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FORM
CURRENT REPORT
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Item 7.01 Regulation FD Disclosure.
On November 2, 2021, Clene Inc. (the “Company”) issued a press release announcing top-line results from its Phase 2 RESCUE-ALS clinical trial in amyotrophic lateral sclerosis (“ALS”). A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K (the “Current Report”) and is incorporated herein by reference.
In connection with the press release issued on November 2, 2021, the Company hosted a conference call to discuss the Phase 2 RESCUE-ALS topline clinical trial results. A copy of the webinar presentation is furnished as Exhibit 99.2 to this Current Report and is incorporated herein by reference.
The information furnished in this Item 7.01, including Exhibit 99.1 and Exhibit 99.2 shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”), as amended, or otherwise subject to the liabilities of that section, and shall not be deemed to be incorporated by reference into any filing made by the Company under the Exchange Act or the Securities Act of 1933, regardless of any general incorporation language in any such filings, except as shall be expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit Number |
Exhibit Description | |
| 99.1 | Press Release dated November 2, 2021 announcing top-line results from the Phase 2 RESCUE-ALS clinical trial | |
| 99.2 | RESCUE-ALS presentation dated November 2, 2021 | |
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL). |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Clene Inc. | ||
| Date: November 2, 2021 | By: | /s/ Robert Etherington |
| Robert Etherington | ||
| President and Chief Executive Officer | ||
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Exhibit 99.1
Clene Nanomedicine Announces Top-Line Results from
Phase 2 RESCUE-ALS Clinical Trial
| ● | RESCUE-ALS Phase 2 Trial did not meet primary MUNIX biomarker endpoint or secondary FVC endpoint at week 36; MUNIX efficacy signal was observed at week 12 (p=0.057) |
| ● | MUNIX trial results demonstrated protection of lower motor neurons in the pre-specified subset of limb onset ALS subjects (Wk12, p=0.0385; Wk36, p=0.0741), which represents approximately 70% of the ALS population |
| ● | Statistically significant reductions in clinically relevant outcomes including ALS disease progression (p=0.0125), ALSFRS-R responder analysis (p=0.035), and improved ALS specific quality of life (p=0.018) |
| ● | Evidence for potential long-term survival benefit |
| ● | Results for Healey ALS Platform Trial Expected in the Second Half of 2022 |
SALT LAKE CITY, Nov. 2, 2021 -- Clene Inc. (Nasdaq: CLNN) along with its subsidiaries “Clene” and its wholly owned subsidiary Clene Nanomedicine Inc., a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of neurodegenerative disease with its potential first-in-class catalytically active nanocrystal suspension, today announced top-line data from RESCUE-ALS, a Phase 2 clinical trial evaluating CNM-Au8 as a disease modifying treatment for people with early amyotrophic lateral sclerosis (ALS).
The trial did not meet the primary or secondary endpoints – Motor Unit Number Index (MUNIX) and forced vital capacity (FVC) – at week 36. However, an efficacy signal was observed for the MUNIX endpoint at week 12 (p=0.057). Furthermore, in a pre-specified analysis in the subset of limb onset ALS, CNM-Au8 demonstrated a significant treatment effect in MUNIX at week 12 (p=0.0385) and a trend for improvement at week 36 (p=0.0741). Limb onset ALS accounts for approximately 70% of the ALS population. MUNIX is a neurophysiological biomarker that estimates the number of functioning lower motor neurons serving selected muscles.
Clinically relevant exploratory endpoints through trial week 36 demonstrated significant benefits with CNM-Au8 treatment, including slowing ALS disease progression (p=0.0125), decreasing the proportion of participants with an ALS Functional Rating Scale Revised (ALSFRS-R) 6-point decline (p=0.035), and improving quality of life as measured by the ALS Specific Quality of Life (ALSSQOL-SF) (p=0.018). In addition, RESCUE-ALS showed evidence for a potential long-term survival benefit when comparing the survival of the trial population to the validated ENCALS predictive model1.
“These data are very encouraging to us in the ALS research and treatment community as they demonstrate clinical benefits with CNM-Au8 treatment in outcomes that matter to patients and provide evidence for improved long-term survival,” said Professor Matthew Kiernan, AM MBBS(Hons), PhD, DSc, FRACP, FAHMS, Bushell Chair of Neurology, University of Sydney and one of the trial’s clinical advisors. “RESCUE-ALS was a proof-of-concept trial intended to establish that treatment of neuronal energetic failure can provide disease-modifying effects in ALS. I am pleased to see the potential effectiveness of CNM-Au8 demonstrated in this trial, and it is important to confirm these results in a larger clinical trial.”
| 1 | Westeneng et al. Lancet Neurol. 2018 May;17(5):423-433. |
Rob Etherington, Clene’s Chief Executive Officer, stated, “We believe these results show the potential of CNM-Au8 to bring meaningful benefit to people living with ALS. Befitting of Lou Gehrig, whose legacy is intertwined with the disease, we swung for the fences and ended with a stand-up triple. In the second half of next year, we expect to report results from the HEALEY ALS Platform Trial with the objective of confirming CNM-Au8 as an effective disease-modifying therapy for people with ALS.”
RESCUE-ALS was a 36-week randomized, placebo-controlled Phase 2 clinical trial that enrolled 45 patients with early ALS, randomized 1:1 to treatment with CNM-Au8 at 30 mg daily or matching placebo on top of standard of care. The primary endpoint of the trial was the percent change of the sum of MUNIX from baseline to week 36. Secondary endpoints were the change in FVC and the absolute change in MUNIX values to week 36. Exploratory endpoints included multiple clinically relevant measures of ALS: disease progression, ALSFRS-R decline, and ALSSQOL-SF.
CNM-Au8 was found to be well-tolerated through 36 weeks of oral daily dosing. There were no reported serious adverse events (SAEs) related to CNM-Au8 treatment. Treatment-emergent adverse events were predominantly mild-to-moderate in severity. The most frequently reported adverse events associated with CNM-Au8 treatment included aspiration pneumonia (n=3) and transient gastrointestinal distress (n=2). Topline results from RESCUE-ALS are expected to be presented at the upcoming International Symposium on ALS/MND, which will take place Dec. 8-10, 2021.
Robert Glanzman, MD, FAAN, Clene’s Chief Medical Officer, concluded, “The results of RESCUE-ALS add to our expanding body of evidence that cellular energetic failure is an important pathophysiological mechanism in ALS. We thank the trial participants and their families for their willingness to engage in clinical research, the site investigators for their research excellence and dedication to patients, and FightMND of Australia for substantially funding the trial.”
Bec Sheean, Research Director of FightMND commented, “FightMND is committed to finding new treatment options for motor neurone disease. We awarded Clene a grant in 2019 to support the conduct of this Phase 2 clinical trial with CNM-Au8 in Australia. These clinical trial results are encouraging for people with ALS. By achieving clinically relevant endpoints, this trial demonstrates the potential for CNM-Au8 to support neuronal health. We are excited to see CNM-Au8 continue its advancement into the clinic so that we can bring this potentially transformative treatment to patients.”
Conference Call and Webcast Details
Clene will host a conference call and live audio webcast today at 8:00 a.m. ET to discuss the Phase 2 RESCUE-ALS topline clinical trial results. The live webcast may be accessed from the Investors section of the Company’s website at www.clene.com. Please connect to the website prior to the start of the conference call to ensure adequate time for any software downloads that may be necessary. Individuals may participate in the conference call by dialing +1 800 309 3488 in the U.S., or +1 929 517 9012 outside the U.S., and using conference ID: 5894034.
An archived version of the webcast will be available for at least one week in the Investors section of the Company’s website at www.clene.com.
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About CNM-Au8®, a gold nanocrystal suspension
Clene’s lead drug candidate, CNM-Au8, a catalytically active gold nanotherapeutic, is the result of a patented manufacturing breakthrough. The catalytically active nanocrystals of CNM-Au8 drive critical cellular energy producing reactions in the brain that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. CNM-Au8 crosses the blood-brain barrier and is not associated with the toxicities related to synthetic gold compounds or nanoparticles manufactured via alternative methods. CNM-Au8 is being evaluated in a Phase 3 registration trial for the treatment of amyotrophic lateral sclerosis (ALS). In the REPAIR Program Phase 2 open-label biomarker clinical trials, CNM-Au8 demonstrated target engagement in the treatment of Parkinson’s disease (PD) and multiple sclerosis (MS). REPAIR-PD has concluded, and REPAIR-MS will continue with the initiation of a second MS dosing cohort. Preclinical data, both published in peer-reviewed journals and presented at scientific congresses, demonstrate that treatment of neuronal cultures with CNM-Au8 improves survival of neurons, protects neurite networks, decreases intracellular levels of reactive oxygen species and improves mitochondrial capacity in response to cellular stresses induced by numerous disease-relevant neurotoxins. Oral treatment with CNM-Au8 improved functional behaviors in rodent models of ALS, MS and PD versus vehicle (placebo). CNM-Au8® is a federally registered trademark of Clene Nanomedicine, Inc.
About RESCUE-ALS
RESCUE-ALS is a Phase 2 multi-center, randomized, double-blind, parallel-group, placebo-controlled trial examining the efficacy, safety, pharmacokinetics and pharmacodynamics of CNM-Au8 in patients with early amyotrophic lateral sclerosis (ALS). The trial completed enrollment in the second half of 2020. In the trial, 45 subjects were randomized 1:1 to receive either active treatment with CNM-Au8 (30 mg) or placebo in addition to their current standard of care over a 36-week treatment period. The objective of the trial is to assess the impact of CNM-Au8 on disease progression in patients with early-stage ALS through changes in motor unit index MUNIX. MUNIX values were evaluated for four muscles in the hand, arm, and leg: the abductor digiti minimi, abductor pollicis brevis, tibialis anterior and biceps brachii from baseline through 36 weeks of treatment. CNM-Au8 was selected by FightMND of Australia, and Clene was provided a substantial grant to investigate efficacy in ALS utilizing novel neurophysiological endpoints at two clinical sites in Australia. For more information, please see ClinicalTrials.gov Identifier: NCT04098406.
About FightMND
FightMND is a not-for-profit registered charity, founded in 2014. It was established to raise the awareness of Motor Neurone Disease (MND) in Australia, to increase funding for research to find an effective treatment and cure and to provide care equipment for MND patients. FightMND has a clear objective – to have a world free from MND.
FightMND is Australia’s largest independent MND foundation focused on funding large-scale, collaborative research and clinical trials. The generous donations contributed by everyday Australians, right across the country, has enabled FightMND to raise and commit millions to cure and care initiatives.
About Clene
Clene is a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of neurodegenerative disease with potential first-in-class nanotherapeutics to treat energetic failure, an underlying cause of many neurological diseases. Our lead drug candidate, CNM-Au8, is an oral suspension of gold nanocrystals that drive critical cellular energetic metabolism in the central nervous system (CNS). CNM-Au8 increases energy production and utilization to accelerate neurorepair and improve neuroprotection. CNM-Au8 is currently being evaluated in a Phase 3 registration trial in amyotrophic lateral sclerosis (ALS) and a Phase 2 trial for the treatment of chronic optic neuropathy in patients with stable relapsing multiple sclerosis (MS). Clene has also advanced into the clinic an aqueous solution of ionic zinc and silver for anti-viral and anti-microbial uses. The company is based in Salt Lake City, Utah, with R&D and manufacturing operations in Maryland. For more information, please visit www.clene.com or follow us on Twitter, LinkedIn and Facebook.
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Forward-Looking Statements
This press release contains “forward-looking statements” which are intended to be covered by 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 should not rely on these forward-looking statements as predictions of future events. Words such as “expect,” “estimate,” “project,” “budget,” “forecast,” “anticipate,” “intend,” “plan,” “may,” “will,” “could,” “should,” “believes,” “predicts,” “potential,” “might” and “continues,” and similar expressions are intended to identify such forward-looking statements. These forward-looking statements involve significant known and unknown risks and uncertainties, many of which are beyond Clene’s control and could cause actual results to differ materially and adversely from expected results. Factors that may cause such differences include Clene’s ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; Clene’s ability to achieve commercial success for its marketed products and drug candidates, if approved; Clene’s ability to obtain and maintain protection of intellectual property for its technology and drugs; Clene’s reliance on third parties to conduct drug development, manufacturing and other services; Clene’s limited operating history and its ability to obtain additional funding for operations and to complete the licensing or development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on Clene’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in Clene’s Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in Clene’s subsequent filings with the U.S. Securities and Exchange Commission. Clene undertakes no obligation to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based, subject to applicable law. All information in this press release is as of the date of this press release. The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this press release.
| Media Contact | Investor Contact | |
| Maggie Beller | John Woolford | |
| Russo Partners, LLC | Managing Director, Westwicke | |
| Maggie.Beller@RussoPartnersLLC.com | clene@westwicke.com | |
| +1-646-942-5631 | +1-443-213-0506 |
Source: Clene Inc.
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Exhibit 99.2
CLNN (NASDAQ) November 2, 2021
2 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 should not rely on these forward - looking statements as predictions of future events . Words such as "expect," "estimate," "project," "budget," "forecast," "anticipate," "intend," "plan," "may," "will," "could," "should," "believes," "predicts," "potential," "might" and "continues," and similar expressions are intended to identify such forward - looking statements . These forward - looking statements involve significant known and unknown risks and uncertainties, many of which are beyond Clene’s control and could cause actual results to differ materially and adversely from expected results . Factors that may cause such differences include Clene’s ability to demonstrate the efficacy and safety of its drug candidates ; the clinical results for its drug candidates, which may not support further development or marketing approval ; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval ; Clene’s ability to achieve commercial success for its marketed products and drug candidates, if approved ; Clene’s ability to obtain and maintain protection of intellectual property for its technology and drugs ; Clene’s reliance on third parties to conduct drug development, manufacturing and other services ; Clene’s limited operating history and its ability to obtain additional funding for operations and to complete the licensing or development and commercialization of its drug candidates ; the impact of the COVID - 19 pandemic on Clene’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in Clene’s recently filed registration statement on Form S - 1 (filed July 22 , 2021 ), as well as discussions of potential risks, uncertainties, and other important factors in Clene’s subsequent filings with the U . S . Securities and Exchange Commission . Clene undertakes no obligation to release publicly any updates or revisions to any forward - looking statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based, subject to applicable law . All information in this presentation is as of the date of presented or the date made publicly available . The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this presentation .
Rob Etherington Clene Nanomedicine, Inc President & CEO 3
4 CNM - Au8 overview & upcoming milestones Rob Etherington, President and Chief Executive Officer I Clene Inc. ALS unmet need & current treatment limitations Steve Vucic, MBBS (Hons I), PhD, DSc, FRACP, FAHMS, Northcott Chair of Neurology I The University of Sydney RESCUE - ALS Intro & Results Robert Glanzman ( Clene CMO), Matthew Kiernan, AM, PhD, DSc, FRACP, FAHMS, Bushell Chair of Neurology I The University of Sydney Questions & Answers Dr. Robert Glanzman ( Clene CMO), Dr. Kiernan, Dr. Vucic , and Rob Etherington ( Clene CEO) 1 2 3 4 CLENE | Webinar Agenda
5 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 increases cellular energy production and utilization to promote neuroprotection and remyelination • Phase 2 ALS proof - of - concept evidence of efficacy across clinical endpoints • Phase 3 Healey ALS platform trial results expected in 2H 2022 • Phase 2 VISIONARY - MS in multiple sclerosis underway Strong Execution Capabilities • Proprietary electrochemical manufacturing process produces nanotherapeutics, scalable to commercialization • Strong IP, including 130+ granted patents, and trade secrets
6 CLENE | Pipeline ƌĞĂƚŝŶŐ ĞůĞŵĞŶƚĂů ƐŽůƵƚŝŽŶƐĨŽƌ ŚƵŵĂŶ ŚĞĂůƚŚ Œ
7 CNM - Au8 | Mechanism of Action Electron transfer (to - and - from) CNM - Au8 nanocrystals drives catalytic activity and increased energy production and utilization CNM - Au8® Nanocrystal Clean Surfaced, Highly Faceted Shape Enhances Catalytic Activity Mechanistic Effects Increased Energy Production & Utilization Vertices, Edges, & Facets Key to Catalytic Activity
Steve Vucic, MD Northcott Chair of Neurology The University of Sydney ϴ
Amyotrophic Lateral Sclerosis: Unmet need Professor Steve Vucic Northcott Chair of Neurology Brain and Nerve Research Centre Concord Clinical School University of Sydney 9
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):942 - 55. Brown et al. Neuroepidemiology. 2021;55(5):342 - 353. Kiernan et al. Nat Rev Neurol 2021 Feb;17(2):104 - 118. Winhammar et al. Lancet Neurol. 2005 Apr;4(4):229 - 38. 10
,PSURYLQJ&OLQLFDO7ULDO2XWFRPHVLQ$/6 Kiernan et al. Nat Rev Neurol 2021 Feb;17(2):104 - 118. 11
Improving Clinical Trial Outcomes in ALS Kiernan et al. Nat Rev Neurol 2021 Feb;17(2):104 - 118. 12 Represents a major limitation to developing effective therapies
ALS Is a Multistep Disease Process 9XFLFHWDO1HXURORJ\ $SU H H $O&KDODELHWDO/DQFHW1HXURO 1RY KWWSV IUHHYHFWRUPDSVFRP Linear Relationship Between Log Incidence and Log - Age Across Multiple ALS Populations 6 - step process Australia 6 - step process Australia 5 - step process South Korea 6 - step process Japan 6 - step process UK, Ireland, & Netherlands 13
Kiernan et al. Nat Rev Neurol 2021 Feb;17(2):104 - 118. 5HSXUSRVHG GUXJV Existing use Targeted pathogenic mechanism ALS trial identifier Primary outcome measures Outcome Tauroursodeoxy cholic acid Familial amyloid polyneuropathy (transthyretin) Endoplasmic reticulum stress, mitochondrial dysfunction NCT03488524 ALSFRS - R Reduction in functional decline NCT03127514 Survival Prolonged Mexiletine Cardiac arrhythmia Neuronal hyperexcitability NCT01811355 Daily cramp frequency Significant reduction in cramp frequency and severity NCT02781454 Change in resting motor threshold Pending NCT01849770 Safety Safe Ezogabine Epilepsy Neuronal hyperexcitability NCT02450552 Change in short - interval intracortical inhibition as measured by transcranial magnetic stimulation Pending Dimethyl fumarate Relapsing – remitting multiple sclerosis Neuroinflammation, upregulation of T reg cells ACTRN1261800053 4280 ALSFRS - R Pending IL - 2 Metastatic melanoma, metastatic renal cancer Neuroinflammation, cytokine signalling, upregulation of T reg cells NCT02059759 Change in number of T reg cells Pending NCT03039673 Survival Pending Edaravone Acute stroke Oxidative stress NCT01492686 ALSFRS - R Significant slowing of disease progression vs placebo Dolutegravir, abacavir and lamivudine (Triumeq) HIV infection HERVK expression NCT02868580 Safety Safe Ibudilast (MN - 166) Chronic obstructive pulmonary disease Neuroinflammation and microglial activation NCT02238626 Safety and tolerability Pending NCT02714036 Safety and tolerability Pending Tamoxifen Breast cancer Neuroinflammation, proteostasis NCT02166944 ALSFRS - R Not significant NCT00214110 Muscle strength Pending NCT01257581 ALSFRS - R No significant effect Memantine Advanced stages of Alzheimer disease Glutamate excitotoxicity NCT01020331 ALSFRS - R No significant effect NCT02118727 ALSFRS - R Pending NCT00409721 ALSFRS - R, FVC, muscle strength, cognitive function Pending NCT00353665 ALSFRS - R No significant effect Perampanel Partial - onset seizures Glutamate excitotoxicity (AMPA - receptor mediated) NCT03019419 ALSFRS - R Pending NCT03377309 Safety Pending NCT03793868 Motor threshold Pending NCT03020797 Safety Pending Rasagiline Parkinson disease Oxidative stress and apoptosis NCT01786603 ALSFRS - R No significant effect Masitinib Mastocytosis , severe asthma Neuroinflammation (microglia) NCT02588677 ALSFRS - R Significant slowing in functional decline NCT03127267 ALSFRS - R Pending Methyl - cobalamin Vitamin B12 deficiency Glutamate excitotoxicity NCT03548311 ALSFRS - R No significant effect Cu(II)ATSM PET ligand Copper deficiency NCT02870634 Safety Pending Arimoclomol Insulin resistance, complications of diabetes mellitus Impaired proteostasis NCT00244244 Safety Safe NCT00706147 Time to death, tracheostomy or permanent assisted ventilation Safe, no significant effect on outcomes NCT03491462 Combined assessment of function and survival Pending NCT03836716 Safety Pending 14
Whole System Approach Normalise Cellular Function – Energy Dependent Processes 15
Whole System Approach Normalise Cellular Function – Energy Dependent Processes 16
Robert Glanzman , MD FAAN Chief Medical Officer Clene Nanomedicine, Inc 17
18 (January 2020); FPFV 16 - Jan - 2020; 45 of 42 enrolled (Nov - 2020) Phase 2 Exploratory Endpoints • ALS disease progression • ALSFRS - R 6 - point decline • Quality of life (ALSSQOL - SF) • ALSFRS - R change • Other Electromyography ( SH i , NP i , MUSIX, MScan ) • Combined Joint - Rank (Survival + ALSFRS - R) % Change in Sum of Motor Unit Index (MUNIX) For the Abductor Digiti Minimi (ADM) , Abductor Pollicis Brevis (APB) , Biceps Brachii (BB) , Tibialis Anterior (TA) 1 ι Key Secondary Absolute MUNIX(4) change Forced Vital Capacity (FVC) 2 ι MUNIX
19 We thank FightMND for its philanthropic support of the RESCUE - ALS study
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)
21 Baseline Value mean ( sd ) Age ( yrs ) Sex n, (%) Male | Female Onset Site n, (%) Limb | Bulbar Months from Diagnosis Months from Onset FVC (% pred.) ALSFRS - R Score ENCALS Risk Profile 1 All (n=45) 59.1 (12.3) M: 26 (58%) F: 19 (42%) L: 33 (73%) B: 12 (27%) 3.1 (3.0) 15.9 (9.3) 81.5 (16.7) 38.7 (5.95) - 4.4 (1.8) CNM - Au8 30mg (n=23) 57.0 (13.3) M: 13 (57%) F: 10 (43%) L: 16 (70%) B: 7 (30%) 3.0 (2.9) 15.5 (7.6) 84.5 (18.3) 38.6 (6.6) - 4.6 (1.7) Placebo (n=22) 61.3 (10.9) M: 13 (59%) F: 9 (41%) L: 17 (77%) B: 5 (23%) 3.3 (3.2) 16.1 (10.9) 78.2 (14.5) 38.8 (5.4) - 4.2 (1.8) | Baseline Demographics ITT Population; Data on File, Clene Nanomedicine, Inc. 1 Van Eijk et al. Neurology 2021;97:528 - 536. ITT Population 89% of participants treated with riluzole as background standard of care
22 Neurophysiology MUNIX 1 Functional Status & QOL (ALSFRS - R, ALS Specific QOL) Pulmonary Function (Forced Vital Capacity) Disease Progression & Survival | Overview 1 2 3 4 1 Study was only powered for MUNIX(4) primary endpoint (Box 1) ITT Population ITT Population; Data on File, Clene Nanomedicine, Inc.
23 • Proof of Concept Established in ALS » MUNIX Wk36 non - significant; Wk12 efficacy signal (p<0.06) » 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 Results) » Protection from significant ALS disease progression (p<0.02) » Consistent evidence of treatment effect in clinically relevant endpoints: ALSFRS - R decline (p<0.04), ALSSQOL (p<0.02) » Evidence of survival benefit using ENCALS model • Well - tolerated with no safety concerns | Results Support Phase 3 Development
Matthew Kiernan, MD Bushell Chair of Neurology The University of Sydney 24
25 | Evidence for Motor Neuron Protection ITT Population; Data on File, Clene Nanomedicine, Inc. Primary Endpoint (MUNIX(4) %, LS Mean Change) All Randomized Limb Onset (Pre - specified)
Pulmonary Function Forced Vital Capacity (FVC)
27 ITT Population; Data on File, Clene Nanomedicine, Inc. Secondary Endpoint 1 (FVC % predicted, LS Mean Change, All Randomized) | Directional FVC Benefit 1 Study Not Powered for FVC change
28 ITT Population; Data on File, Clene Nanomedicine, Inc. Secondary Endpoint 1 (FVC % predicted, LS Mean Change, Continuous Slope, Post Hoc ) All Randomized Limb Onset (pre - specified) 1 Study Not Powered for FVC change | Directional FVC Benefit
Functional Status and QOL (ALSFRS - R, ALSSQOL - SF)
30 | Directional ALSFRS - R Benefit ITT Population; Data on File, Clene Nanomedicine, Inc. Exploratory (ALSFRS - R, Continuous Slope, LS Mean Change) All Randomized Limb Onset (Pre - specified)
31 | Significant Impact on ALSFRS - R Decline ITT Population; Data on File, Clene Nanomedicine, Inc. Exploratory (ALSFRS - R Responder Analysis, All Randomized)
32 | Significantly Improves Quality of Life ITT Population; Data on File, Clene Nanomedicine, Inc. Exploratory (ALSSQOL - SF, All Randomized)
Disease Progression & Survival
34 | Significant Impact on ALS Disease Progression ITT Population; Data on File, Clene Nanomedicine, Inc. Exploratory Endpoint (All Randomized) ALS Disease Progression defined as : • Death, or • Tracheostomy, or • Non - invasive ventilation, or • Gastrostomy tube
35 | Potential Survival Signal Data on File, Clene Nanomedicine, Inc. Exploratory Endpoint (Observed Survival vs. Predicted) ENCALS Predicted Observed Survival Start of Open Label Extension (Wk36+)
36 | 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) • TEAEs were predominantly mild - to - moderate and transient • Most common TEAEs associated with CNM - Au8 (aspiration pneumonia, n=3; nausea, n=2; abdominal discomfort, n=2) Safety Summary
37 CNM - Au8 These Results Support Cellular Energetic Impairment as a Therapeutic Target in ALS Catalytically Active Nanocrystal
Rob Etherington Clene Nanomedicine, Inc President & CEO 38
39 | Results Support Phase 3 Development • Proof of Concept Established in ALS » MUNIX Wk36 non - significant; Wk12 efficacy signal (p<0.06) » 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 Results) » Protection from significant ALS disease progression (p<0.02) » Consistent evidence of treatment effect in clinically relevant endpoints: ALSFRS - R decline (p<0.04), ALSSQOL (p<0.02) » Evidence of survival benefit using ENCALS model • Well - tolerated with no safety concerns
40 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 ι 2 ι Phase 3 Anticipated full unblinded data readout: 2H 2022
41 Anticipated Timeline & Upcoming Milestones 2020 - 2023 2021 2022 2020 2023
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