UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 OR 15(d)
of The Securities Exchange Act of 1934
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(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:
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:
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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 2.02 Results of Operations and Financial Condition.
On August 15, 2022, Clene Inc. (the “Company”) issued a press release announcing its second quarter financial results and recent operating highlights for its quarter ended June 30, 2022. 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.
The information furnished in this Item 2.02, including Exhibit 99.1, 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 (the “Securities Act”), 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 7.01 Regulation FD Disclosure.
Corporate Presentation
In connection with the press release announcing the Company’s second quarter operating and financial results for its quarter ended June 30, 2022, 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 99.2 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 on Form 8-K alerting investors if the Corporate Presentation is updated.
VISIONARY-MS Clinical Trial Topline Results
On August 15, 2022, the Company issued a press release announcing positive topline results for CNM-Au8® in the Phase 2 VISIONARY-MS trial in multiple sclerosis (“MS”). The Company also hosted a conference call and webcast on August 15, 2022 to discuss the VISIONARY-MS topline results. A copy of the press release and presentation are furnished as Exhibit 99.3 and Exhibit 99.4, respectively, to this Current Report and are incorporated herein by reference.
The information furnished in this Item 7.01, including Exhibit 99.2, Exhibit 99.3, and Exhibit 99.4, shall not be deemed to be “filed” for purposes of Section 18 of 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
Exhibit |
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Exhibit Description |
99.1 |
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99.2 |
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99.3 |
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99.4 |
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104 |
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Cover Page Interactive Data File (formatted as Inline XBRL). |
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.
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CLENE INC. |
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Date: August 15, 2022 |
By: |
/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 Second Quarter 2022 Financial Results and Recent Operating Highlights
SALT LAKE CITY, August 15, 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 reported its second quarter 2022 and recent operating highlights.
“We are on the cusp of a transformative period for the Company as we await a key data readout in ALS for our lead asset, CNM-Au8®,” said Rob Etherington, President and CEO of Clene. “The ALS patient population is desperate for new treatments to help mitigate the disease course and following the statistically significant survival benefits demonstrated in our open label trial, we are hopeful that we can deliver an effective therapy for people living with ALS.”
Second Quarter 2022 and Recent Operating Highlights
CNM-Au8®, a gold nanocrystal suspension, for the treatment of amyotrophic lateral sclerosis (ALS)
CNM-Au8 for the treatment of multiple sclerosis (MS)
CNM-ZnAg for the treatment of COVID-19
Second Quarter 2022 Financial Results
Clene’s cash, cash equivalents and marketable investments securities totaled $26.3 million as of June 30, 2022, compared to $50.3 million as of December 31, 2021.
Research and development expenses were $9.2 million for the quarter ended June 30, 2022, compared to $6.5 million for the same period in 2021. The year-over-year increase is primarily attributable to the development of CNM-Au8 and CNM-ZnAg (including the rapid completion of the COVID study due to a viral wave leading to increased patient recruitment), rent expense for the newly-leased facility in Elkton, Maryland, and personnel expenses due to increased headcount as a result primarily of increased manufacturing hours, partially offset by decreased stock-based compensation expense.
General and administrative expenses were $4.5 million for the quarter ended June 30, 2022, compared to $6.9 million for the same period in 2021. The year-over-year decrease is primarily attributable to a decrease in directors’ and officers’ insurance costs, stock-based compensation expense and other general and administrative costs, including decreases in investor relations, accounting and consulting fees. These decreases were offset by increases in personnel compensation due to increased headcount as well as increases on other miscellaneous general and administrative expenses.
Clene reported a net loss of $4.5 million, or $0.07 per share, for the quarter ended June 30, 2022, compared to a net loss of $3.4 million, or $0.05 per share, for the same period in 2021. Included in net loss for the quarter ended June 30, 2022, is an unrealized gain from the change in fair value of contingent earn-out liabilities of $9.4 million, compared to an unrealized gain of $9.9 million in the prior year period.
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.
About CNM-Au8®
CNM-Au8 is an oral suspension of gold nanocrystals developed to restore 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 CNM-ZnAg
CNM-ZnAg, a proprietary zinc-silver ionic solution, has demonstrated broad antiviral and antimicrobial activity.
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; 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.
CLENE INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS)
(In thousands, except share and per share amounts)
(Unaudited)
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Three Months Ended June 30, |
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Six Months Ended June 30, |
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2022 |
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2021 |
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2022 |
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2021 |
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Revenue: |
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Product revenue |
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$ |
2 |
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$ |
138 |
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$ |
9 |
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$ |
337 |
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Royalty revenue |
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33 |
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63 |
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56 |
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77 |
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Total revenue |
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35 |
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201 |
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65 |
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414 |
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Operating expenses: |
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Cost of revenue |
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— |
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555 |
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— |
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798 |
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Research and development |
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9,166 |
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6,472 |
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17,746 |
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12,747 |
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General and administrative |
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4,464 |
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6,949 |
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9,250 |
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12,339 |
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Total operating expenses |
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13,630 |
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13,976 |
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26,996 |
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25,884 |
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Loss from operations |
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(13,595 |
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(13,775 |
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(26,931 |
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(25,470 |
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Other income (expense), net: |
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Interest expense |
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(751 |
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(26 |
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(1,533 |
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(577 |
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Gain on extinguishment of notes payable |
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— |
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— |
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— |
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647 |
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Gain on termination of lease |
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— |
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— |
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420 |
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— |
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Change in fair value of common stock warrant liability |
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20 |
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133 |
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2 |
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133 |
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Change in fair value of Clene Nanomedicine contingent earn-out |
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8,310 |
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8,640 |
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8,253 |
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(16,970 |
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Change in fair value of Initial Stockholders contingent earn-out |
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1,066 |
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1,232 |
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1,054 |
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(1,729 |
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Australia research and development credit |
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356 |
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375 |
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655 |
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714 |
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Other income (expense), net |
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60 |
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(2 |
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192 |
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1 |
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Total other income (expense), net |
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9,061 |
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10,352 |
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9,043 |
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(17,781 |
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Net loss before income taxes |
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(4,534 |
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(3,423 |
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(17,888 |
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(43,251 |
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Income tax benefit |
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— |
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72 |
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— |
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144 |
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Net loss |
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(4,534 |
) |
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(3,351 |
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(17,888 |
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(43,107 |
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Other comprehensive loss: |
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Unrealized loss on available-for-sale securities |
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(37 |
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— |
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(87 |
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— |
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Foreign currency translation adjustments |
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(110 |
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(61 |
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(60 |
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(37 |
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Total other comprehensive loss |
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(147 |
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(61 |
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(147 |
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(37 |
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Comprehensive loss |
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$ |
(4,681 |
) |
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$ |
(3,412 |
) |
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$ |
(18,035 |
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$ |
(43,144 |
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Net loss per share-- basic and diluted |
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$ |
(0.07 |
) |
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$ |
(0.05 |
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$ |
(0.28 |
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$ |
(0.71 |
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Weighted average common shares used to compute basic and diluted net loss per share |
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63,335,271 |
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61,165,018 |
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63,095,400 |
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60,919,340 |
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CLENE INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands, except share and per share amounts)
(Unaudited)
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June 30, |
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December 31, |
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2022 |
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2021 |
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ASSETS |
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Current assets: |
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Cash and cash equivalents |
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$ |
7,253 |
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$ |
50,288 |
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Marketable securities |
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19,033 |
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— |
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Accounts receivable |
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— |
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49 |
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Inventory |
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107 |
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41 |
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Prepaid expenses and other current assets |
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5,194 |
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4,205 |
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Total current assets |
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31,587 |
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54,583 |
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Restricted cash |
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58 |
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58 |
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Right-of-use assets |
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4,808 |
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3,250 |
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Property and equipment, net |
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8,089 |
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5,172 |
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TOTAL ASSETS |
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$ |
44,542 |
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$ |
63,063 |
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LIABILITIES AND STOCKHOLDERS’ EQUITY |
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Current liabilities: |
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Accounts payable |
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$ |
4,526 |
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$ |
1,923 |
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Accrued liabilities |
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2,566 |
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3,610 |
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Operating lease obligations, current portion |
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440 |
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347 |
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Finance lease obligations, current portion |
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123 |
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146 |
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Total current liabilities |
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7,655 |
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6,026 |
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Operating lease obligations, net of current portion |
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5,858 |
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4,370 |
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Finance lease obligations, net of current portion |
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55 |
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97 |
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Notes payable |
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15,551 |
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14,484 |
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Convertible notes payable |
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4,709 |
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4,598 |
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Common stock warrant liability |
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167 |
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474 |
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Clene Nanomedicine contingent earn-out |
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9,847 |
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18,100 |
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Initial Stockholders contingent earn-out |
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1,263 |
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2,317 |
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TOTAL LIABILITIES |
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45,105 |
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50,466 |
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Commitments and contingencies |
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Stockholders’ equity (deficit): |
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Common stock, $0.0001 par value: 150,000,000 shares authorized; 63,421,908 and 62,312,097 shares issued and outstanding at June 30, 2022 and December 31, 2021, respectively |
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6 |
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6 |
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Additional paid-in capital |
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180,534 |
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175,659 |
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Accumulated deficit |
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(181,189 |
) |
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(163,301 |
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Accumulated other comprehensive income |
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86 |
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233 |
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TOTAL STOCKHOLDERS’ EQUITY (DEFICIT) |
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(563 |
) |
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12,597 |
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TOTAL LIABILITIES AND STOCKHOLDERS’ EQUITY |
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$ |
44,542 |
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$ |
63,063 |
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Corporate Presentation August 2022 Exhibit 99.2
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 | Entering a Transformative Period Significant Opportunity Targeting neurodegenerative diseases such as ALS and Multiple Sclerosis >$1B commercial opportunity in each indication CNM-Au8® Emerging Clinical Results Long-term follow-up of RESCUE-ALS Phase 2 participants demonstrated statistically significant survival benefit; 70% decreased risk of death in ALS Positive Topline Results from the Phase 2 VISIONARY-MS Trial; CNM-Au8 demonstrated neurological improvements in stable relapsing MS as adjunctive therapy to immunomodulatory DMTs HEALEY ALS Platform Trial Phase 2/3 topline results expected in 3Q 2022 Proprietary Platform Strong IP Proprietary nanotherapeutic manufacturing, scalable to commercialization 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 By targeting energy metabolism, CNM-Au8 may protect and restore neuronal function. CNM-Au8 Nanocrystal Suspension + =
CNM-Au8 Improves ALS Motor Neuron Function & Survival Induced Pluripotent Stem Cell In Vitro Results – Motor Neuron Markers Preclinical Evidence of Remyelination and Neuroprotection Karen S. Ho et al. “Redox-enhancing nanocatalysis improves motor neuron survival in vitro and SOD1 mouse motor function and survival in vivo.” Presented at 30th International Symposium on ALS/MND 2019. December 4-6, 2019. CNM-Au8 Supports Remyelination Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936. Karen S. Ho et al. “Redox-enhancing nanocatalysis improves motor neuron survival in vitro and SOD1 mouse motor function and survival in vivo.” Presented at 30th International Symposium on ALS/MND 2019. December 4-6, 2019. CNM-Au8 novel MOA may be complementary to existing therapies to enable better disease control Remyelination Neuroprotection
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 Case for Neuroprotection & Remyelination RESCUE-ALS trial supports CNM-Au8 slowed disease progression in ALS 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 Evidence from Multiple Trials Supports CNM-Au8 Clinical Potential REPAIR-MS Phase 2 in non-active progressive MS underway HEALEY ALS Platform Trial topline results expected 3Q 2022 Results provide support to advance CNM-Au8 into Phase 3 clinical development
Over 350 Years of Subject Exposure Without Identified Safety Signals Across ALS, MS & PD Over 350 Years of Subject Exposure Without Identified Safety Signals Patient Exposure Across ALS, MS & PD Long-term dosing experience up to 125 weeks All Animal Toxicology Studies Resulted in No-Adverse Effect Level (NOAEL) Findings Clean Toxicology Findings Multiple species up 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.
1. Zhu et al. Proc Natl Acad Sci USA 2015 Mar 3;112(9):2876-81.. 2. Glanzman et al Improvement of Brain Energy Metabolism in Relapsing Multiple Sclerosis Patients - Results from Phase 2 REPAIR-MS Clinical Trial With CNM-Au8, ACTRIMS February 2022 Two REPAIR Trials Demonstrated Target Brain Engagement and Improved Energy Metabolism in Early Parkinson’s and Stable Relapsing MS Exploratory (ATP Normalization) Study Objective: to demonstrate target engagement for CNM-Au8 on CNS biomarkers related to energetic effects in the brain using Magnetic Resonance Spectroscopy (31P-MRS) 1° Endpoint (integrated PD & MS)2 Results demonstrated a potentially meaningful 10% improvement in NAD+/NADH ratio, an essential molecule for energy production1
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 \. Encouraging Efficacy Signals in Phase 2 Trial Results in favor of CNM-Au8 treatment but study underpowered 1° & 2° Endpoints Study Objective: Detect preservation of motor neuron function in people with early ALS as measured by MUNIX Study Design: 36-week blinded treatment with ongoing long-term open-label follow-up Bulbar Onset ALS (Brainstem) Limb Onset ALS (Spinal Cord) Primary Endpoint: Spinal Cord Lower Motor Neuron Motor Unit Index (MUNIX) Sum Biceps brachii Tibialis Anterior Abductor Pollicis Brevis Abductor Digiti Minimi + + +
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 Across Multiple Pre-specified Exploratory Endpoints
CAFS Results: Slowed Disease Progression Data on File, Clene Nanomedicine, Inc. . Exploratory Endpoint Pre-specified ALSFRS-R Decline Survival CAFS King’s Clinical Stage 4 Modified CAFS Exploratory Endpoint Post Hoc
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. Early CNM-Au8 treatment demonstrated a significant survival benefit: Long-term follow-up compared to initial placebo randomization* 70% decreased risk of death *9-month delayed treatment start or no treatment
CAFS (Joint-Rank) Survival & ALSFRS-R Slow Vital Capacity Survival Change in ALSFRS-R slope + survival Registration Study: 24-Week Treatment Period (3:1 randomization, 120 active [30mg, 60mg]: 40 placebo) 1 2 Phase 2/3 (Stopped for futility) Paganoni et al. Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development. Ann Neurol. 2022; 91:165-175. . Anticipated topline data: 3Q 2022 Weighted Average of Slope Change & Hazard Ratio Weighting based on # of Mortality Events
Core Design Elements Change in Low Contrast Letter Acuity (LCLA) 1 2 https://clinicaltrials.gov/ct2/show/NCT03536559, Data on File, Clene Nanomedicne, Inc. Change in modified MS Functional Composite (mMSFC) Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMTs n=73 of 150 planned – study ended prematurely due to pandemic-related enrollment challenges Phase 2 Study: 48-Week Placebo-Control Treatment Period 2:1 Randomization (Active [15mg, 30 mg]: Placebo) LCLA 9HPT SDMT T25FWT
Baseline Demographics Showed Balanced Randomization and Clinical Profile Baseline Value mean (sd) Age (yrs) Sex n, (%) Female Race n, (%) White Weight (kg) EDSS Score Years from Dx Months Since Relapse CNM-Au8 15 mg (n=24) 38.4 (10.2) 15 (63%) 23 (96%) 78.0 (17.1) 1.83 (1.3) 6.5 (5.0) 53 (57) CNM-Au8 30 mg (n=25) 39.6 (7.6) 16 (64%) 24 (96%) 78.6 (17.3) 1.50 (1.1) 3.4 (3.3) 37 (35) Placebo (n=24) 38.1 (8.3) 20 (83%) 22 (92%) 83.0 (23.3) 1.85 (1.4) 6.6 (3.7) 57 (38) All Participants (n=73) 38.7 (8.6) 51 (70%) 69 (95%) 79.9 (19.3) 1.75 (1.5) 5.5 (4.3) 49 (45) Data on File, Clene Nanomedicine, Inc. All participants were diagnosed with stable relapsing remitting MS with chronic optic neuropathy 92% treated with background DMTs (53% monoclonal antibodies, 32% oral)
Pandemic Significantly Impacted Study Conduct Study was ended prematurely due to COVID enrollment challenges (as announced February 2022) Enrolled 73 of 150 planned Underpowered due to limited enrollment Pre-specified statistical threshold set at p=0.10 COVID restrictions precluded direct Sponsor monitoring Objectives Learn from results Evaluate strength of evidence for further MS development Data on File, Clene Nanomedicine, Inc.
modified ITT (mITT) Analysis Population Censored observations included Change in mobility assist device (cane to walker) for T25FW (n=1) Invalid data from 1 of 11 sites (n=9) with LCLA testing execution errors Multiple testing locations with different light boxes and varying ambient lighting conditions In consultation with study Principal Investigator and external experts, all clinical data from the site were excluded Data on File, Clene Nanomedicine, Inc.
CNM-Au8 treatment significantly improved vision Primary outcome - low contrast letter acuity (LCLA) LCLA in the Affected Eye Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants LCLA 2.5% Contrast
Lead 2nd EP | (m)MFSC Composite Mean Standardized Change (6-domain) CNM-Au8 demonstrated global neurological improvement by the modified MS functional composite LCLA SDMT 9HPT T25FWT Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
CNM-Au8 neurological improvement was driven by cognition, manual dexterity, and low contrast vision LCLA SDMT 9HPT T25FWT Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
2nd EP | mMFSC Averaged Rank Sum Score CNM-Au8 treatment improved functional outcomes Improvement relative to placebo decline Score all subjects versus all other subjects by each mMSFC domain Better function than comparison Same function as comparison Worse function than comparison Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
Safety Summary Treatment Emergent Adverse Events (TEAEs) CNM-Au8 15 mg number (%) CNM-Au8 30 mg number (%) Placebo number (%) Subjects with any TEAE 21 (88%) 25 (100%) 22 (92%) Subjects with SAE 1 (4%) 2 (8%) 2 (8%) Subjects with Related TEAEs 2 (8%) 5 (20%) 2 (8%) Subjects Discontinued due to TEAE -- 1 (4%) 1 (4%) CNM-Au8 treatment was safe and well-tolerated Treatment emergent adverse events (TEAEs) were predominantly mild-to-moderate and transient No dose limiting adverse events; no related serious adverse events Data on File, Clene Nanomedicine, Inc. Placebo SAEs: (1) Lentigo maligna melanoma, (2) pregnancy; CNM-Au8 15mg SAEs: (1) Pneumonia, bacteremia (staph aureus), endocarditis; CNM-Au8 30mg SAEs: (1) Ketamine infusion for pain and paracetamol overdose; (2) deep vein thrombosis (6-months post-discontinuation)
CNM-Au8 Efficacy Summary First therapy to demonstrate global neurological improvement in MS patients on top of background DMT standard of care Independent quantitative biomarkers of myelin and axonal integrity Clinical and functional improvements LCLA vision improvement mMFSC global neurological improvement VEP amplitude & latency improvements Preservation of retinal structure Structural MRI improvements Data on File, Clene Nanomedicine, Inc.
Trade Secrets Global Patent Status b Patent Description Issued & Allowed Patents 150+ Pending Applications ~20 Total Patents/ Applications >170 Process And Method/Device (Clean Surface; Gold CSN) State of Matter (CNM-Au8) Method of Use (Prevent Demyelination & MoA) Method of Use (Bi-Metallic Au/Pt; Antimicrobial) Plasma Conditioning Electrode Design & Cycling Trough Flow, Temp, Pressure Concentration & Filtration Strong IP & Manufacturing Capability Extensive Patent Portfolio With Protection Through 2035a & Proprietary Trade Secrets; Plus 7-year Orphan Drug Designation, and Scalable to Commercialization a With Patent Restoration Term (assuming 5-year extension). b As of 31-December-2021. In-House ISO8 Clean Room Clinical Production in Maryland
Anticipated Timeline & Upcoming Milestones Sufficient Cash to Hit Key Milestones in 2022 June 30, 2022 Cash and investments on hand (unaudited): $26.3M
CLENE | Growing Phase 2 Evidence Supports CNM-Au8 Commercial Potential June 30, 2022 Cash and investments on hand (unaudited): $26.3M ALS Registration Trial Topline data in 3Q 20222 >350 patient years of CNM-Au8 clinical exposure CNM-Au8® a gold nanocrystal suspension, in development as the first cellular energetic catalyst to remyelinate1 & protect neurological function Manufacturing expansion in progress, preparing for possible commercialization in 2023 Strong IP: 150+ patents on Clean-Surface- Nanocrystal technology (CSN®) platform Data on File, Clene Nanomedicine, Inc. 1Robinson et al. Sci Rep. 2020 Feb 11;10(1):1936.2https://clinicaltrials.gov/ct2/show/NCT04414345.
©2022 Clene Inc. Version: 15-Aug-2022 Clene Inc. HQ & Clinical Development 6550 South Millrock Drive, Suite G50 Salt Lake City, UT 84121 R&D and Manufacturing 500 Principio Parkway, Suite 400 North East, MD 21901
Exhibit 99.3
Clene Reports Positive Topline Results for CNM-Au8®
in the Phase 2 VISIONARY-MS Trial in Multiple Sclerosis
SALT LAKE CITY, August 15, 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 diseases, today announced positive topline results from the Phase 2 VISIONARY-MS trial of CNM-Au8®, an investigational gold nanocrystal suspension, in participants with stable relapsing remitting multiple sclerosis (RRMS).
VISIONARY-MS was a Phase 2 proof-of-concept, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of CNM-Au8 (15 mg or 30 mg daily) as adjunctive therapy to currently available disease-modifying therapies (DMTs) versus placebo over 48 weeks in stable RRMS participants with chronic optic neuropathy.
As announced in February 2022, the trial was stopped prematurely due to COVID-19 pandemic operational challenges, limiting enrollment to 73 out of the 150 planned participants. Due to the limited enrollment, the threshold for significance was pre-specified at p=0.10 prior to database lock. The primary analysis was conducted in a modified intent to treat (mITT) population, which censored invalid data. The mITT population excluded data from a single site (n=9) with LCLA testing execution errors and the timed 25-foot walk data from one subject with a change in mobility assist device. The ITT results were directionally consistent with the mITT results, although the ITT results were not significant.
“These data are very encouraging to us in the MS research and treatment community as we work to address functional improvement in patients,” said Benjamin Greenberg, MD, MHS, FANA, FAAN, CRND Professor of Neurology and one of the trial’s clinical advisors. “The MS community has been successful at limiting relapses, but we need therapies to address progression independent of relapse activity (PIRA). This study was designed as a proof-of-concept evaluation to establish that treatment of neuronal and glial energetic failure can support remyelination and neuroprotection in people living with MS. I am pleased to see the potential effectiveness of CNM-Au8 demonstrated in this trial.”
Primary and secondary results from Baseline to Week 48 were:
Consistent improvements favoring CNM-Au8 were observed across multiple paraclinical biomarkers, including multifocal visual evoked potentials (mfVEP) amplitude and latency, optical coherence tomography (OCT), and MRI endpoints, including magnetization transfer ratio and diffusion tensor imaging metrics. Placebo treated patients, in contrast, generally worsened as expected across these
measures during the 48-week period. These data provide independently assessed quantitative physiological evidence that supports the potential neuroprotective and remyelinating effects of CNM-Au8. The full dataset will be reported at an upcoming scientific congress.
CNM-Au8 was well-tolerated, and there were no significant safety findings reported.
Robert Glanzman, MD, FAAN, Clene’s Chief Medical Officer, said, “In this study, CNM-Au8 demonstrated neurological improvements in people with stable relapsing MS as adjunctive therapy to immunomodulatory DMTs. I am very impressed by the consistency of structural and functional improvements demonstrated by CNM-Au8 throughout the neuraxis. With these data, Clene looks forward to initiating a Phase 3 clinical program in people with MS who are experiencing progression independent of relapse activity, the most urgent unmet medical need in MS today. We look forward to the next phase of clinical development.”
Rob Etherington, Clene’s Chief Executive Officer and President, added, “These results further demonstrate the potential of CNM-Au8 to drive neuronal cellular energy production in patients struggling with MS and other neurodegenerative diseases. We also await additional evidence of clinical efficacy from the HEALEY ALS Platform Trial, which is expected to report topline data later in this quarter. Clene will continue to work tirelessly to further CNM-Au8’s development to treat neurodegenerative diseases.”
Conference Call and Webcast Information
Clene will host a conference call and webcast at 7:30 am EDT to discuss the VISIONARY-MS topline results.
Toll free: 1 (888) 770-7152
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 Presentation page. An archived webcast will be available on the Company’s website approximately two hours after the event.
About VISIONARY-MS
VISIONARY-MS was a Phase 2 multi-center, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of CNM-Au8 in participants with stable relapsing remitting multiple sclerosis (RRMS) with a history of chronic visual impairment who are allowed disease-modifying therapy (DMT). Enrolled subjects were randomized 1:1:1 to CNM-Au8 15 mg/day, 30 mg/day, or placebo. As announced in February 2022, the trial was stopped prematurely due to COVID-19 pandemic operational challenges, enrolling 73 out of the 150 planned participants. Due to limited enrollment, the threshold for significance was pre-specified at p=0.10 prior to database lock. The primary endpoint was the change in best corrected-low contrast letter acuity (BC-LCLA) from baseline to week 48 in the clinically affected eye. Key secondary efficacy outcomes assessed neurological function by the modified MS Functional Composite (mMSFC) including 25-Foot Timed Walk, Symbol Digit Modalities Test, 9-Hole Peg Test (dominant and non-dominant hands), and LCLA (affected and fellow eye) from baseline through Week 48. For more information, see ClinicalTrials.gov. Identifier: NCT03536559. The open label extension of VISIONARY-MS is ongoing.
About CNM-Au8®
CNM-Au8 is an oral suspension of gold nanocrystals developed to restore 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; 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 |
|
Source: Clene Inc.
Visionary-MS Webinar 15 August 2022 Exhibit 99.4
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.
Phase 2 Results Treatment of Visual Pathway Deficits In Chronic Optic Neuropathy for Assessment of Remyelination in Non-Active Relapsing MS
Core Design Elements Change in Low Contrast Letter Acuity (LCLA) 1 2 https://clinicaltrials.gov/ct2/show/NCT03536559, Data on File, Clene Nanomedicne, Inc. Change in modified MS Functional Composite (mMSFC) Enrolled stable relapsing remitting MS participants with chronic optic neuropathy on background DMTs n=73 of 150 planned – study ended prematurely due to pandemic-related enrollment challenges Phase 2 Study: 48-Week Placebo-Control Treatment Period 2:1 Randomization (Active [15mg, 30 mg]: Placebo) LCLA 9HPT SDMT T25FWT
Baseline Demographics Showed Balanced Randomization and Clinical Profile Baseline Value mean (sd) Age (yrs) Sex n, (%) Female Race n, (%) White Weight (kg) EDSS Score Years from Dx Months Since Relapse CNM-Au8 15 mg (n=24) 38.4 (10.2) 15 (63%) 23 (96%) 78.0 (17.1) 1.83 (1.3) 6.5 (5.0) 53 (57) CNM-Au8 30 mg (n=25) 39.6 (7.6) 16 (64%) 24 (96%) 78.6 (17.3) 1.50 (1.1) 3.4 (3.3) 37 (35) Placebo (n=24) 38.1 (8.3) 20 (83%) 22 (92%) 83.0 (23.3) 1.85 (1.4) 6.6 (3.7) 57 (38) All Participants (n=73) 38.7 (8.6) 51 (70%) 69 (95%) 79.9 (19.3) 1.75 (1.5) 5.5 (4.3) 49 (45) Data on File, Clene Nanomedicine, Inc. All participants were diagnosed with stable relapsing remitting MS with chronic optic neuropathy 92% treated with background DMTs (53% monoclonal antibodies, 32% oral)
Pandemic Significantly Impacted Study Conduct Study was ended prematurely due to COVID enrollment challenges (as announced February 2022) Enrolled 73 of 150 planned Underpowered due to limited enrollment Pre-specified statistical threshold set at p=0.10 COVID restrictions precluded direct Sponsor monitoring Objectives Learn from results Evaluate strength of evidence for further MS development Data on File, Clene Nanomedicine, Inc.
modified ITT (mITT) Analysis Population Censored observations included Change in mobility assist device (cane to walker) for T25FW (n=1) Invalid data from 1 of 11 sites (n=9) with LCLA testing execution errors Multiple testing locations with different light boxes and varying ambient lighting conditions In consultation with study Principal Investigator and external experts, all clinical data from the site were excluded Data on File, Clene Nanomedicine, Inc.
CNM-Au8 treatment significantly improved vision Primary outcome - low contrast letter acuity (LCLA) LCLA in the Affected Eye Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants LCLA 2.5% Contrast
Lead 2nd EP | (m)MFSC Composite Mean Standardized Change (6-domain) CNM-Au8 demonstrated global neurological improvement by the modified MS functional composite LCLA SDMT 9HPT T25FWT Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
CNM-Au8 neurological improvement was driven by cognition, manual dexterity, and low contrast vision LCLA SDMT 9HPT T25FWT Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
2nd EP | mMFSC Averaged Rank Sum Score CNM-Au8 treatment improved functional outcomes Improvement relative to placebo decline Score all subjects versus all other subjects by each mMSFC domain Better function than comparison Same function as comparison Worse function than comparison Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
Time to repeated clinical improvement was not significant 2nd EP | Time to Repeated Clinical Improvement (Last 2nd EP) Data on File, Clene Nanomedicine, Inc. mITT excludes one site where data inconsistencies were observed in both active and placebo participants
The Visual System is a Window into the MS Brain Quantitative physiological biomarkers of Improved axonal and myelin integrity Balcer et la. Mult Scler. 2017 Apr;23(5):734-747. Visual Evoked Potentials (VEP) Advanced MRI Techniques Optical Coherence Tomography Diffusion Tensor Imaging Magnetization Transfer Ratio Retinal nerve fiber layer thickness Ganglion cell layer thickness multifocal Amplitude multifocal Latency
CNM-Au8 improved visual information processing Multi-focal VEP amplitude – marker of axonal integrity Increased Amplitude (Signal Strength) Data on File, Clene Nanomedicine, Inc.
CNM-Au8 improved myelin integrity Multi-focal VEP latency – marker of remyelination Increased Conduction Velocity (Signal Speed) Supports Remyelination or Enhanced Functional Myelin Integrity Data on File, Clene Nanomedicine, Inc.
CNM-Au8 improved axonal integrity Structural MRI marker of fractional anisotropy Data on File, Clene Nanomedicine, Inc. DTI Diffusion Patterns
CNM-Au8 improved magnetization transfer ratio Increased myelin integrity throughout the brain Data on File, Clene Nanomedicine, Inc.
CNM-Au8 preserved retinal structure Protection of retinal nerve fiber & ganglion cell layers Data on File, Clene Nanomedicine, Inc.
Safety Summary Treatment Emergent Adverse Events (TEAEs) CNM-Au8 15 mg number (%) CNM-Au8 30 mg number (%) Placebo number (%) Subjects with any TEAE 21 (88%) 25 (100%) 22 (92%) Subjects with SAE 1 (4%) 2 (8%) 2 (8%) Subjects with Related TEAEs 2 (8%) 5 (20%) 2 (8%) Subjects Discontinued due to TEAE -- 1 (4%) 1 (4%) CNM-Au8 treatment was safe and well-tolerated Treatment emergent adverse events (TEAEs) were predominantly mild-to-moderate and transient No dose limiting adverse events; no related serious adverse events Data on File, Clene Nanomedicine, Inc. Placebo SAEs: (1) Lentigo maligna melanoma, (2) pregnancy; CNM-Au8 15mg SAEs: (1) Pneumonia, bacteremia (staph aureus), endocarditis; CNM-Au8 30mg SAEs: (1) Ketamine infusion for pain and paracetamol overdose; (2) deep vein thrombosis (6-months post-discontinuation)
CNM-Au8 Efficacy Summary First therapy to demonstrate global neurological improvement in MS patients on top of background DMT standard of care Independent quantitative biomarkers of myelin and axonal integrity Clinical and functional improvements LCLA vision improvement mMFSC global neurological improvement VEP amplitude & latency improvements Preservation of retinal structure Structural MRI improvements Data on File, Clene Nanomedicine, Inc.
Conclusions and Next Steps First proof of neuroprotective and remyelinating treatment for MS Multiple signals of clinical and biomarker improvement Clinical neurological function Axonal integrity and neuroprotection Remyelination and myelin integrity Results support advancement into Phase 3 MS clinical development Data on File, Clene Nanomedicine, Inc.
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