HIGH ENDOFTREATMENT RESPONSE 84% AFTER 4 WEEKS OF R1626, PEGINTERFERON ALFA2A 40KD AND RIBAVIRIN FOL

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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
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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

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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

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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)

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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
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Virological response (HCV RNA lt15 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
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EOT predictability analysis RVR-4
N 21 (91)
YES
N 23
EOT
YES
N 2 (9)
NO
RVR- 4
TRIPLE 1500 R1626 PEG RBV (N31)
N 5 (63)
YES
N 8
EOT
NO
N 3 (37)
NO
Assumes last observation carried forward for 1
patient
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Common adverse events - by week 48
SAE, D/C or required Tx
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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

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