Slide 1: CLNN (NASDAQ)
November 2, 2021 CLNN (NASDAQ)
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: Rob Etherington
Rob Etherington Clene Nanomedicine, Inc President & CEO 3
Slide 4: CLENE | Webinar Agenda
CLENE | Webinar Agenda CNM-Au8 overview 1 & upcoming Rob Etherington, President and Chief Executive Officer I Clene Inc. milestones ALS unmet need & 2 Steve Vucic, MBBS (Hons I), PhD, DSc, FRACP, FAHMS, current treatment Northcott Chair of Neurology I The University of Sydney limitations Robert Glan
Slide 5: CLENE | Company Highlights
CLENE | Company Highlights • Potential first-in-class nanotherapeutic with high catalytic activity to drive Nanotherapeutics energy production and utilization in stressed CNS cells Platform • Applications across neurology, infectious disease, and oncology • CNM-Au8 increases cellular energy producti
Slide 6: CLENE | Pipeline
CLENE | Pipeline Creating elemental solutions for human health ™ 6
Slide 7: CNM-Au8 | Mechanism of Action
CNM-Au8 | Mechanism of Action Electron transfer (to-and-from) CNM-Au8 nanocrystals drives catalytic activity and increased energy production and utilization CNM-Au8® Clean Surfaced, Highly Mechanistic Effects Increased Energy Nanocrystal Faceted Shape Enhances Production & Utilization Catalytic Acti
Slide 8: Steve Vucic, MD Northcott Chair of Neurology
Steve Vucic, MD Northcott Chair of Neurology The University of Sydney 8
Slide 9: Amyotrophic Lateral Sclerosis: Unmet need
Amyotrophic Lateral Sclerosis: Unmet need Professor Steve Vucic Northcott Chair of Neurology Brain and Nerve Research Centre Concord Clinical School University of Sydney 9
Slide 10: MND/ALS
MND/ALS Rapidly progressive neurodegenerative disorder ◦ Motor neurons ◦ Weakness & wasting voluntary muscles Prevalence ◦ 5.2 – 6.2 per 100,000 ◦ Mean age onset 50 – 60 years Median survival ◦ 100% fatal ◦ 2 – 3 years ◦ 20% survive > 5 – 10 years Kiernan et al. Lancet. 2011 Mar 12;377(9769):9
Slide 11: Improving Clinical Trial Outcomes in ALS
Improving Clinical Trial Outcomes in ALS 11 Kiernan et al. Nat Rev Neurol 2021 Feb;17(2):104-118.
Slide 12: Improving Clinical Trial Outcomes in ALS
Improving Clinical Trial Outcomes in ALS Represents a major limitation to developing effective therapies 12 Kiernan et al. Nat Rev Neurol 2021 Feb;17(2):104-118.
Slide 13: ALS Is a Multistep Disease Process
ALS Is a Multistep Disease Process Linear Relationship Between Log Incidence and Log-Age Across Multiple ALS Populations 6-step 6-step process 6-step process Australiaprocess Australia Japan 6-step process UK, Ireland, & Netherlands 5-step process South Korea 13 Vucic et al. Neurology Apr 2020, 94 (
Slide 14: Prior ALS clinical trials of repurposed drugs
Chronic NCT02238626 Safety and tolerability Pending Neuroinflammation Ibudilast obstructive and microglial (MN-166) pulmonary activation NCT02714036 Safety and tolerability Pending disease NCT02166944 ALSFRS-R Not significant Repurposed Existing use Targeted ALS trial Primary outcome Outcome Neuroin
Slide 15: Whole System Approach
Whole System Approach Normalise Cellular Function – Energy Dependent Processes 15
Slide 16: Whole System Approach
Whole System Approach Normalise Cellular Function – Energy Dependent Processes 16
Slide 17: Robert Glanzman, MD FAAN, Chief Medical Officer
Robert Glanzman, MD FAAN Chief Medical Officer Clene Nanomedicine, Inc 17
Slide 18: RESCUE-ALS trial design and endpoints
Phase 2 (January 2020); FPFV 16-Jan-2020; 45 of 42 enrolled (Nov-2020) Exploratory Endpoints % Change in Sum of Motor MUNIX Unit Index (MUNIX) • ALS disease progression 1° For the Abductor Digiti Minimi (ADM), Abductor • ALSFRS-R 6-point decline Pollicis Brevis (APB), Biceps Brachii (BB), Tibialis A
Slide 19: We thank FightMND for its philanthropic support
We thank FightMND for its philanthropic support of the RESCUE-ALS study 19
Slide 20: RESCUE-ALS Phase 2 Trial Topline Results
RESCUE-ALS Phase 2 Trial Topline Results “Befitting of Lou Gehrig, whose legacy is intertwined with ALS, we swung for the fences and ended with a stand-up triple…” Lou Gehrig (1903 – 1941)
Slide 21: Baseline Demographics
| Baseline Demographics ITT Population Baseline Sex Months Onset Site Months ALSFRS- ENCALS Value Age n, (%) n, (%) from from FVC R Risk mean (sd) (yrs) Male | Female Limb | Bulbar Diagnosis Onset (% pred.) Score Profile1 All 59.1 M: 26 (58%) L: 33 (73%) 3.1 15.9 81.5 38.7 -4.4 (n=45) (12.3) F: 19 (
Slide 22: Overview
| Overview ITT Population 1 2 Neurophysiology Pulmonary Function MUNIX1 (Forced Vital Capacity) 3 4 Functional Status & QOL Disease Progression (ALSFRS-R, & Survival ALS Specific QOL) 1 Study was only powered for MUNIX(4) primary endpoint (Box 1) 22 ITT Population; Data on File, Clene Nanomedicine,
Slide 23: Results Support Phase 3 Development
| Results Support Phase 3 Development • Proof of Concept Established in ALS Ø MUNIX Wk36 non-significant; Wk12 efficacy signal (p<0.06) Ø MUNIX results demonstrate lower motor neuron protection in limb onset ALS (Wk12, p<0.04; Wk36 p<0.08) • De-risked Phase 3 Development (Statistically Significant R
Slide 24: Matthew Kiernan, MD Bushell Chair of Neurology
Matthew Kiernan, MD Bushell Chair of Neurology The University of Sydney 24
Slide 25: Evidence for Motor Neuron Protection
| Evidence for Motor Neuron Protection Primary Endpoint (MUNIX(4) %, LS Mean Change) All Randomized Limb Onset (Pre-specified) 25 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 26: Pulmonary Function Forced Vital Capacity (FVC)
Pulmonary Function Forced Vital Capacity (FVC)
Slide 27: Directional FVC Benefit
| Directional FVC Benefit Secondary Endpoint1 (FVC % predicted, LS Mean Change, All Randomized) 1Study Not Powered for FVC change 27 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 28: Directional FVC Benefit
| Directional FVC Benefit Secondary Endpoint1 (FVC % predicted, LS Mean Change, Continuous Slope, Post Hoc) All Randomized Limb Onset (pre-specified) 1Study Not Powered for FVC change 28 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 29: Functional Status and QOL (ALSFRS-R, ALSSQOL-SF)
Functional Status and QOL (ALSFRS-R, ALSSQOL-SF)
Slide 30: Directional ALSFRS-R Benefit
| Directional ALSFRS-R Benefit Exploratory (ALSFRS-R, Continuous Slope, LS Mean Change) All Randomized Limb Onset (Pre-specified) 30 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 31: Significant Impact on ALSFRS-R Decline
| Significant Impact on ALSFRS-R Decline Exploratory (ALSFRS-R Responder Analysis, All Randomized) 31 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 32: Significantly Improves Quality of Life
| Significantly Improves Quality of Life Exploratory (ALSSQOL-SF, All Randomized) 32 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 33: Disease Progression & Survival
Disease Progression & Survival
Slide 34: Significant Impact on ALS Disease Progression
| Significant Impact on ALS Disease Progression Exploratory Endpoint (All Randomized) ALS Disease Progression defined as: • Death, or • Tracheostomy, or • Non-invasive ventilation, or • Gastrostomy tube 34 ITT Population; Data on File, Clene Nanomedicine, Inc.
Slide 35: Potential Survival Signal
| Potential Survival Signal Exploratory Endpoint (Observed Survival vs. Predicted) Observed Survival Start of Open Label Extension (Wk36+) ENCALS Predicted 35 Data on File, Clene Nanomedicine, Inc.
Slide 36: Well Tolerated & No Safety Signals
| Well Tolerated & No Safety Signals Safety Summary • No CNM-Au8 related serious adverse events (SAEs) • No CNM-Au8 related drug discontinuations • No imbalances in treatment emergent adverse event (TEAEs) • TEAEs were predominantly mild-to-moderate and transient • Most common TEAEs associated with
Slide 37: Results Support Cellular Energetic Impairment as a Therapeutic Target in ALS
CNM-Au8 These Results Support Cellular Energetic Impairment as a Therapeutic Target in Catalytically ALS Active Nanocrystal 37
Slide 38: Rob Etherington
Rob Etherington Clene Nanomedicine, Inc President & CEO 38
Slide 39: Results Support Phase 3 Development
| Results Support Phase 3 Development • Proof of Concept Established in ALS Ø MUNIX Wk36 non-significant; Wk12 efficacy signal (p<0.06) Ø MUNIX results demonstrate lower motor neuron protection in limb onset ALS (Wk12, p<0.04; Wk36 p<0.08) • De-risked Phase 3 Development (Statistically Significant R
Slide 40: Registration Study: 24-Week Treatment Period
Phase 3 Registration Study: 24-Week Treatment Period (3:1 randomization, 120 active [30mg, 60mg]: 40 placebo) Exploratory Endpoints Slow Vital Capacity • Combined Joint Rank Change in Anticipated full 1° ALSFRS-R 2° Hand-Held Dynamometry (Survival + ALSFRS-R) • Voice pathology unblinded data Surviva
Slide 41: Anticipated Timeline & Upcoming Milestones
Anticipated Timeline & Upcoming Milestones 2020 - 2023 2020 2021 2022 2023 41
Slide 42: Questions & Answers
Questions & Answers
Slide 43: Clene Inc.
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 ©2021 Clene Inc. Version: 2-November-2021