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Revolutionizing Neurodegenerative Disease Using Bioenergetic Nanotherapeutics to Improve Patients‘ Lives

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Revolutionizing Neurodegenerative Disease Using Bioenergetic Nanotherapeutics to Improve Patients‘ Lives CLENE INC. ANNUAL REPORT 2020 REPORT ANNUAL REVOLUTIONIZING NEURODEGENERATIVE DISEASE USING BIOENERGETIC NANOTHERAPEUTICS TO IMPROVE PATIENTS‘ LIVES ANNUAL REPORT 2020 Breakthrough Needed for Patients Eective treatment of patients with neurodegenerative disorders requires a therapeutic breakthrough. The World Health Organization predicts diseases of neurodegeneration will become the second-most prevalent cause of death within the next 20 years1. Bioenergetic Opportunity Bioenergetic failure underlies the pathophysiology of many neurodegenerative diseases2. However, rescuing failing bioenergetic systems in these diseases has historically been extremely challenging3. Bioenergetic Nanotherapeutics Clene® is rapidly advancing a pipeline of bioenergetic nanotherapeutics, the first of those is CNM-Au8, designed to enhance naturally occurring cellular metabolism with the goal of reversing neurodegeneration. This new class of drugs called bioenergetic nanocatalysts has been created to accelerate neurorepair, improve neuroprotection, and enhance remyelination4. Innovative Platform The innovative platform is an electrochemistry approach to growing clean-surfaced, metallic nanocrystal therapeutics. The nanotherapeutic CNM-Au8 is designed to optimize cellular health and repair through energy enhancing bioenergetic catalysis. Using pure, clean-surfaced gold nanocrystals, we are able to amplify healthy, intracellular reactions necessary for cells to function and defend CLENE themselves from disease4. INNOVATE PROTECT REPAIR BIOENERGETIC NANOTHERAPEUTICS CNM-Au8 Clene Team Clene carefully engineered its lead drug Behind every innovative platform is a candidate, CNM-Au8, a bioenergetic team of inventive minds. Clene nanocatalyst which enhances critical enlisted a leadership team of intracellular bioenergetic reactions seasoned industry veterans united by necessary for repairing and reversing their appetite for innovation and neuronal damage. Orally administered, committed to advancing the CNM-Au8 has demonstrated safety in Phase company’s pipeline rapidly. Our 1 studies, and has been shown to have singular vision is to transform the remyelination and neuroprotective eects in treatment of neurodegenerative preclinical models4. Multiple clinical trials are diseases that steal away peoples’ lives, underway with CNM-Au8. allowing people to thrive. REFERENCES CITED 1. Gammon, K. Neurodegenerative disease: Brain windfall. Nature 515, 299–300 (2014). 2. Camandola, S. & Mattson, M. P. Brain metabolism in health, aging, and neurodegeneration. EMBO J 36, 1474–1492 (2017). 3. Cunnane, S. C. et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of aging. Nat Rev Drug Discov (2020) doi:10.1038/s41573-020-0072-x. 4. Robinson, A. P. et al. Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis. Sci Rep 10, 1936 (2020). The electrochemistry devices which grow the clean-surfaced nanocrystals of CNM-Au8 NEW PARADIGM A Bioenergetic Approach in Neurodegenerative Medicine INNOVATIVE Electrochemistry Drug Development Platform Integrating Physics with Biology BIOENERGETIC NANOTHERAPEUTICS The new class of drugs called bioenergetic nanocatalysts has been created to accelerate neurorepair, improve neuroprotection, and enhance remyelination. BIOENERGETIC NANOTHERAPEUTICS PIPELINE Clene is rapidly advancing a pipeline of nanotherapeutics, the first of those is CNM-Au8, designed to enhance naturally occurring cellular metabolism with the goal of reversing neurodegeneration. CNM-Au8 is being studied in multiple clinical trials, including a Phase 2 study (VISIONARY-MS) for the treatment of stable multiple sclerosis, Phase 2 biomarker studies in MS (REPAIR-MS) and Parkinson’s (REPAIR-PD), and a Phase 2 (RESCUE-ALS) and a Phase 3 (HEALEY-ALS Platform) ALS trials to investigate the potential for disease modification by CNM-Au8 for neurodegenerative diseases. CSN® THERAPEUTIC INDICATION RESEARCH PRECLINICAL IND FILING PHASE 1 PHASE 2 PHASE 3 ANTICIPATED RESULTS or EAP Healey ALS Platform Trial Harvard MGH (Registration Trial) 1H 2022 Amyotrophic Lateral Sclerosis Phase 2 (Australia) 2H 2021 ALS Expanded Expanded Access Program ONGOING CNM-Au8 Access Harvard (MGH) (CSN® gold) * Phase 2 1H 2022 Multiple Sclerosis * Pha se 2 2H 2021 Pha se 2 2H 2021 Parkinson's Disease Pha se 2 Planned 1H 2024 Anti-viral CNM-ZnAg ZnAgSTUDY Phase 2 2H 2021 (CSN® zinc-silver) Anti-bacterial BRAZIL CNM-AgZn17 Wound Healing, CSN® (silver-zinc gel) Burn Treatment CNM-PtAu7 Oncology (CSN® platinum-gold) *Subject to ongoing COVID-19 related site research restrictions generally implemented to protect MS patients taking standard-of-care immunosuppressive therapies TO OUR SHAREHOLDERS Dear Shareholder, I am incredibly proud of the progress Clene made in 2020. Despite the challenges of the pandemic, we advanced our clinical pipeline and became a well-funded publicly traded company. Clene ended the year financially stronger and better positioned to deliver on our mission to shift the paradigm of neurodegenerative disease treatment and improve the lives of patients. New Year’s Eve @ NASDAQ We successfully closed our merger with Tottenham Acquisition I Limited on December 30, 2020, a SPAC (special purpose acquisition company), completed a PIPE (private investment into public equity) of around $22M, and celebrated our first day of trading as a public company by virtually ringing ROB ETHERINGTON the NASDAQ bell on New Year’s Eve. CLNN was proudly featured on the NASDAQ tower in Times Square. PRESIDENT & CHIEF Following our NASDAQ debut, Clene’s market capitalization has increased, we EXECUTIVE OFFICER have over $59 million in cash on our balance sheet as of the end of 2020, and we remain very excited about our prospects as a newly public company. Such a New Year’s Eve celebration was ancillary, however, to the progress Clene made in 2020 on our clinical objectives. Every day, we work to help fulfill the promise that our lead asset CNM-Au8 may bring to patients struggling with devastating neurodegenerative diseases such as Multiple Sclerosis (MS), Parkinson’s, and Amyotrophic Lateral Sclerosis (ALS). Patients enrolled in our studies have been partnering with and counting on Clene as we look forward to the completion of our ongoing Phase 2 clinical trials and our Phase 3 registrational ALS trial. Bioenergetic Nanotherapeutics CNM-Au8 is the first drug asset to emerge from our innovative electrochemistry drug development platform. CNM-Au8 is a first-in-class bioenergetic nanocatalyst designed to optimize neurorepair and health through energy-enhancing bioenergetic catalysis. Our platform is enabling the pioneering discovery and development of novel clean surfaced nanotechnology (CSN®) therapeutics. CSN® therapeutics are comprised of atoms of transition elements that, when assembled in nanocrystalline form, possess unusually high, unique catalytic activities. CNM-Au8 can drive, support, and maintain beneficial metabolic and energetic intercellular reactions within diseased, stressed, and damaged cells. Many individuals and institutions around the world are discovering that Clene has tremendous potential. Our platform of discovery of CSN® therapeutic candidates could bring hope to addressing many high unmet medical needs in several disease areas over the next few years. Amyotrophic Lateral Sclerosis (ALS) Despite the pandemic stymieing clinical R&D progress for many pharmaceutical companies, Clene saw steady progression in its ALS clinical trials. We completed patient enrollment in the Phase 2 RESCUE-ALS proof-of-concept study in 2020. Clene also commenced our registrational partnership with Harvard/Mass General Hospital’s HEALEY ALS Platform trial. We are more than halfway enrolled in this trial. In addition, as of this writing, Clene has ALS patients on CNM-Au8 in our Early Access Protocol being facilitated by Massachusetts General Hospital for more than 78 weeks. Together, these two ALS trials could be the first in the world to demonstrate meaningful improvements in neurological function for ALS patients. Both trials’ clinical endpoints assess how ALS patients might improve their ability to move, walk, talk, eat and breathe—the fundamental qualities of life and living that each of us takes for granted every day. We anticipate that the RESCUE-ALS program will read-out its full unblinded results in the second half of 2021, with unblinded topline data from HEALEY expected in the first half of 2022. Every day, we work to help fulfill the promise that our lead asset CNM-Au8 may bring to patients struggling with devastating neurodegenerative diseases such as Multiple Sclerosis, Parkinson’s, and Amyotrophic Lateral Sclerosis (ALS). Parkinson’s & MS Clene also made progress towards the investigation of how CNM-Au8 works in the brain of Parkinson’s and Multiple Sclerosis patients, with preliminary data demon- strating CNM-Au8 mediated modulation of key brain bioenergetic metabolites. We also presented blinded data at two key Multiple Sclerosis scientific meetings where we showed notable increasing mean improvements in overall MS Functional Compos- ite (MSFC) scores which measure sight, fine-motor, walk, and working memory, as well as key MSFC sub-scales compared to a comparator group (mixed-effects model; p<0.0001 vs. baseline). We believe these data support CNM-Au8’s potential to drive meaningful neurological improvements in MS patients. Additional biomarker data from MS and Parkinson’s disease patients
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