Otsuka Global TB Program Updates

T B i n n o v a t i o n f o r t o m o r r o w .

Otsuka Global TB Program UpdatesCPTR Workshop

October 3, 2012Arlington, VA

Proprietary and Confidential

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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

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RFP

1967 1972 Today

New TB Drug?

1990

IRB (FDA)*

DDI: Drug-drug interactionICH: International Conference on Harmonization

GCP: Good Clinical PracticeGMP: Good Manufacturing PracticeGLP: Good Laboratory Practice

Thorough QTcHigh

1997RFP: Rifampicin (FDA approval)

2005

GMP/GLP (FDA)

19991978

ICH-GMP

DDI (CYP)

ICH created

Prospective Statistics

* US-FDA adopted IRB based on Declaration of Helsinki

1992

ICH-GCP

GLP (OECD)

19961981

Belmont Report (FDA)**

1979

**Ethical guidelines for clinical research

New TB Drugs Overcome Modern RA Hurdles

Proprietary and Confidential

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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 Phase Continuation Phase

Proprietary and Confidential

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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

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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

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Given Encouraging Results, Launch of Phase III (Trial 213)

N = ~300MDR TBCulture +Patients

OBR +Placebo

(n2 = 100)

OBR +Delamanid100 mg BID(n1 = 200)

2 months:•SCC•Clinical Δ

+4 months:•SCC•Clinical Δ•Time to SCC*

+12-18 mos:•Rx outcomes

+6-12 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 monthsTime to SCC over 6 months

• Enrolling in Estonia, Latvia, Lithuania, Peru, Philippines, and South Africa. Adding Moldova and India soon.

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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 patientsStrict Distribution Control— All orders routed through single distributor using web-based tool

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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

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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

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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

Proprietary and Confidential

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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