Douglas Dieterich,1 Vicente Soriano,2 Mark Nelson,3 Jürgen Kurt Rockstroh,4 Keikawus Arastéh,5 Sanjay Bhagani,6 Andrew Talal,7 Cristina Tural,8 Richard Vinisko,9 and Jens Kort 9

STARTVerso 4: High rates of early virologic response in HCV genotype 1/HIV-co-infected patients treated

with faldaprevir plus pegIFN and RBV

1Mount Sinai School of Medicine, New York, NY, USA; 2Hospital Carlos III, Madrid, Spain; 3Chelsea and Westminster Hospital, London, UK; 4University of Bonn, Bonn, Germany; 5EPIMED, Vivantes Auguste-Viktoria Hospital, Berlin,

Germany; 6Royal Free Hospital, London, UK; 7State University of New York, Buffalo, NY, USA; 8Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; 9Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA

20th Conference on Retroviruses and Opportunistic Infections, March 3–6, 2013

Presenter disclosure

I have had financial relationships within the last 12 months relevant to my presentation with:

Boehringer Ingelheim Pharmaceuticals AND

My presentation includes information on faldaprevir, which is an investigational

compound and is not yet approved

Douglas Dieterich, MDMount Sinai School of Medicine,

New York, USA

Introduction to faldaprevir

• Faldaprevir is a potent and selective

inhibitor of the HCV NS3/A4 protease

‒ The pharmacokinetics of FDV allow

oral once daily administration

• Phase IIb data demonstrated potent

antiviral activity against HCV GT-1 for:

‒ Faldaprevir combined with pegIFN/RBV

‒ An IFN-free combination of faldaprevir

with BI 207127 and RBV

• Phase III trials are ongoing for the

iFree and iBased faldaprevir clinical

development programsLlinàs-Brunet M, et al. J Med Chem 2010;53:6466–6476;

Lemke CT, et al. J Biol Chem 2011;286:11434–11443;Sulkowski MS, et al. Hepatology 2013 Jan 28 [Epub ahead of print];

Zeuzem S, et al. AASLD Congress November 9–13, 2012 [Abstract No. 232].

GT, genotype; HCV, hepatitis C virus;IFN, interferon alpha; RBV, ribavirin;BI 207127, a non-nucleoside inhibitor of HCV RNA polymerase

Faldaprevir: Interaction with NS3/4A protease

Green = hydrophobic Blue = mildly polarPurple = H bonding

Phase III open-label, sponsor-blinded study in treatment-naïve and relapser patients with chronic HCV GT-1 and HIV infection

LLoQ, lower limit of quantification <25 IU/mL HCV RNA; pegIFN: pegylated interferon alfa-2a 180 µg once weekly; QD, once daily; SVR, sustained virologic response at 12 weeks after end of treatment.; ETS, early treatment successRBV: ribavirin 1000 or 1200 mg daily dose for body weight <75 kg or ≥75 kg, respectively

Patients with HCV RNA below LLoQ, at Week 4, and HCV RNA below LLoQ target not detected at Week 8 (=ETS) will be re-randomized 1:1 at week 24 to stop treatment or continue pegIFN/RBV through week 48Patients who did not achieve ETS will continue pegIFN/RBV through week 48

STARTVerso 4: Study design (1)

Faldaprevir 120 mg QD + pegIFN/RBV

Day 1 Week 12 Week 24 Week 48

pegIFN/RBV

pegIFN/RBV

Faldaprevir 240 mg QD + pegIFN/RBVFaldaprevir 240 mg QD

+ pegIFN/RBV

pegIFN/RBV

Randomization 1:1

Primary endpoint: SVR12Interim data

STARTVerso 4: Study design (2)

No ART

Raltegravir ormaraviroc

based

120 or 240 mg QD

Efavirenzbased

Darunavir/ritonavir oratazanavir/ritonavir

basedART

regimen

Faldaprevir dosage

RANDOMIZED

120 mg QD240 mg QD

ART, antiretroviral therapy; QD, once daily

ALLOCATED

• HCV GT-1 infection, including compensated cirrhosis

‒ HCV treatment-naive or relapsers

STARTVerso 4: Patient disposition(Week 12 interim data)

Allocated/Randomized(N=153/N=157)

Screen failure(N=143)

aIncludes: viral rebound ≥1 log10 HCV RNA from previous undetected level; lack of HCV RNA reduction from baseline by ≥ 2 log10 at Week 12; lack of viral response at Week 24. bIncludes: protocol violation, withdrawal by subject, or other reasonsAE, adverse event; ATZ, atazanavir; DRV, darunavir; EFV, efavirenz; r, ritonavir

Completed 12 weeks of treatment(N=176)

Faldaprevir (120 or 240 mg QD) + pegIFN/RBV

(N=308)

Screened(N=453)

Not treated(N=2)

HCV treatment-naïve(N=239)

Relapser(N=69)

Not available (N=18)Discontinued (N=45)

15 Due to AE

12 Lack of efficacya

18 Other reasonb

Not available (N=4)Discontinued (N=7)

3 Due to AE

1 Lack of efficacya

3 Other reasonb

Completed 12 weeks of treatment(N=58)

STARTVerso 4: Baseline characteristics

Treatment-naïve(N=239)

Relapser(N=69)

Total(N=308)

Age, years (mean) 47 47 47

Male, n (%) 184 (77) 64 (93) 80

Race, n (%) WhiteBlack or

African AmericanOthera

179 (75)39 (16)21 (9)

63 (91)2 (3)4 (6)

7913 8

ART, n (%) EFV-basedATZ/r- or

DRV/r-basedRal-

based and otherb

No ART (ARV-naïve), n (%)

67 (28)60 (25)

105 (44) 7 (3)

17 (25)7 (10)

41 (59)4 (6)

84 (27)67 (22)

146 (47)11 (4)

Mean baseline CD4+ T cell count, cells/µL 544 549 545

Baseline HCV RNA ≥800 000 IU/mL, n (%) 197 (82) 49 (71) 246 (80)

HCV Genotype-1a, n (%) 184 (77) 55 (80) 239 (78)

Cirrhosis F4 or FibroScan >13 kPa, n (%) 40 (17) 11 (16) 51 (17)aIncludes Asian, Native Hawaiian or other Pacific Islander, American Indian or Alaska Native, and missing data.bIncludes 1 patient taking maraviroc plus emtricitabine/tenofovir disoproxil fumarate, 1 patient taking emtricitabine/tenofovir disoproxil fumarate only. Ral, raltegravir

STARTVerso 4: Interim safety and tolerability

Most frequent AEs in >20% of patients No. of patients (%)

NauseaFatigueDiarrheaHeadacheAsthenia

113 (37)102 (33)83 (27)71 (23)68 (22)

Other AEs of interest No. of patients (%)

Anemia Neutropenia Rash Loss of HIV suppressiona

55 (18)49 (16)55 (18)

0

Most frequent serious AEs (>1 patient) No. of patients (%)

PyrexiaAbdominal painDiarrheaGastroenteritisVomitingAnemiaRashDehydration

4 (1)3 (<1)3 (<1)2 (<1)2 (<1)2 (<1)2 (<1)2 (<1)

aIncrease of HIV plasma RNA >200 copies/mL on two consecutive measurements from prior <40 copies/mLThree deaths: dyspnea; hemorrhage, cerebrovascular accident; Drug reaction with eosinophilia and systemic symptoms

Series10

20

40

60

80

100

8086

60

82

Pro

port

ion

of p

atie

nts

(%)

191/239

143/239

Week 4 Week 12

206/239

195/239

Early virologic response in HIV/HCV co-infected patients: HCV treatment-naïve

Treatment-naïve <LLoQ Treatment-naïve <LLoQ TND

TND target not detected

Series10

20

40

60

80

100

8086

60

82

91 93

74

91

Pro

port

ion

of p

atie

nts

(%)

191/239

143/239

Week 4 Week 12

206/239

195/239

Early virologic response in HIV/HCV co-infected patients: HCV treatment-naïve and relapsers

64/69

63/69

63/69

51/69

Treatment-naïve <LLoQ Treatment-naïve <LLoQ TND

Relapser <LLoQ Relapser <LLoQ TND

Series10

20

40

60

80

100

8086

60

82

91 93

74

91

76

93

Pro

port

ion

of p

atie

nts

(%)

aSILEN-C1 study arm of 240mg QD FDV plus pegIFN/RBV in HCV GT1 treatment-naïve monoinfected patients without cirrhosis; data on file

191/239

143/239

Week 4 Week 12

206/239

195/239

Early virologic response in HIV/HCV co-infected patients: comparison with HCV mono-infected patients

64/69

63/69

63/69

51/69

Treatment-naïve <LLoQ TND

Treatment-naïve <LLoQ Treatment-naïve <LLoQ TND

Relapser <LLoQ Relapser <LLoQ TND

a

a

108/142

132/142

Mono-infected patients, SILEN-C1 study:

Series10

20

40

60

80

100

77

88P

ropo

rtio

n of

pat

ient

s (%

)

184/239

61/69

Response guided therapy criteria (ETS) in STARTVerso 4

Treatment-naïve Relapser

ETS criteria: Wk 4 HCV RNA <LLoQ, + Wk 8 <LLOQ, TND

aData missing for 4 patients.ETS, early treatment success

a

YES

50% Stop treatment at week 24 50% continue with pegIFN/RBV through week 48

Summary and conclusions

• AEs were comparable to those with faldaprevir and pegIFN/RBV in HCV mono-infected patients

• ETS was observed in 80% of patients‒ Half of these patients will stop treatment at Week 24

• 12-week data show high rates of early virologic response to faldaprevir + pegIFN/RBV

• Interim data compare well with early response rates in mono-infected patients

• Sustained virologic response data will be used to determine the feasibility of response-guided therapy with faldaprevir

Overall reductions in HCV RNA Treatment-naïve Relapsers

Week 4 <LLoQ :Week 12 <LLoQ TND:

80%82%

91%91%

• Patients, and study investigators and site staff at 67 study centers:

• Boehringer Ingelheim for sponsoring the study and the Boehringer Ingelheim 1220.19 team

• The external Data Monitoring Committee

Acknowledgments

Brazil Hans Jäger Josep Mallolas Chloe Orkin Marina Nunez

Carlos Eduardo Brandão Mello Arastéh Keikawus Juan Antonio Pineda Alison Uriel Gerald Pierone

Raymundo Ferreira Filho Hartwig Klinker Daniel Podzamczer United States Michael Saag

Paulo Ferreira Jürgen Kurt Rockstroh Cristina Tural John Baxter Michael Somero

Juvencio Furtado Italy Jorge Vergas Maurizio Bonacini Richard Sterling

Beatriz Grinsztejn Giacchino Angarano, Switzerland Cynthia Brinson Mark Sulkowski

Jose Madruga Andrea Antinori Manuel Battegay Douglas Dieterich Andrew Talal

France Giovanni Di Perri Enos Bernasconi Richard Elion Kristen Marks

Marc Bourliere Gaetano Filice Jan Fehr Jerome Ernst

Laurent Cotte Francesco Mazzotta Andri Rauch Douglas G. Fish

Pierre-Marie Girard Paola Nasta United Kingdom Federico Hinestrosa

Caroline Lascoux-Combe Massimo Puoti Kosh Agarwal Mamta Jain

Marc-Antoine Valantin Spain Sanjay Bhagani Anthony LaMarca

Germany Francisco Blanco Martin Fisher Eric Lawitz

Johannes Bogner Manuel Crespo, Ranjababu Kulasegaram Cheryl McDonald

Christian Hoffmann Josep Guardiola Clifford Leen Karam Mounzer

Patrick Ingiliz Juan Carlos Lopez Mark Nelson Ronald Nahass