Science to cure and prevent metabolic syndrome Coporate Overview July 2018 Glaceum Inc. / 28
Philosophy - Holistic Approaches “The duck’s legs are short, but to stretch them out would worry him; the crane’s legs are long, but to cut them down would make him sad. What is long by nature needs no cutting off; what is short by nature needs no stretching .” Zhaung Zhou BC 369-286 www.glaceum.com 2 /11
All roads lead to Mitochondria! www.glaceum.com 3 /11 Image credit: https://nutritionreview.org/2013/09/mitochondrial-dysfunction/
Is it possible to find Universal Solutions? Identifying Compounds cause desirable changes in Going after phenotype a particular target Image credit: https://www.youtube.com/watch?v=D3g1BH6Yo8M www.glaceum.com 4 /11
Science – Imitation precedes creation • Glaceum chose glabridin as a ‘Rosetta Stone’ to understand its pharmacological benefits on the metabolic syndrome and translate into druggable compounds. • Glabridin, an isoflavan in licorice roots has been reported to exhibit various biological properties, such as anti- oxidant, anti-bacterial, anti-inflammatory, anti-tumorigenic, anti-atherogenic, regulation of energy metabolism, anti-osteoporotic and neuro-protective properties. It was also discovered that glabridin has estrogen-like activity in that it binds to the estrogen receptor of vascular tissues, modulating vascular injury and atherogenic processes. 1-3 • However, glabridin is chemically very unstable; it easily decomposes at acidic, basic, aerobic and light condition. Very low content (<1% dry weight) of glabridin exists in natural licorice and it is challenging to make high purity glabridin. • Glaceum took a chemistry-driven Structure Activity Relationship (SAR) approach and was able to identify a series of compounds which show much higher pharmaceutical efficacy than glabridin while keeping the safety. 1. Itamar Yehuda, Zecharia Madar, Alicia Leikin-Frenkel, et al., Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation, Mol. Nutr. Food res . 2016, 60 , 287-299. 2. Charlotte Simmler, Guido F. Pauli, Shao-Nong Chen, Phytochemistry and biological properties of glabridin. Fitoterapia 2013, 90 , 160 – 184. 3. Dalia Somjen, Esther Knoll, Jacob Vaya, et al., Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo. J. Steroid Biochem Mol. Biol. 2004, 91 , 147 – 155. www.glaceum.com 5 /11
Unique positioning of HSG4112 – Energy Expenditure! www.glaceum.com 6 /11
Evidence of Energy Expenditure Enhancement Energy Expenditure Measurement using CLAMS (HSG4112 100mg/kg, 6 weeks) CLAMS: Comprehensive Lab Animal Monitoring System HFD: High Fat Diet RER : Respiratory Exchange Ratio (RER = V CO2 / V O2 ) www.glaceum.com 7 /11
Evidence of Energy Expenditure Enhancement Hypothalamic AMPK activity (HSG4112 100mg/kg, 6 weeks) • Decrease of 5 ’ Adenosine Monophosphate- activated Protein Kinase (AMPK) activity in hypothalamus after oral administration of HSG4112 was observed. • Downregulation of AMPK in hypothalamus means the enhancement of energy expenditure in peripheral tissues (upregulation of AMPK peripherally 1 ). 1. Reference: Ki-Up Lee et al., Anti- obesity effects of α -lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase, Nature Medicine, 2004, 10 , 727-733 www.glaceum.com 8 /11
Global Obesity Epidemic > 1.9B adults overweight, of these > 650M adults obese Source : WHO (2017) http://www.who.int/gho/map_gallery/en/ http://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight www.glaceum.com 9 /11
Glaceum’s Investment Highlights Glaceum Inc. is dedicated to discovering and developing a cure for patients suffering from metabolic syndrome Seeking Fundamental Focus on Orally administrable Expandability of Solution Obesity New Chemical Entities pipeline mitochondrial function A significant Novel IP-protected Obesity drug in Phase 1, is the key unmet medical need, small molecules for preclinical asset for T2DM, to energy metabolism worldwide oral administration and NAFLD/NASH Chronic inflammation, insulin The worldwide prevalence of Glaceum identified a series of Glaceum is currently focused on the resistance, metabolic syndrome, obesity with limited therapeutic compounds originated from development of therapeutic agents cellular respiration, reactive oxygen options is offering a huge market glabridin and strong intellectual for obesity and T2DM. species, mitochondrial dysfunction, opportunity property rights were granted for However, we believe our approach etc. cannot be separable. They both the compounds and synthetic – enhancing mitochondrial aerobic should be studied and understood methods. Glaceum is the ONLY oxidative metabolic capacities – is as a whole in conjunction with company can produce synthetic not limited to these diseases but ageing. glabridin and its derivatives. can be widely expandable to various noncommunicable diseases. www.glaceum.com 10 /11
Science to cure and prevent metabolic syndrome Thank You Corporate Overview July 2018 IR@glaceum.com BD@glaceum.com / 28
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