R&D Strategy for diabetes November 9, ２００６ Keiichi Ono, Ph.D. Executive Director Drug Development Division
Focusing on diabetes Marketed Research Therapeutic Development Classification Compounds Products Stage ◎ Glimicron Repaglinide Insulin Secretagogue Metabolic Syndrome Diabetes Diabetes ◎ Melbin Metformin Insulin Sensitizer ◎ * Glucose Absorption Seibule Inhibitor Complication ◎ Ranirestat Treatment Cardiovas Amlodin vascular disease Cardio- cular ◎ Hypertension etc. Cetapril Irbesartan Almarl 2 * SGLT1 （ Selective Glucose Transporter 1) Inhibitor
Antidiabetic Agents at Clinical Stage (P2 or higher) P2 P3 Marketed Insulin Secretagogue Glimicron （ SU) 1) Rapid Insulin SMP-508 Secretagogue (RIS) （ repaglinide ） Insulin Sensitizer SMP-862 Melbin （ BG) 2) （ metformin ） Glucose Absorption Seibule * Inhibitor （α GI ） Diabetic Complications AS-3201 AS-3201 Treatment (ranirestat) (ranirestat) （ ARI) 3) (Japan) (overseas) 1) Sulfonylurea 2) Biguanide, 3) Aldose Reductase Inhibitor * Co-promotion with Sanwa Chemical 3
SMP-862 【 P Ⅱ b in Japan 】 Generic Name: Metformin （ INN ） • • Brand Name: To be decided • Regulatory Category for Japanese NDA: 1-(4) New Indication, 1-(6) New Strength ★ First-line treatment for Type II Diabetes ★ New dosage higher than currently approved 750 mg/day with evidence based on results from on-going clinical studies • Target Disease: Type 2 Diabetes • Pharmacological Classification: Biguanide ( Suppression of hepatic gluconeogenesis and improvement of insulin sensitivity by increasing peripheral glucose uptake and utilization) 4
Metformin: Blood Glucose Lowering Effect （ US ） Metformin ( mg/ day ） 500 1000 1500 2000 2500 0 1 2 3 4 5 Difference from placebo group -0.5 Δ HbA 1C （％） -1 *** *** -1.5 *** *** -2 *** （ mean ± SE ， *** p<0.001 ） -2.5 Garber AJ. et al., Am J Med 102; 491,1997.
Melbin (Metformin) Observational Research （ MORE ） Study: Effect of metformin on Type 2 diabetes Results from 1197 type II diabetic patients in 74 sites newly administered 500 ～ 750 mg/day of metformin in 2002 0.9% 8.5 8.0 8.2 HbA 1C (% ) 7.5 ** ** ** 7.0 7.3 7.3 7.3 6.5 （ Mean ， * * p<0.001 ） ～ ～ 6.0 0 Initial 3 Months 6 Months 12 Months K. Kaku 、 N.Tajima 、 R.Kawamori Journal of the Japan Diabetes Society 49;325,2006 6
Effect of increased dosage of metformin on HbA 1C and plasma glucose level at fasting state 12-week treatment with 1500 mg/day of SMP-862 (metformin) in Type II diabetic patients whose blood glucose is insufficiently controlled with currently approved metformin dosage of 750 mg/day Plasma Glucose Level at Fastring State （ mg/dL ） HbA 1C Plasma glucose at fasting state 160 7.8 7.6 150 HbA 1C (% ) 7.4 7.2 140 7 130 6.8 6.6 0 O 120 投 与 開 始 前 投 与 終 了 時 Initial 12-week Initial 12-week 7 投与開始前 投与終了時
Expected blood glucose lowering effect of metformin in Japanese type I I diabetic patients MORE* Study Current (750 mg/day) 1500mg/ Day Metformin dosage (mg/day) Expect better blood glucose control with 0.9% optimal dosage of 0.9% metformin in Japanese type II + diabetic patients. Expected HbA 1C α lowering effect (%) * Metformin Observational Research 8
SMP-508 【 P Ⅱ b in Japan 】 Repaglinide （ INN ） • Generic Name: • Brand Name: To be decided • Regulatory category for Japanese NDA: 1-(1) New chemical entity • Target disease: Type II diabetes • Pharmacological classification: Rapid insulin secretagogue CH 3 O H 3 C O OH H N O CH 3 H N 9
－ Plasma glucose control with RIS* － Comparison between Repaglinide and Nateglinide Plasma glucose level at HbA 1C fasting state Repaglinide Repaglinide 220 9.0 Nateglinide Nateglinide 210 Nateglinide Nateglinide 8.8 200 Δ 18mg/ dL 8.6 FPG (mg/dL) 190 8.4 180 Δ 1.04% HbA 1c (%) 8.2 170 8.0 Δ 57mg/ dL 160 7.8 150 7.6 Δ 1.57 % 140 7.4 Repaglinide Repaglinide 130 7.2 120 7.0 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 Treatment Week Treatment Week * Rapid Insulin Secretagogue Rosenstock, J et al. Diabetes Care 27; 1265,2004. 10
Concomitant Treatment with SMP-508 added to α -GI (P2a Study): Postprandial plasma glucose level Effect of 8-week treatment with SMP-508 added to α -GI used at its approved dosage in patients with insufficient control of plasma glucose Postprandial plasma Postprandial plasma glucose level Plasma Glucose Level AUC 0-3h （ mg ・ hr/dL ） glucose level AUC 0-3h 700 300 Initial Plasma Glucose Level (mg/dL) 8-week 650 250 血糖値 （mg/dL） 600 200 550 150 500 450 100 0 Initial 8-Week 投与開始前 投与終了時 0 30 60 90 120 150 180 時間 （分） 11 Time (min)
Concomitant Treatment with SMP-508 added to α -GI (P2a Study): HbA 1C and Plasma Glucose Level at Fasting State Effect of 8-week treatment with SMP-508 added to α -GI used at its approved dosage in patients with insufficient control of plasma glucose Plasma glucose level HbA 1C at fasting state 8 160 Plasma Glucose level （ mg/dL ） 7.6 HbA 1C (% ) 140 7.2 6.8 120 6.4 6 O 100 0 投与開始前 投与終了時 Initial 8-Week 投与開始前 投与終了時 Initial 8-Week 12
Disclaimer Regarding Forward-looking Statements The statements made in this presentation material are forward-looking statements based on management’s assumptions and beliefs in light of information available up to the day of announcement, and involve both known and unknown risks and uncertainties. Actual financial results may differ materially from those presented in this document, being dependent on a number of factors. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice. 13
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