Weight Gain During Pregnancy Among Women Initiating Dolutegravir in Botswana

UKCAB January 2020

Dr Nadine Chamay Medical Advisor ViiV UK

Dr Thom Van Every Medical Director ViiV UK

The content of the presentation has been created in response to a specific request from UKCAB NP-GB-HVX-PPT-200002 – Jan 2020 ➢DOLUTEGRAVIR

➢ WEIGHT GAIN ➢ TANGO

➢PIPELINE

➢ CABOTEGRAVIR- LA ➢ FOSTEMSAVIR

➢ Pipeline and Investigational pipeline ➢ Maturation Inhibitor ➢ Combinectin ➢ BNABs ➢ investigational drugs

➢ Your questions! Drivers of Weight Gain/Loss

Adapted from Hill et al. EACS 2019; Basel, Switzerland. Slides ML1. Drivers of Weight Gain/Loss (cont)

Adapted from Hill et al. EACS 2019; Basel, Switzerland. Slides ML1. ADVANCE: study design

Inclusion criteria: treatment-naïve, HIV-1 RNA level ≥500 copies/mL, no TB or pregnancy, no baseline genotyping

TAF/FTC + DTG N = 351

1053 participants TDF/FTC + DTG N = 351

TDF/FTC/EFV N = 351

96 weeks

Open-label, 96 Week study in Johannesburg, South Africa. Study visits at Baseline, Week 4, 12, 24, 36, 48, 60, 72, 84, and 96.

Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. ADVANCE: baseline characteristics (1/2)

TAF/FTC + DTG TDF/FTC + DTG TDF/FTC/EFV Characteristic (n = 351) (n = 351) (n = 351) Age, mean (SD), years 33 ± 8 32 ± 8 32 ± 7 Female 61% 59% 57% Black 99% 100% 100% Baseline HIV-1 19% 18% 21% 100,001–500,000 copies/mL Baseline HIV-1 3% 3% 2% ≥500,000 copies/mL CD4+ cell count, 349 ± 225 323 ± 234 337 ± 222 mean (SD), cells/mm3

Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. ADVANCE: baseline characteristics (2/2)

TAF/FTC + DTG TDF/FTC + DTG TDF/FTC/EFV Characteristic (n = 351) (n = 351) (n = 351) Weight, mean (kg) Male 67.9 67.1 67.3 Female 68.8 69.5 70.2 BMI, mean (kg/m2) Male 21.7 21.6 21.8 Female 25.6 26.1 26.1 Categories of BMI, n (%) Underweight (<18.5) 42 (12) 35 (10) 37 (11) Normal (18.5–25) 177 (51) 190 (54) 193 (55) Overweight (25–30) 96 (27) 78 (22) 77 (22) Obese (>30) 35 (10) 48 (14) 44 (13)

Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. Changes in DXA body composition: men

3.48 kg 2.59kg

10 9 8 +5.1kg (53% fat) +5.9kg (59% fat) 7 6 +3.5kg (74% fat) 5 +2.7kg (70% fat) 4 3 +0.7kg (100% fat) +1.2kg (100% fat) 2 1

(n=77)

(n=69)

(n=74)

(n=117)

(n=111)

(n=128)

Change in weight (kg) weight in Change

TDF/FTC/EFV TDF/FTC/EFV

TAF/FTC+DTG TAF/FTC+DTG TDF/FTC+DTG Limb Lean TDF/FTC+DTG Trunk Lean Limb Fat Trunk Fat Week 48 Week 96

Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. Changes in DXA body composition: women

6.14kg 3.92kg

10 9 +8.3kg (74% fat) 8 7 +6.3kg (76% fat) 6 +1.6kg (100% fat) +5.3kg (74% fat) 5 4 +3.4kg (74% fat) +3.4kg (91% fat) 3 2 1

(n=79)

(n=93)

(n=91)

(n=137)

(n=157)

TDF/FTC/EFV TDF/FTC/EFV

TAF/FTC+DTG TAF/FTC+DTG

TDF/FTC+DTG TDF/FTC+DTG Limb Lean Trunk Lean

Change in weight (kg) weight in Change Week 48 Week 96

Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. ADVANCE: changes in lipids to Week 48

Lipid (mmol/L) TAF/FTC + DTG TDF/FTC + DTG TDF/FTC/EFV Total cholesterol, median +0.1 -0.1 +0.3 LDL, median +0.1 0.0 +0.1 HDL, median +0.1 +0.1 +0.3 Triglycerides, median 0.0 -0.1 0.0

• Some statistically significant differences between arms: however, of small magnitude (not clinically significant)

Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. Perceptions? administered before weight gain information leaflet and consent

• 69 participants surveyed by 15 July 2019: 51 women, 17 men • No discontinuations for weight gain: most participant’s estimation of their weight gain was similar to the actual weight gain, with a few wild exceptions • 8 women reported unhappiness with weight gain (one actually had lost 1.3 kg); 3 had actually gained <5%, while 4 had >10% weight gain – 2 of those who gained >10% of their baseline weight expressed that they were very unhappy • 6 women participants reported uneven weight gain: 3 abdominal, 2 upper body, 1 hip area, and 1 lower body • 2 men reported unhappiness with weight loss (verified weight loss for both) • Most participants were happy with the weight gain, even though they had to get new clothes as their pre-ART clothes could not fit anymore – Some viewed the weight gain as “return to health” although they had not reported weight loss at screening

Source: Dr Simiso Sokhela Adapted from: Hill A, et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. ADVANCE: Factors Associated Obesity and Weight Gain (2/2) • After multivariable analysis, associated factors were: – Treatment-emergent obesity: • TAF/FTC+DTG, baseline CD4+ count, baseline VL, and baseline BMI • When baseline BMI was excluded the following predictors were also significant: • Female sex, South African nationality, and employment – ≥10% increase in body weight: • TAF/FTC+DTG, baseline CD4+ count, baseline VL, female sex, age, and baseline weight

Adapted from: Hill et al. IAS 2019; Mexico City, Mexico. Slides MOAX0102LB. Weight Gain During Pregnancy Among Women Initiating Dolutegravir in Botswana

Ellen Caniglia,1,2 Roger Shapiro,2,3 Modiegi Diseko,3 Blair Wylie,4 Chloe Zera,4 Sonya Davey,5 Arielle Isaacson,3 Gloria Mayondi,3 Judith Mabuta,3 Rebecca Luckett,4 Joseph Makhema,3 Mompati Mmalane,3 Shahin Lockman,3,6 Rebecca Zash3,4

1New York University School of Medicine; 2Harvard T.H. Chan School of Public Health; 3Botswana-Harvard AIDS Institute Partnership; 4Beth Israel Deaconess Medical Center; 5University of Pennsylvania Perelman School of Medicine, 6Brigham and Women’s Hospital Study Inclusion By Exposure Group

Adapted from: Caniglia et al. IAS 2019; Mexico City, Mexico. Poster LBPEB14. Baseline Characteristics By Exposure Group

Characteristic (mean or %) EFV DTG HIV-negative Age 28.8 28.9 28.3 Primigravid 29.1% 26.6% 32.7% Pre-ART CD4 cell count 419 cells/μl 390 cells/μl -- Pre-pregnancy weight 62.60kg 62.80kg 63.01kg 66.51kg Weight at ART initiation 65.62kg 65.66kg (at firstANC)

Caniglia et al. IAS 2019; Mexico City, Mexico. Poster LBPEB14. Weekly Weight Gain: Unadjusted Mean (kg/week)

Adjusted for: age, CD4, employment, education, parity, gravidity, marital status, site, smoking, alcohol, pre-pregnancy weight, weight at ART initiation (or first ANC), gestational age at ART initiation (or first ANC). Adapted from: Caniglia et al. IAS 2019; Mexico City, Mexico. Poster LBPEB14. Weekly Weight Gain: Adjusted Mean Difference (kg/week)

Adjusted for: age, CD4, employment, education, parity, gravidity, marital status, site, smoking, alcohol, pre-pregnancy weight, weight at ART initiation (or first ANC), gestational age at ART initiation (or first ANC). Adapted from: Caniglia et al. IAS 2019; Mexico City, Mexico. Poster LBPEB14. Changes in BMI associated with antiretroviral regimens in treatment-experienced, virologically suppressed individuals living with HIV

Karam Mounzer, M.D. Philadelphia FIGHT, Philadelphia, PA, USA

Karam Mounzer, Laurence Brunet, Ricky Hsu, Terra Fatukasi, Jennifer Fusco, Vani Vannappagari, Cassidy Henegar, Jean van Wyk, Melissa Crawford, Janet Lo, Gregory Fusco

IDWeek 2019 October 4, 2019

18 OPERA Cohort

• Prospectively captured, routine clinical data from electronic health records • 100,000+ PLWH, 65 cities, 19 States, 1 US Territory

~ 8% of all PLWH receiving care in the US

19 Overall study population (N=10,653)

DTG 9% (n=3,478) 33% EVG/c 18% (n=3,721) RAL (n=545) 5% RPV 35% (n=1,959)

20 22 Summary of findings

Lower increases in mean BMI compared to DTG

EVG/c RAL RPV bDRV vs. DTG vs. DTG vs. DTG vs. DTG Overall 6 -month ↓ ↓ ≈ ↓ 12-month ≈ ≈ ≈ ↓ 24-month ≈ ≈ ≈ ↓ Normal baseline BMI 12-month ↓ ≈ ≈ ↓ Overweight at 12-month ≈ ≈ ≈ ↓ baseline

23 Extreme weight gain (>10% increase from baseline weight), unadjusted

DTG EVG/c RAL RPV bDRV

>10% weight increase at >10% weight increase at >10% weight increase at 6-month 12-month 24-month DTG 173/3,273 (5.3%) 239/2,757 (8.7%) 231/1,548 (14.9%) EVG/c 178/3,484 (5.1%) 280/2,774 (10.1%) 209/1,506 (13.9%) RAL 16/513 (3.1%) 28/402 (7.0%) 25/217 (11.5%) RPV 99/1,830 (5.4%) 157/1,513 (10.4%) 121/795 (15.2%) bDRV 37/880 (4.2%) 53/697 (7.6%) 43/370 (11.6%)

24 Weight change at 96 weeks in treatment-naïve patients: overview

10 DTG + 9 TAF/FTC

8 8 7 DTG + 6 TDF/FTC DTG + BIC/ BIC/ 5 TAF/FTC 5 TAF/FTC TAF/FTC 4 DTG/ DTG + 3TC 3.9 DTG + EFV/ 3.6 ABC/3TC 3.5 3 3.1 TDF/FTC TDF/FTC 2.4 2 2.1 2 1 n=314 n=315 n=320 n=325 n=716 n=717 n=351 n=351 n=351 Weightchange kg baseline, from 0 Study 14891 Study 14902 GEMINI pooled3 ADVANCE4

Median Mean

Adapted from: 1. Wohl DA, et al. Lancet HIV 2019;6:e355–63; 2. Stellbrink HJ, et al. Lancet HIV 2019;6;e364–72; 3. Cahn P, et al. IAS 2019. Oral WEAB0404LB; 4. Hill A, et al. IAS 2019. Oral MOAX0102LB.

EFV, efavirenz. Phase 3 Trials Under-Represent the People at Highest Risk of Adverse Events

Pepperrell et al. EACS 2019. Abstract. Adapted from Hill et al. EACS 2019; Basel, Switzerland. Slides ML1. Risk of Adverse Events Can Differ By Sex and Race

Drug Adverse event Higher risk for: Nevirapine Hepatoxicity Women

Stavudine Lactic acidosis Women

Abacavir Hypersensitivity White people

Efavirenz CNS AEs Black people/Women

DTG/TAF Clinical obesity Black people/Women

NVP: Marinho et al. J Antimicrob Chemother. 2014;69:476-482. d4T: Lactic Acidosis International Study Group. AIDS. 2007;21:2455-2464. ABC: Saag et al. Clin Infect Dis. 2008;46:1111-1118. EFV: Burger et al. Br J Clin Pharmacol. 2006;61:148-154. Dickinson et al. Clin Pharmacokinet. 2016;55:861-873.

Adapted from Hill et al. EACS 2019; Basel, Switzerland. Slides ML1. TANGO Phase III study design

Randomised, open-label, multicentre, parallel-group, non-inferiority study

Screening Randomisationa Early-switch phase Late-switch Continuation 1:1 phase phase

•Adults, virologically suppressed DTG/3TC (N=369)b DTG/3TC (HIV-1 RNA <50 c/mL) for >6 months •Stable TAF-based regimen TAF-based regimen (N=372) DTG/3TC DTG/3TC

Eligibility criteria Day Week Week Week Week Week Week •≥2 documented HIV-1 RNA measurements 1 24 48 96 144 148 196 <50 c/mL •No HBV infection or need for HCV therapy Countries •No prior VF and no documented NRTI or Primary endpointc: participants Australia Germany United INSTI resistance with virologic failure per Belgium Japan Kingdom •TAF/FTC + PI or INI or NNRTI as initial FDA snapshot (ITT-E)d Canada Netherlands United States c regimen France Spain a, Stratified by baseline third agent class (PI, INI, or NNRTI); b, Two patients excluded who were randomised but not exposed to study drug; c, Participants with initial TDF treatment who switched to TAF ≥3 months before screening, with no changes to other drugs in their regimen, were also eligible; d, 4% non-inferiority margin; e, Includes participants who changed a background therapy component or discontinued study treatment for lack of efficacy before Week 48, or who had HIV-1 RNA ≥50 c/mL in the 48 Week window.

Adapted from: van Wyk J, et al. IAS 2019; Mexico City, Mexico. Slides WEAB0403LB. DTG/3TC is non-inferior to a TAF-based regimen at 48 Weeks

Virologic outcomes Adjusted treatment difference (95% CI)b

100 93.293.0 DTG/3TC TAF-based regimen DTG/3TC 0.7 Primary endpoint: 80 -1.2 DTG/3TC non-inferior to (N=369) -0.3 4% non- TAF-based regimen inferiority (≥50 c/mL) at Week 48 60 margin -8 -6 -4 -2 0 2 4 6 8

40 Proportion of Proportion

participants, % participants, TAF-based regimen DTG/3TC 20 Key secondary endpoint: 6.5 6.5 -3.4 3.9 0.3 0.5 DTG/3TC non-inferior to 0 -8% non- 0.2 TAF-based regimen inferiority margin (<50 c/mL) at Week 48 HIV-1 RNA HIV-1 RNA No virologic a -8 -6 -4 -2 0 2 4 6 8 ≥50 c/mL <50 c/mL data Difference, %

• In the per-protocol population, 0/352 participants in the DTG/3TC group and 2/358 participants in the TAF-based regimen group had HIV-1 RNA ≥50 c/mL at Week 48 (adjusted difference, −0.6; 95% CI, −1.3 to 0.2)b a, Primary endpoint (Snapshot virologic non-response, ITT-E); b, Based on Cochran-Mantel-Haenszel stratified analysis adjusting for baseline third agent class. Adapted from: van Wyk J, et al. IAS 2019; Mexico City, Mexico. Slides WEAB0403LB. No confirmed virologic withdrawals with DTG/3TC through 48 Weeks

DTG/3TC TAF-based regimen n (%) (N=369) (N=372) Confirmed virologic withdrawal (CVW)a 0 1 (<1)b Observed resistance mutation at failurec 0 0

a, One assessment with HIV-1 RNA ≥200 c/mL after Day 1 with an immediately prior HIV-1 RNA ≥50 c/mL; b, Treatment interrupted before suspected virologic withdrawal (VL, 38,042 c/mL) and resumed 3 Weeks before VL retest (297 c/mL); c, Plasma HIV-1 RNA resistance genotype at failure is compared with baseline PBMC pro-viral resistance genotype. Adapted from: van Wyk J, et al. IAS 2019; Mexico City, Mexico. Slides WEAB0403LB. Adverse events

DTG/3TC TAF-based regimen n (%) (N=369) (N=371) Any AE 295 (80) 292 (79) Nasopharyngitis 43 (12) 41 (11) Upper respiratory tract infection 31 (8) 32 (9) Diarrhea 30 (8) 26 (7) Headache 24 (7) 17 (5) Syphilis 24 (7) 13 (4) Back pain 21 (6) 28 (8) Fatigue 20 (5) 3 (1) Bronchitis 8 (2) 20 (5) Any drug-related Grade 2-5 AE 17 (5) 3 (1) Drug-related Grade 2-5 AEs occurring in ≥0.5%a Insomnia 4 (1) 0 Constipation 2 (1) 1 (<1) Flatulence 2 (1) 0 Headache 2 (1) 0 AEs leading to withdrawal from the study 13 (4)b 2 (1) Drug-related AEs leading to withdrawal from the study 9 (2) 1 (<1) Any SAEc 21 (6)b 16 (4) • At Week 48, a similar adjusted mean increase from baseline in weight of 0.8 kg was observed in both treatment groups • Increased weight was reported as an AE in 3 (1%) participants treated with DTG/3TC and in 6 (2%) treated with a TAF-based regimen

SAE, serious adverse event. a, All drug-related AEs were of grade 2; b, One fatal AE occurred (homicide); c, No SAEs were drug related. Adapted from: van Wyk J, et al. IAS 2019; Mexico City, Mexico. Slides WEAB0403LB. BHIVA treatment guidelines interim statement presented at Autumn BHIVA 2019*

• Suppressed switch

– Based on TANGO study, DTG/3TC will be ‘recommended’ • Avoid if known/suspected M184V/I

– Based on SWORD study, DTG/RPV will be ‘recommended’ •Caution, prior virological failure and/or NNRTI resistance were exclusions

*Full slides yet to be published.

BHIVA treatment guidelines: interim statement on two-drug regimens. Available at: https://www.bhiva.org/file/5d97749ea9e89/LauraWaters.pdf [Accessed November 2019]. What is ViiV doing to ensure that DTG continues to be as widely affordable and available as possible?

94 countries 121 countries

ADULTS PAEDIATRICS

ViiV Internal data34 Pipeline

35 Committed To Leaving No Patient Behind

Using a patient-centered approach to innovation, we aim to evaluate the safety and efficacy of a variety of medicines throughout the treatment spectrum with the goal of developing new products that meet the needs of all HIV patients

The breadth of our HIV R&D pipeline reflects our commitment to develop medicines for people living with HIV across the world.

* Note, therapies denoted with an (*) are investigational; safety and efficacy in treating/preventing HIV has not been established

Long-acting (LA) Dolutegravir- Treatment Regimens Prevention based Regimens cabotegravir LA + rilpivirine LA* cabotegravir LA*

Search for Remission and Cure Two Drug Regimens Legacy ARV Drug *Investigational dolutegravir/rilpivirine Portfolio Treatments dolutegravir/lamivudine abacavir/lamivudine, ǂ Discovery and Early cabotegravir LA + rilpivirine LA* maraviroc & others Development Programs

Adapted from: https://viivhealthcare.com/en-gb/our-medicines/medicines-in-development/ Accessed Oct 2019 Development Pipeline

Preclinical Phase 1 Phase 2 Phase 3

CAB LA + RPV LA (Treatment) INSTI/NNRTI

CAB LA (Prevention) INSTI

Fostemsavir attachment inhibitor

GSK3640254 maturation inhibitor

GSK3732394 combinectin

Discovery Programs (e.g., capsid inhibitor)

3TC, lamivudine; CAB, cabotegravir; DTG, dolutegravir; INSTI, integrase strand transfer inhibitor; LA, long-acting; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; RPV, rilpivirine; STR, single tablet regimen

Adapted from: https://viivhealthcare.com/en-gb/our-medicines/medicines-in-development Accessed Oct 2019 Cabotegravir Cabotegravir nanosuspension • Drug crystal suspended in aqueous vehicle • Nanomilled to increase surface area and drug dissolution rate – Wet bead milling with terminal sterilisation by gamma irradiation • Higher drug loading versus matrix approaches for lower injection volume

CAB LA 200 mg/mL Component Function Cabotegravir free acid Active drug (d50 ~200 nm) Mannitol Tonicity agent Surfactant system Wetting agent/stabiliser Water for injection Solvent

16th HIV-HEPPK Müller RH et al. Eur J Pharm Biopharm 2011:78;1–9 39 Confidential and proprietary – internal use only Date of preparation: March 2016 CAB + RPV LA combines two different LA injectable ARVs

• CAB LA and RPV LA are extended release suspensions that enable monthly dosing1,2 • CAB and RPV have a number of important attributes that support their use as a LA combination therapy:2–4 – Different MoA and resistance profiles – Lack of DDI between CAB and RPV – Oral formulations of both drugs facilitate treatment initiation, oral bridging and discontinuation strategies

Attribute CAB LA1–3 RPV LA1–4 ARV drug class INI NNRTI Oral tablet size 30 mg 25 mg (t½) (~40 hours) (~50 hours) LA suspension 200 mg/mL 300 mg/mL (t½) (5.6–11.5 weeks) (13–28 weeks) Dose – monthly 400 mg (2 mL) 600 mg (2 mL) Dose – every 2 months 600 mg (3 mL) 900 mg (3 mL)

1. Trezza C, et al. Curr Opin HIV AIDS 2015;10:239–45; 2. Ford SL, et al. Antimicrob Agents ARV, antiretroviral; CAB, cabotegravir; DDI, drug-drug interaction; INI, integrase inhibitor; LA, long acting; Chemother 2013;57:5472–77; 3. Data on File. FLAIR (Study 201584). Available at: MoA, mechanism of action; NNRTI, non-nucleoside reverse transcriptase inhibitor; RPV, rilpivirine http://www.viiv-studyregister.com (accessed November 2019); 4. EDURANT US PI, May 2019 CAB LA Development Program

Indication Phase 2 Phase 3 Phase 3b

ATLAS 2M Treatment LATTE (n=243) FLAIR (n=631) (n=1069) (adults) LATTE-2(n=309) ATLAS (n=618) Q8W dosing Q4W dosing Treatment MOCHA (<18 yrs.) (n~155) Early Phase

Prevention ECLAIR HPTN 083 MSM/TGW (n=127) (n~4500) NHP Cardiac FTI model safety, s DDI H Prevention HPTN 077 HPTN 084 women (n=199) (n~3200)

Simultaneous Global Registration Programs for Treatment and Prevention Monthly Long-Acting Cabotegravir and Rilpivirine is Non-inferior to Oral ART as Maintenance Therapy for HIV-1 Infection: Week 48 Pooled Analysis From the Phase 3 ATLAS and FLAIR Studies

Edgar T. Overton,1 Chloe Orkin,2 Susan Swindells,3 Keikawus Arasteh,4 Miguel Górgolas Hernández-Mora,5 Vadim Pokrovsky,6 Pierre-Marie Girard,7 Shinichi Oka,8 Jaime-Federico Andrade-Villanueva,9 Gary J. Richmond,10 Giuliano Rizzardini,11 Axel Baumgarten,12 Maria Del Mar Masiá,13 Gulam Latiff,14 Sandy Griffith,15 Conn M. Harrington,15 Krischan J. Hudson,15 Marty St. Clair,15 Christine Talarico,15 Veerle Van Eygen,16 Ronald D’Amico,15 Joseph M. Mrus,15 Sterling Wu,17 Ken Chow,18 Jeremy Roberts,18 Simon Vanveggel,16 David A. Margolis,15 Peter Williams,16 Wim Parys,16 Kimberly Smith,15 William R. Spreen15

1University of Alabama at Birmingham, Birmingham, AL, USA; 2Queen Mary University, London, UK; 3University of Nebraska Medical Center, Omaha, NE, USA; 4EPIMED GmbH, Berlin, Germany; 5Fundación Jiménez Díaz, Madrid, Spain; 6Central Research Institute of Epidemiology, Moscow, Russia; 7Hôpital Saint Antoine, Paris, France; 8National Center for Global Health and Medicine, Tokyo, Japan; 9University of Guadalajara, Guadalajara, Mexico; 10Broward Health Medical Center, Fort Lauderdale, FL, USA; 11Fatebenefratelli Sacco Hospital, Milan, Italy; 12MIB Infectious Disease Medical Center, Berlin, Germany; 13Hospital General de Elche, Alicante, Spain; 14Maxwell Centre, Durban, South Africa; 15ViiV Healthcare, Research Triangle Park, NC, USA; 16Janssen Research & Development, Beerse, Belgium; 17GlaxoSmithKline, Collegeville, PA, USA; 42 18GlaxoSmithKline, Mississauga, Ontario, Canada Women?

ATLAS and FLAIR were designed with specific enrolment • One in five enrolees would be women in FLAIR targets for women • One in four enrolees would be women in ATLAS

17th European AIDS Conference; November 6-9, 2019; Basel, Switzerland ATLAS and FLAIR Study Design

*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 + RPV LA at Week 52 for those on CAR; §Participants who withdraw/complete IM CAB + RPV LA must complete 52 weeks of follow-up; ‖Participants received initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4. From Week 8 onwards, participants received CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks; ¶NNRTI RAMs, but not K103N, were exclusionary; **DTG plus two alternative non-ABC NRTIs was permitted if participant was intolerant or HLA-B*5701-positive. Adapted from: Overton et al. IAS 2019; Mexico City, Mexico. Poster MOPEB257. 44 Virologic Snapshot Outcomes at Week 48 for ITT-E non- inferiority Achieved for Primary and Secondary Endpoints

Adapted from: Overton et al. IAS 2019; Mexico City, Mexico. Poster MOPEB257. 45 For internal use only ATLAS and FLAIR pooled: Drug-related AEs to Week 48 (excluding ISRs)

Drug-related AEs Grade 3/4/5* (excluding ISRs) • 28% of the CAB + RPV group and 6% of the CAR group had at least 1 drug-related AE CAB + RPV LA CAR (excluding ISRs) (N=591) (N=591) n (%) Grade 3 Grade 4 Grade 3 Grade 4 • The most common drug-related non-ISR AEs Subjects with any event(s) 6 (1) 2 (<1) 1 (<1) 0 (any grade) were pyrexia, nausea, headache, Pyrexia 1 (<1) Nausea fatigue, asthenia, myalgia, sleep disorders 1 (<1) Headache 2 (<1) and dizziness Diarrhea 1 (<1) Lipase increased 2 <1) • 1% of the CAB + RPV group and <1% of the Anxiety disorder 1 (<1) CAR group had grade 3/4/5 drug-related AEs Depression 1 (<1) (see table) Suicidal ideation 1 (<1) Poor Quality sleep 1 (<1) • One drug-related serious AE was reported Arthritis 1 (<1) from each study arm: arthritis (CAB + RPV Night sweats 1 (<1) LA) and suicidal ideation (CAR) *No grade 5 drug-related events in either arm

99% of drug-related AEs were Grade 1 or 2 with CAB+RPV LA and no AEs of clinical concern

ViiV Healthcare. Data on File; ATLAS and FLAIR CSRs Pooled Injection Site Reactions

• The majority (99%, 3628/3663) of ISRs were Grade 1–2 and most (88%) resolved within ≤7 days

Adapted from: Overton et al. IAS 2019; Mexico City, Mexico. Poster MOPEB257. 47 ATLAS and FLAIR: Injection Tolerability by Subgroup

Patient cumulative data on ISRs over the 48-week time period

ISR*

Subgroup Pain Nodule Induration Swelling

<50 (n=492) 386 (78%) 67 (14%) 56 (11%) 38 (8%) Age (years) ≥50 (n=99) 72 (73%) 14 (14%) 12 (12%) 9 (9%) Male (n=429) 351 (82%) 56 (13%) 36 (8%) 31 (7%) Gender Female (n=162) 107 (66%) 25 (15%) 32 (20%) 15 (9%)

African American/African 66 (61%) 17 (16%) 5 (5%) 6 (6%) Heritage (n=109) Race White (n=430) 351 (82%) 57 (13%) 60 (14%) 37 (9%) Asian/Other (n=52) 41 (79%) 7 (13%) 3 (6%) 3 (6%)

Breakdown of ISRs by age, gender, and race showed: • Overall, minimal differences in cumulative ISR reports by subgroup over the 48-week time period • Slightly lower reporting of pain in female and African American/African heritage participants • Slightly higher reporting of induration in female and white participants Teichner et al. IDWeek 2019; Washington, DC. Slides 884. AE, adverse event; ISR, injection site reaction. *Data are number and percentages of participants with at least 1 of the respective AEs through Week 48. IDWeek; October 2–6, 2019; Washington, DC, USA CAB + RPV LA Participants Showed Higher Treatment Satisfaction (HIVTSQ) Compared with CAR Participants at Week 44 (Pooled Data)

HIVTSQs Total Score* 0 57† Improvement 66 (Max) Difference (95%CI)

CAB + RPV LA 4.3 (2.6–6.1), Women p<0.001 (post-hoc analysis) CAR +5.0 Week 44* Week +0.7

Men 3.1 (2.1–4.1), Men +3.5 p<0.001 (post-hoc analysis)

Week 44* Week +0.5

Total 3.3 (2.5–4.2), Total +3.8+3.9 p<0.001 (pre-specified analysis)

Week 44* Week +0.6+0.5

*Adjusted mean change from baseline; adjusted for baseline score, sex, age, race, and baseline third agent class. Error bars show 95% CI. †Baseline HIVTSQs scores were 57.7 (n=151), 56.9 (n=406), and 57.1 (n=557) for CAB + RPV LA participants (women, men, and total), and 56.2 (n=155), 57.5 (n=395), and 57.1 (n=550) (women, men, and total) for CAR participants. CAB, cabotegravir; CAR, current antiretroviral; CI, confidence interval; HIVTSQs, HIV Treatment Satisfaction Questionnaire (Status); LA, long-acting; RPV, rilpivirine.

17th European AIDS Conference; November 6-9, 2019; Basel, Switzerland The Majority of Women Retained in the ATLAS and FLAIR Studies at Week 48

CAB LA + RPV LA CAR 100 100 93.0 90.0 92.0 92.0 Women Women 80 Total 80 Total

60 60

40 40

20 20 9.0 8.0 8.0 7.0

0 0 Proportion of participants (%) participantsof Proportion

Ongoing/Completed Withdrawn (%) participantsof Proportion Ongoing/Completed Withdrawn

For women, n=93, 54 and 15 for CAB + RPV at Week 48 were, ongoing, completed, or withdrawn, respectively; n=59, 95, and 14 for CAR at Week 48 were ongoing, completed, or withdrawn. For total, n=368, 176, and 47 for CAB + RPV at Week 48 were ongoing, completed, or withdrawn, respectively; n=266, 286, and 39 for CAR at Week 48 were ongoing, completed, or withdrawn. CAB, cabotegravir; CAR, current antiretroviral; LA, long-acting; RPV, rilpivirine.

17th European AIDS Conference; November 6-9, 2019; Basel, Switzerland Pooled ATLAS and FLAIR: CAB + RPV LA was preferred over daily oral ART

Preferences of responding participants*

“For the past 44 weeks you have 2% (9/532) received Long Acting injectable HIV medication every month. Today we would like you to compare your experience on the long-acting injections with the oral CAB + RPV LA medication you received prior to entering the study. Which therapy do you prefer?” CAR

98% (523/532)

98% of responding participants from ATLAS + FLAIR preferred CAB + RPV LA over CAR at Week 48

1. Swindells S, et al. CROI 2019. Abstract 1475 *Responding participants: 98% (523/532) preferred the LA regimen over previous oral therapy 2. Orkin C, et al. CROI 2019. Abstract 3947 ACTG 5359 (LATTITUDE) Long-acting antiretroviral therapy in non-adherent HIV-infected individuals • Randomized, open label study in HIV-infected individuals with prior history of non-adherence to assess if a therapeutic strategy using LA ARV is effective compared to an all-oral Standard of Care • Will enroll previously non-adherent, viremic individuals who will initiate oral SOC for 24 weeks (include financial supplements to drive adherence)

Cross Randomisation Step 2: 48 Weeks over Step 3: 48 Weeks 1:1 CAB + RPV IM 48 wks of CAB + RPV crossover, NOT Licensure Best SOC RANDOMIZED Best SOC 52 weeks SOC after

LA therapy STUDY DESIGN Study entry 24 28 72 76 128 Wk 0 • Target sample size ~140/arm. Virologic success rate at W48 estimated at 75% for the SOC arm and 92% for the ARV-LA strategy • “Best SOC” supplied/supported by ViiV/Janssen- DTG, DRV/c, RPV, EPZ, DCV • Timelines: Enrollment commenced Q1 2019

Clinicaltrials.gov identifier: NCT03635788 • 52 weeks SOC required in subjects who withdraw after ≥1 dose of LA therapy Available from: https://clinicaltrials.gov/ct2/show/NCT03635788 ViiV internal data

52 MOCHA (IMPAACT 2017 )

• Collaborative study with IMPAACT Network • Two phase study to evaluate PK and Safety of CAB LA + RPV LA in adolescents (12 to <18 y/o) at adult doses

Cohort 1 Cohort 2 (Add on to background cART) (No background cART)

n=20 CAB n=100 n=15 RPV

Oral CAB Q4W CAB LA CAB LA + RPV LA Oral CAB Q4W*

Oral RPV Q4W RPV LA + RPV

Day 1 Day

Wk Wk

96 96 24

IM Interim PK analysis Cohort 1 - n=8/arm

Clinicaltrials.gov NCT03497676. Available at:: http://clinicaltrials.gov/ct2/show/NCT03497676 *Q8W dosing may be introduced by amendment following ATLAS-2M results

53 POLAR PO to LA rollover

Screening Phase Maintenance Phase

Q2M CAB LA + RPV LA access via commercial route once Q8W approved

LATTE Subjects access longer-term via DTG/Rilpivirine commercial route

CARLA Dosing Every 2 M

D1 D1

M12

M1 M3 POLAR is an open-label, multicenter study in the US and Canada to enroll participants who successfully fulfilled obligations of the LATTE (LAI116482) study. The LATTE study will end; participants are given the option to: 1) rollover to POLAR study and begin CAB LA + RPV LA Q2M (until commercially available) 2) rollover to POLAR and begin DTG/RPV (provided for 48 weeks or until commercially available) 3) discontinue participation and not enter POLAR Participants receiving at least one LA injection who discontinue the regimen for any reason enter a 52- week long-term follow-up phase and remain on suppressive HAART during that period of time. Clinicaltrial.gov identifier: NCT03639311 Available from: https://clinicaltrials.gov/ct2/show/NCT03639311 ViiV internal data

54 Fostemsavir Week 96 Safety and Efficacy of the Novel HIV- 1 Attachment Inhibitor Prodrug Fostemsavir in Heavily Treatment-Experienced Participants Infected With Multi-Drug– Resistant HIV-1 (BRIGHTE Study)

M. Lataillade,1 J. Lalezari,2 J. Aberg,3 J.-M. Molina,4 M. Kozal,5 P. Cahn,6 M. Thompson,7 R. Diaz,8 A. Castagna,9 M. Gummel,10 M. Gartland,11 A. Pierce,11 P. Ackerman,1 C. Llamoso1

1ViiV Healthcare, Branford, CT, USA; 2Quest Research, San Francisco, CA, USA.; 3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France; 5Yale University School of Medicine, New Haven, CT, USA; 6Fundación Huésped, Buenos Aires, Argentina; 7AIDS Research Consortium of Atlanta, Atlanta, GA, USA; 8Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 9Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy; 10GlaxoSmithKline, Upper Providence, PA, USA; 11ViiV Healthcare, Research Triangle Park, NC, USA Temsavir Mode of Action

Temsavirgp120 trimer gp41 trimer prevents gp120 gp160 conformationaAttachment inhibited by temsavir binding near l CD4 binding CD4 binding site change,site inhibiting HIV-1 Temsavir attachment Temsavir binds near the gp120CD4 trimer bindinggp41 site trimer

gp160

CD4 receptor CCR5/ CXCR4

Conceptualization and design by Max Lataillade (ViiV Healthcare) and John Wong (Synaptik Digital), funded by ViiV Healthcare. Adapted from: Lataillade et al. IAS 2019; Mexico City, Mexico. Slides MOAB0102. Viruses accumulate in extracellular spacespace… and are subsequently removed by the host immune system

BRIGHTE is an ongoing Phase 3 randomized, placebo-controlled, double-blind trial

Randomized Cohort:* Blinded HTE participants failing current FTR 600 mg regimen with confirmed HIV-1 RNA BID + failing regimen ≥400 c/mL and: Randomized Open-label FTR 600 mg BID + OBT • 1 or 2 ARV classes remaining 3:1 Blinded with ≥1 fully active† approved placebo + agent per class failing • Unable to construct viable regimen regimen from remaining agents Day 1 Day 8 Day 9 Week 24‡ Week 48‡ Week 96‡,** End of Primary Open-label Study§ Non-randomized Cohort:* Endpoint FTR + OBT HTE participants failing current regimen with confirmed HIV-1 RNA ≥400 c/mL and: Non-randomized Open-label FTR 600 mg BID + OBT • 0 ARV classes remaining and no remaining fully active† approved agents¶ Day 1 Week 24 Week 48 Week 96** End of Study§

† *There were no screening TMR IC50 criteria. Fully active = no current or historical evidence of resistance & the participant is tolerant of, eligible for, and willing to take (in the case of enfuvirtide) the ARV. ‡Measured from the start of open-label FTR 600 mg BID + OBT. §The study is expected to be conducted until an additional option, rollover study, or marketing approval is in place. ¶Use of investigational agents as part of OBT was permitted. **Week 96 database lock August 14, 2018. BID, twice daily; OBT, optimized background therapy. Adapted from: Lataillade et al. IAS 2019; Mexico City, Mexico. Slides MOAB0102. Baseline Characteristics

Non-randomized Randomized Cohort Cohort Total Placebo BID FTR 600 mg BID Total randomized FTR 600 mg BID Treated Participants Parameter (N=69) (N=203) (N=272) (N=99) (N=371) Age, years, median (range) 45 (19–66) 48 (18–73) 48 (18–73) 50 (17–72) 49 (17–73) <50 years, n (%) 46 (67) 116 (57) 162 (60) 44 (44) 206 (56) Gender, n (%) 12 (17) 60 (30) 72 (26) 10 (10) 82 (22) Female Race, n (%) White 48 (70) 137 (67) 185 (68) 74 (75) 259 (70) Black/African American 18 (26) 42 (21) 60 (22) 23 (23) 83 (22)

HIV-1 RNA log10 c/mL, median (IQR) 4.5 (3.6–5.2) 4.7 (4.0–5.1) 4.7 (3.9–5.1) 4.3 (3.6–4.8) 4.6 (3.9–5.0) HIV-1 RNA c/mL, n (%) <400 7 (10) 14 (7) 21 (8) 5 (5) 26 (7) 400 to <1000 3 (4) 7 (3) 10 (4) 4 (4) 14 (4) 1000 to <100,000 35 (51) 126 (62) 161 (59) 75 (76) 236 (64) ≥100,000 24 (35) 56 (28) 80 (29) 15 (15) 95 (26) CD4+ T cells/µL, median (IQR) 100 (23–244) 99 (15–203) 99 (15–203) 41 (6–161) 80 (11–202) CD4+ T cells/µL, n (%) <20 17 (25) 55 (27) 72 (26) 40 (40) 112 (30) 20 to <50 6 (9) 19 (9) 25 (9) 14 (14) 39 (11) 50 to <200 26 (38) 76 (37) 102 (37) 25 (25) 127 (34) 200 to <500 16 (23) 42 (21) 58 (21) 18 (18) 76 (20) ≥500 4 (6) 11 (5) 15 (6) 2 (2) 17 (5) AIDS history,* n (%) 61 (88) 170 (84) 231 (85) 89 (90) 320 (86)

*AIDS history recorded if a participant has nadir CD4+ count <200 cells/µL, or prior history of AIDS defining illness. Adapted from: Lataillade et al. IAS 2019; Mexico City, Mexico. Slides MOAB0102. Virologic Response Through Week 96 Observed Analysis

Randomized Cohort (N=272) Non-randomized Cohort (N=99)

100 100 90 88 85 86 87 80 84 86 80 79 79 68 61 67 65 60 62 60 53 55 59 59 57 54 49 48 49 40 40

Participants (%) (%) Participants Participants (%) (%) Participants HIV-1 RNA copies/mL HIV-1 RNA copies/mL 20 <400 20 <400 <200 <200 <40 <40 0 0 Baseline Wk 24 Wk 48 Wk 72 Wk 96 Baseline Wk 24 Wk 48 Wk 72 Wk 96 (N=272)* (n=246) (n=233) (n=221) (n=214) (N=99)† (n=89) (n=83) (n=75) (n=66)

*At baseline 8 participants had HIV-1 RNA <400 copies/mL, 5 had HIV-1 RNA <200 copies/mL, and 1 had HIV-1 RNA <40 copies/mL. †At baseline 5 participants had HIV-1 RNA <400 copies/mL, 4 had HIV-1 RNA <200 copies/mL, and 1 had HIV-1 RNA <40 copies/mL. Adapted from: Lataillade et al. IAS 2019; Mexico City, Mexico. Slides MOAB0102. Mean Change From Baseline in CD4+ T-cell Count Through Week 96

By baseline CD4+ T-cell category By Randomized and Non-randomized Cohort Randomized Cohort

450 450 Baseline CD4+ T cells/µL Randomized Cohort

SD 400 400 <20 (n=72) ± Non-randomized Cohort 350 350 20 to <50 (n=25)

300 300 50 to <100 (n=39) 100 to <200 (n=63) 240

from baseline from 250 205 250 from baseline from 172 (n=213) ≥200 (n=73) 200 (n=217) 200

139 (cells/µL) counts cell

cell counts (cells/µL) counts cell - - (n=228) 150 150 90

Mean change Mean (n=247)

100 change Mean 100

119 in CD4+ T CD4+ in

in CD4+ T CD4+in 96 (n=65) 50 64 (n=72) 50 41 (n=83) 0 (n=87) 0 Baseline Week 24 Week 48 Week 72 Week 96 Baseline Week 24 Week 48 Week 72 Week 96

• Among randomized participants with CD4+ T-cell count <50 cells/µL at baseline (n=71), 56% had ≥200 cells/µL at Week 96 – Subgroup data are presented in poster MOPEB234

*Mean baseline: Randomized Cohort 153 cells/µL; Non-randomized cohort 99 cells/µL. Adapted from: Lataillade et al. IAS 2019; Mexico City, Mexico. Slides MOAB0102. Week 96 Safety Summary

Randomized Non-randomized Total Cohort Cohort treated participants Parameter, n (%) (N=272)* (N=99) (N=371) Any event 249 (92) 98 (99) 347 (94) Any Grade 2-4 AE 216 (79) 87 (88) 303 (82) Drug-related Grade 2-4 AEs 57 (21) 22 (22) 79 (21) Any Grade 3/4 AE 78 (29) 49 (49) 127 (34) Any SAE† 92 (34) 48 (48) 140 (38) Drug-related SAE‡ 9 (3) 3 (3) 12 (3) Any AE leading to discontinuation 14 (5) 12 (12) 26 (7) Any CDC Class C event 23 (8) 15 (15) 38 (10) Death§ 12 (4) 17 (17) 29 (8)

All safety data reflect cumulative results collected through the data cutoff date of August 14, 2018. *Includes participants randomized to the placebo group who received FTR 600 mg BID during the open-label phase; only data from initiation of open-label FTR dosing are presented. †The only SAEs occurring in at least 2% of participants were pneumonia (n=15), cellulitis (n=8), and acute kidney injury (n=6). ‡Drug-related SAEs (16 events in 12 participants) included: nephrolithiasis (n=2); immune reconstitution inflammatory syndrome (n=3); and one each of acute kidney injury, renal impairment, hyperglycemia, hyperkalemia, loss of consciousness, myocarditis, hepatocellular injury, rhabdomyolysis, fetal growth restriction, disorientation, and rash. §18/29 deaths were due to AIDS-related events or acute infections (one case was considered treatment-related: immune reconstitution inflammatory syndrome, related to recurrent atypical mycobacterial infection). 5/29 deaths occurred after the participant had discontinued from the study. Adapted from: Lataillade et al. IAS 2019; Mexico City, Mexico. Slides MOAB0102. Drug-Related Grade 2-4 AEs and AEs Leading to Discontinuation

Randomized Non-randomized Total Cohort Cohort treated participants Parameter, n (%) (N=272)* (N=99) (N=371) Drug-related Grade 2-4 AEs 57 (21) 22 (22) 79 (21) Occurring in ≥2% of participants in either cohort Nausea 9 (3) 5 (5) 14 (4) Diarrhea 6 (2) 3 (3) 9 (2) Headache 6 (2) 1 (1) 7 (2) IRIS 7 (3) 0 7 (2) Vomiting 4 (1) 2 (2) 6 (2) Fatigue 3 (1) 2 (2) 5 (1) Asthenia 2 (<1) 2 (2) 4 (1) AE leading to discontinuation 14 (5) 12 (12) 26 (7) In ≥2 participants Abdominal pain 2 (<1) 0 2 (<1) Electrocardiogram QT prolonged 2 (<1) 1 (1) 3 (<1) Non-cardiac chest pain 1 (<1) 1 (1) 2 (<1) Hepatic failure 0 2 (2) 2 (<1)

Gag polyprotein is cleaved by HIV-1 protease to form the virion structural proteins X HIV-1 Gag P17 MA P24 CA SP1 P7 NC SP2 P6 CA/SP1 cleavage site – the target of MIs (Rate determining proteolytic cleavage step)

• HIV-1 protease cleaves Gag in a stepwise fashion into six pieces; Gag polyprotein is the main structural protein of HIV-1 • MI’s inhibit the last protease cleavage between the CA-SP1 subunit (effect similar to protease block); non-infectious, immature HIV-1 particles result1 • Pursuing further optimized MIs for oral or long acting regimens • 2 Immature Mature GSK ‘254 for oral, FDC w/ DTG and monoentity Non-infectious Infectious • GSK ‘937 for long acting injectable, SQ and IM • CtFTIH in 4Q2019, study start in 2020

1. Adapted from Salzwedel K et al. AIDS Rev, 2007;9: 162-72 2. https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT03231943Accessed October 2019 Phase 1: Combinectin Combinectin: GSK3732394

o Novel, long-acting biologic o 3 distinct, non-overlapping MOA designed to prevent HIV-1 viral entry o weekly dosing via subcutaneous administration

HSA a-gp41 NH COOH 2 a-CD4 a-gp41 o FTIH study in healthy participants started in July 2019 (ongoing)2

1. Wensel D et al. J Virol doi.10.1128/JVI.00907-19 2. https://clinicaltrials.gov/ct2/show/NCT03984812 Accessed October 2019 Phase 1: N6LS bNAb (GSK3810109) N6LS: Broadly Neutralizing Antibody (bNAb) Targeting HIV

• N6LS is a potent bNAb that targets the viral envelope • Mechanism of action:1

Neutralization of viral entry

Enhanced antiviral immune response

N6LS

• long half-life • N6LS (IV) & CAB (IM) to be administered once every 3 months • Monthly self-administered subcutaneous combination regimen

• Upcoming clinical trials: • 2H2020 – Phase IIa PoC trial – single dose in treatment naïve subjects • 2H2022 – Phase IIb trial – repeat dose N6LS + CAB in early switch subjects

1. Grobben M et al. Curr Opin Virol, 2019;38:70-80 2. https://clinicaltrials.gov/ct2/show/NCT03538626 Accessed October 2019 Investigational Pipeline The following information includes modalities and mechanisms in Discovery. Capsid Inhibitor

Capsid is a novel viral target • Highly conserved binding pocket • Broad spectrum coverage • ViiV inhibitors are very potent (EC50 < 100 pM) • Long acting potential based IM/SC Rat PK study • Targeted profile IM Q3M/2M (HCP) or SC Q1M (self-administration) • CS 4Q19 NRTTI – LAI EFdA Prodrugs

EFdA (MK-8591) • Discovered at Yamasa, licensed to Merck in 2012

• Highly potent: EC50=0.2 nM; good resistance profile • Merck focused on treatment: QD, Q7D (PO) and prevention: Q1M (PO), Q12M (SC Implant) • Prodrugs reduce the aqueous solubility of EFdA and make it amenable to injection depot therapy: targeting 1-3 month duration • Six VH patent applications filed; CS 4Q19 Your questions!

• Any updates/advances in paediatric formulations?

• What are the cure strategies at the moment? Potential Methods to Overcome the Challenge of Cure: Summary

Stem cell transplants Therapeutic vaccination6 – cord blood transplants1

– HLA mismatches2,3 Latency reversing agents6

– optimised conditioning chemotherapy4,5 Gene therapy7: – optimised vector safety modified immunosuppressive – and specificity therapy2

Combination approaches are likely to be needed to achieve a cure

Adapted from: 1. Petz L. Stem Cells Transl Med 2013;2:635–7 2. Durand C, et al. Biol Blood Marrow Transplant 2012;18:S172–S176 3. Brunstein C, et al. Blood 2011;118:282–7 4. Katlama C, et al. Lancet 2013;381:2109‒17; 5. Stan R and Zaia J. Curr HIV/AIDS Rep 2014;11:11–9 6. Mylvaganam G, et al. Curr Opin Immunol 2015;35:1–8; 7. Nalla A and Trobridge G. Biomedicines 2016;4:8 75