PULMINIQ™ (cyclosporine, USP) Inhalation Solution

1. PULMINIQ™(cyclosporine, USP) Inhalation Solution Pulmonary-Allergy DrugsAdvisory Committee June 6, 2005

2. PULMINIQ™(cyclosporine, USP) Inhalation SolutionIntroduction/Regulatory History Michael Scaife, PhD Senior Vice President, Regulatory Affairs, Quality and ComplianceChiron | BioPharmaceuticals

3. The Clinical Development of CyIS Initial open label trials in patients with refractory acute rejection Initial preclinical trials ACS001ends 1988 1993 Aug 2003 1983 1991 1997 Cyclosporine approved by FDA Initial open- label trials in chronic rejection ACS001 begins

4. Regulatory History of CyIS First patient receives CyIS in early access program Chiron acquires rights to develop CyIS Chiron conducts animal toxicology studies of CyIS NDA action letter due NDA submitted Apr 2003 Jan 2004 Oct 2004 Mar 2005 July 14, 2005 Nov 2003 May 2004 Dec 2004 June 6, 2005 CyIS granted Orphan Drug Status FDA CyIS pre-NDA meeting Priority review status granted Advisory Committee meeting

5. Chiron Briefing Document Figure 1.3.2-1 Survival Benefit 1.0 0.9 0.8 0.7 0.6 Survival 0.5 0.4 0.3 CyIS Placebo 0.2 0.1 0.0 0 6 12 18 24 30 36 42 48 54 60 Time ( months)

6. Agenda

7. Chiron William Capra, PhDAssociate Director, Biostatistics Dale Johnson, PharmD, PhDVP, Drug Assessment and Development Darlene Rosario, MBA, RAC Senior Director, Regulatory Affairs Tyler Martin, MD VP, Clinical Development, General Medicine Carlos Rodriguez, PhDAssociate Director, Pharmacokinetics Judith Vensak, RN, BSN, CCTCMedical Science Liaison External Elbert Trulock III, MDWashington UniversitySt. Louis, Missouri Tim Corcoran, PhDUniversity of Pittsburgh Medical Center Allen Singer, DVM, DACVP Battelle Science and Technology International Additional Experts