Clene : 2023 Annual Report to Stockholders

WE ENVISION A FUTURE WHERE THE

BOUNDARIES OF NEURODEGENERATIVE

DISEASES ARE TRANSCENDED,

WHERE INDIVIDUALS NOT ONLY

SURVIVE BUT THRIVE

2 0 2 3

A N N U A L R E P O R T

FOCUSED ON IMPROVING MITOCHONDRIAL

HEALTH AND PROTECTING NEURONAL FUNCTION

TO TREAT NEURODEGENERATIVE DISEASES

THE PROBLEM

• Neuronal decline, a natural part of aging, is intensified in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), where energy deficits worsen the dysfunction.

• The World Health Organization forecasts neurodegenerative diseases to rank as the second-most prevalent cause of death within the next

20 years, underscoring the urgent need for therapeutic advancements.1

• Impaired mitochondrial activity and compromised cellular metabolism in these diseases contribute to neuronal death, highlighting the critical role of addressing energetic deficits in developing treatments.

A NEW APPROACH

• Clene is pioneering catalytic nanotherapeutics to treat neurodegenerative diseases, such as ALS, multiple sclerosis (MS) and Parkinson's disease (PD).

• By targeting the improvement of mitochondrial function via the nicotinamide adenine dinucleotide pathway, Clene's first-in-class drug, CNM-Au8®, is pioneering a new way to restore and protect neuronal function.

1 Gammon, K. Neurodegenerative disease: Brain windfall. Nature 515, 299-300 (2014). https://doi.org/10.1038/nj7526-299a

EVIDENCE OF CNMAU8

THERAPEUTIC POTENTIAL TO TREAT ALS

Improved Survival and Delayed Time to Clinical Worsening From Two Phase 2 ALS Trials and Real-World Evidence through EAPs

	RESCUE-ALS	RESCUE-ALS	TWO EXPANDED
	& HEALEY ALS	& HEALEY ALS	ACCESS
	Double Blind	Open Label	PROGRAMS
	Trial Period	Extensions (OLEs)	(EAPs)
ALS Patient	Early-to-	Early-to-	Real-World
Late-Stage	Late-Stage	Experience
Demographics
n=206	n=170	n=256
Duration	Up to 36 weeks	Up to 173 weeks	Over 4 years
Survival
Delayed Time to
Clinical Worsening			Not routinely
Progression	NfL*	NfL*	collected
Biomarkers

Safety	>600 years of subject exposure without identified
safety signals across ALS, MS, and PD

*Neurofilament light

RESCUE-ALS, a Phase 2 multi-center, randomized, double-blind,parallel-group,placebo-controlled trial, examined the ecacy and safety of CNM-Au8 in 45 patients with early early ALS conducted in Australia. Subjects were randomized 1:1 to receive either active treatment with CNM-Au8 (30 mg) or placebo in addition to their current standard of care over a

36-week treatment period. For more information, please see ClinicalTrials.govIdentifier: NCT04098406.

The HEALEY ALS Platform Trial is a perpetual multi-center, randomized, double-blind,placebo-controlled Phase 2 program designed to evaluate the ecacy and safety in people living with ALS. Subjects were randomized 3:1 to receive active treatment or placebo for the 24-weekdouble-blind treatment period followed by the option to enroll in the OLE in which all subjects receive active drug. For more information, please see ClinicalTrials.govIdentifier: NCT04297683.

EAP01 with Massachusetts General Hospital (MGH), started in 2019 to oer people with ALS access to Clene's investigational drug CNM-Au8.

EAP02 with MGH and 17 centers across the United States, started in 2023, is ongoing. This EAP was initiated to allow people with ALS who were participants in the Healey ALS Platform Trial continued access to CNM-Au8 once the long-term extension of the regimen ended.

EVIDENCE OF CNMAU8 THERAPUETIC

POTENTIAL TO TREAT MULTIPLE SCLEROSIS

IMPROVEMENT in LONG-TERM FUNCTION, VISION and COGNITION with CNM-Au8 treatment observed in up to 3 years of follow up

VISIONARY-MS, a Phase 2 trial designed to investigate the protection or improvement of neurological function in stable relapsing remitting MS participants with chronic optic neuropathy treated with CNM-Au8

			Patients	Stable relapsing remitting MS with chronic optic neuropathy
	Stable background	92% on eective immunomodulatory disease-modifying
				therapy	therapies (DMTs)
					Double Blind Period	Long Term Extension (LTE)
		Participants &	48 weeks	Additional 96 weeks
		Trial Duration	N=73	N=55/69 (80%)
	Low Contrast Vision
		Cognition &
		Working Memory
Neurological Function
		(low contrast vision,
cognition, upper extremity
function, and walking speed)
		MRI Biomarkers	Improved axonal integrity	Improved axonal integrity
VEP: Visual evoked potential	Preservation of white	Preservation of white
DTI: Diusion tensor imaging
matter integrity	matter integrity
				Safety	>600 years of subject exposure without identified
				safety signals across ALS, MS, and PD
					Clinicians noted that observed clinical improvements for participants with stable
					disease, over and above background immunomodulatory DMTs, are unprecedented.

VISIONARY-MS was a Phase 2 multi-center, randomized, double-blind,placebo-controlled trial evaluating the ecacy and safety of CNM-Au8 (15 mg or 30 mg daily) versus placebo over 48 weeks of double-blind treatment. The primary outcome was low contrast

letter acuity (LCLA) improvement. Global neurological improvement, measured by the modified Multiple Sclerosis Functional Composite (mMSFC) including vision, cognition, upper extremity function, and walking speed assessment was the secondary

outcome. In the double-blind portion of the trial, 73 participants were randomized, with 55 of 69 eligible (80%) participants continuing in the LTE. For more information, see ClinicalTrials.govIdentifier: NCT03536559.

2024 CLENE PRIORITIES

				01
			Advance regulatory
			agency discussions
			with FDA and EMA
02		for CNM-Au8 path	03
		forward in ALS
Launch Global					Expand
Phase 3 ALS Trial			collaboration with
						advocacy groups

04		and people living
		with ALS
Pursue opportunities
for MS clinical
development with
a focus on high
unmet need

DEAR SHAREHOLDER

OUR MISSION REMAINS FOCUSED on a future where the boundaries of neurodegenerative diseases are transcended, and individuals not only survive but thrive. We are reshaping the scientific approach to brain disorders through supporting mitochondrial health and protecting neuronal function. The entire Clene team is singularly focused on bringing our first-in-class therapy to market across multiple neurodegenerative indications.

We are increasingly convicted that CNM-Au8® has a survival benefit for people living with the devastation of amyotrophic lateral sclerosis (ALS). This conviction is reinforced by three independent data sets, including the Harvard/MGH Healey ALS Platform study's secondary endpoint alongside concordant survival data from the RESCUE-ALS Phase 2 long-term data and the two compassionate use Expanded Access Programs.

This year, we have continued to advance our regulatory discussions for ALS with the U.S. Food and Drug Administration (FDA). Through our discussions with the FDA in the fourth quarter of last year, we have a clear understanding of the additional data required to support an accelerated approval pathway filing for CNM-Au8 in ALS. We are working to provide additional supportive evidence to the FDA by mid-2024 and anticipate providing new data on biomarkers as well as additional clinical and survival outcomes. These data will build on foundational discussions with the FDA with the potential to file an NDA later this year.

Clene recently released long-term data from the VISIONARY-MS Phase 2 trial that showed CNM-Au8 improved vision and cognition on top of standard-of-care disease modifying drugs (DMT) in stable patients. Such functional improvements on top of DMTs has never been shown previously in multiple sclerosis (MS). These vision and cognition improvements, among other functional and structural benefits, were recently presented at the American Academy of Neurology annual meeting, showing evidence of neuron protection in the brain after treatment with CNM-Au8.

Our long-term clinical data in ALS and MS continues to support that CNM-Au8 treatment is safe and well-tolerated, reinforcing the exceptional safety profile.

We are grateful for the support of you, our investors, who share our mission.

Sincerely,

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

• ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2023
  or
• TRANSITION REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _____________ to _____________
  Commission file number: 01-39834

					CLENE INC.
			(Exact name of registrant as specified in its charter)
Delaware							85-2828339
(State or other jurisdiction of								(I.R.S. Employer
incorporation or organization)								Identification No.)
6550 South Millrock Drive, Suite G50
Salt Lake City, Utah							84121
(Address of principal executive offices)								(Zip Code)
			[phone]
			(Registrant's telephone number, including area code)
			Securities registered pursuant to Section 12(b) of the Act:
Title of each class			Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.0001 par value					CLNN		The Nasdaq Capital Market
Warrants, to acquire one-half of one share of Common Stock			CLNNW		The Nasdaq Capital Market
for $11.50 per share

Securities registered pursuant to Section 12(g) of the Act: None.

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in Rule 12b-2 of the Exchange Act.

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☒	Smaller reporting company	☒
		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. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management's assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant's executive officers during the relevant recovery period pursuant to §240.10D-1(b).☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒

The aggregate market value of the registrant's common stock held by non-affiliates as of June 30, 2023, the last business day of the registrant's most recently completed second fiscal quarter, was approximately $78.1 million, based on the closing price of the registrant's common stock on the Nasdaq Capital Market of $0.88 per share.

The number of shares outstanding of the Registrant's shares of common stock as of March 8, 2024 was 128,430,098.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant's definitive proxy statement relating to its 2024 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. The definitive proxy statement will be filed with the U.S. Securities and Exchange Commission within 120 days after the end of fiscal year to which this report relates.

CLENE INC.

Annual Report on Form 10-K for the Year Ended December 31, 2023

PART I		3
Item 1.	Business	6
Item 1A.	Risk Factors	43
Item 1B.	Unresolved Staff Comments	75
Item 1C.	Cybersecurity	75
Item 2.	Properties	79
Item 3.	Legal Proceedings	79
Item 4.	Mine Safety Disclosures	79
PART II		80
Item 5.	Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	80
Item 6.	[Reserved]	80
Item 7.	Management's Discussion and Analysis of Financial Condition and Results of Operations	81
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	93
Item 8.	Financial Statements and Supplementary Data	94
Item 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	95
Item 9A.	Controls and Procedures	95
Item 9B.	Other Information	96
Item 9C.	Disclosures Regarding Foreign Jurisdictions that Prevent Inspections	96
PART III		97
Item 10.	Directors, Executive Officers and Corporate Governance	97
Item 11.	Executive Compensation	97
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	97
Item 13.	Certain Relationships and Related Transactions, and Director Independence	97
Item 14.	Principal Accountant Fees and Services	97
PART IV		98
Item 15.	Exhibit and Financial Statement Schedules	98
Item 16.	Form 10-K Summary	100

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