Slide 1: Revolutionizing Treatment to Restore and Protect Neuronal Health
Revolutionizing Treatment to Restore and Protect Neuronal Health for Those Living with Neurodegenerative Diseases B® cLene clene.com )\_4 NANOMEDICINE™
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of Section 21€ 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 create
Slide 3: ALS is a Progressive, Fatal Disease with No Cure
ALS is a Progressive, Fatal Disease with No Cure i* ES 3 ALS is a progressive and fatal neurodegenerative disease that destroys motor neurons that control Us Yy movement, speech, swallowing, and breathing. ~100 | ~100 ~35,000 people in the U.S are — a —_ | living with ALS. Diagnosed Deaths Weekly We
Slide 4: People Living with ALS Experience Substantial Burden
People Living with ALS Experience Substantial Burden ALS patients often experience diagnostic delays, progressive loss of function, and increasing care needs throughout every stage of the disease journey. ALS Patient Journey (5) 6 End Stage Early Symptoms Diagnosis Functional Decline Early weakness
Slide 5: Significant Unmet Need Remains Despite the Current Standard of Care
Significant Unmet Need Remains Despite the Current Standard of Care These suboptimal outcomes underscore the need for new approaches that meaningfully slow disease progression and improve long-term outcomes. NO CURE TREATMENT GAP DISEASE PROGRESSION BURDEN PERSISTS o—_o—_—_o_©® FDA-approved therapie
Slide 6: Our Mission: Extend Survival for People Living with ALS
Our Mission: Extend Survival for People Living with ALS Clene Nanomedicine is a clinical-stage biopharmaceutical company advancing CNM-Au8® for ALS. CNM-Au8® is a gold nanocrystal therapeutic designed to improve neuronal energy metabolism and protect neuronal function Restore mitochondrial Enhance c
Slide 7: CNM-Au8 is Scientifically Designed to Support Mitochondrial Function and Enhance Neuronal Resilience
CNM-Au8 is Scientifically Designed to Support Mitochondrial Function and Enhance Neuronal Resilience CNM-Au8 Clean-surfaced, catalytically active suspension r | Y Blood-brain-barrier penetrant Y Taken orally, by mouth or feeding tube ¥ 30mg/60 mL once daily CNM-Au8s im CLene 7 Data on File, Clene Na
Slide 8: Two Independent Clinical Trials + NIH-Sponsored EAP Strengthen Cross-Study Confirmation of NfL Findings
Two Independent Clinical Trials + NIH-Sponsored EAP Strengthen Cross-Study Confirmation of NfL Findings HEALEY ALS Platform Trial Design NIH Expanded Access Program Nfl Biomarker Collection 3 Active:t Placebo Randomization Nfl Biomarker Cees 1:1 Randomization cit Nfl Biomarker Collection fz== Open L
Slide 9: NfL Provides Measure of Neuroaxonal Injury in ALS
NfL Provides Measure of Neuroaxonal Injury in ALS What is Neurofilament Light Chain (NfL) 7 NfL is a structural protein abundant in axons. Neuronal axonal eqdothellst cells injury releases NfL into CSF and blood, enabling repeat measurement from plasma or serum. . A js Ependymal cells Neurofilament
Slide 10: ALS NfL Trajectory Increase is Associated with Mortality Risk
ALS NfL Trajectory Increase is Associated with Mortality Risk NfL Clinical Dose-Response NfL Trajectory NIL Decrease (protective) NIL Increase (adverse) In observational datasets, increasing NfL levels are associated with a significantly increased risk of death, while decreasing NfL levels are prote
Slide 11: HEALEY ALS: Early NfL Reduction Preceded Long-Term Survival
HEALEY ALS Platform Trial Early NfL Reduction Preceded Long-Term Survival Although no ALSFRS-R functional benefit was observed during the 24-week double-blind period, CNM-Au8& significantly reduced NfL. Early NfL reduction (double-blind period) 24-WEEK RANDOMIZED PERIOD Early NFL 10% Reduction Lower
Slide 12: ~10% NfL Reduction Was Reproduced Across Two Independent ALS Populations
~10% NfL Reduction Was Reproduced Across Two Independent ALS Populations Confirmatory analyses conducted in response to FDA feedback. Reproducible NfL EY A . REAL-WORLD EVIDENCE @ @® RANDOMIZED, _ Reduction DOUBLE-BLIND NIH-SPONSORED EAP ACT CONTROLLED TRIAL wunneeeee| lower plasma NfL vs. placebo r
Slide 13: Evidence Framework for NfL Response as a Surrogate Biomarker
Evidence Framework for NfL Response as a Surrogate Biomarker Reasonably Likely to Predict Clinical Benefit EVIDENCE QUESTION POPULATION COMPARISON CNM-Au8 Treatment Effect allcnm-aus- | => Among CNM-Au8 treated participants, does NfL treated Cvs > response correspond with clinical outcomes? i CNM-Au
Slide 14: CNM-Au8 mg Treatment NfL Response Showed Improved Survival
CNM-Au8 30 mg Treatment NfL Response Showed Improved Survival | HEALEY and RESCUE-ALS NfL Response drives a survival benefit compared to non-NfL Responders | Within arm comparison. HEALEY ALS Dx) RESCUEALS Platform Trial 52% 76% Trend for lower adjusted Significantly lower adjusted mortality hazard
Slide 15: HEALEY ALS: NfL Response Drives Survival Benefit
HEALEY ALS NfL Response Drives Survival Benefit, Consistent with a Platform Trial Biological Signal NfL Responders lived significantly longer vs concurrently randomized controls. 38% Significantly lower adjusted mortality hazard 15 _ Dstaon File, Clene Nanomedicine, Inc. Post-hoc exploratory analyse
Slide 16: RESCUE-ALS Provides Supportive Evidence, Linking NfL Response to Long-Term Survival Benefit
RESCUE-ALS Provides Supportive Evidence, Linking NfL £2 RESCUEALS Response to Long-Term Survival Benefit NfL responders demonstrated a survival benefit vs propensity-matched controls. 69% Significantly lower adjusted mortality hazard NfL P 16 _ Dataon ile, lene Nanomedicine, inc. Post-hoc explorator
Slide 17: Significant Preservation of ALSFRS-R and SVC in NfL Platform Trial Responders
HEALEY ALS Significant Preservation of ALSFRS-R and SVC in NfL Platform Trial Responders Among CNM-Au8-teated participants, NfL stabilization or decline was associated with clinical benefit versus randomized concurrent control, supporting Nfl response as a clinically relevant biomarker. Elevated NfL
Slide 18: Composite Assessment of Function and Survival (CAFS) Outcomes Concentrated in NfL Responders
HEALEY ALS Composite Assessment of Function and Survival (CAFS) Platform Trial Outcomes Concentrated in NfL Responders Combined survival and functional benefits are greatest in NfL responders vs concurrently randomized controls. CAFS prioritizes survival outcomes before ranking functional decline CA
Slide 19: Clinical Benefit Concentrated in Predicted NfL Responders
HEALEY ALS Clinical Benefit Concentrated in Predicted NfL Responders © 4 Ptrorm tia (Evidenced by Randomization-based Causal Analysis) Survival and functional benefit is concentrated in participants whose baseline profile predicts NfL response. stratum Overall survival CAFS (function + survival] 19
Slide 20: Favorable Safety Profile with Long-Term Exposure
Favorable Safety Profile with Long-Term Exposure * Over 1250 years of patient exposure * CNM-Au8 continuous daily long-term treatment duration over 6.8 years * Nearly 900 patients treated in clinical and EAP programs + No CNM-Au8®-related serious adverse events reported across clinical and expanded
Slide 21: FDA Guidance Frames NfL as a Potential Surrogate Endpoint for Accelerated Approval
FDA Guidance Frames NfL as a Potential Surrogate Endpoint for Accelerated Approval ; Accelerated Approval Pathway Requirements V Q1 2026 - Type C Meeting The Agency requested that the Company provide additional ‘ information in its NDA, including to support a connection ~ The indication must address
Slide 22: Evidence Package Supports Planned NDA Submission and RESTORE-ALS Phase 3 Confirmatory Trial
Evidence Package Supports Planned NDA Submission and RESTORE-ALS Phase 3 Confirmatory Trial Concordant biomarker and survival findings from HEALEY, RESCUE-ALS, and the NIH-EAP inform the planned accelerated approval submission and RESTORE-ALS Phase 3 confirmatory trial . PI d NDA Submissi Integrated
Slide 23: RESTORE-ALS Phase 3 Trial Snapshot
RESTORE-ALS Phase 3 Trial Snapshot Study Overview @ Primary endpoint * Improved overall survival (delayed time to death or PAV * 108-week duration * 2:1 randomization active to placebo * N=690 * Global @ Secondary & Exploratory Endpoints * Delayed time to ALS clinical worsening @ Inclusion * svc * A
Slide 24: Evidence Supports Pipeline in a Product Therapeutic Potential to Treat Neurodegeneration
Evidence Supports Pipeline in a Product Therapeutic Potential to Treat Neurodegeneration Cash and equivalents on hand: >1,200 . CNM-Au8 treated participant years of $12.9M patients whose NfL CNM-Au8 clinical declined or stabilized Sufficient cash and clined or st exposure lived significantly longer
Slide 25: Clene Inc.
25 > CLene NANOMEDICINE Clene Inc. HO & Clinical Development 6550 South Millrock Drive, Suite G50 Salt Lake City, UT84121 R&D and Manufacturing 500 Principio Parkway, Suite 400 North East, MD 21901 ©Clene Inc. Aug 10, 2026