# EDGAR Filing Document

**Accession Number:** 0001822791
**File Stem:** 0001437749-25-036712
**Filing Date:** 2025-12
**Character Count:** 17784
**Document Hash:** 6887cc0d251b410ae9ba92a01c15bdc1
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001437749-25-036712.hdr.sgml**: 20251203

**ACCESSION NUMBER**: 0001437749-25-036712

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 14

**CONFORMED PERIOD OF REPORT**: 20251203

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251203

**DATE AS OF CHANGE**: 20251203

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Clene Inc.
- **CENTRAL INDEX KEY:** 0001822791
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 852828339
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-39834
- **FILM NUMBER:** 251545031

**BUSINESS ADDRESS:**
- **STREET 1:** 6550 SOUTH MILLROCK DRIVE, SUITE G50
- **CITY:** SALT LAKE CITY
- **STATE:** UT
- **ZIP:** 84121
- **BUSINESS PHONE:** 801-676-9695

**MAIL ADDRESS:**
- **STREET 1:** 6550 SOUTH MILLROCK DRIVE, SUITE G50
- **CITY:** SALT LAKE CITY
- **STATE:** UT
- **ZIP:** 84121

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Chelsea Worldwide Inc.
- **DATE OF NAME CHANGE:** 20200827

?xml version='1.0' encoding='ASCII'? clnn20251203_8k.htm

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**UNITED STATES**

**SECURITIES AND EXCHANGE COMMISSION**

**WASHINGTON, D.C. 20549**

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**FORM**8-K**

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**CURRENT REPORT**

**Pursuant to Section 13 OR 15(d)** 

**of The Securities Exchange Act of 1934**

**Date of Report (Date of earliest event reported):**December 3, 2025**

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**CLENE INC.**

(Exact name of registrant as specified in its charter)

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| | | |
|:---|:---|:---|
| **Delaware** | **001-39834** | **85-2828339** |
| (State or other jurisdiction | (Commission File Number) | (IRS Employer |
| of incorporation) |  | Identification No.) |
| **6550 South Millrock Drive**,**Suite G50**<br> **Salt Lake City**,**Utah** |  | **84121** |
| (Address of principal executive offices) |  | (Zip Code) |

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**(**801**)**676-9695**

(Registrant's telephone number, including area code)

**N/A**

(Former name or former address, if changed since last report.)

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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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| | | |
|:---|:---|:---|
| **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-fortieth of one share of Common Stock for $230.00 per share | CLNNW | The Nasdaq Capital Market |

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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. ☐

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**Item 8.01 Other Events.**

On December 3, 2025, Clene Inc. issued a press release announcing statistically significant amyotrophic lateral sclerosis ("ALS") biomarker results supporting an accelerated approval pathway for CNM-Au8. A copy of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

**Item 9.01 Financial Statements and Exhibits.**

(d) Exhibits

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| | |
|:---|:---|
| **Exhibit Number** | **Exhibit Description** |
| 99.1 | [Press release, dated December 3, 2025, announcing statistically significant ALS biomarker results supporting accelerated approval pathway for CNM-Au8.](ex_894886.htm) |
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL). |

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**SIGNATURES**

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, hereunto duly authorized.

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| | | |
|:---|:---|:---|
|  | CLENE INC. | CLENE INC. |
| Date: December 3, 2025 | By: | /s/ Robert Etherington |
|  |  | Robert Etherington |
|  |  | President and Chief Executive Officer |

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## Exhibit 99.1

**Exhibit 99.1**

**CLENE ANNOUNCES STATISTICALLY SIGNIFICANT ALS**

**BIOMARKER RESULTS SUPPORTING**

**ACCELERATED APPROVAL PATHWAY FOR CNM-Au8<sup>®</sup>**

● *FDA recommended biomarker analyses show statistically significant reductions in NfL and GFAP in participants treated with CNM-Au8* 

● *Biomarker improvements are strongly associated with longer survival, reinforcing CNM-Au8's potential disease modifying activity* 

● *Company has requested a Type C meeting in the first quarter of 2026 to present the newly completed analyses supporting a planned NDA submission under the accelerated approval pathway* 

● *Clene is hosting an investor webcast today at 8:30 am ET* 

**SALT LAKE CITY, December 3, 2025** -- Clene Inc. (Nasdaq: CLNN) (along with its subsidiaries, "Clene" or the "Company") and its wholly owned subsidiary Clene Nanomedicine, Inc., a late clinical-stage biopharmaceutical company focused on revolutionizing the treatment of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), today announced completion of the FDA-recommended biomarker analyses for CNM-Au8<sup>®</sup> in people living with ALS. The results demonstrate statistically significant reductions in both neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) and provide compelling evidence linking biomarker decline to improved survival.

"We followed the FDA's roadmap — and the data delivered," said Rob Etherington, President and CEO of Clene. "Statistically significant NfL reductions in more advanced real-world ALS patients; a second independent disease-specific biomarker (GFAP) that moves in lock-step with NfL and is itself statistically significant; and clear evidence in placebo switchers (placebo-to-CNM-Au8) showing that CNM-Au8-treated participant's biomarkers follow nearly identical trajectories seen in the original active arm during the double-blind treatment phase of the HEALEY ALS Platform Trial. This is a remarkably consistent dataset that makes a strong case for accelerated approval. We look forward to presenting these analyses to the Division in the requested Type C meeting in the first quarter of 2026 and working with the FDA toward an NDA submission for accelerated approval."

The analyses follow FDA recommendations to support the persuasiveness of the original NfL findings observed in the HEALEY ALS Platform Trial by extending the analyses to the NIH-sponsored EAP (NIH-EAP) for CNM-Au8 in ALS. These biomarker findings build on prior constructive FDA interactions in support of a planned NDA submission under the accelerated approval pathway for the treatment of ALS.

**New Biomarker Analyses**

In late 2024, the FDA recommended three specific analyses to strengthen the persuasiveness of CNM-Au8's effect on NfL and its relationship to clinical benefit (i.e., effects on survival): (1) NfL change in the NIH-EAP, (2) evaluation of additional disease-relevant biomarkers, and (3) evaluation of NfL trajectory in HEALEY placebo participants who later transitioned to CNM-Au8 in the open-label extension (OLE):

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;1. <u>Statistically significant decrease in NfL levels compared to matched ALS controls across the full analysis set (all evaluable matched participants) in the NIH-EAP.</u> The Week 36 AUC (area under curve) difference (SEM) of NfL (Ln(pg/mL)\*Week) was: –0.0899 (0.0430), p = 0.0373, equivalent to a geometric mean ratio (GMR) difference of 0.914, 95% CI: 0.840 – 0.995. The effect size was similar to the NfL decline observed in the original double-blind phase of the HEALEY ALS Platform Trial: HEALEY W24 AUC GMR of 0.901, 95% CI: 0.845 – 0.959, p=0.0013 compared to the NIH-EAP W24 AUC GMR of 0.911, 95% CI: 0.836 – 0.993, p=0.0339. Multiple pre-specified supportive analyses in the NIH-EAP across the full analysis set at Week 24 and Week 48 confirmed the robustness of the findings (p<0.05). Pre-specified subgroups showed significant effects in participants including those with an age younger than the median, on background riluzole treatment, and in participants with bulbar onset (p<0.05). In the primary analysis population in non-bulbar onset participants (i.e., predominantly limb onset), the Week 36 AUC NfL change was not significant (p=0.2085).

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;2. <u>Additional disease-relevant biomarker effects on GFAP were identified with statistically significant declines observed during the double-blind period in the HEALEY ALS Platform Trial (p<0.05)</u> and was highly correlated with NfL change. GFAP is a structural protein in astrocytes. GFAP increase in ALS is a marker of harmful reactive astrogliosis, astrocytic injury, and degenerative processes that contribute to motor neuron loss. High GFAP levels are associated with a statistically significant increase in mortality risk in ALS patients. In comparison, placebo participants demonstrated increases across both NfL and GFAP biomarkers during the 24-week double-blind period. Consistent with these findings, in the matched NIH-EAP population, the magnitude and timing of NfL and GFAP reduction were closely correlated (Pearson's r >0.85, p<0.0001) demonstrating concordant effects for NfL and GFAP in the HEALEY ALS Platform Trial and NIH-EAP participants.

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;3. <u>Among placebo-treated participants who transitioned to CNM-Au8 in the HEALEY ALS Platform Trial OLE, NfL trajectories generally showed decline or stabilization compared to increases observed during the double-blind period</u>. With only relatively few ex-placebo participants (n=31), these analyses had limited power, but the relative decline compared to the double-blind period showed comparable GMR differences (OLE Week 28 GMR: 0.885, 95% CI: 0.737 – 1.063, p=0.185). These findings are consistent with the NfL effects previously published for CNM-Au8 vs. placebo during the 24-week double-blind period (Week 24 GMR difference: 0.905, 95% CI: 0.822 – 0.996, p=0.040).

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;4. <u>NfL and GFAP biomarker decline is associated with improved survival</u>. Among participants treated in the HEALEY ALS Platform Trial with CNM-Au8 30 mg, participants with the greatest declines across both NfL and GFAP biomarkers during the double-blind period had the largest long-term overall survival improvement relative to all participants treated with CNM-Au8 30 mg (NfL and GFAP average AUC decline < 25th percentile): Cox HR: 0.191, 95% CI: 0.047 – 0.782, p=0.0210, an 80% reduction in the risk of death compared to Regimen A concurrent controls.

**CNM-Au8 Strengthens Overall Survival Signal in the HEALEY ALS Platform Trial Open-Label Extension Period**

Updated survival analyses (April 2025 data cut) in participants originally randomized to CNM-Au8 30 mg in the HEALEY ALS Platform Trial continue to demonstrate clinically meaningful and statistically significant survival benefit versus concurrent Regimen A controls. Analyses were conducted at intervals of one year (pre-specified OLE timepoint) and beyond using the prespecified HEALEY ALS Platform Trial covariate model across two populations: the full analysis set (FAS), including all available participant data; and a risk-balanced population, the comparable risk set (CRS) (filtered for disease severity by NfL levels (Ln(NfL) > 3.5 and TRICALS risk score) due to imbalances with significantly more low-progression risk patients present in the Regimen A group.

CNM-Au8 30 mg treatment demonstrated statistically significant improved survival across both the FAS and CRS populations based on a Cox proportional hazard model and restricted mean survival time (RMST) analyses.

In the FAS population:

● 1-year Cox proportional hazard ratio: 0.2723, 95% CI: 0.0961 – 0.7719, p=0.0144 → 73% reduction in risk of death

In the CRS population:

● 1-year Cox proportional hazard ratio: 0.229, 95% CI: 0.07 – 0.752, p = 0.0151 → 77% reduction in risk of death

Even the small cohort of placebo-to-CNM-Au8 switchers (n=31, starting treatment ~6 months later in disease progression) showed a significant RMST benefit of +30.7 days at one year following treatment initiation (95% CI 7.52 – 53.85, p=0.0094).

**Strong CNM-Au8 Safety Profile**

Across over 1,000 patient years of CNM-Au8 exposure data, treatment with CNM-Au8 continues to demonstrate a safety profile without significant safety concerns or safety trends identified. No serious adverse events (SAEs) have been identified as related to CNM-Au8 treatment by any investigator to date.

**ALS Key Opinion Leader Commentary**

"We believe these data show the potential enduring effect of CNM-Au8, because this NIH-EAP data includes participants who are generally more advanced than a typical ALS clinical trial population and still show concordant NfL decline", said Dr Jinsy Andrews, MD, MSc, Director of the Amyotrophic Lateral Sclerosis Center and Medical Director of Clinical Trials in the Department of Neurology at NYU Grossman School of Medicine and principal investigator of the NIH-sponsored EAP. "The consistency of NfL and GFAP reductions in more advanced patients treated in the Expanded Access Program is particularly compelling and suggests potential disease-modifying activity of CNM-Au8."

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**Clene Submitted a Type C Meeting Request to Align on Accelerated Approval NDA Submission**

Clene has requested a Type C meeting with the FDA and anticipates the meeting will occur during the first quarter of 2026 to present the full dataset. The Company plans to submit an NDA under the accelerated approval pathway in the same quarter, with the planned Phase 3 RESTORE-ALS trial serving as the post-approval confirmatory study.

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**The Company will host a conference call and webcast at 8:30 am ET today, on Wednesday, December 3, 2025, to provide an update on its CNM-Au8 program in ALS. Those who would like to participate may access the live webcast here:**

**Webcast Information:**

<u>Title</u>: CNM-Au8 ALS Program Update

<u>Presenters</u>: Rob Etherington, CEO and President; Dr. Ben Greenberg, Head of Medical; Michael Hotchkin, Chief Development Officer, and a KOL

<u>Date</u>: Wednesday, December 3, 2025

<u>Start Time</u>: 8:30 a.m. EST

<u>Webcast link</u>: <u>https://viavid.webcasts.com/starthere.jsp?ei=1744985&tp_key=9fb9583d33</u>

<u>Dial number</u>: 1-877-407-0779 (US) or 1-201-389-0914 (international), Conference ID#13757380

**About Clene**

Clene Inc. (Nasdaq: CLNN), along with its subsidiaries, "Clene" and its wholly owned subsidiary Clene Nanomedicine, Inc., is a late clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and multiple sclerosis. CNM-Au8<sup>®</sup> is an investigational first-in-class therapy that improves central nervous system cells' survival and function via a mechanism that targets mitochondrial function and the NAD pathway while reducing oxidative stress. CNM-Au8<sup>®</sup> is a federally registered trademark of Clene Nanomedicine, Inc. The company is based in Salt Lake City, Utah, with R&D and manufacturing operations in Maryland. For more information, please <u>visit www.clene.com</u> or follow us on <u>X</u> (formerly <u>Twitter</u>) and <u>LinkedIn</u>.

**About the NIH-Sponsored Expanded Access Program (NIH-EAP) for CNM-Au8 in ALS:**

This EAP is a collaborative effort between Clene Nanomedicine, NYU, and Synapticure, with a grant awarded by the NIH (NCT06408727). The program enrolled 183 participants at eight sites across the United States. Comparisons of NIH-EAP participants to natural history ALS controls were made using the U.S. ANSWER ALS dataset. A previously considered large European natural-history dataset was determined, upon detailed quality review, not to meet FDA-required quality standards. Clene therefore selected the U.S. ANSWER ALS dataset to ensure the most reliable and defensible external comparator for regulatory purposes.

**About CNM-Au8<sup>®</sup>**

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<sup>®</sup> is a federally registered trademark of Clene Nanomedicine, Inc.

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**Forward-Looking Statements**

**<u>Investor Contact</u>:** Kevin Gardner, LifeSci Advisors; <u>kgardner@lifesciadvisors.com</u>; 617-283-2856