Science to cure and prevent metabolic syndrome Coporate Overview - - PowerPoint PPT Presentation

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Science to cure and prevent metabolic syndrome Coporate Overview - - PowerPoint PPT Presentation

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Science to cure and prevent metabolic syndrome Coporate Overview July 2018 Glaceum Inc. / 28 Philosophy - Holistic Approaches The ducks legs are short, but to stretch them out would worry him; the cranes legs are long, but to cut

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Science to cure and prevent metabolic syndrome

Coporate Overview July 2018 Glaceum Inc.

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Philosophy - Holistic Approaches

Zhaung Zhou BC 369-286

“The duck’s legs are short, but to stretch them

  • ut 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.”

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All roads lead to Mitochondria!

3 Image credit: https://nutritionreview.org/2013/09/mitochondrial-dysfunction/

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Is it possible to find Universal Solutions?

4 Image credit: https://www.youtube.com/watch?v=D3g1BH6Yo8M

Going after a particular target Identifying Compounds cause desirable changes in phenotype

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Science – Imitation precedes creation

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  • Glaceum chose glabridin as a ‘Rosetta Stone’ to understand its pharmacological benefits
  • n 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-
  • xidant, 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.

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Unique positioning of HSG4112 – Energy Expenditure!

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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 = VCO2 / VO2 )

Evidence of Energy Expenditure Enhancement

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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

  • f

energy expenditure in peripheral tissues (upregulation of AMPK peripherally1).

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 8

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Global Obesity Epidemic

9 Source: WHO (2017) http://www.who.int/gho/map_gallery/en/ http://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight

> 1.9B

adults overweight, of these

> 650M

adults obese

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Glaceum’s Investment Highlights

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Glaceum Inc. is dedicated to discovering and developing a cure for patients suffering from metabolic syndrome Seeking Fundamental Solution

mitochondrial function is the key to energy metabolism

Chronic inflammation, insulin resistance, metabolic syndrome, cellular respiration, reactive oxygen species, mitochondrial dysfunction,

  • etc. cannot be separable. They

should be studied and understood as a whole in conjunction with ageing.

Focus on Obesity Orally administrable New Chemical Entities Expandability of pipeline

A significant unmet medical need, worldwide

The worldwide prevalence of

  • besity with limited therapeutic
  • ptions is offering a huge market
  • pportunity

Novel IP-protected small molecules for

  • ral administration

Glaceum identified a series of compounds originated from glabridin and strong intellectual property rights were granted for both the compounds and synthetic

  • methods. Glaceum is the ONLY

company can produce synthetic glabridin and its derivatives.

Obesity drug in Phase 1, preclinical asset for T2DM, and NAFLD/NASH

Glaceum is currently focused on the development of therapeutic agents for obesity and T2DM. However, we believe our approach – enhancing mitochondrial aerobic

  • xidative metabolic capacities – is

not limited to these diseases but can be widely expandable to various noncommunicable diseases.

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Science to cure and prevent metabolic syndrome Thank You

Corporate Overview July 2018 IR@glaceum.com BD@glaceum.com