2019 Ryan White HIV/AIDS Program CLINICAL CONFERENCE

HIV Entry Inhibitors: Novel Antibodies

Coreceptor Binding Leronlimab (PRO 140)

CD4 Binding

Virus-Cell Fusion

CCR5 Inhibitors maraviroc*

enfuvirtide*

Fostemsavir Ibalizumab*

gp41

gp120 V3 loop

CD4

UB-421

Cell Membrane

CCR5/CXCR4 (R5/X4)

* FDA approved

Slide courtesyofTripGulick,MD;Adapted fromMoore JP, PNAS 2003;100:10598-10602.

Slide34of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.

UB-421: Antibody against CD4

PlasmaVL

• 29 people with virologic suppression on oral ART • Received up to 8 infusions of UB-421 ▫ Weekly: cohort 1 ▫ Every 2 wks: cohort 2 • Oral ART stopped after first infusion • All participants remained virologically suppressed during infusions • Rash: 52%: mild and transitory; 1 person stopped Ab because of more severe rash • Approval in China for a phase 3 ART substitution trial

Wang,C-Yetal,NEnglJMed2019;380:1535-1545;http://www.unitedbiopharma.com/news_detail.php?id=365

Slide35of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.

Leronlimab (PRO 140)

Monoclonal antibody against CCR5 Weekly subcutaneous injection

• •

• Being studied as a single agent for maintenance of suppression and for people with drug resistant HIV • Single agent for maintenance of suppression ▫ Participants with virologic suppression and R5 tropic HIV (Trofile DNA) ▫ Virologic failure rate: 14-66% ▫ Participants who had virologic failure re- suppressed on baseline ART ▫ No tropism shifts

DhodyCetal,CROI2019,Abstr486

Slide36of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.