BIOGRAPHICAL SKETCH

Tezapsidis, Nikolaos

Founder, Chairman, President & CEO of Neurotez, Inc.

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE

Completion

Date

FIELD OF STUDY

Aristotle University, Thessaloniki, Greece B.Sc. 1985 Chemistry The University of Sussex, Brighton, UK M.Sc. 1986 Biochemistry The University of Sussex, Brighton, UK D.Phil. 1991 Biochemistry A. Personal Statement

I have a broad background in biochemistry, with specific training and expertise in neuroendocrinology, neuroscience and specifically on Alzheimer’s disease. As PI or co-Investigator on several NIH-and state funded grants, I founded Neurotez and assembled a team of experts who collectively laid the groundwork of the company’s mission. Neurotez’s research and development efforts included a drug candidate for Alzheimer’s disease, currently prepared for clinical trials. Company-led studies of molecular and physiological mechanisms underlying Leptin’s role in preserving neuronal integrity and function and other novel discovery efforts, including stem cell research and screening technologies have resulted in multiple patent applications submitted globally, with several being already granted. In addition, I successfully administered the projects (e.g. staffing, research projections, budget), collaborated with other researchers, outsourced activities to contract research organizations, monitored outsourcing and led intellectual property strategy. The team produced several peer-reviewed publications from each project, including reviews and book chapters that have been well received from the scientific community. Company closely worked with Contract Manufacturing Organization (CMO) to generate a GMP-Master Cell Bank and Process for production of a Biologic Active Pharmaceutical Ingredient (API). Company prepared the strategy for IND- enabling studies, comprising Safety, Toxicology and Pharmacokinetics in animal models and a protocol for testing the compound in humans in Phase I and Phase II trials. Neurotez successfully closed equity-based crowdfunding campaigns that raised $350K from private investors and reached out to accredited and institutional investors. Recently, had a commitment for $3 million equity by a VC group and an offer for a $50million equity line by an alternative investment group with $4billion in global assets to be use once becoming a public company. B. Positions and Honors

Positions and Employment

1988-1990 Research Assistant: Biochemistry Department, School of Biological Sciences, Sussex University, U.K.

1990-1992 Postdoctoral Research Assistant: Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, University of London, U.K. 1992-1994 Postdoctoral Fellow: Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD

1994-1996 Research Associate: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 1997-1998 Res. Assis. Professor: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 1998-2000 Laboratory Director: Department of Molecular Biology, NYS Institute for Basic Research, Staten Island, NY

2000-2001 Res. Assis. Professor: Department of Neurology, NYU Medical Center, New York, NY 2001-2004 Officer of Research, College of Physicians and Surgeons, Columbia University, New York, NY 2003-2004 Council Member, Gerson Lehrman Group

2004- Founder, of Neurotez, Inc.

2005- Chairman, President & CEO, Neurotez, Inc., Bridgewater, NJ Honors

1988-1989 Research Fellowship awarded by the Wellcome Trust, U.K. 1989-1992 Research Fellowship awarded by the Science and Engineering Research Council, U.K. C. Contribution to Science

Most publications relevant to Neurotez’s Leptin for AD work

(1) Fewlass DC, Noboa K, Pi-Sunyer FX, Johnston JM.,Yan SD and Tezapsidis N (2004) Obesity-related leptin regulates Alzheimer’s Ab. FASEB J 18, 1870-1878.

(2) Greco SJ, Sarkar S, Johnston JM, Zhu X, Su B, Casadesus G, Ashford JW, Smith MA, Tezapsidis N

(2008) Leptin reduces Alzheimer's disease-related tau phosphorylation in neuronal cells. Biochem Biophys Res Commun. 376, 536 – 541 Sep 16.

(3) Greco, S.J., Sarkar, S., Johnston, J.M. and Tezapsidis, N. (2009) Leptin regulates tau phosporylation and amyloid through AMPK in neuronal Biochem Biophys Res Commun. 380, 98 – 104.

(4) Tezapsidis, N., Johnston, J.M., Smith, M.A., Ashford, J.W., Casadesus,G., Robakis, N.K., Wolozin, B., Perry,G., Zhu,X., Greco, S.J. and Sarkar, S. (2009) Leptin: A Novel Therapeutic Strategy for Alzheimer’s Disease. Journal of Alzheimer’s Disease 16, 1155-67.

(5) Greco SJ, Sarkar S, Casadesus G, Zhu X, Smith MA Ashford JW, Johnston JM and Tezapsidis N.

(2009) Leptin inhibits glycogen synthase kinase-3 to prevent tau phosphorylation in neuronal cells Neuroscience Letters 2009 455, 191-4

(6) Greco SJ, Bryan KJ, Sarkar S, Zhu X, Smith MA, Ashford JW, Johnston JM, Tezapsidis N, Casadesus G. (2010) Chronic Leptin Supplementation Ameliorates Pathology and Improves Cognitive Performance in a Transgenic Mouse Model of Alzheimer’s Disease. J Alzheimer Disease 19: 1155-1167

(7) Johnston J.M., Greco S.G., Hamelzou A, Ashford J.W and Tezapsidis N (2011) Repositioning leptin as a therapy for Alzheimer’s disease. Therapy 8 (5), 481-490.

(8) Greco SJ, Hamzelou A, Johnston JM, Smith MA, Ashford JW, Tezapsidis N. (2011) Leptin Boosts Cellular Metabolism by Activating AMPK and the Sirtuins to Reduce Tau Phosphorylation and β-Amyloid in Neurons. Biochem Biophys Res Commun 414:170-174.

(9) Greco SJ, Perry G, Ashford JW, Hamzelou A, Johnston JM, Tezapsidis N. (2013) Leptin rescues neurons from Alzheimer’s disease-related pathways triggered by lipid burden. Adv Alz Dis 2:31-39.

(10) Johnston JM, Hu WT, Fardo DW, Greco SJ, Perry G, Montine TJ, Trojanowski JQ, Shaw LM, Ashford JW,Tezapsidis N. (2014) Low plasma leptin in cognitively impaired ADNI subjects: gender differences and diagnostic and therapeutic potential Current Alzheimer Res 11 (2) 165-74.

(11) Johnston JM, Tezapsidis N (2019) Leptin, Inflammation and Alzheimer’s disease. Horizons in Neuroscience Research 37: Chapter 2.

Additional publications of importance

(1) Bouras, C., Shioi, J., Tezapsidis, N., and Robakis, N.K. (1996) Presenilin-1 polymorphism and Alzheimer’s disease. The Lancet 347, 1185-1186

(2) Elder GA, Tezapsidis N, Carter J, Shioi J, Bouras C, Li HC, Johnston JM, Efthimiopolous S, Friedrich VL and Robakis NK (1996) Identification and neuron specific expression of the S182/presenilin 1 protein in human and rodent brains. Journal of Neuroscience Research 45, 308 – 320.

(3) Giannakopoulos, P., Bouras, C., Kovari, E., Shioi, J., Tezapsidis, N., Hof, P.R. and Robakis, N.K.

(1997) Presenilin-1 neurons are preserved in late-onset Alzheimer disease. American Journal of Pathology 150, 429-436.

(4) Tezapsidis, N., Li, H.-C., Ripellino, J.A., Efthimiopoulos, S., Vassilacopoulou, D., Sambamurti, K., Toneff, T., Yasothornsrikul, S., Hook, V.Y.H., and Robakis, N.K. (1998) Release of Non- transmembrane Full-Length Alzheimer’s Amyloid Precursor Protein from the Lumenar Surface of Chromaffin Granule Membranes. Biochemistry, 37, 1274-1282.

(5) Johnsingh AA, Johnston JM, Merz G, Xu J, Kotula L, Jacobsen JS and Tezapsidis N (2000) Altered binding of mutated presenilin with cytoskeletal-interacting proteins. FEBS Letters 465, 53 –58.

(6) Tezapsidis, N., Merz, P., Merz, G., Hong, H. (2003) Microtubular interactions of presenilin direct kinesis of A peptide and its precursors. FASEB J, 17, 1322-4

(7) Johnston JM, Burnett P., Thomas AP and Tezapsidis N (2006) Calcium oscillations in type-1 astrocytes, effect of a presenilin 1 (PS) mutation. Neuroscience letters 395, 159-164.

(8) Greco SJ, Hamzelou A, Johnston JM, Richardson S, Smith MA, Perry G, Ashford JW, Tezapsidis N

(2012) Isotyping the Human TOMM40 Variable-Length Polymorphism by Gene Amplification and Restriction Digest. Curr Alzheimer Res. 2012 9(10), 1168-73. Patent / Patent Applications.

US Patent 8,227,408: “Leptin As An Anti-Amyloidogenic Biologic And Methods For Delaying The Onset And Reducing Alzheimer's Disease-Like Pathology”

US Patent 8,642,543: “Methods For Treating, Preventing, Diagnosing And Monitoring A Progressive Cognitive Disorder, Disease Or Condition Resulting From Accumulation Of Neurofibrillary Tangles”

US Patent 8,716,220: “Leptin Compositions And Methods For Treating Progressive Cognitive Function Disorders Resulting From Accumulation Of Neurofibillary Tangles And Amlyoid Beta”.

US Patent 8,642,543 also was filed during national phase and is pending in the following countries: Europe, Japan (granted), Canada, Australia, India, China, S Korea and S Africa (granted).

US Patent 8,716,220 also was filed during national phase in the following countries: Europe, Japan, Canada, Australia (granted), India, China, S Korea and S Africa (granted).

US Patent Appl.: Ser. No. 13/415,940 “Isotyping the Human TOMM40 Variable-Length Polymorphism by Gene Amplification and Restriction Digest

US Patent Appl.: Ser. No. 61/534,500 “Compositions And Methods For Delaying Senescence Or Cell Death In Neurons”

US Patent Appl.: Ser. No. 61/706,550 “Leptin Rescues Neurons From Alzheimer`S Disease-Related Pathways Triggered By Lipid Burden”

US Patent Appl.: Ser. No. 13/799,932 “Fragments, Mutants And Chimeric Fusion Proteins Of Leptin For Treating Alzheimer`S Disease”

US Patent Appl.: Ser. No. 61/807,841 “Low Plasma Leptin Levels Plus at Least One E4 Allele as a Potential Enrichment Strategy for MCI Clinical Trials” D. Research Projects Funded (appr. $5,000,000 total). Completed research

• R44 AG02967-05, NIH Tezapsidis, Principal Investigator 2010 - 2012 Leptin as a treatment for Alzheimer’s Disease

The goal of this study is to further characterize leptin and prepare for a human trial in mild-probable Alzheimer’s patients

Role: PI

• R43 AG029670, NIH Tezapsidis, Principal Investigator 2007 - 2009

“Leptin as a treatment for Alzheimer’s disease”

To study the effect of chronic leptin treatment on amyloid pathology and cognition & behavior in AD-transgenic mice.

Role: PI

• New Jersey Commission on Science and Technology 2008 - 2010 Award for postdoctoral fellowship

Role: Director

• Alzheimer's Disease and Related Disorders Association Tezapsidis PI 2001 - 2004

“Convergence of PS-1 and ApoE pathways and impact on amyloid burden” [Investigating a possible role for Presenilins in mediating ApoE’s function as an Abeta chaperone]. IIRG The long term objective of the project was to establish an interplay between the presenilins, major cytoskeletal proteins and pathways associated with lipid cellular homeostasis. Leptin emerged as an important regulator of this interplay

Role: PI

• Alzheimer's Disease and Related Disorders Association Tezapsidis PI 1997 - 2000

"Presenilins and Alzheimer's Disease" [Investigated the biological function of Presenilins with emphasis on Amyloid Precursor Protein (APP) processing. IIRG

The long-term objective of this project was to investigate mechanisms of Abeta production mediated through presenilin and evaluate these pathways as new therapeutic targets for AD. CLIP-170/Restin, a cytoskeleton- associated protein, has been identified as a presenilin binding protein. We hypothesize that this interaction is important for APP trafficking, ultimately linked to the amyloidogenic pathway. Role: PI

• New Jersey Commission on Science and Technology 2010 - 2011 Bridge Award

Role: Co-director

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