1. What’s Next – and When: An Update on Injectable Prevention
Alex R Rinehart, PhD
Director, Global HIV Prevention Strategy
ViiV Healthcare

2. Cabotegravir LA (CAB LA) for PrEP
CAB is an investigational HIV integrase strand transfer inhibitor and analogue of dolutegravir
Low solubility crystalline drug suspended in an aqueous vehicle for intramuscular injection
No requirement for protection from light or refrigeration
3-year shelf life at room temperature; up to 30°C > 24 mo (all ICH climatic zones)
In vitro and clinical data suggest potent anti-HIV activity and a high barrier to resistance
NHP models show high levels of protection from infection against rectal, vaginal and parenteral SIV/SHIV challenges
Strong preclinical/clinical data package supports PrEP Phase 3 start

3. CAB LA Development Program
Simultaneous Global Registration Programs for Treatment and Prevention
Indication Phase Phase 3
Pearson correlation = 0.86, p=0.003
LATTE
LATTE-2*
FLAIR (I/M)
ATLAS (switch)
Treatment
Oct 2016 start
Prevention MSM/TGW
ECLAIR
(n=127)
HPTN 083
(n=4500)
Early Phase
Dec 2016 start
Prevention
women
HPTN 077#
(n=199)
HPTN 084 (n=3200)
4Q2017 start
*Safety and Efficacy of Long-acting CAB and RPV as Two Drug IM Maintenance Therapy: LATTE-2 Week 96 Results (MOAX0205LB)
#Safety, tolerability and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected women and men: HPTN 077 (TUAC0106LB)

4. CAB LA PrEP Phase 2 Safety and PK Studies
D W W4 W W W W25 W W W W W W W81
1°analysis
CAB 30 mg PO qd
CAB LA 200mg/mL gluteal IM
Follow-Up Phase
Placebo
PO qd
Placebo (0.9% saline) gluteal IM
Additional 24 wks of f/u added
ECLAIR - all subjects mg q12 wks (2 x 2mL)
HPTN Cohort mg q12 wks (2 x 2mL)
HPTN Cohort mg q8 wks (1 x 3mL) IM IM IM IM IM IM IM IM IM IM IM
HIV negative, at-risk adults (excluding high risk)
Drug PK sampling (blood plasma) in all study participants
ViiV ECLAIR Study (NCT )
n=126 (completed study)
800 mg IM
5:1 randomization
Men including MSM
US only (10 sites)
HPTN 077 Study (NCT )
n=199 (110 Cohort 1; 89 Cohort 2) ongoing
Two Cohorts (800 and 600mg IM)
3:1 randomization
60% enrolment of women
US, Brazil, SA, Malawi (8 sites) 4

5. HPTN 083: CAB LA 600mg
To Prevent HIV Acquisition in MSM and TGW Landovitz and Grinsztejn, Protocol Chairs
Step 1
Daily oral CAB and TDF/FTC placebo
TDF/FTC and
oral CAB placebo
Step 2
CAB LA at two time points 4 weeks apart and every 8 weeks
thereafter and TDF/FTC placebo
TDF/FTC and injectable
placebo at two time points 4 weeks apart and every 8 weeks thereafter
Step 3
Open-label TDF/FTC to
cover the PK tail
Cover the PK tail
Add logo
Primary Objective: Reduce HIV Incidence (non-inferiority, double blind, double dummy design)
N=4500; Study duration: Enrollment months; follow-up ~ 4.5 years
Enrollment goals:
Minimum 50% of US enrollment Black MSM (~ 950)
Overall minimum 10% TGW (~ 450)
Overall > 50% under age 30

6. HPTN 084: CAB LA 600mg
To Prevent HIV Acquisition in Women Delaney-Moretlwe and Hosseinipour, Protocol Chairs
Step 1
Daily oral CAB and TDF/FTC placebo
Oral TDF/FTC and
oral CAB placebo
Step 2
CAB LA and oral TDF/FTC placebo at two time points 4 weeks apart and every 8 weeks thereafter
Oral TDF/FTC and injectable
placebo at two time points 4 weeks apart and every 8 weeks thereafter
Step 3
Open-label oral TDF/FTC to
cover the PK tail
Primary Objective: Reduce HIV Incidence (superiority, double blind, double dummy design)
Study duration: Enrollment 24 months; follow-up up to 4.5 years, N=3200

7. A Global Public-Private Partnership
Multiple research collaborations with Aaron Diamond, CDC, and NIH (pre-clin to Phase 2)
Phase 3 registrational studies
65 sites across 13 countries
sponsored by DAIDS (NIH)
jointly funded by NIH, Bill & Melinda Gates Foundation, and ViiV

8. Excitement and Challenges Ahead…
Enrolling studies will take time – end of trials is uncertain and will depend on background incidence and seroconversion rates
How best to handle the ‘PK tail’? What is the potential for the development of resistance?
Excitement
Efficacy demonstrated in NHP models
Safety, tolerability demonstrated in Phase 2 studies
Hope to bring a viable, new option for HIV prevention
Familiar delivery platform
Planning for Success
Efficient regulatory approvals
Development plan for demonstration projects/implementation research
Clinical questions (removal of oral lead-in, PK tail, resistance development, dose interval)
Increasing access and uptake (end-user research, delivery channels, demand creation), settings to give injections, etc.
Identify collaborators and funders for next stage of public-private partnership