HIV-1 infected subjects treated with an autologous dendritic cell therapy (AGS-004), exhibited a significant reduction in viral load (when compared to pre-ART viral load) and delay in the time to viral rebound during a 12 week structured treatment interruption (STI) J.P. Routy 1, J. Angel 2, S. Vezina 3, C. Tremblay 4, M. Loutfy 5, J. Gill 6, J.-G. Baril 7, F. Smaill 8, R. G. Jain 9, I. Y. Tcherepanova 9, M.-R. Boulassel 10, T. Monesmith 9, R. P. Sekaly 11, C. A. Nicolette 9, and AGS Study Group 1 McGill University Health Centre, INSERM Unit 743, Montréal, Canada, 2 Ottawa Hospital, Ottawa, Canada, 3 Clinique Médicale l'Actuel, Montréal, Canada, 4 Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada, 5 Maple Leaf Clinic, Toronto, Canada, 6 Southern Alberta Clinic, Calgary, Canada, 7 Clinique Medicale du Quartier Latin, Montréal, Canada, 8 Hamilton Health Sciences - McMaster University Medical Centre, Hamilton, Canada, 9 Argos Therapeutics Inc, Durham NC, United States, 10 McGill University Health Centre, Montréal, Canada, 11 University of Montréal Research Centre, Montréal, Canada Funded by NIAID, NIH (NO1-A ), CTN-CIHR #239 and Argos Therapeutics, Inc.

Background and rationale ART represents a major breakthrough for the management of HIV-infected patients, however is not without side effects and is a life long commitment Therapeutic vaccines to enhance immune response and control viral replication are needed to limit exposure to ART AGS-004, (Argos Therapeutics) which consists of autologous monocyte-derived dendritic cells co-electroporated with in vitro transcribed RNA encoding four of the patient’s own HIV antigens (Gag, Vpr, Rev, and Nef) was developed A phase 1 study demonstrated CTL induction without activating CD4 + T cells (Routy et al. Clin Immunol 2010 )

Study Design: Phase 2 AGS-004 dosing every 4 weeks 8 weeks12 weeks ART 12 Week STI Booster Phase ART Study design: Single-arm, open-label, multicenter, Phase 2 study to assess safety and antiviral activity of AGS doses of AGS-004 while on ART, 2 doses off ART and then dosed when VL< copies/ml End points: Time to VL rebound, Pre-ART vs. Wk 12 of STI change in VL, tolerance, restart ART when CD4 < 350 /mm 3 Key Criteria: First ART with VL <50 copies/ml, CD4 ≥450/mm 3 for at least 90 days, nadir ≥200/mm 3 Booster phase if VL < copies/ml

Time from ART Interruption to Viral Load Rebound, n=22 Median time to viral load rebound (≥50 copies/mL) = 3.86 weeks Mean time: 3.77 weeks  22 Patients out of 29 who received AGS-004 immunotherapy: Interim analysis Blood sampling q 2 weeks Increase in the proportion of patients with VL rebound ≥ day 14 was seen from historical control. Swiss cohort, Fischer et al. AIDS 2003; 17; 195 Fisher’s exact test, the p-value for the difference = 

The median reduction for responders (n=14) was log No association between the change in viral load and susceptible (B*31, B*45, B*35) or protective (B*27, B*51, B*57) HLA alleles Pre-ART vs. Week 12 of STI Log Change in Viral Load N=22 Mean reduction in viral load log (n=22) For those who had lower VL than pre-ART(n=14) Mean reduction in viral load = log

Conclusion Administration of AGS-004 immunotherapy: Feasible in a multicenter study Safe, with no additional risk observed during STI Long delay in viral rebound Lower viral load when compared to pre-ART levels CD4 T cell counts: No significant decrease from the median of the last three CD4 + T cell counts on ART vs. in the STI (p-value = 0.20) Immune correlate: – CD8 T-cells was consistent with an effector/memory response – Absence of CD4 induced activation – Poster THPE0181, C Nicolette These results warrant further evaluation: – Phase 2 b, NIH-supported double-blind, placebo-controlled, randomized study, AGS in US and Canada