HIGH END-OF-TREATMENT RESPONSE (84%) AFTER 4 WEEKS OF R1626, PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN FOLLOWED BY A FURTHER 44 WEEKS OF PEGINTERFERON ALFA- 2A AND RIBAVIRIN EASL 2008-Update Nelson et. al.

What is the Mechanism of Action of R1626  R1626 is a nucleoside analogue HCV polymerase inhibitor Polymerase and Protease are essential enzymes for HCV replication  R1626 is the first in class compound Only 1 other nucleoside polymerase inhibitor in the clinic  Roche/Pharmasset in phase 1

What are the advantages of R1626 over other antivirals  Being a nucleoside analogue R1626 is active against all genotypes Protease inhibitors are less active in GT2/3  R1626 is less prone to cause resistance as compared to protease inhibitors and non-nuc polymerase inhibitors Per today not a single case of resistance in both monotherapy and combination

What do we expect from R1626: Target Product Profile  15% increase in SVR for naïve GT1,4 patients and shortening of treatment duration to 6 months for RVR patients  30% SVR for treatment failures  No major safety concerns that cannot be managed  Pill count up to 6 per day (BID dosing)

High end-of-treatment response rate (84%) after 4 weeks of R1626, Pegasys and ribavirin followed by 44 weeks of Pegasys and ribavirin David Nelson, Paul J. Pockros, Eliot Godofsky, Maribel Rodriguez-Torres, Greg Everson, Michael W. Fried, Reem H. Ghalib, Stephen A. Harrison, Lisa M. Nyberg, Mitchell L. Shiffman, Anna Chan, George Z. Hill

Virological response (HCV RNA <15 IU/mL) over time* 84% 65% 52% Study Week Percentage of patients with virological response** Dual 1500Dual 3000Triple 1500SOC 66% *Roche COBAS TaqMan HCV Test ** Last observation carried forward for 1 patiet in Triple 1500 and 1 patient in SOC

N = 5 (63%) N = 3 (37%) N = 8 YES NO N = 23 RVR- 4 YES NO N = 21 (91%) YES EOT* NO EOT* N = 2 (9%) TRIPLE 1500 R PEG + RBV (N=31) EOT predictability analysis: RVR-4 * Assumes last observation carried forward for 1 patient

Common adverse events - by week 48 Adverse Event Dual 1500 (N=21) Dual 3000 (N=32) Triple 1500 (N=31) SOC (N=20) Fatigue62%66%74%65% Nausea38%69%71%65% Headache71%53%61%60% Diarrhea38%81%35% Chills71%50%35%45% Insomnia38% 48%50% Neutropenia*52%66%39%- Pyrexia43%38%39%40% Myalgia19%34%35%55% Arthralgia38%34%23%35% Rash33%16%48%25% Irritability38%19%45%15% Vomiting10%50%26%10% Cough10%38%19%25% Depression10%25%35%15% Dizziness33%19%23%20% Pain38%22%23%10% * SAE, D/C or required Tx

 High EOT response for 4 week triple therapy of R1626 followed by SOC 84% HCV RNA negative EOT vs Telaprevir 65% (PROVE1)  Lack of viral resistance  Dosing of R1626 was limited by neutropenia during the 4 weeks treatment period  Neutropenia and other lab abnormalities were fully reversible and comparable to SOC by week 48 R1626 Phase 2 a Conclusions

פגסיס. מרשם להצלחה הצלחה פורצת גבולות