1 University of Nebraska Medical Center, Omaha, NE, United States; - PowerPoint Presentation

1University of Nebraska Medical Center, Omaha, NE, United States; 2University of Guadalajara, Guadalajara, Mexico; 3Broward Health Medical Center, Fort Lauderdale, FL, United States; 4Fatebenefratelli Sacco Hospital, Milan, Italy; 5Center for Infectious Diseases, ZIBP, Berlin, Germany; 6Hospital General Universitario de Elche, Alicante, Spain; 7Maxwell Centre, Durban, South Africa; 8Central Research Institute of Epidemiology, Moscow, Russian Federation; 9ViiV Healthcare, Research Triangle Park, NC, United States; 10GlaxoSmithKline, Mississauga, ON, Canada; 11Janssen Research and Development, Beerse, Belgium LONG-ACTING CABOTEGRAVIR + RILPIVIRINE FOR MAINTENANCE THERAPY: ATLAS WEEK 48 RESULTS S Swindells,1 JF Andrade-Villanueva,2 GJ Richmond,3 G Rizzardini,4 A Baumgarten,5 M Masiá,6 G Latiff,7 V Pokrovsky,8 JM Mrus,9 J Huang,10 KJ Hudson,9 DA Margolis,9 KY Smith,9 P Williams,11 WR Spreen9

HIV therapy has been simplified to once-daily, oral regimens containing 2 or 3 antiretroviralsDespite the success of daily oral therapy, considerable interest exists in LA treatment optionsCabotegravir (CAB) is an HIV-1 integrase strand transfer inhibitorOral 30 mg tablet: t½ ~40 hoursLong-acting IM injection, 200 mg/mL: t½ ~40 daysRilpivirine (RPV) is an HIV-1 non-nucleoside reverse transcriptase inhibitorOral 25 mg tablet: t½ ~50 hours Long-acting IM injection, 300 mg/mL: t½ ~90 daysLATTE-2: CAB LA + RPV LA given every 4 or 8 weeks maintained HIV-1 RNA <50 c/mL for >3 years1 Two pivotal phase 3 studies (ATLAS and FLAIR2) have reached their primary endpoints at 48 weeksATLAS BackgroundSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.CAB, cabotegravir; IM, intramuscular; LA, long-acting; RPV, rilpivirine; t½, half-life.1. Margolis D, et al. HIV Glasgow 2018; UK. Poster 118; 2. Orkin C, et al. CROI 2019; Seattle, WA. Abstract 3947.

ATLAS Study Design: Randomized, Multicenter, International, Open-Label, Noninferiority Study in Adults with Virologic Suppression (Ongoing) Swindells S, et al. CROI 2019; Seattle, WA. Abstract 1475. ART, antiretroviral therapy; CAB, cabotegravir; CAR, current antiretroviral; IM, intramuscular; INSTI, integrase strand transfer inhibitor; LA, long-acting; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside RTI; PI, protease inhibitor; RPV, rilpivirine; VL, viral load. *Uninterrupted ART 6 months and VL <50 c/mL at Screening, 2× VL <50 c/mL ≤12 months; † INSTI-based regimen capped at 40% of enrollment; Triumeq excluded from study; ‡ Optional switch to CAB LA + RPV LA at Week 52 for those on CAR; §Participants who withdraw/complete IM CAB LA + RPV LA must complete 52 weeks of follow-up; ‖ Participants received an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, participants received CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks. CAB LA (400 mg) + RPV LA (600 mg) § I M monthly n=303 Screening Phase Maintenance Phase Extension Phase ‡ PI, NNRTI or INSTI † Current daily oral ART n=308 N=705 PI-, NNRTI-, or INSTI-based regimen with 2 NRTI backbone* Randomization 1:1 Extension Phase or transition to the ATLAS-2M study Oral CAB + RPV n=308 Primary Endpoint Day 1 Baseline Week 96 Week 48 Week 4‖ Week 52

Objective Establish noninferior antiviral activity of monthly IM CAB LA + RPV LA vs continuing CARPrimary endpoint Proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 using the FDA Snapshot algorithm6% noninferiority margin on difference between groupsSelected secondary endpointsHIV-1 RNA <50 copies/mL at Week 48 (Snapshot)*Safety and tolerabilitySelected exploratory endpointParticipant-reported preferences of the LA regimen§ ATLAS Objectives and Endpoints Swindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.CAB, cabotegravir; CAR, current antiretroviral; CVF, confirmed virologic failure; FDA, Food and Drug Administration; IM, intramuscular; LA, long-acting; RPV, rilpivirine. *Predefined key secondary endpoint; †Defined as 2 consecutive HIV-1 RNA measurements ≥200 copies/mL; ‡HIVTSQs, HIV Treatment Satisfaction Questionnaire (Status); §Single-item question for participant-reported preference on the LA and daily oral regimen. Viral resistance in participants experiencing CVF † Patient-reported outcomes ‡

ATLAS – Baseline Characteristics: ITT-E PopulationSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; CAB, cabotegravir; CAR, current antiretroviral; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; ITT-E, intention-to-treat exposed; LA, long-acting; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate .*Common backbone regimens included: FTC/TDF (LA 60% vs CAR 56%), FTC/TAF (LA 16% vs CAR 17%), ABC/3TC (LA 13% vs CAR 13%). ParameterCAB LA + RPV LA N=308 CAR N=308 Total N=616 Median age (range) – year 40 (21 – 74) 43 (18 – 82) 42 (18 – 82) Age ≥50 years – n (%) 66 (21) 96 (31) 162 (26) Female – n (%) 99 (32) 104 (34) 203 (33) Race – n (%)      White214 (69) 207 (67)421 (68) Black or African American62 (20)77 (25)139 (23)Other 32 (10) 24 (8) 56 (9)Median body mass index (range) – kg/m2 26 (15–51)26 (18–58) 26 (15–58)Median CD4+ cell count (range) – cells/mm3654 (185–1903)  653 (150–2543) 653 (150–2543)Median duration of prior ART (range) – year 4 (1–19) 4 (1–21) 4 (1–21) Baseline third ART agent class – n (%)*       NNRTI 155 (50) 155 (50)310 (50)INSTI102 (33)99 (32)201 (33)PI51 (17)54 (18)105 (17)

ATLAS Virologic Snapshot Outcomes at Week 48 for ITT-E: Noninferiority Achieved for Primary and Secondary Endpoints Swindells S, et al. CROI 2019; Seattle, WA. Abstract 1475. Primary endpoint: LA noninferior to CAR (HIV-1 RNA ≥50 c/mL) at Week 48 Difference (%) -1.2 2.5 0.6 CAR CAB LA + RPV LA 6% NI margin Virologic Outcomes Adjusted Treatment D ifference (95% CI)* CAB, cabotegravir; CAR, current antiretroviral; CI, confidence interval; ITT-E, intention-to-treat exposed; LA, long-acting; NI, noninferiority; RPV, rilpivirine . * Adjusted for sex and baseline third agent class. Virologic nonresponse (≥50 c/mL)

ATLAS Virologic Snapshot Outcomes at Week 48 for ITT-E: Noninferiority Achieved for Primary and Secondary Endpoints Swindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.Virologic Outcomes Adjusted Treatment Difference (95% CI)* Virologic nonresponse (≥50 c/mL) Virologic success (<50 c/mL) No virologic data CAB, cabotegravir; CAR, current antiretroviral; CI, confidence interval; ITT-E, intention-to-treat exposed; LA, long-acting; NI, noninferiority; RPV, rilpivirine . * Adjusted for sex and baseline third agent class. Primary endpoint: LA noninferior to CAR (HIV-1 RNA ≥50 c/mL) at Week 48 Difference (%) -1.2 2.5 0.6 CAR CAB LA + RPV LA 6% NI margin Key secondary endpoint: LA noninferior to CAR (HIV-1 RNA <50 c/mL) at Week 48 Difference (%) -6.7 0.7 -3.0 CAR CAB LA + RPV LA −10% NI margin

ATLAS Snapshot Outcomes at Week 48 for ITT-ESwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.AE, adverse event; CAB, cabotegravir; CAR, current antiretroviral; ISR, injection site reaction; ITT-E, intention-to-treat exposed; LA, long-acting; RPV, rilpivirine.*Discontinued due to AEs: LA arm (n) – ISR (3); hepatitis A (2); acute hepatitis B (1); acute hepatitis C (1); headache (1); depression suicidal (1); memory impairment (1); diarrhea/nausea/headache (1); CAR arm (n) – colitis (1); blood creatinine increased (1); renal impairment (1); anxiety disorder/depression/suicidal ideation (1); †Death: methamphetamine overdose (1); ‡Other reasons for discontinuation included: LA arm (n): pregnancy (4), lost to follow up (1), non-compliance with treatment (1), and relocation (1); CAR arm: pregnancy (1), lost to follow up (1), and withdrawal by participant due to frequency of visits (4). n (%) CAB LA + RPV LA N=308 CAR N=308 HIV-1 RNA <50 copies/mL 285 (92.5) 294 (95.5) HIV-1 RNA ≥50 copies/mL 5 (1.6) 3 (1.0) Data in window not below threshold 1 (0.3) 1 (0.3) Discontinued for lack of efficacy 3 (1.0) 2 (0.6) Discontinued for other reason while not below threshold 1 (0.3) 0 No virologic data 18 (5.8) 11 (3.6) Discontinued due to AE* 11 (3.6) 4 (1.3) Discontinued due to death † 0 1 (0.3) Discontinued for other reasons ‡ 7 (2.3) 6 (1.9)

Sex, Country, HIV-1 Subtype Previous CAR SVF Timepoint Viral Load at SVF/CVF (c/mL) SVF Timepoint RAMs (HIV-1 RNA) Drug Sensitivity at SVF † (Fold Change) Baseline RAMs (PBMC/HIV-1 DNA; Day 1) RT INSTI* RT INSTI* F, Russia, A/A1 3TC, AZT, LPV/r Week 8 79,166 / 25,745 E138A L74I RPV (2.4) CAB (0.8)DTG (0.9)E138E/A L74I F, France, AG3TC, AZT, NVP to 3TC, ABC, NVP Week 12695 / 258V108I E138K NoneRPV (3.7)CAB (1.2)DTG (1.0) V108V/I E138KNone M, Russia, A/A1 FTC, RAL, TDF to ABC, EFV, 3TC Week 20 544 / 1841 E138E/K N155H L74I RPV (6.5) CAB (2.7)DTG (1.2)NoneL74IATLAS Confirmed Virologic Failure: CAB LA + RPV LA ArmSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.3TC, lamivudine; ABC, abacavir; AZT, azidothymidine; CAB, cabotegravir; CAR, current antiretroviral; CVF, confirmed virologic failure; DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; LA, long-acting; LPV, lopinavir; NVP, nevirapine; PBMC, peripheral blood mononuclear cell; r, ritonavir; RAL, raltegravir; RAM, resistance-associated mutation; RPV, rilpivirine; RT, reverse transcriptase; SVF, suspected virologic failure; TDF, tenofovir disoproxil fumarate.*L74I is not considered an INSTI RAM by IAS-US guidelines and has no impact on CAB activity; †Monogram biological /clinical cutoffs are: RPV=2.0, CAB=2.5, and DTG=4.0.Plasma CAB and RPV concentrations at the time of failure were below the population means but within the range for the large majority of individuals who maintained virologic suppression

ATLAS Confirmed Virologic Failure: CAR ArmSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.3TC, lamivudine; AZT, azidothymidine; c, cobicistat; CAR, current antiretroviral; CVF, confirmed virologic failure; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; PBMC, peripheral blood mononuclear cell; RAM, resistance-associated mutation; RT, reverse transcriptase; SVF, suspected virologic failure; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. Sex, Country, HIV-1 Subtype Study CAR SVF Timepoint Viral Load at SVF/CVF (c/mL) SVF timepoint RAMs (HIV-1 RNA) Baseline RAMs (PBMC/HIV-1 DNA; Day 1) RT INSTI RT INSTI M, Russia, A1 EFV, 3TC, AZT Week 20 1295 / 9727 M184V G190S L74I M184M/I L74IM, USA,BEVG/c, FTC, TAF Week 20 339 / 264 NoneNone NoneNone F, USA,BEVG/c, FTC, TDF Week 32524 / 815M184I None None None M, USA, B EVG/c, FTC, TDF Week 40 392 / 512 M230M/I NoneNoneNone

Plasma concentrations after IM CAB and RPV were comparable with those during efficacious oral regimensATLAS Plasma CAB and RPV Trough Concentrations by Visit Following CAB LA and RPV LASwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.CAB, cabotegravir; IM, intramuscular; LA, long-acting; PA, protein-adjusted; RPV, rilpivirine. Median (5th, 95th percentile) concentration–time data for CAB (left) and RPV (right) following monthly LA administration. 4 48 8 12 16 20 24 28 32 36 40 44 Visit (Week) 0.1 1 10 Plasma CAB (μg/mL) CAB (n=308) PA-IC 90 (0.166 µg/mL) 4 48 8 12 16 20 24 28 32 36 40 44 Visit (Week) 10 100 Plasma RPV (ng/mL) RPV (n=308) PA-IC 90 (12 ng/mL)

84/88 (95%) of CAB LA + RPV LA participants with drug-related AEs had maximum grade 1 or 2†No cases of drug-related SAEs, drug hypersensitivity, or drug-induced liver injury observed on CAB LA + RPV LA armATLAS Adverse Events (Excluding ISRs)AE, adverse event; CAB, cabotegravir; CAR, current antiretroviral; ISR, injection site reaction; LA, long-acting; RPV, rilpivirine; SAE, serious AE.*AEs leading to withdrawal: LA arm (n) – hepatitis A (2); acute hepatitis B (1); acute hepatitis C (1); headache (1); depression suicidal (1); memory impairment (1); diarrhea/nausea/headache (1); asthenia & myalgia (1); anxiety (1); CAR arm (n) – colitis (1); blood creatinine increased (1); fatal methamphetamine overdose (1); renal impairment (1); anxiety disorder/depression/suicidal ideation (1); †Grade 3 drug-related AEs: LA arm (n): pyrexia (1); nausea (1); diarrhea (1); and headache (2); and grade 4 lipase increase (1).Swindells S, et al. CROI 2019; Seattle, WA. Abstract 1475. CAB LA + RPV LA N=308 CAR N=308 Any AE ( ≥10 %), n (%) Any event (per participant) 264 (86) 220 (71) Nasopharyngitis 52 (17) 42 (14) Upper respiratory tract infection 32 (10) 25 (8) Headache 34 (11) 17 (6) Drug-related AEs ( ≥3 %), n (%) Any event (per participant) 88 (29) 8 (3) Fatigue 11 (4) 0 Pyrexia 11 (4) 0 Headache 11 (4) 0 Nausea 11 (4) 0 All AEs leading to withdrawal * 10 (3) 5 (2)

The majority (99%,1439/1460) of ISRs were grade 1–2 and most (88%) resolved within ≤7 daysATLAS Injection Site ReactionsSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475.CAB, cabotegravir; IM, intramuscular; ISR, injection site reaction; LA, long-acting; RPV, rilpivirine.Bars represent incidence of onset ISRs relative to the most recent IM injection visit. Event CAB LA + RPV LA N=308 Participants receiving injections, n 303 Injections given, n 6978 ISR events, n (%) 1460 (20.9) Pain 1208 (82.7) Nodule 54 (3.7) Induration 54 (3.7) Swelling 48 (3.3) Grade 3 ISR pain 20 (1.7) Median duration of ISRs, days 3 Participants with ISR leading to withdrawal, n (%) 4 (1.3) ISR Incidence by Week

Week 24*Week 44* Single-item question on participants’ preference at Week 48 ITT-E population: 86% (266/308) preferred LA; 2% (7/308) preferred daily oral therapyResponding participants: 97% (266/273) preferred the LA regimen over previous oral therapyATLAS: High Participant Satisfaction (HIVTSQs) and Preference for Injectable TherapySwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475. CAB, cabotegravir; CAR, current antiretroviral; HIVTSQs, HIV Treatment Satisfaction Questionnaire (Status); ITT-E, intention-to-treat exposed; LA, long-acting; RPV, rilpivirine. *Adjusted mean change from baseline; a djusted for baseline score, sex, age, race, and baseline third agent class. Error bars show 95% confidence interval. n=300 for CAB + RPV at Week 24 and n=300 at Week 48; n=288 for CAR at Week 24 and n=294 at Week 48. 55 66 Improvement HIVTSQs Total Score* 50 Patient Preference Survey (LA Arm) 5.39 ( 4.17–6.60 ), p<0.001 5.68 ( 4.37–6.98 ), p<0.001 Difference (95%CI) The CAB + RPV group were more satisfied with the monthly injectable treatment compared with participants receiving CAR

Monthly CAB LA + RPV LA was noninferior to 3-drug oral CAR at Week 48 per SnapshotLow rate of HIV-1 RNA ≥50 c/mL: 1.6% vs 1.0%HIV-1 RNA <50 c/mL: 92.5% vs 95.5%Low confirmed virologic failure rate (1%) across both treatment armsTwo of 3 participants on CAB LA + RPV LA had NNRTI RAMs in baseline PBMCsInjection site reactions were mostly grade 1 or 2 and short-lived with few associated discontinuationsGrade 3/4 and serious AEs were infrequent in both treatment armsSignificantly greater increase in treatment satisfaction reported with LA regimen over time vs CAROverall, these results support the therapeutic potential of monthly CAB LA + RPV LA ATLAS ConclusionsSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475. AE, adverse event; CAB, cabotegravir; CAR, current antiretroviral; CVF, confirmed virologic failure; LA, long-acting; NNRTI, non-nucleoside reverse transcriptase inhibitor; PBMC, peripheral blood mononuclear cell; RAM, resistance-associated mutation; RPV, rilpivirine.

We thank everyone who has contributed to the success of the studyAll study participants and their familiesThe ATLAS clinical investigators and their staff in Argentina, Australia, Canada, France, Germany, Italy, Mexico, Republic of Korea, Russian Federation, South Africa, Spain, Sweden, and the United StatesAcknowledgmentsSwindells S, et al. CROI 2019; Seattle, WA. Abstract 1475. Argentina CahnCassettiLupo Porteiro Australia Baker Bloch Roth Shields Canada AngelBarilSmithTrottier Wong de Pokomandy France Ajana Delobel Girard Katlama Khuong-Josses Molina Reynes Yazdanpanah GermanyArastehBaumgartenDegenEsserJaegerLutzRockstrohStellbrinkStephanStollItalyCastelli RizzardiniMexicoAndrade-VillanuevaRepublic of KoreaChoiKim S-WKim S-IKim YLeeRussian FederationBelonosovaBorodkinaChernovaGusevKulaginNagimovaPokrovskyShuldyakov TonkikhTsybakovaVolkovaVoroninYakovlevSouth AfricaHoosenLatiffLombaardMithaMngqibisaNortjeOrrellTayobvan ZylSpainAntela-LopezGracia-Deltoro Falco-FerrerCastaño-CarracedoKnobel-FreudMallolas-MasferrerMasiá CanutoMontes-RamirezMoreno-Guillen Negredo Puigmal Ocampo-HermidaRivero-RománRubio-GarciaViciana-Fernández Sweden GisslénThalmeTreutigerUnited StatesAberg BettacchiBrarBredeekBrennanBrinson CrofootCunninghamDe VenteFelizartaFichtenbaumGoldsteinHoffman-TerryHsiaoKatnerKumarLichtensteinLuetkemeyerMarkowitz MillsOlivetOvertonPieronePolkPrestiRamgopal RichmondRuaneSchreibmanScottShonSimonSwindellsTaiwoWheelerWohl The ViiV Healthcare, GlaxoSmithKline, and Janssen study team members ATLAS is funded by ViiV Healthcare and Janssen R&D