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Ausio Pharmaceuticals, LLC
Medicines
for an
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
HO
• Intestinal
Bacteria
• Dietary
Carbohydrate
O
Daidzein
(a soy isoflavone)
HO
O
S-equol
Intestinal Metabolism and Absorption
Population
% Equol Producers
Asians
>70%
North Americans
<20%
Ausio Pharmaceuticals, LLC
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Equol Producers have Health Benefits
•
•
•
•
•
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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
Ausio Pharmaceuticals, LLC
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S-Equol is Well Absorbed in Man
Plasma Concentration (ng/mL)
Setchell et al. Am J Clin Nutr 81: 1072-079, 2005
500
500
S-Equol:
20 mg oral dose
400
400
Elimination half-life = 4.9 h
300
300
200
200
100
100
Equol
Concentration
in Japanese
00
00
55
10
10
15
15
20
20
25
25
Time (h)
Ausio Pharmaceuticals, LLC
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S-equol: Mechanism of Action
•
•
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•
•
Binds selectively to ER-β
Antioxidant
Chemoprotective
Down regulates ER- and androgen receptor
Activates NOS and NO production
Ausio Pharmaceuticals, LLC
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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
Ausio Pharmaceuticals, LLC
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Ausio’s Strategy
Develop S-equol as an oral drug for
Vasomotor Symptoms and Benign
Prostatic Hypertrophy
Ausio Pharmaceuticals, LLC
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Progress in Drug Development
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•
•
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•
Commercial scale synthetic process
Stable drug product
Animal pharmacology supports clinical
development
IND filed with FDA
Phase 1 safety studies
Ausio Pharmaceuticals, LLC
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Safety Studies for IND
•
•
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No effect on the uterus
Genotoxicity (all negative)
Safety Pharmacology (all negative)
– Respiratory (rat)
– Neurotoxicity (rat)
– Cardiovascular (monkey)
Ausio Pharmaceuticals, LLC
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Safety Studies for IND
•
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ADME (rat, monkey)
28-day GLP toxicity studies
– Rat
– Monkey
– Large safety margin for human studies
Ausio Pharmaceuticals, LLC
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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
Ausio Pharmaceuticals, LLC
11
Summary
•
•
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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
Ausio Pharmaceuticals, LLC
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