UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 5, 2021
Clene Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-39834 | 85-2828339 | ||
| (State or other jurisdiction | (Commission File Number) | (IRS Employer | ||
| of incorporation) | Identification No.) |
|
6550 South Millrock Drive, Suite G50 Salt Lake City, Utah |
84121 | |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code: (801) 676 9695
N/A
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||
| Common Stock, par value US$0.0001 per share | CLNN | The Nasdaq Stock Market LLC | ||
| Warrants, to acquire one-half of one share of Common Stock for $11.50 per share | CLNNW | The Nasdaq Stock Market LLC |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01 Regulation FD Disclosure.
On August 5, 2021, Clene Inc. (the “Company”) issued a press release announcing positive top-line results from its Phase 2 REPAIR clinical trials in Parkinson’s disease and multiple sclerosis. A copy of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
In connection with the press release issued on August 5, 2021, the Company released an updated corporate presentation (the “Corporate Presentation”) on its website, www.clene.com. A copy of the Corporate Presentation is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference. The Company plans to use its website to disseminate future updates to the Corporate Presentation and may not file or furnish a Current Report on Form 8-K alerting investors if the Corporate Presentation is updated.
The information furnished in this Item 7.01, including Exhibits 99.1 and 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, 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
1
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: August 5, 2021 | By: | /s/ Robert Etherington |
| Robert Etherington | ||
| President, Chief Executive Officer and Director | ||
2
Exhibit 99.1
Clene Reports
Positive Top-line Results from its Phase 2 REPAIR Clinical
Trials in Parkinson’s Disease and Multiple Sclerosis
Achieved a statistically significant increase in the Phase 2 program’s primary endpoint
(mean change in brain NAD+/NADH ratio)
CNM-Au8Ò, a gold nanocrystal suspension, significantly improved brain energetic metabolism
Trial results demonstrate consistent brain target engagement in PD and MS patients
Data provide clinical proof-of-mechanism and
support the potential of CNM-Au8 to drive meaningful
neurological functional improvements in the treatment of neurodegenerative disorders
SALT LAKE CITY, August 5, 2021 -- Clene Inc. (NASDAQ: CLNN) along with its subsidiaries “Clene” and its wholly owned subsidiary Clene Nanomedicine, Inc., a clinical-stage biopharmaceutical company dedicated to the treatment of neurodegenerative disease using nanotechnology to treat energetic failure, today reported positive top-line results from the Phase 2 REPAIR clinical trials investigating the improvement of brain energetic metabolism in Parkinson’s disease (PD) and multiple sclerosis (MS).
The objective of the REPAIR clinical trial program was to demonstrate the effects of Clene’s energy-enhancing nanotherapeutic, CNM-Au8Ò, on brain energy metabolites in two sister studies of patients with Parkinson’s disease (REPAIR-PD) and multiple sclerosis (REPAIR-MS). Patients were imaged using 31phosphorous magnetic resonance spectroscopy, an innovative non-invasive brain imaging technique, before and after 12 or more weeks of daily oral dosing with CNM-Au8. End of treatment results at week 12 were compared to baseline in 24 patients, 13 patients in REPAIR-PD and 11 patients in REPAIR-MS (all study participants with repeat imaging data).
The results for the primary endpoint, the mean change in the brain NAD+/NADH ratio (the ratio of the oxidized to reduced form of nicotinamide adenine dinucleotide), demonstrated a statistically significant increase by an average of 0.589 units (10.4%) following 12-weeks of treatment with CNM-Au8 (p=0.037, paired t-test), in the pre-specified integrated analysis of the REPAIR-PD and REPAIR-MS studies. Key secondary endpoints, mean change from baseline in the NAD+ fraction and NADH fraction of the total NAD pool, were concordant with the primary endpoint, demonstrating the NAD+ fraction increased (p=0.026), while the NADH fraction decreased (p=0.026). The individual results for these sister studies demonstrated consistent statistical trends toward improvement in the NAD+/NADH ratio with results of p=0.11 and p=0.14, for REPAIR-PD and REPAIR-MS, respectively.
Analyses of pre-specified exploratory endpoints demonstrated that homeostatic equilibrium was achieved across essential energetic metabolites, including adenosine triphosphate (ATP), intracellular phosphorous (Pi(in)), phosphocholine (PC), and phosphorylation potential index (b-ATP/ADP*Pi(in)). For these metabolites and indices, the percent change from baseline to the week 12 end-of-treatment was significantly inversely correlated with baseline levels, such that participants with relatively lower baseline levels demonstrated increases, and subjects with relatively higher baseline levels demonstrated a re-balancing effect with levels decreased to the baseline population mean. This relationship was observed both on an integrated basis across the two studies, and independently in both REPAIR-PD and REPAIR-MS, respectively, for: b-ATP (r2 = 0.82, p < 0.0001; r2 = 0.71, p = 0.0011), phosphorylation potential (r2 = 0.72, p = 0.0002; r2 = 0.68, p = 0.0019), PC (r2 = 0.78, p < 0.0001; r2 = 0.54, p = 0.0095), and Pi(in) (r2 = 0.42, p = 0.017; r2 = 0.48, p = 0.018). In addition, multiple other 31phosphorous energetic metabolites and indices showed consistent homeostatic changes, which will be presented in publications and at forthcoming scientific congresses.
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Robert Glanzman, MD FAAN, Clene’s Chief Medical Officer, commented on the REPAIR results, “We believe the REPAIR program represents a critical breakthrough for Clene, demonstrating that catalytically active CNM-Au8 improves energy production and utilization in the brains of people with Parkinson’s disease and multiple sclerosis. Using a novel, noninvasive brain imaging approach, the study demonstrated that a key driver of cellular ATP energy production, the ratio of NAD+/NADH, was significantly increased in the brains of patients after three months of daily CNM-Au8 oral administration. Remarkably, the data also show a significant rebalancing of brain beta-ATP levels in these patients, a metabolic response to treatment that suggests improved ATP energy efficiency. Our next step will be to demonstrate that these brain energetic changes result in clinically meaningful results in patients with Parkinson’s disease and multiple sclerosis.”
CNM-Au8 treatment was well tolerated with all treatment emergent adverse events reported as predominantly mild and unrelated to study drug. There were no serious adverse events or treatment discontinuations related to adverse events in either study. As expected, the clinical endpoint of MDS-UPDRS in REPAIR-PD showed no worsening of clinical status across the study population (safety endpoint). The REPAIR-MS clinical endpoints included the modified MS functional composite (m)MSFC (exploratory endpoint), which showed consistent improvements across its four scales of symbol digit modalities test (SDMT), low contrast letter acuity (LCLA), nine-hole peg test (9HPT), and timed 25-foot walk test (T25FW).
Rob Etherington, Clene’s Chief Executive Officer, concluded, “Clene is a company driven to pioneer the development of cellular energy-enhancing nanotherapeutics for the treatment of neurodegenerative diseases. We believe the study results also strongly support Clene’s ongoing Phase 2 and Phase 3 clinical programs investigating how CNM-Au8’s neuro-reparative and neuroprotective properties may impact disease progression in amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson’s disease, and may be broadly applicable to the treatment of neurodegenerative diseases.”
REPAIR-PD study results will be presented at the upcoming International Parkinson and Movement Disorders Society, MDS Virtual Congress 2021 meeting, September 17-22, 2021. REPAIR-MS results will be presented at the upcoming 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, October 13-15, 2021.
The REPAIR program was conducted at the University of Texas Southwestern in collaboration with Dr. Richard Dewey, Jr., Professor in the UT Southwestern Medical Center Department of Neurology and Director of the Clinical Center for Movement Disorders (REPAIR-PD), Dr. Benjamin Greenberg, Professor in the UT Southwestern Medical Center Department of Neurology and Vice Chair of Clinical & Translational Research (REPAIR-MS), and Jimin Ren, PhD, Associate Professor at the UT Southwestern Advanced Research Imaging Center (both studies).
Clene thanks the study participants who directly supported this novel clinical research in the REPAIR program, the research dedication of the UT Southwestern principal investigators, Dr. Richard Dewey Jr. and Dr. Benjamin Greenberg, research colleagues at the Neuro Translational Research Center, and the advanced imaging techniques developed by Jimin Ren, PhD, of the UT Southwestern Advanced Research Imaging Center.
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About REPAIR-PD and REPAIR-MS
REPAIR-MS and REPAIR-PD are Phase 2 single-center, active-only, sequential group studies examining the brain metabolic effects, safety, pharmacokinetics and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with MS within 15 years of screening or in patients with PD who have been diagnosed within three years of screening. Investigators and participants are blinded to dose. Participants received orally delivered CNM-Au8 daily each morning for 12 weeks. Participants undergo 31P-MRS brain imaging scans to semi-quantitatively measure central nervous system (CNS) energetic metabolites at baseline, prior to administration of drug, and at the end-of-study following at least 12 weeks of exposure to CNM-Au8. The objective of these studies is to demonstrate target engagement for CNM-Au8 on CNS biomarkers related to energetics and neuronal membrane stability in patients with MS and PD. The studies are taking place at the University of Texas Southwestern Medical Center with a team of internationally recognized experts in brain imaging and treatment of disorders of the CNS. For more information see ClinicalTrials.gov Identifiers: NCT03993171 and NCT03815916.
About CNM-Au8Ò
Clene’s lead drug candidate, CNM-Au8, is an aqueous suspension of catalytically-active, clean-surfaced, faceted gold nanocrystals. Resulting from a patented manufacturing breakthrough, the catalytically active nanocrystals of CNM-Au8 drive critical cellular energy producing reactions in the brain that enable neurorepair 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 has demonstrated safety in Phase 1 studies in healthy volunteers and has shown both remyelination and neuroprotective effects in multiple preclinical (animal) models. 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-Au8Ò, a gold nanocrystal suspension, is a federally registered trademark of Clene Nanomedicine, Inc.
About Clene
Clene, a clinical-stage biopharmaceutical company focused on neurodegenerative disease treatments, is leading the way by using nanotechnology to treat energetic failure, which underlies many neurological diseases. Clene has innovated a novel nanotherapeutic platform to create a new class of drugs. Clene’s lead drug candidate, CNM-Au8, is an aqueous suspension of catalytically-active, clean-surfaced, faceted gold nanocrystals that drive critical cellular energetic metabolism in the central nervous system (CNS). CNM-Au8 increases cellular energy production to accelerate neurorepair and improve neuroprotection. CNM-Au8 is currently being evaluated in a Phase 3 registration trial in amyotrophic lateral sclerosis (ALS), a Phase 2 trial examining disease progression via a novel electromyography technique in patients with early ALS, a Phase 2 trial for the treatment of chronic optic neuropathy in patients with stable relapsing multiple sclerosis (MS), and Phase 2 brain target engagement studies in patients with Parkinson’s disease (PD) and 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
Gwendolyn Schanker
LifeSci Communications
(269) 921-3607
gschanker@lifescicomms.com
Investor Contact
Bruce Mackle
LifeSci Advisors, LLC
(929) 469-3859
bmackle@lifesciadvisors.com
Source: Clene Inc.
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Exhibit 99.2
CLNN (NASDAQ)
Forward Looking Statements 2 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 - 4 /A 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 .
Lanxide Corporation Dupont Lanxide Composites Lanxide Armor Company Lanxide Performance Materials Lanxide Electronic Components CDO CLENE | Management Team Ted Jeong , DM 3
4 Clene Nanomedicine Cash on hand: 48M End of Q1 + PIPE & Venture debt of $24M Topline data from One Registrational Trial 1 by 1H 2022 and 4 Phase 2 Trials 2 by end of 2021 >180 patient years of CNM - Au8 clinical exposure CNM - Au8® in clinical development as the first energetic catalyst to repair & improve neurological function Manufacturing expansion in progress, preparing for possible commercialization in 2023 Strong IP: 130+ patents on Cle a n - S u r fac e - Nanocrystal technology (CSN®) platform 1. HEALEY - ALS: https://clinicaltrials.gov/ct2/show/NCT04414345?term=CNM - Au8&cond=ALS&draw=1&rank=1 . 2. RESCUE - ALS: https://clinicaltrials.gov/ct2/show/NCT04098406?term=CNM - Au8&cond=ALS&draw=1&rank=3 . REPAIR - PD: https://clinicaltrials.gov/ct2/show/NCT03815916?term=cnm - au8&draw=2&rank=. REPAIR - MS: https://clinicaltrials.gov/ct2/show/NCT03993171?term=cnm - au8&draw=2&rank=3 . Anti - viral study: https://clinicaltrials.gov/ct2/show/NCT04610138.
Novel electro - chemistry platform produces catalytic Clean Surface Nanocrystal drugs designed to avoid toxicities associated with synthetic chemistry 130+ Gr a n t ed Patents CLENE | Platform & Pipeline (Anticipated Launch in 2021) Brain Imaging Biomarker Study Brain Imaging Biomarker Study 1H 2022 2H 2021 O ngo i n g 5 2H 2022* 2H 2021 2H 2021 1H 2024 2H 2021 *Subject to ongoing COVID - 19 related site research restrictions generally implemented to protect MS patients taking standard - of - care immunosuppressive therapies Bioenergetic Na noc a t a lyst
Chinese & Ayurvedic Gold Preparations (China, Arabia, India) Monoatomic Gold Salts for Rheumatoid Arthritis (IM Sodium Aurothiomalate; IM Aurothioglucose; Oral Auranofin) gold 3,4,5 - triacetyloxy - 6 - (acetyloxymethyl oxane - 2 - thiolate; triethylphosphanium Au ( Gold) 2020+ Catalytic Clean Surfaced Faceted Gold Nanocrystals 1950s – 2000s 2500 – 1000 BC 1 9 30 – 1980s Surface Modified and Functionalized Colloidal Gold Particles Drug Carriers; Photothermal Therapy 6 Evolution of Gold as a Therapeutic Modality Pioneering Bioenergetic Na noc a t a l y s i s Clene’s Patented Breakthrough
CNM - Au8® | Energy Enhancing Nanotherapeutic Improved Cellular Energy Production & Utilization E nergy > 100 Trillion Nanocrystals per 60 mL Dose (At 30mg) Oral Suspension; Once Daily 13 nm Median Diameter (Ribosome = 20 - 30 nm) Clean Surfaced Faceted Nanocrystal Novel mechanism of action to address a range of CNS diseases CNM - Au8 Nanocrystal Cellular 7
CNM - Au8 | Integrating Physics With Biology Electron Transfer Is Fundamental to Energy Production Surface Based Catalytic Activity Electrons (e - ) Move Freely Across Nanocrystal Surface Vertices, Edges, & Faces Key to Catalytic Activity AuNP Catalyzed Oxidation of Ascorbic Acid 1 a. Rayleigh scattering measured by dark field microscopy of surface plasmon resonance of scattering spectra of the AuNP decahedron before and at 1 , 2 , 3 and 60 min after electron injection by ascorbate ions . b. Spectral shift as a function of time for the catalysis reaction and for the control experiment .. 1 Novo et al. Nature Nanotech 3, 598 – 602 (2008). Clean - Surfaced Nanocrystals Up to 4,600 e - per second per nanocrystal 1 8
Treating Energetic Failure | Common Pathological Mechanism In Neurodegenerative Disorders (MS, ALS, PD) Respiratory In s u ff icie ncy D y sp h agia/ Dysarthria Cognitive Im p a i rm ent Muscle Weakness/Atrophy ALS Neuronal Metabolic Failure MS Oligodendrocyte Remyelination Failure and Neuronal Die - Off Vandoorne et al. Acta Neuropathologica (2018) 135:489 – 509. Rone et al. J Neurosci. 2016 Apr 27;36(17):4698 - 707. Cognitive Im p a i rm ent Spinal Cord (Move m ent) Dexterity & Coo r di n atio n Visual Im p a i rm ent Neu r o n Ac ti v at e d A str ocy te Demyelination Oligodendrocyte Myelin She ath Com pr om is e d Axon Dendritic R e tra c ti o n Neuromuscular Junction Impairment A c tivat e d Astrocyte 9
CNM - Au8 | MOA Therapeutic Effects a Nicotinamide Adenine Dinucleotide a 10
11 CNM - Au8 | Significant Global Opportunity 707,158 103,903 828,703 596,407 256,455 1,407,701 0 4 00 , 0 0 0 800,000 1 , 2 00 , 00 0 1 , 6 00 , 0 0 0 U . S . C a n a d a W. Europe Central/E. Europe J a p a n C h i n a Est. Diagnosed PD Patients by Region Source: Lancet Neurol. 2018 Nov;17(11):939 - 953. PARKINSON’S DISEASE ~7M pts globally; $6B projected by 2025 3 2 ND most common neurodegenerative disorder; only symptomatic treatments 62,531 10,013 71,288 10,946 13,893 54,405 0 2 0 , 00 0 40,000 6 0 , 00 0 8 0 , 00 0 U . S . C a n a d a W. Europe C e n t r a l / E . E ur o p e J a p a n C h i n a Est. Diagnosed MND Patients by Region Source: Lancet Neurol. 2018 Dec;17(12):1083 - 1097. MND includes amyotrophic lateral sclerosis, spinal muscular atrophy, hereditary spastic paraplegia, primary lateral sclerosis, progressive muscular atrophy, and pseudobulbar palsy MOTOR NEURON DISEASE (ALS, Other Orphan Disorders) ALS sales >$1B globally by 2029 1 . Current drugs are largely ineffective, mostly generic Source: Lancet Neurol. 2019 Mar;18(3):269 - 285 511,855 79,419 543,862 204,591 46,249 103,194 0 1 5 0 , 0 0 0 300 , 00 0 4 5 0 , 0 0 0 600,000 U . S . C a n a d a W. Europe C e n t r a l / E . E ur o p e J a p a n C h i n a Est. Diagnosed MS Patients by Region MULTIPLE SCLEROSIS ~2.5M pts globally; $23B market 2 Only approved treatments are immunomodulators 1 Clarivate, DRG, ALS 2020 . 2 Westad et al. 2017, doi:10.1038/nrd.2017.107. 3 Parkinson’s Market Data Forecast, February 2020.
12 CNM - Au8 | Evidence for Energetic Improvement Therapeutic Activity Across Remyelination + Neuroprotection Models 1 Robinson et al. Sci Rep. 2020, DOI: 10.1038/s41598 - 020 - 58709 - w. . 2 Ho et al. Society for Neuroscience Meeting, 2019. Ho et al. Motor Neuron Disease Associating Meeting, 2019. Data on File, Clene Nanomedicine, Inc. 1 2
CNM - Au8 | MOA & Remyelination Data Published Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936. doi: 10.1038/s41598 - 020 - 58709 - w Lysolecithin R emye li n ati on Data 13
Successful Phase 1 First - In Humans Safety Trial + Chronic Animal Toxicity Studies Phase 2 Brain Target Engagement 31 P - Magnetic Resonance Phase 2 MS Clinical Remyelination & Neurorepair CNM - Au8 | Clinical Program Overview Phase 3 Phase 2 & 3 ALS Clinical Neurorepair Phase 2 14
CNM - Au8 | Clean Toxicology Findings All Studies Resulted in No Adverse Effect Level (NOAEL) a Standard ICH M3(R2) Toxicology Program Genotoxicity In Vitro & In Vivo (Rodent) Safety Pharmacology CNS, CV, Renal Dose Range Finding Rodent, Minipig Single Dose Tox icokin e tic s Canine Multi - Dose Tox icokin e tic s Canine (7 - Day) MTD Toxicokinetics Canine (4 - Wk) Max Feasible Tox icokin e tic s Rodent (1 - Wk, SQ) Max Feasible Tox icokin e tic s Canine (3 - Wk) Chronic Toxicity Rodent Rodent (6 - Month) Chronic Toxicity Canine Canine (9 - Month) High Dose Toxicokinetics Rodent (3 - Wk) a NOAEL = No Dose Limiting Toxicities Observed Carcinogenicity Dose Range Finding rasH2 (1 - Month) 15
• Most frequent TEAEs by System Organ Class: Nervous/GI - Nearly all of the TEAEs were Grade 1 severity (mild) • No serious TEAEs, TEAEs leading to discontinuation of treatment, or TEAEs considered severe, life - threatening, or resulting in death • No dose responsive TEAEs observed in SAD or MAD • Single - ascending dose – 4 cohorts of 8 subjects plus one repeat (n=40) – 15, 30, 60, 90 mg – 3:1 randomized ( ac t ive:con t rol) – 1 dose; 17 - day follow - up • Multi - ascending dose – 4 cohorts of ~12 subjects (n=46) – 15, 30, 60, 90 mg – 3:1 randomized ( ac t ive:con t rol) – 21 days daily dosing + follow - up (Up to 50 days) Phase 1 First In Human Study Completed (n=86) CNM - Au8 | Well Tolerated; No Dose - Limiting Safety Issues + Long - Term Extension 16 + Long - Term Extension Phase 2 & 3 Clinical (>180 Years Exposure) Up to 89 Weeks Exposure in Clinical Trials; Up to 96 Weeks in ALS Expanded Access + Long - Term Extension
17 • Difference in brain NAD+ and NADH fraction at Week 12 - 16 • Difference in bioenergetic metabolites (e . g . , ATP, PCr, 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 ι 2 ι CNM - Au8 Effects on Brain Energetic Metabolites A Phase 2 , Open Label, Sequential Group, Investigator Blinded Study of Magnetic Re sonance Spectro s co p y ( 31 P - M R S) to A sses s the Effects of C N M - A u 8 f or t h e Bioe n ergetic I m prove m ent of Impaired Neuronal R edox State (REPAIR) Visit Safety Assessment Dispense Drug Visit Safety Assessment Dispense Drug Visit Primary Endpoint Visit F ollo w - up Visit Ba seline Assessments Dispense Drug - 16 N = Up to 15 per dosing cohort (7.5, 15, 30, or 60 mg) Phase 2 Top - Line Results Repair - PD: 2H 2021 Repair - MS: 2H 2021 *Subject to ongoing COVID - 19 related site research restrictions generally implemented to protect MS patients taking standard - of - care immunosuppressive therapies Exploratory
18 NAD + /NADH | Age Related Decline By 31 P - MRS Imaging Zhu et al. Proc Natl Acad Sci USA . 2015 Mar 3;112(9):2876 - 81. Closed squares = averaged data by age group: 21 – 26 yrs, 33 – 36 yrs, and 59 – 68 yrs old; Open squares= individual subject values ~0.5% NAD + /NADH unit decline per decade (~0.13 mV units per year) NAD + Decline &. NADH Increase (Aging Change by Decade)
CNM - Au8 Improved Brain Energy Ratio Elevated NAD+/NADH Ratio 19 Data on File, Clene Nanomedicine, Inc. Phase 2
(January 2020); FPFV 16 - Jan - 2020; 45 of 42 enrolled (Nov - 2020) Phase 2 Anticipated full unblinded data readout: 2H 2021 Exploratory Endpoints • Other Electromyography (SH i, NP i, MUSIX, MScan) • ALSFRS - R • Change in Rate of ALSFRS - R progression • QOL • Combined Joint - Rank (Survival + ALSFRS - R) Change in Sum of Motor Unit Index For the Abductor Digiti Minimi (ADM), Abductor Pollicis Brevis (APB), Biceps Brachii (BB), Tibialis Anterior (TA) 1 ι Key Secondary: Forced Vital Capacity 2 ι 20
Predictive Endpoints of Disease Progression Clinical E ndpoint s • ALSFRS - R • Pulmonary Function (Vital Capacity) • Mortality • Loss of Motor Units Motor Unit Index (MUNIX) Measuring ALS Disease Progression Electromyography: Predictive Biomarker of Clinical Progression MUNIX Longitudinal Progression 21
Primary Endpoint: Emerging Evidence of MUNIX Benefit Phase 2 Improvement Robert Glanzman MD FAAN, et al. “A Blinded Interim Update on RESCUE - ALS: A Randomized, Placebo - Controlled, Phase 2 Study to Determine the Effects of CNM - Au8 to Slow Disease Progression in Amyotrophic Lateral Sclerosis” Presented at ENCALS 2021 Virtual Meeting, 12 - May - 2021. 22
SVC Avg. Slope Decline (% points/month) Slope Est. (9 - mo n t h s) Empower ( − 2.73%) - 24.6% Benefit ( − 2.74%) - 24.7% PRO - ACT ( - 2.90%) - 26.1% − 10. 5 − 19. 6 − 6. 7 Andrews et al. JAMA Neurol. 2018;75(1):58 - 64. Phase 2 Robert Glanzman MD FAAN, et al. “A Blinded Interim Update on RESCUE - ALS: A Randomized, Placebo - Controlled, Phase 2 Study to Determine the Effects of CNM - Au8 to Slow Disease Progression in Amyotrophic Lateral Sclerosis” Presented at ENCALS 2021 Virtual Meeting, 12 - May - 2021. 23 Secondary Endpoint: Emerging Evidence of Clinical Benefit | Forced Vital Capacity
Exploratory Endpoints • Combined Joint Rank (Survival + ALSFRS - R) • Voice pathology • PRO (ALSAQ) • Pharmacodynamic markers Slow Vital Capacity Hand Held Dynamometry Change in ALSF RS - R Registration Study: 24 - Week Treatment Period (3:1 randomization, 120 active [30mg, 60mg]: 40 placebo) (July 2020) (n=160) (n=160) (n=160) 1 ι 2 ι Phase 3 Multiple Independent Regimens with Pooled Placebo Anticipated full unblinded data readout : 1 H 2022 24
Exploratory Endpoints Treatment of Vis ual Pathway Deficits I n Chronic O ptic N europathy for A ssessment of R em y elination 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=150) • Optical Coherence Tomography (OCT) • Multi - focal VEP Amplitude & Latency • Full field - VEP Amplitude & Latency • MRI Endpoints • Visual Function (High Contrast) • QOL / EDSS 1 ι 2 ι Change Composite Clinical Response 9HPT / SDMT / T25FW / LCLA / EDSS Phase 2 - 42 to - 1 24 - Week Blinded Fixed Treatment Period Up to 24 - Week Blinded Extension Period (Until LPLV 24Wk Visit) LPLV Anticipated top - line unblinded data: 2H 2022* 25 *Subject to ongoing COVID - 19 related site research restrictions generally implemented to protect MS patients taking standard - of - care immunosuppressive therapies
LCLA Phase 2 Primary: Functional Visual Improvement LCLA Correlates with clinically meaningful deficits in QOL, EDSS and MSFC, MRI, and OCT MS Functional Endpoints Phase 2 Exploratory: Neuroprotection/Remyelination Endpoints The Visual System is a Window into the Brain ( T L T V + E = 1 2 3 4 5 6 7 8 9 KEY 9 - Hole Peg Test 26 Symbol Digit Modalities Timed 25 - Ft Walk Measuring MS Functional Improvement
LCLA (Best - Corrected) Emerging Evidence of Clinical Improvement Glanzman, R., H. Beadnall, M. T. Hotchkin, A. Klistorner, M. Barnett, R. Sergott, A. Rynders, K. S. Ho, and Mark G. Mortenson. “Update to a Phase 2 clinical trial of catalytic gold nanocrystals, CNM - Au8, for the treatment of chronic optic neuropathy.” Presented at the ACTRIMS Forum 2021, February 26, 2021. SD M T 6 - Component Integrated (m)MSFC Phase 2 Improvement Improvement Improvement ( T L T V + E = 1 2 3 4 5 6 7 8 9 KEY ( T L T V + E = 1 2 3 4 5 6 7 8 9 KEY Z - Score change compared to the least - affected patients at Baseline (with EDSS <= 1.5) 27 All Available Values (by Completed Subject Visit) Mixed Effects Model, Dunnett’s test for multiplicity; * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001
C S N 28 ® Clean surface nanocrystal (CSN) therapeutics Trade Secrets Patent Status Issued & Allowed Patents 130+ Pending Applications >30 Total Patents/ Applications >160 Patent Description Process And Me thod/ D e vic e (Clean Surface; Gold CSN) State of Matter (CNM - Au8) Method of Use (Prevent Demyelination & MoA) Method of Use (Bi - Metallic Au/Pt; Antimicrobial) Plasma Conditioning Electrode Design & Cycling Trough Flow, Temp, Pressure Concentration & Filtration Strong Intellectual Property Extensive Patent Portfolio With Protection Through 2035 a & Proprietary Trade Secrets; Plus 7 - year Orphan Drug Designation a With Patent Restoration Term (assuming 5 - year extension).
Clene | Proprietary Nanocrystal Manufacturing In - House ISO8 Clean Room Clinical Production in North East, MD Validated CMC Processes 29 Designed to be Scalable to Commercialization Patented H ydro - electr o - Crystallization Proprietary Trade Secrets
Anticipated Timeline & Investor Catalysts 2020 - 2023 30
31 Unmet Medical Need & Market Opportunity Lead Asset: CNM - Au8 for Neuro Repair Clinical D e v e lo p m en t Pipeline Strong IP Portfolio Financials CNM - ZnAg for COVID - 19 CLENE | Investment Highlights • Energy enhancing nanotherapeutic • Robust Preclinical Remyelination & Neuroprotection Data Across Multiple Animal Models in: MS, ALS, and Parkinson’s Disease • NOAEL Findings From All Toxicity Studies • Acceptable Phase 1 Safety Profile • Up to 89 Weeks Exposure in Clinical Trials; Up to 97 Weeks in ALS Expanded Access (EAP) • Two Phase 2 Brain Target Engagement Studies in PD and MS with Top Line Results Reported Aug 2021 • Three Phase 2 POC Studies in ALS, MS, and COVID with Results Anticipated in the next 12 - 18 Months • Phase 3 ALS Registrational Trial in with Full Results Anticipated in 1H 2022 • Ongoing ALS Early Access Program • USA FDA Granted ALS Orphan Drug Designation • CLNN (NASDAQ) • $ 31 . 9 M USD (Gross) Raised via SPAC merger + PIPE ( 2020 ) • Cash on Hand at end of Q 1 2021 of $ 48 . 0 M (Unaudited) • Anticipated Cash Runway to EOY 2022 • $ 114 M USD Raised Privately (Series A - D) • +$16.7M in Additional Grant and Indirect Financial Support for ALS and MS Phase 2 & 3 Clinical Programs • $24.3M USD (Gross) Raised via PIPE + Venture debt for MFG • Zinc - Silver Antiviral + Immune Support • Phase 2 Trial in Brazil To Treat Acutely Symptomatic Non - Hospitalized COVID - 19 Patients Underway 1st Endpoint: Prevention of Hospitalization 2nd Endpoint: Time to S y m p t o m at i c Imp r o vemen t (Up to 28 Days) • Results Anticipated 2H 2021 • 130+ Issued Patents Worldwide; 30+ Pending Patent Applications • State of Matter Claims Cover Myelin Protection M ech a nisms , Remyelination, and Neuroprotection to 2035 (with Patent Restoration Term) • Manufacturing Device and Process Patents to 2030 and Beyond • No Effective Disease - Modifying Drugs for ALS or PD • No MS Therapies Clinically Impact Remyelination & Neurorepair • Remyelination and Neurorepair Sales Could Exceed $10B per annum 1 ALS is a Lethal Motor Neuron Disease With Suboptimal Therapies PD is Highly Prevalent With No Disease Modifying Treatments 1 Data on file, Clene Nanomedicine, Inc.
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