1. CB-1 PULMINIQ™ (cyclosporine, USP) Inhalation Solution Benefit-Risk/Conclusions Stephen Dilly, MD, PhD Chief Medical Officer Chiron | BioPharmaceuticals

2. CB-2 The Case for Approval of CyIS Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS, but some outstanding questions remain Approval of CyIS is warranted, with appropriate postapproval commitment

3. CB-3 The Case for Approval of CyIS Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS, but some outstanding questions remain Approval of CyIS is warranted, with appropriate postapproval commitment

4. CB-4 The Case for Approval of CyIS Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS, but some outstanding questions remain Approval of CyIS is warranted, with appropriate postapproval commitment

5. CB-5

6. CB-6 The Case for Approval of CyIS Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS, but some outstanding questions remain Approval of CyIS is warranted, with appropriate postapproval commitment

7. CB-7 The Case for Approval of CyIS Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS, but some outstanding questions remain Approval of CyIS is warranted, with appropriate postapproval commitment

8. CB-8 The Case for Approval of CyIS Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS, but some outstanding questions remain Approval of CyIS is warranted, with appropriate postapproval commitment

9. CB-9 Postapproval Questions Outstanding questions –How to give CyIS Duration of therapy Practical considerations of delivery –Increase precision of survival benefit Survival, rejection, lung function Optimization of treatment regimen –Further exploration of safety profile Detection of low-frequency safety signals

10. CB-10 Postapproval Commitment Open-label, multinational study using contemporary prospective matched controls –250 patients treated with CyIS 300 mg CyIS or maximum tolerated dose (MTD), prolonged treatment (5 years) –Placebo control not appropriate or necessary > 1000 matched controls from UNOS database Contemporaneous controls receiving standard-of-care without CyIS Efficacy endpoints –Primary: chronic rejection-free survival –Secondary: all-cause mortality and change in FEV 1 Safety endpoints –Infections requiring hospitalization, renal dysfunction, malignancy

11. CB-11 Conclusion Lung transplant is a small, well-defined population Significant unmet need in lung transplantation Strong evidence for benefit –Sound scientific rationale for CyIS –Robust survival advantage Small risk of harm Lung transplant patients will live longer with CyIS Outstanding questions can be addressed with a postapproval study Approval of CyIS is appropriate now