Otsuka Global TB Program Updates

1. October 3, 2012 Arlington, VA Otsuka Global TB Program Updates CPTR Workshop

2. Overview Challenges in TB Drug Development Recent Publications/Presentations NEJM Results from Trial 204 ERJ Report on long-term follow-up IAS and ICAAC DDI studies with anti-retroviral drugs Ongoing Phase III Trial Responsible Access Public Health Advocacy, Awareness and Education 2

3. New TB Drugs Overcome Modern RA Hurdles New TB Drug? High Thorough QTc ICH-GMP DDI (CYP) ICH-GCP GLP (OECD) ICH created IRB (FDA)* Belmont Report (FDA)** GMP/GLP (FDA) RFP Prospective Statistics 1967 1972 1978 1979 1981 1990 1992 1996 1997 1999 2005 Today GCP: Good Clinical Practice RFP: Rifampicin (FDA approval) GMP: Good Manufacturing Practice DDI: Drug-drug interaction GLP: Good Laboratory Practice ICH: International Conference on Harmonization **Ethical guidelines for clinical research * US-FDA adopted IRB based on Declaration of Helsinki

4. Otsuka’s Studies of Delamanid to Provide 6-months of Treatment and 24 Month Follow-up Trial 116 Trial 204 Delamanid 2 mo Trial 208 with varying time of entry for 6 month exposure OBR Intensive Phase Continuation Phase Long-Term Outcome at 24 mo 4

5. Phase II Results Demonstrate Long- and Short-Term Efficacy of Delamanid Short-Term Efficacy As reported in the New England Journal of Medicine (NEJM), results from Trial 204 demonstrate treatment with delamanid + OBR led to 53% increase in SCC compared to placebo + OBR If SCC achieved within first 2 months, patients have considerably higher likelihood of successful treatment outcome Long-Term Efficacy As reported in the European Respiratory Journal (ERJ), combined analysis of Trials 204/208/116 shows Among all patients (N=421) 74.5% achieve favorable outcome with DLM >6mo delamanid vs. 55.0% with <2mo (1% mortality in patients receiving DLM ≥ 6mo vs. 8.3% ≤ 2mo) Among all patients (N=421) 1% mortality in patients receiving DLM ≥ 6mo vs. 8.3% ≤ 2mo 5

6. Safety Results Demonstrate Delamanid was Well-Tolerated Among Study Subjects Most AEs within mild to moderate range and balanced among delamanid and placebo groups; consistent with OBR • Higher incidence of QTcF prolongation, which did not result in any clinical manifestations • As reported at International AIDS and ICAAC 2012 Conferences, DDI studies in healthy subjects show no significant interactions when delamanid co-administered with tenofavir, efavirenz or Kaletra 6

7. Given Encouraging Results, Launch of Phase III (Trial 213) OBR + Delamanid 100 mg BID (n1 = 200) N = ~300 MDR TB Culture + Patients +6-12 mos: Relapse • 2 months: • SCC • Clinical Δ • +4 months: • SCC • Clinical Δ • Time to SCC* • +12-18 mos: • Rx outcomes OBR + Placebo (n2 = 100) • Total duration – 30 mos. • Total enrollment – 400 patients sputum culture positive for MDR-TB • Stratification – HIV+ (S Africa); bilateral cavities on CXR • Co-primary endpoints • SCC – @ 2 months • Time to SCC over 6 months • Enrolling in Estonia, Latvia, Lithuania, Peru, Philippines, and South Africa. Adding Moldova and India soon. 7

8. Committed to the Rational Use of Delamanid – Responsible Access Plan (RAP) Professional Education • Medical education program targeting physicians and patients • Focus topics such as diagnostic options, timely and accurate SAW reporting, background on development of drug resistance, among others Comprehensive Registry • A multi-center, EU-wide post-authorization study to assess the safety and drug usage of Delamanid in MDR-TB patients Strict Distribution Control • All orders routed through single distributor using web-based tool 8

9. Otsuka’s Commitment to Improving Patient Care • Support and/or develop approaches to excellence in TB case management (Moldova) • Explore models of patient support leading to individual and community socio-economic improvement • Advocate for sustained international commitment and response to the TB crisis from funders and policymakers • Increase public awareness of TB as a universal health issue

10. Making an Impact – One Patient at a Time Mildred Fernando • Battled TB for a total of 10 years, since age 19 • Diagnosed twice with XDR-TB, received two, 18 month courses of treatment • Father died of TB, two sisters diagnosed and survived • Mildred participated in delamanid RCT and open-label study • Today she is living TB-free and works at the Lung Center of the Philippines, helping other TB patients. She is also a strong patient-advocate for the WHO and other international organizations

11. Otsuka’s Commitment to TB Education, Awareness & Advocacy • To capture stories like Mildred’s, photo magazine created with TB/MDR-TB life stories (Estonia, Philippines, Peru) • Collaboration with European Respiratory Society (ERS) • Aimed at illustrating MDR-TB as a potentially treatable and winnable disease, providing hope and encouragement to other patients

12. Conclusion Global TB Program a long-term investment by Otsuka New compound represents only a first step in a comprehensive disease management package that aims to FighTBack against TB from all angles (diagnostics, pediatrics, public health, etc.) Actively working with global TB stakeholders and other third-parties with mutual goals of addressing unmet medical needs in TB while promoting rational use of new compounds and minimizing resistance 12