Building Bridges to Long-Term Growth. R&D strategy. Director, Corporate Officer Development Headquarters Ken-ichi Yanagisawa.

Transcription

1 Building Bridges to Long-Term Growth R&D strategy Director, Corporate Officer Development Headquarters Ken-ichi Yanagisawa November 8, 2005

2 New products development status - NDA filed / Phase III Product (Generic name) Remicade (Infliximab) Maintate (Bisoprolol) Gastrom (Ecabet) Remicade (Infliximab) Remicade (Infliximab) Category / Indications Anti-TNF monoclonal antibody (Behcet s disease) Selective 1 antagonisit (Chronic heart failure) Gastrointestinal mucus protecting agent (Ulcerative colitis) Anti-TNF monoclonal antibody (Crohn s disease, maintenance) Anti-TNF monoclonal antibody (RA, changeof dosage and administration) Development In-house Origin: Centocor In-house JP:In-house US/EU: Tanabe AAL LLC In-house Origin: Centocor In-house Origin: Centocor Red Stage changed since 1Q

3 New products development status Phase II/III, Phase II Product (Generic name) Category / Indications Stage Japan EU/US Development APTA-2217 Roflumilast) PDEIV inhibitor (asthma) PDEIV inhibitor (COPD / / Co-development with ALTANA Pharma TA-8317 (Oral transmucosal fentanyl) Narcotic analgesic (breakthrough cancer pain) In-house Origin: Cephalon TA-1790 PDEV inhibitor (erectile dysfunction) Licensed to VIVUS TA-2005 (Carmoterol) Long-acting 2 inhibitor (asthma, COPD) Licensed to Chiesi TA-6666 DPP-IV inhibitor (diabetes) In-house T-0047 Cell adhesion inhibitor (MS, IBD etc.) Licensed to GSK Red Stage changed since 1Q

4 New products development status Phase I Product (Generic name) Category / Indications Stage Japan EU/US Development T-0128 DNA topoisomerase I inhibitors (cancer) Licensed to Menarini TA-5538 NK-1 receptor antagonist (overactive bladder) In-house TA-1702 BK channel opener (overactive bladder) Licensed to GSK RedStage changed since 1Q

5 LCM for Remicade

6 TA-650 RA: Change of dosage and administration Target RA Patients with insufficient efficacy by MTX treatment Male and female between the age from 20 to 75 Observation period Open period (14 weeks) Evaluation period (54 weeks) Blind period (40 weeks) weeks RegistrationWithin 4 weeks Allocation Written informed consent 3mg/kgAdministration with open samples : 3mg/kg: 6mg/kg: 10mg/kg (Administration with blind samples

7 LCM strategy for Remicade Ulcerative colitis (additional indication) prepared Psoriasis (additional indication) preparing Ankylosing spondylitis(additional indication) preparing RA (change of dosage and administration) Ph.3 on going Crohn's disease /maintenance therapy Ph.3 on going Behcet's disease Registered Crohn's disease /induction therapy Launched Rheumatoid arthritis Launched

8 APTA-2217 (Roflumilast)

9 Roflumilast shows equal efficacy to Montelukast in improving FEV1 in asthma over 24 weeks n=957

10 Montelukast comparison in asthma advantages in smoking/ex-smoking patients

11 Consistent effect on post-bronchodilator FEV 1 sustained for 1 year

12 Moderate/severe exacerbations in patients with GOLD stage IV

13 TA-6666 (DPP-IV inhibitor)

14 TA-6666 Target indication: Type II diabetes Mechanism of action: DPP-IV inhibition Profile: Suppressing degradation of GLP-1 and enhancing post-prandial insulin secretion with fewer side effects such as hypoglycemia and obesity. Development stage: US, Phase II (ongoing) Present data Potent dose-dependent DPP-IV-inhibitory activity from low dose.

15 Side effects in anti-diabetic medications Glitazones edema, weight increase, hepatic function test monitoring Alfa glucosidase inhibitors gastrointestinal side effects SU/Insulin hypoglycemia, weight increase Metformin gastrointestinal side effects, lactic acidosis No DPP-IV inhibition-specific side effect has been reported until now.

16 Expected action of DPP-IV inhibitor SU/Insulin Metformin α-gis Glitazones DPP-IV inhibitor Insulin secretion stimulate insulin secretion Glucose influx Slow gastric emptying Hepatic glucose output Suppress glucagon secretion and hepatic glucose production Peripheral glucose uptake

17 TA-1702 (BK channel opener)

18 Pathophysiology of overactive bladder and MoA Normal micturition Supra Spinal OAB Supra Spinal S. Cord NK-1 antagonist S. Cord BK channel opener Muscarinic antagonist

19 MoA and expected characteristics Classification Mechanism of Action Expected Characteristics Muscarinic antagonists NK-1 antagonists (TA-5538) BK channel openers (TA-1702) Control micturition by suppressing bladder contraction through blockade of Muscarinic receptor Increase bladder capacity by suppressing afferent signal transduction from baldder in the spinal cord Increase bladder capacity by suppressing excitation of bladder smooth muscle and sensory nerve Clinical efficacy established, side effects such as dry mouth and urinary retention Maintain bladder contraction force at micturition, less side effects like dry mouth, effects on "urgency" Maintain bladder contraction force at micturition, less side effects like dry mouth, effects on "urgency" Above characteristics expected from publications or non-clinical studies Clinical efficacy of NK-1 antagonists / BK channel openers yet to be established