The Cystic Fibrosis Therapeutics Development Network and CF Clinical Research at UNM

1. The Cystic Fibrosis Therapeutics Development Network and CF Clinical Research at UNM Jennifer L. Taylor-Cousar, MD Assistant Professor, Adult CF Program/Associate CF Center Director, University of New Mexico CF Center March 19, 2009

2. CF Therapeutics Development Network (CF TDN) CF TDN Initially created in 1982 (Research Development Center) In 2008 made up of 18 centers With increasing number of potentially therapeutic drugs, it became clear that there were not enough patients at these 18 centers 2 years ago, RFA distributed to increase number of CF research centers In January 2009, UNM became part of the CF TDN

3. Cystic Fibrosis Therapeutics Development Pipeline

4. Summary of pH Cascade in CF CFTR Mutation PDEi Altered pH in CF cells Abnormal glycosylation pattern Predisposition to adherence by P. aeruginosa Inflammatory response Chronic lung damage/early death

5. Sildenafil (Revatio™) in CF ENaC ENaC CFTRwt CFTRm Inflammation Na+ Na+ Infection sildenafil H+ H+ Normal cell CF Cell ENaC ENaC CFTRm CFTRm Inflammation Na+ Infection H+ H+ CF cell CF cell

6. Study Design • Placebo-controlled, blinded, randomized cross-over study of sildenafil in clinically stable patients with mild to moderate CF lung disease • Length of participation for each subject will be approximately 15 weeks, and will consist of: • Screening visit • Two outpatient study visits with initiation of study drug and/or placebo • One interim visit during each therapy period (to review concomitant medications and assess side effects) • One visit at the end of each therapy period (to reassess inflammatory markers, laboratory studies and side effects) • A 28-day washout period with coordinator phone call • A follow-up assessment 2 weeks after subject completion