UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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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.
Healey ALS Platform Trial Topline Results
On October 3, 2022, Clene Inc. (the “Company”) issued a press release announcing topline results for CNM-Au8® in the HEALEY ALS Platform Trial. The Company also hosted a conference call and webcast on October 3, 2022 to discuss the topline results. A copy of the press release and presentation are furnished as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K (the “Current Report”) and are incorporated herein by reference.
Corporate Presentation
In connection with the press release announcing topline results for CNM-Au8 in the Healey ALS Platform Trial, the Company released an updated corporate presentation (the “Corporate Presentation”) on its website, invest.clene.com. A copy of the Corporate Presentation is furnished as Exhibit 99.3 to this Current Report 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 alerting investors if the Corporate Presentation is updated.
The information furnished in this Item 7.01, including Exhibit 99.1, Exhibit 99.2, and Exhibit 99.3, 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, as amended, 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
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Exhibit Description |
99.1 |
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99.2 |
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99.3 |
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104 |
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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.
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CLENE INC. |
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Date: October 3, 2022 |
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/s/ Robert Etherington |
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Robert Etherington |
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President and Chief Executive Officer |
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Exhibit 99.1
Clene Reports Topline Results Demonstrating Survival Signal
for CNM-Au8® in Healey ALS Platform Trial
SALT LAKE CITY, Oct. 3, 2022 -- 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, today announced topline study results showing a survival benefit in the Healey ALS Platform trial of CNM-Au8®, an investigational gold nanocrystal suspension, in participants with amyotrophic lateral sclerosis (ALS).
The primary endpoint of slope of change in ALS Functional Rating Scale Revised (ALSFRS-R) scores adjusted for mortality was not significant (2% slowing, 95% CI: -20% to +19%) at 24 weeks. Secondary endpoints of Combined Assessment of Function and Survival (CAFS) and slow vital capacity (SVC) were also not met at 24 weeks across the combined 30 mg and 60 mg CNM-Au8 doses.
The prespecified exploratory analyses of the secondary survival endpoint demonstrated a >90% reduction in risk of death alone or in risk of death/permanently assisted ventilation at 24 weeks, when adjusted for baseline imbalances in risk (p=0.028 to p=0.075, unadjusted for multiple comparisons) with the CNM-Au8 30 mg dose. These survival results were statistically consistent for the 30 mg dose between the regimen only and full analysis sets, which included shared placebo from other regimens participating in the Healey ALS Platform trial (Regimens A, B, and D). This survival signal is consistent with results previously reported by Clene in the Phase 2 RESCUE-ALS trial with CNM-Au8.
The full analyses, including data on biomarkers of neurodegeneration and exploratory efficacy results, are expected later in 2022. The open-label extension will continue to follow participants and provide data updates in the future. Clene is in discussions with the Healey & AMG ALS Center to offer a broader EAP of CNM-Au8 30 mg for eligible participants of closed regimens and others.
Based on these topline findings, Clene has selected the CNM-Au8 30 mg dose for continued development in ALS. The CNM-Au8 60 mg dose did not demonstrate a survival benefit.
CNM-Au8 was well-tolerated, and there were no drug-related serious adverse events or significant safety findings reported.
“There remains a high unmet medical need for treatments for people living with ALS. The potential survival benefit with CNM-Au8 at 30 mg is encouraging. Additional pre-specified exploratory analyses of both the RCT and open-label extension part of the study will be shared once available,” said Merit Cudkowicz, M.D., MSc, principal investigator and sponsor of the Healey ALS Platform Trial, director of the Sean M. Healey & AMG Center for ALS, chief of the Department of Neurology at Massachusetts General Hospital, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “We are thankful to the many people who participated in this study. We will learn from these results and continue to use these data to inform future advances in ALS trial design,” she concluded.
Robert Glanzman, M.D., FAAN, Clene’s Chief Medical Officer, said, "We are very pleased to see a survival benefit in a broad population of people who had already been living with ALS for up to three years. Importantly, this is the second Phase 2 study
demonstrating a survival benefit following CNM-Au8 treatment. CNM-Au8’s mechanism of enabling energy metabolism and efficiency may not be reflected in the slope of ALSFRS-R change after only 24 weeks of treatment. These Healey ALS Platform Trial results support advancement of the CNM-Au8 30 mg dose. We look forward to discussions with U.S. regulatory authorities at an End of Phase 2 meeting for our CNM-Au8 development program in ALS.”
Rob Etherington, Clene’s President and CEO, added, “The survival results from this trial together with the consistent benefit seen in the open-label extension of the Phase 2 RESCUE-ALS trial, based on up to 31.5 months of long-term follow-up, support the rationale for treating neuronal and glial energetic failure with CNM-Au8. We have now completed multiple Phase 2 studies in ALS and MS, building a body of evidence demonstrating that CNM-Au8 supports cellular energy production, improving myelination and neuronal viability. We believe supporting brain energetic capacity translates to patient benefit, including survival. We will work closely with regulatory health authorities, ALS experts, and patient representatives to determine the proper path for FDA and EMA approval. Clene remains committed to advancing CNM-Au8 clinical programs to the ultimate goal of FDA approval. To support this effort, Clene is pursuing paths, including strategic partnerships, and is in dialogue with various potential partners.”
Michael Hotchkin, Clene’s Chief Development Officer, concluded, “We thank the ALS community for its support of the Healey ALS Platform trial. Furthermore, we thank the site investigators for their research excellence and dedication to patients, and we thank Dr. Cudkowicz and the team at the Healey & AMG ALS center for their leadership and for the development of the platform trial. Most importantly, we thank people living with ALS who participated in the study and their families for their effort and willingness to engage in clinical research.”
Conference Call and Webcast Information
Clene will host a conference call and webcast at 8:30 am EDT to discuss the Healey ALS Platform trial topline results for CNM-Au8. Members of Clene’s executive team will lead the discussion.
Time and Date: 8:30 a.m. EDT on Oct. 3, 2022
Investors: 1 (888) 660-6179 (toll-free) or 1 (929) 203-1946 (toll)
Conference ID: 5318408
Press *1 to ask or withdraw a question, or *0 for operator assistance.
To access the live webcast, please register online at this link. Participants are requested to register at a minimum 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months. A live audio webcast of the call will be available on the Investors section of the Company’s website Events page. An archived webcast will be available on the Company’s website approximately two hours after the event.
About the Healey ALS Platform Trial
The Healey ALS Platform Trial is a perpetual multi-center, randomized, double-blind, placebo-controlled program designed to evaluate the efficacy and safety of multiple investigational products utilizing a shared placebo group in people living with amyotrophic lateral sclerosis (ALS). In the CNM-Au8 regimen, 161 participants were randomized to 30 mg CNM-Au8, 60 mg CNM-Au8, or placebo as adjunct to standard of care for a 24-week treatment period. Active drug was offered to all participants who were eligible and elected to continue into the open-label extension. The primary outcome of the trial was the change in disease severity over time as measured by ALSFRS-R through 24 weeks accounting for mortality (analyzed using a Bayesian shared parameter model). Prespecified secondary efficacy endpoints included the Combined Assessment of Function and Survival joint rank test (CAFS), change in respiratory function as measured by slow vital capacity (SVC), and overall survival. For more information, please see ClinicalTrials.gov Identifier: NCT04297683.
About CNM-Au8®
CNM-Au8 is Clene’s lead asset in mid- and late-stage clinical development for the treatment of multiple sclerosis and amyotrophic lateral sclerosis. An oral suspension of gold nanocrystals, CNM-Au8 was developed to protect neuronal health and function by increasing energy production and utilization. The catalytically active nanocrystals of CNM-Au8 drive critical cellular energy producing reactions that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. CNM-Au8® is a federally registered trademark of Clene Nanomedicine, Inc.
About Clene
Clene is a clinical-stage biopharmaceutical company focused on revolutionizing the treatment of neurodegenerative disease by targeting energetic failure, an underlying cause of many neurological diseases. 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.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the “safe harbor” provisions created by those laws. Clene’s forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding our future operations. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “contemplate,” “continue,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “will,” “would,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements represent our views as of the date of this press release and involve a number of judgments, risks and uncertainties. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update forward-looking statements to reflect events or circumstances after the date they were made, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Accordingly, forward-looking statements should not be relied upon as representing our views as of any subsequent date. As a result of a number of known and unknown risks and uncertainties, our actual results or performance may be materially different from those expressed or implied by these forward-looking statements. Some factors that could cause actual results to differ include our ability to demonstrate the efficacy and safety of our drug candidates; the clinical results for our 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; our ability to achieve commercial success for our drug candidates, if approved; uncertainty regarding whether potential strategic partnerships will result in any agreements or transactions, or, if completed, any agreements or transactions will be successful or on attractive terms; our limited operating history and our ability to obtain additional funding for operations and to complete the development and commercialization of our drug candidates; and other risks and uncertainties set forth in “Risk Factors” in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this press release, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to rely unduly upon these statements. 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 |
Ignacio Guerrero-Ros, Ph.D., or David Schull |
Kevin Gardner |
Russo Partners, LLC |
LifeSci Advisors |
Ignacio.guerrero-ros@russopartnersllc.com |
kgardner@lifesciadvisors.com |
David.schull@russopartnersllc.com |
617-283-2856 |
(858) 717-2310 |
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Source: Clene Inc.
Healey ALS Platform Trial CNM-Au8 Results Webcast October 2022 Exhibit 99.2
Introduction & CLNN Program Update Rob Etherington, President and Chief Executive Officer I Clene Inc. HEALEY ALS Platform Trial Results for CNM-Au8 Merit Cudkowicz, M.D., MSc I Chief of Neurology at Massachusetts General Hospital Director of the Sean M. Healey & AMG Center for ALS Clene Milestones Q&A session Rob Etherington, President and Chief Executive Officer I Clene Inc. Robert Glanzman M.D., FAAN, Chief Medical Officer I Clene Inc. Michael Hotchkin, Chief Development Officer I Clene Inc. Merit Cudkowicz, M.D., MSc I Massachusetts General Hospital 01 02 03 Healey ALS Platform Trial Results Webcast
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the “safe harbor” provisions created by those laws. Clene’s forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding our future operations. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “contemplate,” “continue,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “will,” “would,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements represent our views as of the date of this presentation and involve a number of judgments, risks and uncertainties. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update forward-looking statements to reflect events or circumstances after the date they were made, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Accordingly, forward-looking statements should not be relied upon as representing our views as of any subsequent date. As a result of a number of known and unknown risks and uncertainties, our actual results or performance may be materially different from those expressed or implied by these forward-looking statements. Some factors that could cause actual results to differ include our substantial dependence on the successful commercialization of our drug candidates, if approved, in the future; our inability to maintain the listing of our common stock on Nasdaq; our significant net losses and net operating cash outflows; our ability to demonstrate the efficacy and safety of our drug candidates; the clinical results for our 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; our ability to achieve commercial success for our drug candidates, if approved; our ability to obtain and maintain protection of intellectual property for our technology and drugs; our reliance on third parties to conduct drug development, manufacturing and other services; our limited operating history and our ability to obtain additional funding for operations and to complete the licensing or development and commercialization of our drug candidates; the impact of the COVID-19 pandemic on our clinical development, commercial and other operations; changes in applicable laws or regulations; the effects of inflation; the effects of staffing and materials shortages; the possibility that we may be adversely affected by other economic, business, and/or competitive factors; and other risks and uncertainties set forth in “Risk Factors” in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to rely unduly upon these statements. All information in this presentation is as of the date of this presentation. The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this presentation.
CLENE | Growing Clinical Evidence Across ALS and MS Supports CNM-Au8 Therapeutic Potential Data on File, Clene Nanomedicine, Inc. 1Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936.2https://clinicaltrials.gov/ct2/show/NCT04414345. 70% decreased risk of death in ALS CNM-Au8® a gold nanocrystal suspension, in development as the first cellular energetic catalyst to remyelinate1 & protect neurological function Strong IP: 150+ patents on Clean-Surface- Nanocrystal technology (CSN®) platform >400 patient years of CNM-Au8 clinical exposure Demonstrated global neurological improvement in MS patients on adjunctive DMT standard of care Proprietary Nanotherapeutic Manufacturing
Building the Clinical Case for Neuroprotection & Remyelination Demonstrated statistically significant survival; 70% decreased risk of death Established brain target engagement in early PD and stable relapsing MS patients First therapy to demonstrate global neurological improvement in MS patients on top of background DMT standard of care Growing Body of Clinical Evidence Across ALS and MS Supports CNM-Au8 Therapeutic Potential
CNM-Au8® | Pioneering A New Drug Class To Improve Cellular Energy Production And Utilization Improved Energy Production and Utilization CNM-Au8 Nanocrystals Clean Surfaced, Highly Faceted Shapes Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936. Data on File, Clene Nanomedicine, Inc. Mechanistic Effects By targeting energy metabolism, CNM-Au8 may protect neuronal health CNM-Au8 Nanocrystal Suspension =
Over 400 Years of Subject Exposure Without Identified Safety Signals Across ALS, MS, and PD Over 400 Years of Subject Exposure Without Identified Safety Signals Patient Exposure Across ALS, MS & PD Long-term dosing experience up to 150 weeks All Animal Toxicology Studies Resulted in No-Adverse Effect Level (NOAEL) Findings Clean Toxicology Findings Multiple species up to 9-months treatment Up to maximum feasible dosing without any toxicology findings related to CNM-Au8 Assessed as Predominantly Mild-to-Moderate Severity and Transient Well Tolerated Adverse Event (AE) Profile No SAEs related to CNM-Au8 considered severe, life-threatening, or resulting in death AEs predominantly mild-to-moderate Data on File, Clene Nanomedicine, Inc. MS: Multiple Sclerosis, ALS: Amyotrophic lateral sclerosis, and PD: Parkinson's Disease.
Merit Cudkowicz, M.D., MSc Director of the Sean M. Healey & AMG Center for ALS Chief of the Department of Neurology at MGH, and the Julieanne Dorn Professor of Neurology at Harvard Medical School Principal Investigator and Sponsor of the Healey ALS Platform Trial Results for CNM-Au8 Regimen
CAFS (Joint-Rank) Slow Vital Capacity (SVC) Survival (Death + PAV) Change in ALSFRS-R slope adjusted by mortality Registration Study: 24-Week Treatment Period (3:1 randomization, 120 active [30mg, 60mg]: 40 placebo) 1 2 Paganoni et al. Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development. Ann Neurol. 2022; 91:165-175. . Weighted Average of Slope Change & Hazard Ratio Weighting based on # of Mortality Events
Participant Disposition | With Shared Placebo 523 assessed for eligibility for Regimens A, B, or D 163 assessed for eligibility for Regimen C (CNM-Au8) 400 were excluded from Shared Placebo 369 randomized to active (Regimen A, B, or D) 31 excluded due to: screen failures (14), timed out of screening (9), early terminated (7), or died (1) 123 randomized to Placebo across Regimens A, B, or D 2 were excluded from Regimen C 1 died during screening 1 timed out of screening window 161 randomized within Regimen C 686 assigned to Regimens A, B, C, or D 59 randomized to CNM-Au8 30mg 61 randomized to CNM-Au8 60mg 41 randomized to Placebo 123 + 41 = 164 for Shared Placebo CNM-Au8 Total = 120
Primary | No Effect on Mortality Adjusted ALSFRS-R Change at 24 Weeks (30mg & 60mg combined) All shared controls ALSFRS-R component includes only survivors Mortality is accounted for using common treatment effect Model adjusts for covariates: Time since symptom onset Pre-baseline ALSFRS-R slope Edaravone use Riluzole use Effect CI* -2% -20% to +19% *Credible interval
No Effect on Key Secondary Endpoints at 24 Weeks (30mg & 60mg combined) Combined Assessment of Function and Survival (CAFS) change at 24 weeks was not significant No effect on Slow Vital Capacity (SVC) at 24 weeks
24-Week Survival Signal | >90% Risk Reduction at 30mg *Shared Placebo Across Regimens * p-values are not adjusted for multiple comparisons; exploratory analyses by dose *CNM-Au8 Regimen Only
Safety Occurrence of TEAEs were balanced between CNM-Au8 and placebo No SAEs were assessed as related to CNM-Au8 Higher incidence of SAEs at 60mg dose Treatment Emergent Adverse Events (TEAEs) Placebo (%) CNM-Au8 30 mg (%) CNM-Au8 60 mg(%) Subjects with Any TEAE 90% 92% 93% Subjects with Related TEAEs 39% 29% 43% Subjects with SAE 9% 10% 16% Subjects Withdrawn due to TEAE 7% 7% 7%
Healey ALS Platform Trial CNM-Au8 Summary No evidence for treatment effect at 24 weeks for either adjusted ALSFRS-R, CAFS, or SVC (combined doses) Potential survival signal: >90% decreased risk at 30mg Mortality/PAV, p=0.028; Mortality = 0.057 (Regimen only) Mortality/PAV, p=0.042; Mortality = 0.075 (Shared placebo) Well tolerated with no definitive safety signals
Robert Glanzman, M.D., FAAN Clene Chief Medical Officer
CNM-Au8 Has Demonstrated ALS Survival Benefit at 30 mg Dose in Two Phase 2 Studies Long-term follow-up up to 2.5 years show 70% decreased risk of death (original active vs original placebo randomization), P=0.0115 (i) Risk of Death or (ii) Risk of Death or Permanently Assisted Ventilation at 24 weeks in Regimen-Only and in Full Analysis (Shared Placebo) (P=0.028 to 0.075) CNM-Au8 demonstrated a >90% risk reduction of death at 30 mg CNM-Au8 demonstrated 70% decreased risk of death Data on File, Clene Nanomedicine, Inc.
Growing Body of Evidence for Clene Nanotherapeutics Data on File, Clene Nanomedicine, Inc. Disease 2022 2021 2023 Demonstrated survival benefit Demonstrated survival signal at 6 months Established brain target engagement & safety Demonstrated global neurological improvement in MS patients on adjunctive DMT standard of care Established brain target engagement & safety Key Findings Ongoing to establish target engagement & safety in non-active, progressive MS Ongoing
CNM-Au8 Question and Answers Merit Cudkowicz, M.D., MSc Chief, Department of Neurology at MGH Director of the Sean M. Healey & AMG Center for ALS Robert Glanzman, M.D., FAAN Chief Medical Officer Clene Nanomedicine, Inc. Rob Etherington Chief Executive Officer Clene Nanomedicine, Inc. Michael Hotchkin Chief Development Officer Clene Nanomedicine, Inc.
Corporate Presentation October 2022 Exhibit 99.3
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended, which are intended to be covered by the “safe harbor” provisions created by those laws. Clene’s forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding our future operations. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “contemplate,” “continue,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “will,” “would,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements represent our views as of the date of this presentation and involve a number of judgments, risks and uncertainties. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update forward-looking statements to reflect events or circumstances after the date they were made, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Accordingly, forward-looking statements should not be relied upon as representing our views as of any subsequent date. As a result of a number of known and unknown risks and uncertainties, our actual results or performance may be materially different from those expressed or implied by these forward-looking statements. Some factors that could cause actual results to differ include our substantial dependence on the successful commercialization of our drug candidates, if approved, in the future; our inability to maintain the listing of our common stock on Nasdaq; our significant net losses and net operating cash outflows; our ability to demonstrate the efficacy and safety of our drug candidates; the clinical results for our 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; our ability to achieve commercial success for our drug candidates, if approved; our ability to obtain and maintain protection of intellectual property for our technology and drugs; our reliance on third parties to conduct drug development, manufacturing and other services; our limited operating history and our ability to obtain additional funding for operations and to complete the licensing or development and commercialization of our drug candidates; the impact of the COVID-19 pandemic on our clinical development, commercial and other operations; changes in applicable laws or regulations; the effects of inflation; the effects of staffing and materials shortages; the possibility that we may be adversely affected by other economic, business, and/or competitive factors; and other risks and uncertainties set forth in “Risk Factors” in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and you are cautioned not to rely unduly upon these statements. All information in this presentation is as of the date of this presentation. The information contained in any website referenced herein is not, and shall not be deemed to be, part of or incorporated into this presentation.
CLENE | Building Clinical Neuroprotective Evidence Significant Opportunity Targeting neurodegenerative diseases such as ALS and Multiple Sclerosis >$1B commercial opportunity in each indication CNM-Au8® Clinical Results Long-term follow-up of RESCUE-ALS Phase 2 participants demonstrated statistically significant survival benefit; 70% decreased risk of death Positive Topline Results from the Phase 2 VISIONARY-MS Trial; CNM-Au8 demonstrated global neurological improvements in stable relapsing MS as adjunctive therapy to immunomodulatory DMTs CNM-Au8 demonstrated a >90% reduction in risk of death or permanently assisted ventilation for the 30 mg dose at 24 weeks in pre-specified exploratory results in the HEALEY ALS Platform Trial Proprietary Platform Strong IP Proprietary nanotherapeutic manufacturing Strong IP, including 150+ granted patents and manufacturing trade secrets
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. Neurodegenerative Diseases Share A Common Mechanism: A Decline In The Brain’s Ability To Produce Energy ~0.5% NAD+/NADH unit decline per decade (~0.13 mV units per year by 31P-MRS Imaging) Brain Energy Potential Declines With Normal Aging Closed squares = averaged data by age group: 21–26 yrs, 33–36 yrs, and 59–68 yrs old; Open squares = individual subject values PARKINSON’S DISEASE Dopaminergic Neurons AMYOTROPHIC LATERAL SCLEROSIS Motor Neurons HUNTINGTON’S DISEASE Medium Spiny Neurons FRONTOTEMPORAL DEMENTIA Spindle Neurons Specific Neuronal Populations Are Vulnerable to Energetic Failure MULTIPLE SCLEROSIS Axonal Degeneration Energetic impairments in the CNS both pre-dispose and drive progression in neurodegenerative diseases
CNM-Au8® | Pioneering A New Drug Class To Improve Cellular Energy Production And Utilization Improved Energy Production and Utilization CNM-Au8 Nanocrystals Clean Surfaced, Highly Faceted Shapes Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936. Data on File, Clene Nanomedicine, Inc. Mechanistic Effects CNM-Au8 Nanocrystal Suspension = By targeting energy metabolism, CNM-Au8 may protect neuronal health
Significant Global Opportunity for Treatment in Combination with Standard of Care 1 Clarivate, DRG, ALS 2020. 2. https://pubmed.ncbi.nlm.nih.gov/17974351/ 3. Westad et al. 2017, doi:10.1038/nrd.2017.107;. 4. Parkinson’s Market Data Forecast, April 2021.. 5. Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol 2010;67:715-725.. Urgent unmet need to develop neuroprotective treatment to support cells’ energetic efficiency and resilience (MS) (PD)
Building the Clinical Case for Neuroprotection & Remyelination CNM-Au8 demonstrated statistically significant survival benefit 70% decreased risk of death Established brain target engagement in early PD and stable relapsing MS patients CNM-Au8 demonstrated neurological improvements in people with stable relapsing MS as adjunctive therapy to immunomodulatory DMTs Growing Body of Clinical Evidence Across ALS and MS Supports CNM-Au8 Therapeutic Potential
Proportion with <6 point decline CNM-Au8 Improved Patient Function and QOL, and Slowed ALS Disease Progression 1ALS Disease Progression defined as: Death, or Tracheostomy, or Non-invasive ventilation, or Gastrostomy tube Vucic et al. RESCUE-ALS Trial Results: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CNM-Au8 to Slow Disease Progression in Amyotrophic Lateral Sclerosis; Presented at International Symposium on ALS/MND; 7-10 December 2021 ALS Specific QOL ALS Disease Progression Phase 2 Study: 36-Week Placebo-Control Treatment Period 1:1 Randomization (Active 30 mg: Placebo); 45 enrolled with early ALS
Demonstrated Significant Impact on Long-Term Survival with 70% Decreased Risk of Death RESCUE-ALS Active vs. Placebo Randomization Long-Term Observed Survival (Interim Analysis) Data on File, Clene Nanomedicine, Inc. Time to all-cause mortality amongst participants originally randomized to CNM-Au8 compared to participants originally randomized to placebo through 31-Aug-2022. Vital status and date of death (as applicable) were captured for all subjects withdrawn from the study. Lost-to-follow-up (active, n=1; placebo, n=1) censored as of the date of last study contact (Active: Feb-2021; Placebo: Feb-2022). All OLE ex-placebo CNM-Au8 transitioned participants within the placebo group. All alive subjects are right censored as of 31-Aug-2022. Early CNM-Au8 treatment demonstrated a significant survival benefit: Follow-up of active compared to initial placebo randomization* 70% decreased risk of death *9-month delayed treatment start (ex-placebo) or no treatment
CNM-Au8 Demonstrated Global Neurological Improvement in Stable MS patients on DMTs Change in Low Contrast Letter Acuity (LCLA) 1 2 Change in modified MS Functional Composite (mMSFC) Phase 2 Study: 48-Week Placebo-Control Treatment Period 2:1 Randomization (Active [15mg, 30 mg]: Placebo) Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMTs n=73 of 150 planned – study ended prematurely due to COVID-19 pandemic-related enrollment challenges Data on File, Clene Nanomedicine, Inc.
CNM-Au8 Improved Axonal Integrity and Retinal Structure Data on File, Clene Nanomedicine, Inc. Increased Amplitude (Signal Strength) Exploratory Endpoint Improved Temporal Segment GCL & RNFL Exploratory Endpoint mf-VEP amplitude OCT retinal nerve fiber & ganglion cell layers
CAFS (Joint-Rank) Slow Vital Capacity Survival (Death + PAV) Change in ALSFRS-R slope adjusted by mortality Registration Study: 24-Week Treatment Period (3:1 randomization, 120 active [30mg, 60mg]: 40 placebo) 1 2 Paganoni et al. Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development. Ann Neurol. 2022; 91:165-175. . Weighted Average of Slope Change & Hazard Ratio Weighting based on # of Mortality Events
Healey ALS Platform Trial CNM-Au8 Results No evidence for treatment effect at 24 weeks for either adjusted ALSFRS-R, CAFS, or SVC (combined 30 & 60 mg doses) Potential survival signal: >90% decreased risk of death at 30mg Mortality/PAV, p=0.028; Mortality = 0.057 (Regimen only) Mortality/PAV, p=0.042; Mortality = 0.075 (Shared placebo) Well tolerated with no definitive safety signals Data on File, Clene Nanomedicine, Inc.
24-Week Survival Signal | >90% Reduced Risk of Death at 30 mg *Shared Placebo Across Regimens * p-values are not adjusted for multiple comparisons; exploratory analyses by dose *CNM-Au8 Regimen Only Data on File, Clene Nanomedicine, Inc.
Over 400 Years of Subject Exposure Without Identified Safety Signals Across ALS, MS, and PD Over 400 Years of Subject Exposure Without Identified Safety Signals Patient Exposure Across ALS, MS & PD Long-term dosing experience up to 150 weeks All Animal Toxicology Studies Resulted in No-Adverse Effect Level (NOAEL) Findings Clean Toxicology Findings Multiple species up to 9-months treatment Up to maximum feasible dosing without any toxicology findings related to CNM-Au8 Assessed as Predominantly Mild-to-Moderate Severity and Transient Well Tolerated Adverse Event (AE) Profile No SAEs related to CNM-Au8 considered severe, life-threatening, or resulting in death AEs predominantly mild-to-moderate Data on File, Clene Nanomedicine, Inc. MS: Multiple Sclerosis, ALS: Amyotrophic lateral sclerosis, and PD: Parkinson's Disease.
CNM-Au8 Has Demonstrated ALS Survival Benefit at 30 mg Dose in Two Phase 2 Studies Long-term follow-up up to 2.5 years show 70% decreased risk of death (original active vs original placebo randomization), P=0.0115 (i) Risk of Death or (ii) Risk of Death or Permanently Assisted Ventilation at 24 weeks in Regimen-Only and in Full Analysis (Shared Placebo) (P=0.028 to 0.075) CNM-Au8 demonstrated a >90% risk reduction of death at 30 mg CNM-Au8 demonstrated 70% decreased risk of death Data on File, Clene Nanomedicine, Inc.
Growing Body of Evidence for Clene Nanotherapeutics Data on File, Clene Nanomedicine, Inc. Disease 2022 2021 2023 Demonstrated survival benefit Demonstrated survival signal at 6 months Established brain target engagement & safety Demonstrated global neurological improvement in MS patients on adjunctive DMT standard of care Established brain target engagement & safety Key Findings Ongoing to establish target engagement & safety in non-active, progressive MS Ongoing
Evidence Supports CNM-Au8 Therapeutic Potential to Treat Neurodegenerative Diseases Data on File, Clene Nanomedicine, Inc. 1Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936.2https://clinicaltrials.gov/ct2/show/NCT04414345. 70% decreased risk of death in ALS CNM-Au8® a gold nanocrystal suspension, in development as the first cellular energetic catalyst to remyelinate1 & protect neurological function Strong IP: 150+ patents on nanotherapeutic platform >90% decreased risk of death with 30 mg in ALS >400 patient years of CNM-Au8 clinical exposure Demonstrated global neurological improvement in MS patients on adjunctive DMT standard of care As of June 30, 2022, cash and investments on hand (unaudited): $26.3M
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