EX-99.4 5 clnn-ex99_4.htm EX-99.4

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Visionary-MS Webinar 15 August 2022 Exhibit 99.4


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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.


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Phase 2 Results Treatment of Visual Pathway Deficits In Chronic Optic Neuropathy for Assessment of Remyelination in Non-Active Relapsing MS


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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


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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)


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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.


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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.


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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


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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


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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


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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


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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


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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


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CNM-Au8 improved visual information processing Multi-focal VEP amplitude – marker of axonal integrity Increased Amplitude (Signal Strength) Data on File, Clene Nanomedicine, Inc.


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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.


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CNM-Au8 improved axonal integrity Structural MRI marker of fractional anisotropy Data on File, Clene Nanomedicine, Inc. DTI Diffusion Patterns


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CNM-Au8 improved magnetization transfer ratio Increased myelin integrity throughout the brain Data on File, Clene Nanomedicine, Inc.


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CNM-Au8 preserved retinal structure Protection of retinal nerve fiber & ganglion cell layers Data on File, Clene Nanomedicine, Inc.


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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)


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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.


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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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