Slide 1 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. IAS–USA David L. Wyles, MD Associate Professor of Medicine University of California San Diego Don’t Blink: The Rapid Evolution of IFN-Free Therapy for HCV From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA.

Slide 2 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. Why do we need IFN-free regimens? Efficacy Poorly interferon responsive – African Americans – Prior IFN failure Null responder cirrhotics Acceptance and tolerability Poor patient acceptance Providers reluctance – Resource intensive Monitoring: toxicity Support services Interferon ineligible populations Decompensated ESLD Severe psychiatric disease Medical co-morbidities 100 HCV RNA+ Patients 40 Eligible Patients 5 Cured 30% refusal 75% dropout or nonresponse 60% Ineligible 28 Treated Falck-Ytter, Y. Annals, 2002.

Slide 3 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. Limitation of first generation PIs Complicated dosing regimens and treatment algorithms – Food restrictions High potential for drug-drug interactions Increased side effects (over Peg/RBV) Limited efficacy in those with the greatest medical need

Slide 4 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. Retreatment Success Depends on Fibrosis Stage and Previous Response Zeuzem S. NEJM TVR-based therapy; HCV mono-infected

Slide 5 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. BOC and TVR Increase Adverse Events Jacobson I. NEJM 2011; Poordad F. NEJM Adverse Event, %TVR Arms (n = 727) PegIFN/RBV Arm (n = 361) Pruritus Nausea Rash Anemia Diarrhea Discontinuation due to AE91 Adverse Event, %BOC Arms (n = 78) PegIFN/RBV Arm (n = 363) Anemia4929 Dysgeusia Discontinuation due to AE1416 Telaprevir (TVR) Boceprevir (BOC)

Slide 6 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. IFN-Free Regimens for HCV gt1 DrugsClassesPopulationDurationN SVR (1a/1b) Daclatasvir/ Asunaprevir NS5A/PI Nulls IFN intolerant 24 wks % (22/100) 77% DCV/ASU/ BMS NS5A/PI/N NI Naïve Non-cirrhotic 12 wks 24wks 16 94% 94% $ SOF/RBVNI Naïve Nulls 12 wks % 10% SOF/RBV GT 2/3 NI Naïve/intolerant Non-responders 12 wks 12/16 wks /95 67% (97/56) 50/73% SOF/DCV±RBV SOF/LDV/RBV NI/NS5A Naïve Naïve/Null 24wks 12wks 44 25/ % 100/100% SOF/SMV±RBVNI/PI Null (F0-F2) 12wks % * 93% * FAL/ BI /RBV PI/NNI Naïve Cirrhosis 28 wks7868% (43/83) Mericitabine/ Danoprevir + RBV NI/PI Naïve (F0-F2) 24 wks6441% (26/71) ABT-450r/267/ 333±RBV PI/NS5A/N NI Naïve Nulls % 93% Lok A. NEJM Suzuki F. #14 EASL Everson G. AASLD Gane EJ AASLD Gilead press release Feb Sulkowski M. AASLD Gane EJ. CROI Lawitz E CROI Zeuzem S. #101 EASL Poordad F. EASL King M. CROI $ SVR 4 * SVR 8

Slide 7 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. Lessons learned with IFN-free therapies HCV cure is achievable without IFN – With much shorter durations Subtype matters with less potent regimens Ribavirin matters with less potent regimens Cirrhotics and null responders can be effectively treated Tolerability and side effects are improved

Slide 8 of 8 From DL Wyles, MD, at Atlanta, GA: April 10, 2013, IAS-USA. Unknowns with IFN-free therapies Efficacy in HCV/HIV subjects – No reason to suspect efficacy will suffer – Drug-drug interaction limiting factor How restrictive will payers be? – SOF + DCV or SOF + SMV “off label” early 2014 Impact of selected HCV resistance? Decompensated cirrhosis data needed