2019 Ryan White HIV/AIDS Program CLINICAL CONFERENCE

Antibodies with improved potency and breadth: Reduction in VL after VRC01LS or VRC07-523LS Infusion

6

6

Subject1

Subject8 Subject9 Subject10 Subject11 Subject12 Subject13 Subject14 Subject15 Subject16

Subject2 Subject3

5

5

Subject4

4

4

Subject5 Subject6

2 log 10 virus load 3

2 log 10 virus load 3

Subject7

(copies/ml)

(copies/ml)

LOD

LOD

1

1

0

2

4

6

8

10 12 14

0

2

4

6

8

10 12 14

Dayspost infusion

Dayspost infusion

VRC01LS

VRC07-523LS

- Day 7:2/7decrease of at least 0.9 log10 - Day 14:2/7decrease of at least 1.6 log10 (all subjects off ARVs)

- Day 7:8/9decrease of at least 1.2 log10;2/9 decrease of least 2 log10 - Day 14:6/9decrease of at least 1.6 log10;7/9 decrease of at least 0.6 log10 (all subjects off ARVsuntil after Day 14)

Study ofLAcabotegravir+ VRC07- 523LSbeing launched (ACTG)

ChenG IAS2019WEAA0305LB

Slide40of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.

Selected other investigational drugs in the pipeline

http://i-base.info/htb/wp-content/uploads/2019/07/PIPELINE-2019-FINAL-full-version.pdf

Slide41of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.

New Delivery Systems (in development)

 Long acting injectables: o Elsulfavirine (NNRTI); raltegravir; atazanavir/ritonavir; combinectin (entry inhibitor) o Considerations: managing toxicities if they develop; what to do if recipients become pregnant; what happens if doses missed  Implants: o Islatravir: NRTTI o TAF: NRTI o Biodegradable, removable, polymer-based implants with multiple drugs  Patches  Oral once-weekly delivery system  Novel antibody delivery systems: viral vectors; synthetic DNA GulickR&Flexner C.AnnRevMed2019;70:137-50;FlexnerC.CurrOpinHIVAIDS2018;BenhabbourSRetal,NatureComm2019;Rajolietal. Eur Jof PharmaandBiopharm2019.GiardielloM NatureComm2016;KirtaneA,etal. NatureComm2018.WiseMetal, JCI,2019

Slide42of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.