Idenix Pharmaceuticals: Building a Leading Antiviral Franchise. Jean-Pierre Sommadossi, Ph.D. Chairman and CEO Spring 2005

Transcription

1 Idenix Pharmaceuticals: Building a Leading Antiviral Franchise Jean-Pierre Sommadossi, Ph.D. Chairman and CEO Spring 2005

2 Safe Harbor This presentation includes forward-looking statements about Idenix and its business, including without limitation, statements regarding drug discovery, research and clinical development, regulatory approval processes and commercialization activities. These forward-looking statements are subject to risks and uncertainties that may cause actual events or results to differ materially from our current expectations. These risks and uncertainties are detailed in our filings with the Securities and Exchange Commission. All forward-looking statements speak only as of the date of this presentation and, except as required by law, we undertake no obligation to update such statements. 2 2

3 Idenix Building a Leading Antiviral Franchise Mission Products Founded in 1998 to discover, develop and commercialize innovative antiviral drugs addressing unmet medical needs in large and growing markets 3 clinical stage drugs Alliance Novartis global alliance enhances commercial and financial position Global Structure 150 employees at 3 locations in U.S. and Europe Financial Position Strong balance sheet 3 3

4 Building a Leading Antiviral Franchise Most Advanced Antiviral in Development for Hepatitis C Treatment Indication Program Preclinical Phase Ib/IIa Phase IIb Phase III HBV HCV HIV Telbivudine (LdT) Valtorcitabine (val-ldc) Valopicitabine (NM283) NV-08 NV-05 90% of antiviral nucleosides with successful Phase I/II results have led to NDA approval 1 4 Source: 1 International Antiviral News Vol.7, No.7 and Vol.8 No.1 (01/00) 4

5 Chronic HCV Market Large and Underserved $3 Billion Market in 2003 Projected to Grow to $5.1 Billion in M 1 people 2.9 M 2 people 1.5 M 2 people U.S. EU Japan Treatment Pegylatedinterferon U.S. Top 5 EU Japan Avg.Cost Est per patient 2 Sales 3 Avg. Cost Est per patient 2 Sales 3 Avg. Cost Est per patient 2 Sales 3 $ 13,200 $980 M $10,360 $460 M $10,490 $250 M Ribavirin $ 10,000 $800 M $7,275 $310 M $11,130 $70 M 5 Sources: 1 Decision Resources 05/03; 2 CDC N Hanes III; 3 WHO; 5

6 HCV Market Dynamics No Direct Antivirals on the Market Treatment Failure Patients 400,000 patients in U.S. have failed the current standard of care <10% of these respond to retreatment Valopicitabine (NM283) plus pegylated interferon in phase IIb Treatment Naïve Patients 170 million patients WW are infected with HCV 60-70% in major markets are HCV type 1, responding poorly to treatment Valopicitabine (NM283) plus pegylated interferon in phase IIa 6 Source: Company research; Strader et al. Hepatology 04/04; WHO 6

7 Hepatitis C Competitive Landscape NM283 is Most Advanced Specifically Targeting HCV Replication Brand Name Target/Type Company U.S. Status Valopicitabine (NM283) Nucleoside analog Idenix Phase IIb BILN-2061 Protease inhibitor Boehringer Ingelheim Phase II (hold) ISIS Antisense Isis Pharmaceuticals Phase II (hold) MBI-3253 Glucosidase inhibitor Migenix Phase II JTK-003 Non-nucleoside Japan Tobacco/Akros Phase I / II Isatoribine (ANA245) TLR7/Nucleoside analog Anadys Phase Ib HCV-086 Non-nucleoside Wyeth/Viropharma Phase Ib (hold) VX-950 Protease inhibitor Vertex Phase Ib SCH-7 Protease inhibitor Schering-Plough Phase I R803 Non-nucleoside Rigel Phase I (hold) HCV-796 Non-nucleoside Wyeth/Viropharma Phase I R 1626 Nucleoside analog Roche Phase I 7 Source: Company Research 7

8 Valopicitabine (NM283) To Treat Hepatitis C Potential First-to-market Direct HCV Antiviral Drug Development of a more effective treatment than ribavirin, in combination with pegylated interferon Oral, once-daily administration Successful phase I clinical trial in 95 HCV type 1 patients (87% prior treatment failures) with a mean HCV RNA reduction of 1.2 log 10 at 800 mg/day with 2 weeks of treatment U.S. patent (notice of allowance) protection through

9 Valopicitabine (NM283) Clinical Development Treatment Failure Patients Phase IIb trial 171 non-responders HCV genotype 1 24-week trial with analysis of data at 12 and 24 weeks 3 treatment regimens NM283 alone NM283 plus pegylated-interferon pegylated-interferon plus ribavirin Treatment Naïve Patients Phase IIa trial 4 week drug-drug interaction trial Trial extended to 48 weeks Phase IIb trial planned for 2005 Phase III Development Program Contemplates First NDA in Treatment Failure Patients 9 9

10 Introduction/Background Peg-IFNα-2b monotherapy has 20% ETR (Week 48) and 5-8% SVR in HCV-1 patients 1 Addition of ribavirin to Peg-IFNα-2b increases SVR to 42% in HCV-1 patients 2 Valopicitabine (NM283) HCV RNA in a Phase I/II trial: 3 Mean 1.2 log 10 (94%) reduction in HCV RNA in two weeks at optimal valopicitabine dosing levels 87% of patients had previously failed IFN-based therapies Valopicitabine and IFNα show synergistic antiviral effects in BVDV model in vitro Supports early clinical investigation of valopicitabine plus Peg-IFNα, to maximize antiviral efficacy and minimize resistance 1 Lindsay et al, Manns et al, Godofsky DDW 2004; Afdhal AASLD

11 Valopicitabine Phase IIa Trial: Initial Study Design Safety, antiviral activity, and pharmacokinetics of valopicitabine versus valopicitabine + peg-ifnα-2b during 28 days treatment Open-label PK interaction and safety study 30 treatment-naïve adults with compensated CHC HCV-1, HCV RNA >5 log 10 IU/mL, ALT <5 times ULN Randomized 2:3 to valopicitabine (n=12) vs valopicitabine + peg-ifnα (n=18) Peg-IFNα-2b: 1.0 µg/kg given weekly (Days 8, 15 and 22) Valopicitabine: mg/d to Day 8, then 800 mg/d to Day

12 Valopicitabine Phase IIa Trial: Protocol Amendments for Extension of Treatment Encouraging early data treatment extended to 12, then 24, and finally to 48 weeks via protocol amendments, with FDA & investigator agreement Continuation of valopicitabine 800mg/d or valopicitabine 800mg/d + weekly peg-ifnα-2b 1.0 µg/kg Virologic response and tolerability at Week 12 determined eligibility for extended treatment Study is ongoing: 12- and 24-week data to date will be presented today First longer-term efficacy & safety data for an HCV-specific small-molecule antiviral Pilot evaluation of extended treatment with the combination of NM283 + peg-ifn, as a prelude to Phase IIb-III studies 12 12

13 NM283 Phase IIa Trial: Baseline Demographics All patients were treatment naïve, HCV-1, with compensated liver disease 800mg QD 800 mg QD + Peg-IFNα QW n Age: Mean yrs (SD) Race (% Hispanic/Latino) (% Caucasian) (% African American) 46 (10.5) % Male 58 HCV RNA: Mean log 10 IU/mL (SD) (0.55) 44 (11.5) (0.70) Total 44 (11.0) (0.64) ALT: Mean IU/mL (SD) 63.9 (39.6) 70.8 (40.1) 68.1 (39.3) 13 13

14 NM283 Phase IIa Trial: Patient Disposition 30 patients enrolled Valopicitabine MonoRx (n=12) 2 Discontinuations before Wk 12; - 1 Pt Lost to Follow-up at Day 43-1 Pt withdrew after Day Pts completed 12 Weeks Rx; - 9 Pts dc d at Wk 12 for no EVR - 1 Pt continued on Rx to Wk 24 Valopicitabine + Peg-IFNα ComboRx (n=18) 2 Discontinuations before Wk 12; - 1 Pt dc d at Day 8, refused Peg-IFN - 1 Pt dc d Peg at Day 71 IFN AEs 1 Pt recently began Rx 15 Pts completed 12 Weeks Rx - 3 Pts dc d at Wk 12 for no EVR - 1 Pt withdrew consent at Wk 12-2 Pts ongoing, pre-wk 24-9 Pts completed 24 Wks Rx 14 14

15 NM283 Phase IIa Trial: Safety & Tolerance (1) Clinical safety satisfactory overall No serious adverse events or dose-limiting toxicities Most frequent adverse events, regardless of attributability to study drug Valopicitabine (n=12) Valopicitabine + IFN (n=18) N (%) N (%) NAUSEA 4 (33.3) 11 (61.1) HEADACHE 5 (41.7) 8 (44.4) VOMITING 4 (33.3) 8 (44.4) DYSPEPSIA 3 (25.0) 5 (27.8) INFLUENZA LIKE ILLNESS (44.4) ARTHRALGIA 2 (16.7) 5 (27.8) DIARRHEA 2 (16.7) 5 (27.8) FATIGUE 1 (8.3) 5 (27.8) 15 15

16 NM283 Phase IIa Trial: Safety & Tolerance (2) Typical IFN side effects no unexpected side effects Nausea/vomiting common in both Rx groups, typically transient, probably related to both valopicitabine and IFN Only 1 grade 3/4 lab abnormality was observed during treatment: Grade 3 ANC (620/mm 3 ) at Day 11 in a patient receiving ComboRx ANC returned to baseline levels at Day 15, remained stable for the duration of treatment No dose interruption or treatment modification required 16 16

17 Valopicitabine (NM283) Phase IIa Trial 12-week Interim Data Mean Decrease in HCV RNA from Baseline HCV RNA Change from Baseline (log10 IU /m L) All 28 Patients with Data Past Week mg NM283 QD Weekly Peg-IFN dosing commenced on Day 8 (then Day 15, 22 etc.) Study Day Week 12 = Day 85 NM283 MonoRx log 10 IU/mL ComboRx log 10 IU/mL NM283 (n=12) NM ug/kg Peg-IFN-2b (n=16) 17 17

18 . Valopicitabine Phase IIa Trial: Mean HCV RNA Level, Baseline to Week 24 All 9 ComboRx Patients & 1 MonoRx Patient Completing Week 24 Mean Serum HCV RNA (IU/mL) Amplicor LLOQ (600 IU/mL) Amplicor LLOD (50 IU/mL) TaqMan LLOD (10 IU/mL) Week 12 = Day Study Day Valopicitabine (n=1) VL: 5.2 Log 10 IU/mL VL : -1.9 Log 10 IU/mL Week 24 = Day 169 Valopicitabine + Peg-IFNα (n=9) VL: 1.43 Log 10 IU/mL VL : -4.5 Log 10 IU/mL 18 18

19 NM283 Phase IIa Trial: Individual HCV RNA Plots All 9 ComboRx Patients Completing Week 24 At Week 24: 8 of 9 Patients <LLOQ Amplicor (600 IU/mL) Serum HCV RNA (IU/mL) of 9 Patients <LLOD Amplicor (50 IU/mL) 6 of 9 Patients <LLOD TaqMan (10 IU/mL) Study Day 19 19

20 Valopicitabine Phase IIa Trial: Week Individual HCV RNA Levels for the 5 ComboRx Patients Who Were Still PCR+ at Week 12 Week patients PCR- by Week 12 Multi-log HCV RNA reductions in 4 of 5 other patients after Week 12, shown here Week 24 Serum HCV RNA (IU/mL) Study Day 20 20

21 NM283 Phase IIa Trial: Conclusions To Date (1) 21 Marked antiviral activity for valopicitabine + peg-ifnα: Proportion of PCR-neg patients at Weeks 12 and 24 appears better than peg-ifnα-2b alone by historical comparison 1 For 9 ComboRx patients completing Week 24: Mean HCV RNA 4.5 log 10 IU/mL (range: to -6.2 log 10 ) 9 of 9 pts have achieved at least 2 log 10 decrease from Baseline: 8 of 9 patients below LLOQ for Amplicor PCR (< 600 IU/mL) 6 of 9 patients below LLOD for Taqman PCR (<10 IU/mL) Continuing late HCV RNA reductions are common: 4 of 5 pts with detectable HCV RNA at Week 12 had subsequent multi-log drops by Wk 24 Kinetics of response to Valopicitabine plus Peg-IFNα may differ from kinetics of response to peg-ifn/rbv 1 Lindsay et al. 2001; PCR- at Week 48 = 20% for HCV-1 pts 21

22 Valopicitabine Phase IIa Trial: Conclusions To Date (2) No HCV RNA breakthroughs to date Viral genotyping (HCV Pol) underway Good Tolerability Negligible hematologic side effects possible safety advantage Larger Phase IIb trials in prior treatment failures and treatment-naives - underway Valopicitabine may offer improved efficacy and safety, especially for HCV-1 patients and prior treatment failures 22 22

23 Novartis Licensing Option Terms Valopicitabine (NM283) Option to License Prior to Initiation of Phase III $25 million milestone received June 2004 Upon licensing, Novartis will reimburse 100% of development costs on go-forward basis Up to $525 million in license fees and regulatory milestone payments Sales milestones Co-promote and profit split in U.S. and 5 major EU countries 23 23

24 2005 Expected to be an Event-driven Year Telbivudine 2-year phase IIb data Spring Phase III data Fall NDA filing by year-end Valopicitabine (NM283) Complete phase IIa in treatment naïve population 12-week data on all patients in Spring Complete data (24 weeks) in Fall Complete phase IIb in treatment-failure population 12-week data in Fall Pre-clinical Advance HCV and HIV drug candidates 24 24

25 Idenix Pharmaceuticals: Building a Leading Antiviral Franchise Investor Contact: Amy Sullivan Executive Director, Corp. Comm investor@idenix.com