Bictegravir/F/TAF Switch Study: Efficacy and Safety Assessment

Switch to Bictegravir/F/TAF From DTG and ABC/3TC Jean-Michel Molina,1Douglas Ward,2Indira Brar,3Anthony Mills,4Hans J rgen Stellbrink,5 Luis L pez-Cort s,6Peter Ruane,7Daniel Podzamczer,8Cynthia Brinson,9Joseph Custodio,10Hui Liu,10Kristen Andreatta,10Hal Martin,10Andrew Cheng,10Erin Quirk10 1H pital Saint Louis, Paris, France; 2Dupont Circle Physicians, Washington DC; 3Henry Ford Hospital, Detroit, MI; 4Southern California Men s Medical Group, Los Angeles, CA; 5ICH Study Center, Hamburg, Germany; 6Unidad Cl nica de Enfermedades Infecciosas, Microbiolog a y Medicina Preventiva, Hospital Universitario Virgen del Roc o/Instituto de Biomedicina de Sevilla, Spain; 7Peter J. Ruane, MD Inc., Los Angeles, CA; 8Hospital Universitari de Bellvitge, Barcelona, Spain; 9Central Texas Clinical Research, Austin, TX; 10Gilead Sciences, Inc., Foster City, CA CROI 2018, Abstract 022 March 4 7, 2018 Boston, MA

Introduction Bictegravir (BIC, B) is a novel, unboosted, potent INSTI with a high in vitro barrier to resistance and low potential for drug-drug interactions1,2 Co-formulated with emtricitabine and tenofovir alafenamide as a single-tablet regimen (B/F/TAF) Dosed once-daily with or without food In three large phase 3 trials, B/F/TAF was noninferior to: dolutegravir (DTG)-containing regimens in treatment naive patients3,4 boosted ATV or DRV-containing regimens in virologically suppressed patients5 No treatment emergent viral resistance to B/F/TAF was identified through Week 48 We assessed the efficacy and safety of switching from DTG/Abacavir/3TC (DTG/ABC/3TC) to B/F/TAF 1. Gallant JE, et al. J Acquir Immune Defic Syndr 2017;75:61-6; 2. Tsiang M, et al. Antimicrob Agents Chemother 2016.60:7086-97; 3. Gallant J, et al Lancet 2017; 4. Sax PE, et al. Lancet 2017. 5. Daar, ID Week 2017, Abstract 67504. 2

Study 380-1844: Design Primary Endpoint Week 0 48 B/F/TAF 50/200/25 mg qd HIV-suppressed adults on regimen containing DTG, ABC & 3TC* n=282 OLE B/F/TAF DTG/ABC/3TC placebo qd HIV-1 RNA <50 copies/mL for 3 mo eGFRCG 50 mL/min No active HBV infection No known resistance to study drugs 1:1 DTG/ABC/3TC 50/600/300 mg qd OLE B/F/TAF n=281 B/F/TAF Placebo qd Phase 3, randomized, double-blind, multicenter, active-controlled study (NCT02603120): North America, Europe, Australia Primary endpoint: proportion with HIV-1 RNA 50 copies/mL at Week 48 Noninferiority margin of 4% based on FDA snapshot algorithm *Could be components of single-tablet regimen. OLE, open label extension. 3

Baseline Characteristics Study 380-1844 B/F/TAF n=282 DTG/ABC/3TC n=281 Median age, years (range) 47 (21-71) 45 (20-70) Male, % 88 90 Race, % White 73 73 Black or African descent 21 22 Hispanic/Latino Ethnicity, % 16 19 Median CD4 cell count, cells/ L (IQR) 732 (554,936) 661 (478,874) Median eGFRCG, mL/min (IQR) 101(84,119) 101(85,122)

Virologic Outcome at Week 48 Study 380-1844 Treatment Difference in RNA 50, % (95.002% CI) Virologic Outcome p=0.59 95.0 93.6 100 Favors B/F/TAF Favors DTG/ABC/3TC B/F/TAF (n=282) DTG/ABC/3TC (n=281) 80 Patients, % 60 0.7 40 -1.0 2.8 p=0.62 20 5.3 4.6 1.1 0.4 0 -4% 0 4% HIV-1 RNA 50 c/mL 3 282 HIV-1 RNA <50 c/mL 264 282 No Virologic Data 15 282 267 281 1 281 13 281 Switching to B/F/TAF was noninferior to remaining on DTG/ABC/3TC 5

Virologic Outcome at Week 48 Study 380-1844 Treatment Difference in RNA 50, % (95.002% CI) Virologic Outcome p=0.59 95.0 93.6 100 Favors B/F/TAF Favors DTG/ABC/3TC B/F/TAF (n=282) DTG/ABC/3TC (n=281) 80 Patients, % 60 0.7 40 -1.0 2.8 p=0.62 20 5.3 4.6 1.1 0.4 0 -4% 0 4% HIV-1 RNA 50 c/mL 3 282 HIV-1 RNA <50 c/mL 264 282 No Virologic Data 15 282 267 281 1 281 13 281 Switching to B/F/TAF was noninferior to remaining on DTG/ABC/3TC No participant developed treatment-emergent resistance 6

Adverse Events Leading to Study Drug Discontinuation Study 380-1844 B/F/TAF n=282 6 (2) 2 1 1 1 1 0 DTG/ABC/3TC n=281 2 (1) 1 0 0 0 0 1 Patients, n (%) Overall Headache Vomiting Cerebrovascular accident Abnormal dreams Suicidal ideation* Pruritis *Not considered related to study treatment by investigator. 2 deaths occurred in the B/F/TAF arm, unrelated to study medication: Male, 71 years old: sudden death, atherosclerotic CVD on autopsy Female, 46 years old: alcohol and opioid toxicity 7

Most Common Adverse Events Through Week 48 Study 380-1844 B/F/TAF n=282 DTG/ABC/3TC n=281 Patients, n (%) Any AE (all grades) 225 (79.8) 225 (80.1) AEs occurring in 5% of patients Upper respiratory tract infection 29 (10) 27 (10) Nasopharyngitis 20 (7) 22 (8) Headache 19 (7) 21 (7) Diarrhea 24 (9) 14 (5) Arthralgia 19 (7) 10 (4) Insomnia 8 (3) 14 (5) 8

Study Drug-Related AEs Through Week 48 Study 380-1844 B/F/TAF n=282 DTG/ABC/3TC n=281 All Grades p-Value Any study drug-related AE, n (%) 23 (8) 44 (16) 0.01 Study drug-related AE in 1%, n (%) Headache 7 (3) 8 (3) Abnormal dreams 1 (<1) 5 (2) Flatulence 0 5 (2) Nausea 0 5 (2) Diarrhea 2 (<1) 4 (1) Fatigue 1 (<1) 3 (1) Insomnia 0 3 (1) p-value from Fisher exact test 9

Laboratory Abnormalities Through Week 48 Study 380-1844 B/F/TAF n=282 DTG/ABC/3TC n=281 Grade 3 or 4 Lab Abnormalities, n (%) Any 47 (17) 32 (11) in 2% of patients LDL elevation 14 (5) 13 (5) Increased amylase 7 (2) 0 ALT elevation 6 (2) 0 CK elevation 6 (2) 6 (2) Fasting hyperglycemia 6 (2) 2 (<1) No cases of rhabdomyolysis All amylase elevations were transient and not associated with pancreatitis; 4/7 cases had normal lipase Grade 3 and 4 ALT abnormalities were not study treatment related, did not result in study drug interruption, and were associated with other AEs: acute HCV infection (n=3), acute HAV infection (n=1), alcohol abuse (n=1), and NASH (n=1) 10

Change in eGFRCG Over Time Study 380-1844 B /F /T A F B/F/TAF A B C /D T G /3 T C DTG/ABC/3TC 2 0 Median Change From Baseline eGFRCG, 1 0 mL/min (Q1, Q3) 1.0 mL/min p <0.001* 0 -1.8 mL/min - 1 0 - 2 0 0 4 8 1 2 2 4 3 6 4 8 Week No discontinuations due to renal AEs and no cases of renal tubulopathy in either arm *From 2-sided Wilcoxon rank-sum test. 11

Changes in Quantitative Proteinuria at Week 48 Study 380-1844 Retinol-Binding Protein:Creatinine p=0.31* Albumin:Creatinine 2-microglobulin:Creatinine p=0.53* p=0.74* Median % Change From Baseline (Q1, Q3) 96 B/F/TAF 100 84 DTG/ABC/3TC 75 72 66 75 63 50 29 21 20 17 25 14 9 0 -6 -7 -25 -19 -20 -22 -34 -50 Baseline 5.6 mg/g 5.4 mg/g 99 g/g 96 g/g 75 g/g 77 g/g *From 2-sided Wilcoxon rank-sum test for % change from baseline at Week 48 for each marker for treatment comparison. 12

Changes in Spine and Hip BMD Through Week 48 Study 380-1844 Spine Hip 2 2 From Baseline (95% CI) 1 1 0.69 Mean % Change p=0.33* 0.30 0.16 p=0.47* 0.42 0 0 -1 -1 -2 -2 0 24 48 0 24 48 Week Week B/F/TAF n=256 DTG/ABC/3TC n=262 244 253 233 244 256 265 246 253 229 242 *From ANOVA model for comparison of B/F/TAF vs DTG/ABC/3TC at Week 48. 13

Fasting Lipid Changes at Week 48 Study 380-1844 Triglycerides Total LDL HDL Total Cholesterol p=0.77 Cholesterol p=0.42 Cholesterol p=0.13 Cholesterol:HDL p=0.56 3 0 Median Change From Baseline, mg/dL* p=0.028 2 5 2 0 1 5 B/F/TAF DTG/ABC/3TC 1 0 3 2 2 5 1 0 0 0 0 0 -1 -5 -5 -1 0 113 118 49 48 111 111 3.7 3.8 Baseline mg/dL 182 186 *p-values from 2-sided Wilcoxon rank-sum test. 14

Study 380-1844 Conclusions Switching to B/F/TAF was non-inferior to remaining on DTG/ABC/3TC No treatment emergent resistance was observed in either arm B/F/TAF was well tolerated Adverse events were comparable between arms at Week 48 The lipid, bone and renal safety profiles of switching to B/F/TAF were comparable to remaining on DTG/ABC/3TC through 48 weeks of treatment B/F/TAF offers an effective and safe alternative to DTG/ABC/3TC Study 380-1961: Switching to B/F/TAF in women (Kityo et al. Poster 500) 15

Acknowledgements We extend our thanks to: The participants, their families, and all participating study investigators and staff: AUSTRALIA: D Baker, M Bloch, D Smith BELGIUM: L. Vandekerckhove CANADA: L Charest, J de Wet, K Kasper, RP LeBlanc, B LeBouche FRANCE: J-M Molina, G Pialoux, P Pugliese, F Raffi GERMANY: K Arast h, A Baumgarten, M Bickel, J Bogner, S Esser, H J ger, J Rockstroh, H-S Stellbrink ITALY: A Antinori SPAIN: A Antela, B Clotet Sala, M Gutierrez, LF Lopez-Cortes, MJ P rez, D Podzamczer, A Rivero Roman UNITED KINGDOM: AE Clark, MA Johnson, J Ross, G Schembri, AP Ustianowski UNITED STATES: H Albrecht, J Bartczak, P Benson, D Berger, M Berhe, I Brar, C Brinson, JH Burack, BP Cook, D Coulston, C Creticos, GE Crofoot Jr, FA Cruickshank, E DeJesus, C Dietz, MP Dube, H Edelstein, C Fichtenbaum, J Flamm, JE Gallant, JC Gathe Jr, R Grossberg, DP Hagins, WK Henry, RK Hsu, M Johnson, CA Kinder, D Klein, A LaMarca, K Lichtenstein, N Lin, CT Martorelli, A Mills, JO Morales Ramirez, K Mounzer, CL Newman, G Oguchi, O Osiyemi, C Parspns, P Peyrani, G Pierone Jr, DJ Prelutsky, M Ramgopal, B Rashbaum, GJ Richmond, PJ Ruane, L Santiago, AJ Scarsella, SR Schrader, A Scribner, P Shalit, C Shikuma, ASO Shon, J Slim, J Stephens, WJ Towner, TJ Vanig, BH Wade, MB Wohlfeiler, AK Wurapa, BG Yangco. This study was funded by Gilead Sciences, Inc. 16