LBA7 A Phase 2b, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir (GS-5806), an Oral RSV Fusion Inhibitor, for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplantation Recipients Roy F. Chemaly,1 Sanjeet S. Dadwal,2 Anne Bergeron,3 Per Ljwman,4 Yae-Jean Kim,5 Guang Shing Cheng,6 Sudhakar Pipavath,7 Ajit Limaye,7 Elodie Blanchard,8 Drew J. Winston,9 Patrick Stiff,10 Francisco M. Marty,11 Tsila Rosenvald-Zuckerman,12 Silvy LaChance,13 14 15 16 17 18 19 6 20 20 20 20 20 20 20 20 6,7 Galia Rahav, Catherine B. Small, Kathleen M. Mullane, Roberto Patron, Dong-Gun Lee, Hans H. Hirsch, Alpana Waghmare, Matt McKevitt, Robert Jordan, Ying Guo, Polina German, Danielle Porter, David Gossage, Timothy R. Watkins, Jason W. Chien, Michael Boeckh Gilead Sciences, Inc. 333 Lakeside Drive 1 2 3 4 5 6 7 8 9 10 The University of Texas MD Anderson Cancer Center, Houston, TX; City of Hope, Duarte, CA; Hôpital Saint Louis, Paris, France; Karolinska Universitetssjukhuset, Stockholm, Sweden; Samsung Medical Center, Seoul, South Korea; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington School of Medicine, Seattle, WA; Centre Hospitalier Universitaire de Bordeaux, France; Ronald Reagan UCLA Medical Center, Los Angeles, CA; Loyola University Medical Center, Maywood, IL; Foster City, CA 94404 11Dana-Farber Cancer Institute, Boston, MA; 12Rambam Health Care Campus, Haifa, Israel; 13Hôpital Maisonneuve-Rosemont, Montreal, Québec, Canada; 14Sheba Medical Center, Ramat Gan, Israel; 15Weill Cornell Medical Center, New York, NY; 16The University of Chicago Medical Center, IL; 17Mayo Clinic, Phoenix, AZ; 18College of Medicine, The Catholic University of Korea, Seoul, South Korea; 19Universitätsspital, Basel, Switzerland; 20Gilead Sciences, Inc., Foster City, CA 800-445-3235

–– Inadequately treated, clinically significant bacteremia or fungemia ≤7 d before screening, Introduction or bacterial, fungal, or viral pneumonia ≤2 wk before screening HCT-Related Baseline Characteristics Coprimary Endpoint: % of Patients Developing LRTC Postbaseline F-Gene Population Sequencing tt 20 Endpoints: Patients, n (%) Presatovir, n=95 Placebo, n=90 Placebo Patients, n (%) Presatovir, n=89 Placebo, n=87 Respiratory Syncytial Virus (RSV) –– Primary: time-weighted average change in nasal RSV viral load from Days 1 to 9 Autologous 23 (24) 17 (19) With data 86 (97) 44 (51) ttRSV is a significant cause of morbidity and mortality among children aged <5 y (DAVG9) as measured by quantitative reverse-transcription PCR (RT-qPCR) Matched-related 24 (25) 32 (36) Any substitutions at resistance positions 10 (11) 0 1 Donor type 15 –– Worldwide: ~3.4 million hospitalizations, with up to 200,000 deaths –– Coprimary: % of patients who developed LRTC through Day 28 as determined by blinded Mismatched-related 3 (3) 6 (7) Developed known resistance mutations to presatovir* 8 (9) 0 2 endpoint adjudication committee (1 infectious disease specialist, 1 chest radiologist, and 1 –– USA: ~60,000 hospitalizations among infants aged <24 mo Unrelated 44 (46) 35 (39) T400A/I 4 — pulmonologist) Presatovir ttRSV infections also cause significant morbidity and mortality in adults Bone marrow 11 (12) 8 (9) F140I 2 — ŸŸ LRTC defined as primary RSV lower respiratory tract infection (LRTI), secondary bacterial LRTI, 10 –– Elderly with underlying cardiopulmonary disease (prevalence 5–8%); ~10,000 deaths LRTI due to unusual pathogens, or LRTC of unknown etiology Cord blood 7 (7) 5 (6) L141F/W 2 — 3 each year among adults aged >50 y –– Secondary: % of patients developing respiratory failure (of any cause) requiring Cell source Other 2 (2) 1 (1) LRTC Rate, % S398L 2 — –– Immunocompromised: hematopoietic cell transplant (HCT) and lung transplant patients mechanical ventilation (invasive or noninvasive) or all-cause mortality through Day 28 Peripheral blood stem cell 72 (76) 75 (83) 5 D338Y 1 — (prevalence 2–17%); ~25% of upper respiratory tract infections (URTIs) progress to lower tt † respiratory tract (LRT)4 Statistical methods: Unknown 3 (3) 1 (1) Other presatovir-associated mutation 1 (1) 0 –– All endpoints were summarized using descriptive statistics (sample size, mean, standard Yes 33 (35) 36 (40) M396I 1 — tt No effective treatment for RSV infection is available Acute or chronic graft- 0 deviation (SD), median, first quartile [Q1], third quartile [Q3], minimum, and maximum) for No 37 (39) 37 (41) Fusion inhibitor resistance mutations‡ 2 (2) 0 continuous data, and by number and % of patients for categorical data vs-host-disease 1 3 5 7 9 13 17 22 28 Presatovir: Oral Small-Molecule RSV Fusion Inhibitor Not applicable, autologous 23 (24) 16 (18) Day G143S 1 — –– Efficacy: n at risk (events)= ttDose-proportional low-variability pharmacokinetics (PK); half-life ~33–35 h K394R 1 — ŸŸ Primary efficacy analysis was evaluated in full analysis set (FAS), which included all randomized Presatovir 89 (1) 86 (4) 83 (5) 83 (5) 83 (6) 80 (8) 79 (9) 77 (10) 76 (10) tt Placebo 87 (0) 86 (1) 85 (5) 78 (9) 76 (10) 74 (11) 71 (15) 68 (17) 67 (17) Other substitutions at known resistance positions§ 2 (2) 0 Concentrates in the lung patients with RSV log10 viral load ≥ lower limit of quantitation of RT-qPCR assay in Day 1 nasal RSV-Related Baseline Characteristics sample (determined by RT-qPCR at central lab) who received ≥1 dose of study drug D486V 1 — –– Extracellular lining fluid:plasma area under concentration-time curve ratio ~9.4 in multiple Presatovir, n=95 Placebo, n=90 Patients Developing LRTC, n/n (%) Presatovir Placebo p-Value ŸŸ Primary endpoint was analyzed using a parametric analysis of covariance model with animal models st E487G 1 — corresponding baseline RSV viral load and stratification factors as covariates Median duration of RSV symptoms before 1 dose, d (IQR) 4 (3, 5) 4 (3, 5) FAS 10/89 (11) 18/87 (21) 0.11 tt Potent activity against RSV Ÿ Mean baseline viral load, log copies/mL (SD) 6.3 (1.9) 6.5 (1.4) Primary RSV LRTI 2 2 — *Mutations previously selected by presatovir treatment in clinical studies or in vitro and shown to reduce susceptibility to presatovir, including L138F/I, F140I/L, Ÿ Coprimary endpoint was analyzed using a 2-sided Cochran-Mantel-Haenszel (CMH) test, 10 L141F/W, T323A, D338Y, S398L, K399I/N, T400A/I/V, I474T, D486N, E487D, F488L/S/Y and N517I; †Mutations developed during presatovir treatment in clinical –– ‡ Mean half-maximal effective concentration 0.4 nM for 75 clinical RSV (types A and B) adjusting for stratification factors Presence of lymphopenia (<200 cells/µL), n (%) 15 (16) 14 (16) Secondary bacterial LRTI 1 0 — studies for which presatovir susceptibility was unable to be characterized, including M396I and T397S; Mutations previously selected by or shown to reduce st susceptibility to other RSV fusion inhibitors in vitro for which presatovir susceptibility is unknown, including G143S, V144A, D392G, K394R, D401E, D486E, isolates ŸŸ To control overall Type I error rate of 0.05, RSV viral load was 1 tested at α=0.01; development § Received RBV on 1st dosing day, n (%) 25 (26) 21 (23) LRTI due to unusual pathogens 0 0 — F488I/V, and D489E/Y; Amino-acid substitutions at known fusion inhibitor resistance-associated positions for which presatovir susceptibility is unknown. –– 4-log reduction in RSV viral load, and significant reductions in signs and symptoms of of LRTC was tested at α=0.05 if p ≤0.01 for RSV viral load or α=0.04 if p >0.01 for viral load LRTC of unknown etiology 7 15 — RSV infection in human RSV challenge study5 ŸŸ Secondary endpoint was analyzed using CMH test, adjusting for stratification factors Inhaled* 4 5 Ÿ Oral* 21 14 PPAS 8/86 (9) 17/84 (20) 0.04 ttFavorable safety profile with ~500 adults dosed Ÿ All endpoints were analyzed using 2-sided tests for treatment differences Primary and Secondary Endpoints by Resistance Status –– Safety: performed for all patients who received ≥1 dose of study drug, and summarized Intravenous* 0 0 FAS sensitivity analysis* 10/89 (11) 18/87 (20) 0.07 † Presatovir by treatment using number (%) of patients with events/abnormalities for categorical data Adenovirus 1 (1) 1 (1) Multivariate Cox proportional hazard model ratio (95% CI) 0.44 (0.19, 0.99) 0.09 No resistance, n=79 Resistance, n=10 Placebo, n=87 and descriptive statistics for continuous data Coronavirus (229E, HKU1, NL63, OC43) 2 (2) 5 (6) *Assumed that patients who were dead and had unknown LRTC status before death, had LRTC; †Adjusted for lymphopenia, RBV use, site, and hospitalization Objectives Copathogen status at 1st dose. Median DAVG9 (IQR) -1.42 (-1.96, -0.79) -0.19 (-0.51, -0.06) -0.81 (-1.67, -0.19) types, n (%) Parainfluenza (1, 2) 2 (2) 0 ttPrimary: to evaluate the effect of presatovir on RSV viral load in autologous and LRTC, n (%) 9 (11) 1 (10) 17 (20) Rhinovirus 2 (2) 3 (3) allogeneic HCT recipients with acute RSV URTI Results Respiratory failure or death, n (%) 5 (6) 0 5 (6) st ttSecondary: Hospitalized on 1 dosing day, n (%) 41 (43) 24 (27) Ad hoc Analyses of Presatovir Treatment Effect on LRTC –– To evaluate the effects of presatovir on development of LRT complications (LRTCs), and Patient Disposition Unplanned hospitalization 27 11 in Subpopulations progression to respiratory failure and all-cause mortality Related to RSV 24 8 Patients Developing LRTC, n/n (%) Presatovir Placebo p-Value 213 Screened –– To evaluate the PK, safety, and tolerability of presatovir *From FAS. Lymphocyte <200 cells/µL 2/15 (13) 9/14 (64) 0.008 Conclusions 24 Excluded tt 14 RSV positivity >6 d before screening Symptom duration ≤4 d 5/48 (10) 13/49 (27) 0.07 Statistical significance for coprimary and secondary endpoints 2 Concurrent medication use st 2 Concurrent viral infection Hospitalized at 1 dose 7/39 (18) 11/24 (46) 0.02 was not achieved; however, strong and consistent trends toward a Methods 2 O saturation 92% Mean Presatovir Exposures >4x paEC95 for ≥21 Days* 2 <365 d after treatment 5/50 (10) 12/47 (26) 0.06 1 Allergy 10,000 presatovir benefit were seen: 1 Symptom duration >7 d ––Treatment difference for DAVG9 was -0.33 in favor of presatovir (p=0.04) Study Design 1 Unwilling to complete study procedure ttNo significant impact on % of patients developing respiratory failure or mortality 1 Liver function test abnormality –– Day 1 9 22 28 56 (presatovir n=5/89 [6%]; placebo n=5/87 [6%]) There was a 45% reduction in LRTC events with presatovir treatment 189 Randomized 1000 (11 vs 20%; p=0.11; hazard ratio 0.51, 95% CI 0.23, 1.13; nominal Presatovir 200 mg q4d x5 p=0.09) Optional Extended Viral Follow-up 96 Assigned to presatovir 93 Assigned to placebo Safety Summary Placebo q4d x5 –– 1 Did not receive treatment 3 Did not receive treatment Patients, n (%) Presatovir, n=95 Placebo, n=90 In presatovir-treated patients with lymphopenia, there was an 80% Viral Load 100 reduction in LRTC events (presatovir 2/15 [13%] and placebo 9/14 Symptoms Study Visit ( 24 h) 7 D/C treatment 7 D/C study prematurely 7 D/C study prematurely 10 D/C treatment TEAE 76 (80) 78 (87) 3 AEs 3 Withdrew consent 3 Withdrew consent 4 AEs Plasma Presatovir, ng/mL [64%]; nominal p=0.008) 3 Withdrew consent 2 Deaths 3 Deaths 2 Withdrew consent Grade ≥3 22 (23) 21 (23) tt 1 Death 1 AE 1 Investigator decision 2 Deaths ––Hospitalized patients had a 61% reduction in LRTC events (nominal 189 RSV-positive patients with evidence of URTI only were randomized 1:1 to 1 Lost to follow-up 2 Investigator decision 0 Serious TEAE 18 (19) 23 (26) 1 h 2 h 4 h 6 h Day 3 Day 5 Day 9 Day 9 Day 22 receive presatovir vs placebo st Early drug D/C due to TEAE 3 (3) 5 (6) p=0.02) 88 Completed treatment 88 Completed study 83 Completed study 80 Completed treatment Post 1 Dose Anytime Predose Predose 2h Postdose Anytime tt –– Stratification criteria: *Circles, observed values; dotted line, 4x plasma-binding—adjusted effective concentration required to inhibit RSV replication by 95% (paEC95). Early study D/C due to TEAE 3 (3) 3 (3) Patients with fewer days of symptoms had a 63% reduction in LRTC –– 95 Included in SAS 90 Included in SAS Presence or absence of lymphopenia (<200 cells/µL) 89 Included in FAS 87 Included in FAS Treatment-emergent death 2 (2) 3 (3) events (nominal p=0.07) –– Treatment of current RSV infection (yes or no) with ribavirin (RBV; oral, intravenous, or 86 Included in PPAS 84 Included in PPAS TEAE, treatment-emergent AE. ––Patients within 1 year after HCT had a 62% reduction in LRTC events aerosolized) AE, adverse event; D/C, discontinued; PPAS, per-protocol analysis set; SAS, safety analysis set. Coprimary Endpoint: DAVG9 in Full Analysis Set (nominal p=0.06) ttKey assessments at each study visit: 8 Viral Load 1 Change From Baseline ttNo significant imbalance in TEAEs tt –– Nasal sampling for viral testing (RSV viral load, respiratory virus multiplex, and sequencing) 7 0 –– Presatovir-treated patients had fewer infection-related Grade ≥3 TEAEs (8 vs 17%) Presatovir treatment was well tolerated Baseline Characteristics tt –– –– O2 saturation assessment 6 -1 No significant imbalance in laboratory abnormalities Presatovir was associated with fewer infection-related Grade ≥3 –– Presatovir, n=95 Placebo, n=90 -2 Electrocardiograms (Days 1, 17, and 28) 5 TEAEs (8 vs 17%) Median age, y (IQR) 54 (43, 61) 53 (41, 64) –– Safety assessments and blood draws -3 tt 4 Treatment-Emergent Grade 3 and 4 Laboratory RSV F-gene mutations were detected in 11% of presatovir-treated tt Male, n (%) 55 (58) 55 (61) Copies/mL (1, 3) -4

Key inclusion criteria: 10 3 Abnormalities patients, but the clinical implication of this is unknown –– Received autologous or allogeneic HCT using any conditioning regimen Median duration from transplant before 1st dose, d (IQR) 278 (82, 657) 275 (67, 693) -5 2 Patients, n (%) Presatovir, n=94 Placebo, n=90 tt –– RSV in upper (eg, nasal swab, nasopharyngeal swab, or nasal wash) respiratory tract ≤90 d, n (%) 27 (28) 27 (30) -6 Presatovir treatment of URTI in HCT patients may reduce nasal 1 Presatovir Alanine aminotransferase >5x ULN 2 (2) 2 (2) as determined by local testing (eg, polymerase chain reaction [PCR], direct fluorescent Placebo -7 RSV viral load and the risk of development of LRTC, especially in

90–365 d, n (%) 27 (28) 23 (26) Median Log Aspartate aminotransferase >5x ULN 1 (1) 2 (2) antibody, respiratory viral panel assay, or culture) 0 >365 d, n (%) 40 (42) 40 (44) -8 Liver highly immunocompromised patients ŸŸ All samples must have been collected ≤6 d before Day 1 1 3 5 7 9 13 17 22 28 1 3 5 7 9 13 17 22 28 Alkaline phosphatase >5x ULN 1 (1)* 2 (2)* Acute leukemia 44 (46) 49 (54) –– New onset or worsening of ≥1 respiratory symptom for ≤7 d before Day 1: nasal Day Day Bilirubin >2.5x ULN 1 (1) 1 (1) n= References Chronic lymphocytic leukemia 4 (4) 1 (1) congestion, runny nose, cough, or sore throat Presatovir 89 65 87 78 86 86 84 84 83 89 65 87 78 86 86 84 84 83 Hemoglobin <7.5 g/dL 17 (18) 16 (18) 1. Nair H, et al. Lancet 2010;375:1545-55; 2. Hall CB, et al. N Engl J Med 2009;360:588-98; 3. Thompson WW, et al. JAMA 2003;289:179-86; 4. Kim Y-J, et al. J Infect Dis 2014;209:1195-204; 5. DeVincenzo JP, et al. N Engl J Med 2014;371:711-22. –– No evidence of new abnormalities on chest X-ray obtained <48 h before screening Underlying Lymphoma 11 (12) 14 (16) Placebo 87 63 87 84 83 81 84 83 82 87 63 87 84 83 81 84 83 82 Leukocytes <1500/mm3 4 (4) 10 (11) diagnosis, n (%) ttKey exclusion criteria: Myeloma 24 (25) 13 (14) Presatovir, n=95 Placebo, n=90 p-Value Hematology Lymphocytes <500/mm3 24 (26)† 21 (24)† Acknowledgments We extend our thanks to the patients and their families. This study was funded by Gilead Sciences, Inc. –– Admitted to hospital primarily for LRT disease of any cause Refractory anemia 1 (1) 0 Adjusted mean DAVG9 (95% CI) -1.1 (-1.37, -0.84) -0.78 (-1.05, -0.5) 0.04 Neutrophils <750/mm3 10 (11)† 10 (11)† –– Positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, Other 15 (16) 13 (14) Treatment difference (95% CI) -0.33 (-0.64, -0.02) Platelets <50,000/mm3 6 (6) 18 (20) Disclosures adenovirus, human metapneumovirus, and coronavirus) from LRT sample as determined R.F. Chemaly: Gilead, Ablynx, ADMA Biologics, Ansun, Janssen; S.S. Dadwal, A. Bergeron, P. Ljungman, Y.-J. Kim, G.S. Cheng, S. Pipavath, A. Limaye, E. Blanchard, D.J. IQR, interquartile range. CI, confidence interval. *%s calculated from presatovir, n=90; and placebo, n=86; †%s calculated from presatovir, n=93; and placebo, n=88. ULN, upper limit of normal. Winston, P. Stiff, F.M. Marty, T. Rosenvald-Zuckerman, S. LaChance, G. Rahav, C.B. Small, K.M. Mullane, R. Patron, D.-G. Lee, H.H. Hirsch, M. McKevitt, R. Jordan, Y. by local testing Guo, P. German, D. Porter, D. Gossage, T.R. Watkins, J.W. Chien, and M. Boeckh: Gilead; A. Waghmare: Gilead, Aviragen.

©2018 Gilead Sciences, Inc. All rights reserved. Presented at BMT Tandem Meetings, February 21–25, 2018, Salt Lake City, Utah