Antiviral InteliStrat Inc.

Uses genes from pt’s own viral strains (obtained from plasma samples taken immediately prior to starting antiretroviral therapy, from which viral RNA can be amplified) in vaccine, making it a “personalized” vaccine;

Designed to enhance CD8-specific responses to HIV;

Mature dendritic cells from the pt are submitted to electroporation with antigen-encoding RNAs, with the whole immunotherapy process called Arcelis™ by the sponsor

Ref.: Gay CL et al., AIDS Res Hum Retroviruses. 2018 Jan;34(1):111-122 (www.ncbi.nlm.nih.gov/pubmed/28636433); Routy & Nicolette. Immunotherapy. 2010 Jul;2(4):467-76 (www.ncbi.nlm.nih.gov/pubmed/20636001); Tcherepanova I et al., PLoS One. 2008 Jan 30;3(1):e1489 (www.ncbi.nlm.nih.gov/pubmed/18231576)

In Phase I trial, primary endpoints of safety and induction of T-cells response to pt-specific HIV antigens were reached;

Phase I results were presented at XVII International AIDS Conference (Mexico City, Aug. 2008; Routy et al., Abstract TUPDA101):

• 10 HIV-infecred pts under successful HAART (viral load suppressed under 40 copies/mL) and with CD4+ T-cell counts over 350 cells/µL were included in the study and received their respective treated dendritic cells in the form of 4 intradermal injections of 0.6mL containing 1.2x10 ⁷ cells with a follow-up of 12 months maximum (ARV treatment uninterrupted)
• Adverse events were mild and included flu-like and gastrointestinal symptoms, fatigue, and injection site reactions
• No increases were seen in HIV viral load ("blips") and no significant changes in either absolute CD4 or CD8 cell counts were seen
• A significant increase in CD8 T-cell proliferative response (at least double the baseline value) was noted in 4 of the 10 pts, and a partial response (significant increase above untreated controls) in a further 3 pts, and these responses were specific for the 4 HIV antigens selected
• Pts treated with HAART early in the course of their infection (within 6 months) showed a trend towards more robust antiviral immune responses compared to those in whom therapy was started 6 months or more post-infection

Results of Phase IIb NCT01069809 were published in Jacobson JM et al., J Acquir Immune Defic Syndr 2016 May 1;72(1):31-8 (www.ncbi.nlm.nih.gov/pubmed/26751016):

• Phase IIb trial was a randomized, double-blind, placebo-controlled study enrolling 54 HIV-1-infected pts on ART with viral loads <50 copies per milliliter, current CD4 T-cell counts >450 cells/mm3, and nadir counts >200 cells/mm3, who received intradermal injections of AGS-004 into the axillary lymph node region every 4 weeks; At week 16, a 12-week analytical treatment interruption (ATI) was undertaken
• No difference in the end-of-ATI viral loads (average of values from weeks 11 and 12) between the 2 arms of the study [4.39 (4.17, 4.69) vs. 4.47 (3.76, 4.64) log10 HIV-1 RNA; P = 0.73]
• No change was observed between pre-antiretroviral therapy viral loads and the end-of-ATI viral loads [-0.06 (0.24, -0.32) vs. -0.17 (0.17, -0.32) log10 HIV-1 RNA; P = 0.43] in study arms
• When IFN-γ, IL-2, TNF-α, CD107a, and granzyme b expressions were measured by multicolor flow cytometry, a greater percentage of AGS-004 than of placebo recipients had multifunctional cytotoxic T-lymphocyte responses induced in the CD28+/CD45RA-CD8 effector/memory T-cell population to dendritic cells electroporated with autologous antigens
• AEs consisted of transient, mild (grade 1) local injection site reactions
• Authors concluded that despite induction of HIV-specific effector/memory CD8 T-cell responses, no antiviral effect was seen after the administration of AGS-004 when compared with placebo