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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 1 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 2 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 Ausio Pharmaceuticals, LLC 3 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 4 S-equol: Mechanism of Action • • • • • Binds selectively to ER-β Antioxidant Chemoprotective Down regulates ER- and androgen receptor Activates NOS and NO production Ausio Pharmaceuticals, LLC 5 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 6 Ausio’s Strategy Develop S-equol as an oral drug for Vasomotor Symptoms and Benign Prostatic Hypertrophy Ausio Pharmaceuticals, LLC 7 Progress in Drug Development • • • • • Commercial scale synthetic process Stable drug product Animal pharmacology supports clinical development IND filed with FDA Phase 1 safety studies Ausio Pharmaceuticals, LLC 8 Safety Studies for IND • • • No effect on the uterus Genotoxicity (all negative) Safety Pharmacology (all negative) – Respiratory (rat) – Neurotoxicity (rat) – Cardiovascular (monkey) Ausio Pharmaceuticals, LLC 9 Safety Studies for IND • • ADME (rat, monkey) 28-day GLP toxicity studies – Rat – Monkey – Large safety margin for human studies Ausio Pharmaceuticals, LLC 10 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 • • • 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 12