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EASL 2008-Update

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. Nelson et. al. EASL 2008-Update. What is the Mechanism of Action of R1626.

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EASL 2008-Update

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  1. 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 Nelson et. al. EASL 2008-Update

  2. 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

  3. 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

  4. 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)

  5. 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

  6. Virological response (HCV RNA <15 IU/mL) over time* Dual 1500 Dual 3000 Triple 1500 SOC 100 84% 80 66% 65% 60 52% Percentage of patients with virological response** 40 20 0 0 4 8 12 16 20 24 28 32 36 40 44 48 Study Week *Roche COBAS TaqMan HCV Test ** Last observation carried forward for 1 patiet in Triple 1500 and 1 patient in SOC

  7. EOT predictability analysis: RVR-4 N = 21 (91%) YES N = 23 EOT* YES N = 2 (9%) NO RVR- 4 TRIPLE 1500 R1626 + PEG + RBV (N=31) N = 5 (63%) YES N = 8 EOT* NO N = 3 (37%) NO * Assumes last observation carried forward for 1 patient

  8. R1626 Phase 2 a Conclusions • 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

  9. פגסיס. מרשם להצלחה הצלחה פורצת גבולות

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