TB innovation for tomorrow. Otsuka Global TB Program Updates CPTR Workshop October 3, 2012 Arlington, VA

Proprietary and Confidential 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

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

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

Proprietary and Confidential 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

Proprietary and Confidential 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

Proprietary and Confidential 7 Given Encouraging Results, Launch of Phase III (Trial 213) N = ~300 MDR TB Culture + Patients OBR + Placebo (n 2 = 100) OBR + Delamanid 100 mg BID (n 1 = 200) 2 months: SCC Clinical Δ +4 months: SCC Clinical Δ Time to SCC* mos: Rx outcomes mos: Relapse 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.

Proprietary and Confidential 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

Proprietary and Confidential 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

Proprietary and Confidential Making an Impact – One Patient at a Time 10 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

Proprietary and Confidential Otsuka’s Commitment to TB Education, Awareness & Advocacy 11 − 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

Proprietary and Confidential 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