ot NOME... ZN: <> bs es UIE. \ San ans iin eine FEARS x Bi a : clene
Slide 7: Two REPAIR Trials Demonstrated Target Brain Engagement and Improved Energy Metabolism
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 8: RESCUE Encouraging Efficacy Signals in Phase 2
6% RESCUE Encouraging Efficacy Signals in Phase 2 Ti 1° & 2° Endpoints —— aoe Rescue-ALS Primary & Secondary . (Wk 36 LS Mean Change = 95% Cl) “fpnalcord | | motor neuron function ir relief — a5 @ mconomen pomp 1 bcos) | “Umb Onset (BE MUNK Sum (% Change). = +—»— ane vse nat Study Design: veek blind
Slide 9: RESCUE CNM-Au8 Improved Patient Function, QOL, and Slowed Time to ALS Clinical Worsening
Pk 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 decline ALSFRS
Slide 10: RESCUE OLE | Preserved ALSFRS-R Functional Decline
6s RESCUE OLE | Preserved ALSFRS-R Functional Decline Early CNM-Au8 Treatment Impacts Long-Term Function Compared to Original Placebo ALSERS-R Slope ALSFRS-R Slope ALSFRS-R Slope Baseline to Week 48 Week 60 [OLE Week 24] to Week 120 Summary ‘ALS. Shope Change OLE ALSFR te of ein ors per pardon Sop M
Slide 11: RESCUE OLE | Decreased ALS Time to Clinical Worsening
as RESCUE’ 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 Hazard ratio= 0.478 95% Wald CI= 0.225 t0 1.015 Logrank, p= 0.0494 18: The risk of ALS clinical worsening was decreas
Slide 12: RESCUE 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 in
Slide 13: HEALEY ALS Platform Trial Design
— 3 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
Slide 14: 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 Cox Proportional Hazard Full Analysis Set (All Shared Placebo, Regimens A, B, C, D) ‘% Hazard Reduction at Week 24 (1--Hazard Ratio, 95% Confidence interval) coat chong 24% Decreas
Slide 15: Time to Clinical Worsening Events Platform Trial
Time to Clinical Worsening Events Platiorr ‘ial Death Permanent Assisted Hospitalization Feeding Tube Assisted Ventilation ae and Al Placement Ventilation use ) | uO & ease: iste == day + Time to clinical worsening events were prespecified in the protocol and analysis plan * p-values provided are un
Slide 16: Delayed Time to ALS Clinical Worsening (Composite)
Delayed Time to ALS Clinical Worsening (Composite) Platiorr ‘ial Reduction in Time to ALS Clinical Worsening (Composite) Frist Instance of Death, Tracheostomy, PAV, or Feeding Tube Clinical Worsening Composite Fisk Adjusted Cox Proportional Hazara Modal Primary Covarato Mod) (Time to First Instance)
Slide 17: Delayed Time to Clinical Event Summary
Delayed Time to Clinical Event Summary CNM-Au8 30mg | Within Regimen Analysis (Primary Model) "7 CNM-Au8 30mg delayed time to clinical worsening at 6 months CNM-Au8 30mg I Clinical Event Risk Reduction ‘Within Rapimen Analysis cy Regimen On) Fisk Agusted Cox Proportional Hazard Percent) Hazard Reduc
Slide 18: Plasma NfL Difference | CNM-Au8 vs. Placebo
Plasma NfL Difference | CNM-Au8 vs. Placebo All RGC Participants 145: 1.10: 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) = -0.10 (0.048); p= 0.040 0.90: Weeks (Post-Randomization) 23% -O Placeb
Slide 19: Consistent Plasma NfL Effects in Higher Risk Patients
Consistent Plasma NfL Effects in Higher Risk Patients finest 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 ‘aseine NL > Medan Fase Progssr| tS Prsrewm
Slide 20: 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 HEALEY ALS Platform CNM-A 30mg Decreased Time to Clinical Worsening ALS Clinical Worsening ITT Populaton, ll Randomized Kaplan-Meier Estimate, Percent Event Free ss ome one p=
Slide 21: CNM-Au8 Has Demonstrated ALS Survival Benefit at 30mg Dose in Two Phase 2 Studies
CNM-Au8 Has Demonstrated ALS Survival Benefit at 30 mg Dose in Two Phase 2 Studies eased risk of HEALEY ALS >90% risk reduction of death through 120 PE CMIIREE death at 30mg at 24 weeks weeks ” i hasaaRater o40e |! ies sx WisCt 0177 909K 101 5. peateo lope p= 00820 H ea = os = = eos Posen) ask omens
Slide 22: 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-Au& CNM-Au8 Treatment Emergent 30 me 60 mg Adverse Events (TEAEs) 9 ) ) Participants with Any TEAE ‘Participants with Related TEAEs 20% 43% | Participants with
Slide 23: ALS Summary | CNM-Au8 Has Demonstrated Survival Benefit
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 24: VISIONARY-MS Core Design Elements
VISIONARY-MS Core Design Elements sTuoY Phase 2 Study: 48-Week Placebo-Control Treatment Period 2:1 Randomization (Active [15mg, 30 mg]: Placebo) seeming DO ESE 0-+/-0-0 0 _0—_@—_0-—@ : = * Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMTs * n=73 of
Slide 25: Baseline Demographics and Study Analysis
Baseline Demographics and Study Analysis QVISIONARY-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 Baseline Value Weight mean (sd) y
Slide 26: 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 Significantly Improved Vision Global Neurological & Improvement or o Change in Low Contrast Letter Acuity (LCLA) Change in modified MS Functional Composite (mMSFC) {HPT doin emit, SMT LCLA Cha
Slide 27: VISIONARY-MS Measures of Axonal Integrity
x @VISIONARY-MS VISIONARY-MS Measures of Axonal Integrity ia Visual Evoked Potentials (VEP) Advanced MRI Techniques Multi-focal Amplitude and Latency Changes Diffusion Tensor Imaging (DT!) changes Frattional Anisotropy Brain Ditfusivity cer ‘ )| & ou , )| vo , | t What Happens in the Visual System H
Slide 28: 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 Population, LS Mean = SEM, Segments Nested by Participant VEP Affected Eye ‘VEP Follow Eye Wi 48 LS-Mean Ditforonce = 6.1 Wx 48 LS-Moan Ditfrence = 9.7, 95% Cl=-06 0 127 p= 0.0730 10.
Slide 29: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity Throughout the —@v!sionary-ms Brain Preserved Whole Brain White Matter Integrity Consistent Effect Across All Brain Regions Diffuion Tensor Imaging | Fractional Anisotropy (FA) Change Diftusion Tensor Imaging | Fractional Anisotropy (FA) ‘Whole Brain (Corebru
Slide 30: Summary | Consistent Paraclinical Evidence of Neuroprotective Effects
Summary | Consistent Paraclinical Evidence of Neuroprotective Effects Favoring CNM-Au8 Treatment Implications within the whole brain (erebrum) p=00189 Diffusion Tensor Improvementsof Neuroprotection and preservation Imaging (OT) ee conse mona intgrityand of white mattrintegrty measure of Fractional
Slide 31: VISIONARY-MS Safety Summary
VISIONARY-MS Safety Summary QUISIONARY —x 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 Treatment Emergent Adverse Events CNM-Au8 CNM-Aus
Slide 32: 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 33: 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 Findings Adverse Event (AE) Profile All Animal Toxicology Studies Assessed as Predominantly Mild-to- ect Level (NOAEL) Moderate Severity Findings and Transient Patient Exposure
Slide 34: Growing Body of Evidence for CNM-Au8
Growing Body of Evidence for CNM-Au8° Disease 2021 2022 2023 Key Findings Demonstrated nna ent reseed unetin andslowed incl arsnigie the Amyotrophic or Lateral Sclerosis (ALS) aD F Demonstated unalone ake E stemontne Parkinsons Exnbisnedban toast rangement ate Demartated obsinevoopes MS Cea i Imarov
Slide 35: Clene | Anticipated Catalysts Over the Next Year
Clene | Anticipated Catalysts Over the Next Year MID-2023 2024 MID-2024 | ! n rg + UrinaryP75 Clinical Data up-to-18 months + Serum Creatinine (ALSERS, Clinical Worsening) Long Term Survival Data Survival & Clinical data up- Clinical data tosayes up-to-3-y1s BB pie ae sero s) pctene mm as
Slide 36: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases Strong IP: devsopents the cot | 150+ patents on to remyelinate’ & protect nanotherapeutic neurological function platform x RESCUE. HEALEY ALS Platform Trial > cLene
Slide 37: Clene
® cLene )\_4 NANOMEDICINE