Slide 1: Clene Nanomedicine
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Clene's actual results may differ from its expectations, estimates, and projections and consequently, you sho
Slide 3: CLENE | Leadership
CLENE | Leadership Transforming the treatment of neurodegenerative disorders by restoring and protecting neurological function
Slide 4: CLENE | Overview
CLENE | Overview December 31, 2021 Cash and restricted cash on hand (audited): $50.3M ALS Registration Trial Topline data in 2H 20222 >300 patient years of CNM-Au8 clinical exposure CNM-Au8® a gold nanocrystal suspension, in development as the first cellular energetic catalyst to remyelinate1 & prot
Slide 5: CLENE | Pipeline
CLENE | Pipeline NANOTHERAPEUTIC INDICATION —|RESEARCH PRECLINICAL NDING ase PHASE? puases ANTICIPATED RESULTS “ee fF nescucrt Phase 2 1 " 22025 sBFnescucrn Phase? 5 CNN Agznt7 CCNM-PtAu7 Seem) staal (CNM Aus | pcvene
Slide 6: Neurons With High Energetic Demand Are At Increased Risk For Neurodegenerative Disease
Fu, H., et al; Nature Neuroscience (2018) 21: 1350-1358. Zhu et al. Proc Natl Acad Sci USA . 2015 Mar 3;112(9):2876-81. Rone et al. J Neurosci. 2016 Apr 27;36(17):4698-707. Neurons With High Energetic Demand Are At Increased Risk For Neurodegenerative Disease ~0.5% NAD+/NADH unit decline per decade
Slide 7: CNM-Au8 | Catalytically-Active Nanocrystals
Vertices, Edges, & Facets Key to Catalytic Activity CNM-Au8 Catalytically Active Nanocrystal Suspension Clean Surfaced, Highly Faceted Shape Enhances Catalytic Activity CNM-Au8 Nanocrystal CNM-Au8® | Catalytically-Active Nanocrystals Intersection of Physics and Biology Electron Sharing Drives Cataly
Slide 8: CNM-Au8 Nanocrystal Mechanistic Effects
CNM-Au8 Nanocrystal Mechanistic Effects Improved Energy Production and Utilization Promotes Neuroprotection and Remyelination CNM-Au8® | Improves Energy Production to Promote Neuroprotection and Remyelination
Slide 9: CNM-Au8 | Preclinical Evidence for Energetic Improvement
CNM-Au8® | Preclinical Evidence for Energetic Improvement Therapeutic Activity Across Remyelination + Neuroprotection Models Data on File, Clene Nanomedicine, Inc. Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936. MN Neuroprotection ALS SOD1, In Vitro Forebrain Neuroprotection C9ORF72 In Vitro Alzhei
Slide 10: CNM-Au8 | Significant Global Opportunity
CNM-Au8® | Significant Global Opportunity Source: Lancet Neurol. 2018 Nov;17(11):939-953; ~6.1M patients globally, data as of 2016.. PARKINSON’S DISEASE ~6.1M pts globally; $6B projected by 20263 2ND most common neurodegenerative disorder; only symptomatic treatments Source: Lancet Neurol. 2018 Dec;
Slide 11: CNM-Au8 | Neuroprotection & Remyelination Clinical Trials
CNM-Au8® | Neuroprotection & Remyelination Data on File, Clene Nanomedicine, Inc. Phase 2 and Phase 3 Clinical Trials CNM-Au8 treatment effect on ALS disease progression Ongoing Established brain target engagement & safety Planned: Demonstrate Disease Modification Concluded enrollment due to COVID E
Slide 12: CNM-Au8 | Safety Summary
CNM-Au8® | Safety Summary Over 300 Years of Subject Exposure Without Any Safety Signals Patient Exposure Across PD, MS, & ALS Long-term dosing experience up to 125 weeks All Animal Toxicology Studies Resulted in No-Adverse Effect Level (NOAEL) Findings Clean Toxicology Findings Multiple species up t
Slide 13: CNM-Au8 Effects on Brain Energetic Metabolites
Difference in brain NAD+ and NADH fraction at Week 12 (End of Treatment) Difference in bioenergetic metabolites (e.g., ATP, NAD) concentration at Week 12 – 16 Difference in brain membrane markers (PE, PC, etc.) at Week 12 – 16 Change in Brain Bioenergetic Potential (NAD+/NADH) vs. Baseline 1 2 CNM-A
Slide 14: CNM-Au8 Improves Brain Energy Metabolism
CNM-Au8 Improves Brain Energy Metabolism Increases NAD+/NADH Ratio in MS & PD Phase 2 Results 1° Endpoint 2° Endpoint NAD is an essential molecule responsible for cellular energy production Exploratory (ATP Normalization) Glanzman et al. 2021. International Parkinson and Movement Disorder Society (M
Slide 15: RESCUE-ALS Phase 2 Trial Design
(January 2020); FPFV 16-Jan-2020; 45 of 42 enrolled (Nov-2020) Phase 2 1 Study was powered for MUNIX primary endpoint Neurophysiology MUNIX1 Pulmonary Function Forced Vital Capacity Function & QoL ALSFRS-R, ALSSQOL-SF Disease Progression & Survival Vucic et al. BMJ Open. 2021 Jan 11;11(1):e041479. D
Slide 16: Pioneered Use of MUNIX Biomarker Primary Endpoint
| Pioneered Use of MUNIX Biomarker Primary Endpoint: Spinal Cord Lower Motor Neuron Protection Muscle Fibers Spinal Cord Motor Neuron Bulbar Onset ALS (Brainstem) Limb Onset ALS (Spinal Cord) Primary Endpoint: Spinal Cord Lower Motor Neuron Motor Unit Index (MUNIX) Sum Biceps brachii Tibialis Anteri
Slide 17: Evidence for Motor Neuron Protection
| Evidence for Motor Neuron Protection Primary Endpoint (MUNIX %, LS Mean Change) All Randomized All Placebo Limited Rate of MUNIX Decline in Bulbar Onset Insufficient Spinal Cord Lower Motor Neuron Progression in Early Bulbar Trial Participants RESCUE-ALS: A Phase 2, randomized, double-blind, place
Slide 18: Significant Impact on ALSFRS-R Decline
| Significant Impact on ALSFRS-R Decline Exploratory (ALSFRS-R Responder Analysis, < 6-point decline) All Randomized All Bulbar All Limb Sensitivity RESCUE-ALS: A Phase 2, randomized, double-blind, placebo-controlled study of CNM-Au8 to slow disease progression in ALS. MNDA Virtual Symposium, 2021 D
Slide 19: Significant Quality of Life Improvement
| Significant Quality of Life Improvement Exploratory (ALS Specific QOL-SF) All Randomized RESCUE-ALS: A Phase 2, randomized, double-blind, placebo-controlled study of CNM-Au8 to slow disease progression in ALS. MNDA Virtual Symposium, 2021 Data on File, Clene Nanomedicine, Inc.
Slide 20: Significant Impact on ALS Disease Progression
| Significant Impact on ALS Disease Progression Exploratory Endpoint (Disease Progression) 1ALS Disease Progression defined as: Death, or Tracheostomy, or Non-invasive ventilation, or Gastrostomy tube All Bulbar All Limb Sensitivity RESCUE-ALS: A Phase 2, randomized, double-blind, placebo-controlled
Slide 21: Joint Rank: Survival & ALSFRS-R Scoring
| Joint Rank: Survival & ALSFRS-R Scoring Berry et al. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Apr;14(3):162-8. ALSFRS-R Decline Survival CAFS All Randomized Exploratory Endpoint Pre-specified (Combined Assessment of Survival and Function [CAFS]) Score participants based on relative fun
Slide 22: Impact on Joint Rank Score to Wk36
| Impact on Joint Rank Score to Wk36 Post Hoc (Combined Assessment of (i) Survival, (ii) King’s Clinical Stage 4, (iii) ALSFRS-R) Data on File, Clene Nanomedicine, Inc. ALSFRS-R Decline Survival Non-Invasive Ventilation Gastrostomy Tube King’s Clinical Stage 4 By Average of Summated Scores
Slide 23: Potential Impact on Survival
| Potential Impact on Survival Exploratory Endpoint (Observed Survival vs. Median Predicted) ENCALS Predicted Median Survival Observed Survival Data on File, Clene Nanomedicine, Inc.
Slide 24: Well Tolerated & No Safety Signals
| Well Tolerated & No Safety Signals Data on File, Clene Nanomedicine, Inc. No CNM-Au8 related serious adverse events (SAEs) No CNM-Au8 related drug discontinuations No imbalances in treatment emergent adverse event (TEAEs) by system organ class TEAEs were predominantly mild-to-moderate and transien
Slide 25: Phase 3 ALS Registration Study Design
Exploratory Endpoints Combined Joint Rank (Survival + ALSFRS-R) Voice pathology PRO (ALSAQ) Pharmacodynamic markers Slow Vital Capacity Hand-Held Dynamometry Survival Change in ALSFRS-R Registration Study: 24-Week Treatment Period (3:1 randomization, 120 active [30mg, 60mg]: 40 placebo) 1 2 Phase 3
Slide 26: VISIONARY-MS Phase 2 Trial Design
Exploratory Endpoints Treatment of Visual Pathway Deficits In Chronic Optic Neuropathy for Assessment of Remyelination in Non-Active Relapsing MS Change in Low Contrast Letter Acuity (LCLA) At Week 24 Up to 48-Week Placebo-Control 2:1 Randomization (Active: Placebo) 15mg, 30mg, Placebo (n=73 of 150)
Slide 27: LCLA Primary: Functional Visual Improvement
LCLA Phase 2 Primary: Functional Visual Improvement LCLA Correlates with clinically meaningful deficits in QOL, EDSS and MSFC, MRI, and OCT1 MS Functional Endpoints Phase 2 Exploratory: Neuroprotection/Remyelination Endpoints The Visual System is a Window into the Brain 9-Hole Peg Test Symbol Digit
Slide 28: Significant Clinical Improvement Across Blinded Study Population
Significant Clinical Improvement Across Blinded Study Population Primary Endpoint: LCLA (Best-Corrected) & Secondary Endpoint: (m)MSFC Phase 2 2° | (m)MSFC 1° | LCLA Glanzman et al. VISIONARY-MS: Update to a Phase 2 Clinical Trial of CNM-Au8, Catalytically Active Gold Nanocrystals Suspension, for th
Slide 29: COVID-19 Trial Endpoints
Proportion of participants who require COVID-19 related hospitalization, or died at Day 28 Secondary Endpoint Exploratory Endpoints Primary Endpoint Time to substantial alleviation of COVID-19 symptoms through Day 28 Number of hospital free days through Day 28 Mean change in SARS-CoV-2 viral load Ch
Slide 30: Strong Intellectual Property
Trade Secrets Patent Status b Patent Description Issued & Allowed Patents 150+ Pending Applications ~20 Total Patents/ Applications >170 Process And Method/Device (Clean Surface; Gold CSN) State of Matter (CNM-Au8) Method of Use (Prevent Demyelination & MoA) Method of Use (Bi-Metallic Au/Pt; Antimic
Slide 31: Proprietary Nanocrystal Manufacturing
Clene | Proprietary Nanocrystal Manufacturing In-House ISO8 Clean Room Clinical Production in Maryland Designed to be Scalable to Commercialization Validated CMC Processes Patented Hydro-electro- Crystallization Proprietary Trade Secrets
Slide 32: Anticipated Timeline & Upcoming Milestones 2020 - 2024
Anticipated Timeline & Upcoming Milestones 2020 - 2024 VISIONARY-MS
Slide 33: CLENE | Company Highlights
Nanotherapeutics Platform Potential first-in-class nanotherapeutic with high catalytic activity to drive energy production and utilization in stressed CNS cells Applications across neurology, infectious disease, and oncology Lead Asset: CNM-Au8 for Neurorepair CNM-Au8 improves cellular energy produc
Slide 34: Version: 11-March-2022 Clene Inc. HQ & Clinical Development 6550 South Millrock Drive, Suite G50
©2022 Clene Inc. Version: 11-March-2022 Clene Inc. HQ & Clinical Development 6550 South Millrock Drive, Suite G50 Salt Lake City, UT 84121 R&D and Manufacturing 500 Principio Parkway, Suite 400 North East, MD 21901