Clene Inc. · NASDAQ:CLNN
Clene — Investor Presentation (April 2023)
33 slides from Clene's investor presentation, Apr 17, 2023
Slide 1: Clene
cuene NASDAQ: CLNN clene.com
Slide 2: Forward Looking Statements
Forward Looking Statements ‘This presentation contains Tarwardooking statements" within the meaning of Seetion 21 ofthe Securities Exchange Act af 1934, a8 amended, and Section 27A of the Securities Act of 193, ‘amended, which are intended tobe covered by the “ste harbor” provisions ceated by thse l
Slide 3: CNM-Au8 survival benefit and remyelination results
a RESCUE Y CNM-Au8 demonstrated statistically significant survival benefit of 60% decreased risk of death through 120 wks Ren yelination CNM-Au8 demonstrated global neurological improvement in stable relapsing MS as an adjunct to immunomodulatory DMTs
Slide 4: Neurodegenerative Diseases Share A Common Mechanism: Decline In Brain Energy
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 8 8 Mutmipte SCLEROSIS FRONTOTEMPORAL ‘
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-Au8 Mechanistic Effects Improved Energy Production and Nanocrystals Utilization {lean Surfaced, Highly Faceted _ Shapes Increased NAD Increased ATP Decreased corre EB EI oxygen spi CNM-Aus = panacea Incr
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 sic%.... Sclerosis (MS) Disease (PD) ee AOU et INOS Ba NDE Shee oo cet (@) PMs Se a Poe
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 ‘e
Slide 8: Encouraging Efficacy Signals in Phase Trial
Encouraging Efficacy Signals in Phase 2 Trial 1° & 2° Endpoints = Rescue-ALS Primary & Secondary eisai (Wk 36 LS Mean Change = 95% Ci) ent ; “Qiroruntigee —_—— | “© Muni sum (% change) ‘eno 1 impasse measured by MUNIX Ss | + inane | pnacsam hang) as as + roar a omic) Study Design: “oat —te—+ © FVC 0
Slide 9: RESCUE-ALS: Improved Function, QOL, Slowed Time to ALS Clinical Worsening
a 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 AIS Specific QOL ALS Clinical Worsening point dectine ALS Dise
Slide 10: RESCUE-ALS OLE | Preserved ALSFRS-R Functional Decline
6% RESCUE\\S 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 ‘ALsFns. ope Chango Wek ALGER Sape Change OL Paras Peer
Slide 11: RESCUE-ALS OLE | Decreased ALS Time to Clinical Worsening
6 RESCUE |S 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 Cl= 0.2250 1.015 Logvank,p= 0.0494 The risk of ALS clinical worsening was decreased ~50
Slide 12: RESCUE-ALS Demonstrated Significant Impact on Long-Term Survival
(fs RESCUE ,- Demonstrated Significant Impact on Long-Term Survival 60% Decreased Risk of Death through 120 weeks ‘Long-Term Survival (Al-Cause Mortality): Originally Randomized Active vs. Placebo Interim Analysis (14-July-2022), ITT Population, All Subjects from Randomization {Long-term vital statu
Slide 13: 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-Aus in Participants with Amyotrophic Lateral Sclerosis 24-Week Treatment Period (3:1 randomization, 120 act
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) MES ang Death or Dest B
Slide 15: Time to Clinical Worsening Events
. sc : ats Time to Clinical Worsening Events Biatiorm ‘rial Death Permanent Assisted Hospitalization Feeding Tube Assisted Ventilation —_ and All Placement Ventilation use - (A. day * Time to clinical worsening events were prespecified in the protocol and analysis plan * p-values provided are uncorr
Slide 16: Delayed Time to ALS Clinical Worsening (Composite)
. ver : j HEALEY ALS Delayed Time to ALS Clinical Worsening (Composite) Platform Trial Reduction in Time to ALS Clinical Worsening (Composite) Clinical Worsening Composite fk Ajsod Gon Propatoal Haare Noval binary Govt Mod) (Time to First Instance) ‘% Hazard Reduction to Week 24 (Double-Blind Period
Slide 17: 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 ‘CNM-Aus 30mg | Clinical Event Risk Reduction ‘Within legimen Anaiyets(Efeay Regimen Ony) Fisk Acusted Cox Proportional Hazard Model Percent (4) H
Slide 18: 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 30
Slide 19: 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 Treatment Emergent Bal Adverse Events (TEAEs) Participants with Any TEAE. 93% 92% 93% Participants with Related TEAES (39% 30% 29% 43% Participants with SA
Slide 20: VISIONARY-MS Core Design Elements
VISIONARY-MS Core Design Elements STUDY Phase 2 Study: 48-Week Placebo-Control Treatment Period 2: Randomization (Active [15mg, 30 mg]: Placebo) amie: Gan 2 e aa ‘30 ‘36 42 ‘48 O-+?#-0-0 @ O @ O @ 0 @ Day 0s * Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on backg
Slide 21: Baseline Demographics and Study Analysis
Baseline Demographics and Study Analysis QVISIONAR * All participants 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 1.83
Slide 22: 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 Neuro! & | k Improvement oe ‘Change in Low Contrast Letter Acuity (LCLA) ‘Change in modified MS Functional Composite (mMSFC) nificantly Impro a | sae LOLA Change in the Affected Eye LOL
Slide 23: VISIONARY-MS Measures of Axonal Integrity
VISIONARY-MS Measures of Axonal Integrity Visual Evoked Potentials (VEP) Multi-focal Amplitude and Latency Changes What Happens in the Visual System Happens Throughout the MS Brain @VISIONARY-MS Advanced MRI Techniques Diffusion Tensor Imaging (DT!) changes Fractional Anisotropy O| a h| lal Brain Di
Slide 24: 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 Paticpant EP Affected Eye VEP Fellow Eye Wk 48 LS-Mean Diflerence = 6.1 Wk 48 LS-Mean Difference = 9.7 95% Cl=-0.6t0 12.7 9596 Cl=3.1 016
Slide 25: CNM-Au8 Preserved White Matter Integrity Throughout the Brain
CNM-Au8 Preserved White Matter Integrity Throughout the 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 (Corebrum) "Week 48 Cha
Slide 26: Summary | Consistent Paraclinical Evidence of Neuroprotective Effects
Summary | Consistent Paraclinical Evidence of Neuroprotective Effects Favoring CNM-Au8 Treatment FA within the whole brain (Cerebeum) peoo1s9 Diffusion Tensor Improvements of Neuroprotection and preservation Imaging (O71) ‘axonal integrity and fof white matter integrity FA within total Cerebral Whit
Slide 27: 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 “Placebo. i Subjects with any TEAE 22 (92%) 21 (88%
Slide 28: 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 29: Over 400 Years of Subject Exposure Without Identified Safety Signals
Over 400 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 Assessed Over 400 Years of St Exposure Wit as Predominantly Mild-to- Moderate Severity Identified Safet
Slide 30: Growing Body of Evidence for CNM-Au8
Growing Body of Evidence for CNM-Au8° Lateral aa on Parkinsons tatiet base Disease (PD) rem “rssgeren boty Multiple = MS abshedorintorget engsserent Sclerosis (MS) ‘sie es Pee une _ Poe
Slide 31: Clene | Anticipated Catalysts Over the Next Year
Clene | Anticipated Catalysts Over the Next Year MID-2023 2024 MID-2024 1 L n | (ALSFRS, Clinical Worsening) Long Term Survival Data BE cpt ater Sons) Survival & Cina ata up- ery up-to-3yrs > cLene — x
Slide 32: Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases Fevisionar i RESCUE > cLene
Slide 33: Clene Nanomedicine
m® CLene \ NANOMEDICINE