Medicines

for an
Ausio Pharmaceuticals, LLC Aging Population

The 2nd Polyphenol Meeting

Recent Progress of Equol Science

Tokyo, Japan
July 25, 2008

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S-equol is Present in Man as a Metabolic
Transformation of Daidzein
OH
O

• Intestinal
Bacteria
• Dietary
HO O Carbohydrate HO O

Daidzein
S-equol
(a soy isoflavone)
Intestinal Metabolism and Absorption

Population % Equol Producers

Asians >70%
North Americans <20%

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Equol Producers have Health Benefits

• Less osteoporosis with greater bone density

• Menopausal symptoms less severe
• Prostate and breast cancer risk reduced
• Lower risk of cardiovascular diseases
• Learning and memory may be enhanced
• Improved glucose metabolism

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S-Equol is Well Absorbed in Man
Setchell et al. Am J Clin Nutr 81: 1072-079, 2005

Plasma Concentration (ng/mL) 500

500 S-Equol:
20 mg oral dose
400
400
Elimination half-life = 4.9 h
300
300

200
200

100
100
Equol
Concentration
00 in Japanese
00 55 10
10 15
15 20
20 25
25
Time (h)

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S-equol: Mechanism of Action

• Binds selectively to ER-β

• Antioxidant
• Chemoprotective
• Down regulates ER- and androgen receptor
• Activates NOS and NO production

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S-equol is a Potent, Non-steroidal,
ER β Selective Agonist
OH

HO O S-equol

Ki (nM) ER-β ER-

S-equol 0.73 ± 0.2 6.41 ± 1.0
R-equol 15.4 ± 1.3 27.4 ± 3.8
Estradiol 0.13 0.15

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Ausio’s Strategy

Develop S-equol as an oral drug for

Vasomotor Symptoms and Benign
Prostatic Hypertrophy

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Progress in Drug Development

• Commercial scale synthetic process

• Stable drug product
• Animal pharmacology supports clinical
development
• IND filed with FDA
• Phase 1 safety studies

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Safety Studies for IND

• No effect on the uterus

• Genotoxicity (all negative)
• Safety Pharmacology (all negative)
– Respiratory (rat)
– Neurotoxicity (rat)
– Cardiovascular (monkey)

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Safety Studies for IND

• ADME (rat, monkey)

• 28-day GLP toxicity studies
– Rat
– Monkey
– Large safety margin for human studies

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Regulatory and Clinical Development

 Pre IND Meeting with FDA

 IND submission
 Phase 1 studies
– Single rising dose (August)
– Multi rising dose (October)

 Phase 2 studies
– Vasomotor Symptoms
– Benign Prostatic Hypertrophy

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Summary

• Since S-equol has been in man for 4,000 years,

we believe it to be safe
• Equol producers have many health benefits
• Ausio is in a strong position to develop S-equol
as a drug
– Strong patent position
– High purity product
– IND submitted
• Clinical data will confirm safety and efficacy

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