NAPWA’s Treatment Horizons: Pathways to a Functional Cure IAS 2011, Rome, Italy 19th July 2011

Vacc4x: A Therapeutic HIV-1 Vaccine Based on Modified Peptides Maja A. Sommerfelt Ph.D. CSO NAPWA’s Treatment Horizons: Pathways to a Functional Cure IAS 2011, Rome, Italy 19th July 2011

Therapeutic Vaccination and Functional Cure for HIV-1 Infection • Therapeutic vaccination • Antiviral responses • T-cell approaches:Kill infected cells • Antibody approaches: Block/inactivate the virus • Generalised immune activation induced by HIV • Immune responses induced by therapeutic vaccination can reach regions of the body not accessed by ART • An effective therapeutic vaccine will provide valuable information that can help towards a successful preventative vaccine Vacc-4x Vacc-C5

Vacc-4x: Based on conserved domains of HIV-1 p24CA • 4 modified peptides to p24CA • Sustained immune responses to p24CA are associated with delayed disease progression* • Strong responses to Gag are associated with virus control (LTNP) in the absence of ART¤ • Conserved ‘Sectors’ within p24CA particularly immunologically vulnerable andimportant for virus control§ • Vacc-4x largely corresponds to ‘Sector 3’ p24CA Image WSJ *Weber et al. 1987 Lancet 1:119-22 ; Cheingsov-Popov et al. 1991 BMJ 302 :23-6 ; ¤ Kiepiela et al. 2007 Nature Med. 13:46-53; Zuniga et al. 2006 J. Virol. 80:3122-5. §Dahirel et al. 2011 www.pnas.org/cgi/doi/10.1073/pnas.1105315108; # Schoofs 2011 Wall Street Journal (WSJ) 21st June Images Dahirel et al. 2011

Bionor Immuno Peptide Design Considers Virus Diversity Human Diversity • Conserved Domains • Cross Clade • Most prevalent HLA in • diverse human populations • Human-like sequences excluded • Peptides are modified using a proprietary design technology to improve • Uptake • Antigen processing & presentation • Simple & cost-effective manufacture

Vacc-4x: Phase IIB Study • 135 patients (US+EU); 2/3 active and 1/3 placebo • 6 immunizations (1,2 mg Vacc-4x + GMCSF over 18wks) • Off ART wk 28-52 (LTFU during year 2) Study design • 18-55 y of age • Chronic HIV infection (>1 y) • Stable on ART >6 months (VL < 50 copies/mL) • Pre-study CD4 cell count > 400 x 106 / L • Nadir CD4 cell count > 200 x 106 / L Inclusion criteria • Primary: Resumption of ART • CD4 < 350 x106 / L or 50% decrease • VL >300.000 copies/mL • Co-primary: Change of CD4 • Secondary: Viral Load / ELISPOT / Proliferation / ICS Endpoints

IIB StudySchedule

Vacc-4x IIB study: 18 sites Last Patient Completed wk52: June 2010 Last Patient Completed wk104: June 2011 No Vacc-4x -related SAE reported

Phase IIB Baseline Characteristics

Primary End Points • There was no difference in the time to return to ART (p=0.89) • There was no difference in mean change in CD4 counts over time (p=0.12)

Secondary End Points: Viral Load

Secondary End Points: Viral Load Change from PreART Subjects who remained off ART until week 52. Vacc-4x group change from preART 0.55 log, p=0.0003, n=44. Placebo group change from preART 0.08 log, p=0.89, n=18

Secondary End Points: ELISPOT Responses This indicates a potential qualitative rather than a quantitative difference in immunological responses to p24 between Vacc-4x and placebo groups. Further immunological analyses are ongoing.

Acknowledgments All Participating Study Volunteers Phase I & IIA Phase IIB Haukeland Hospital Participating Clinical Trial Sites Ullevål University Hospital University of Lausanne & UC Davis Mericon AS SRA Global Clinical Development Ltd. Bionor Laboratories AS Covance Mericon AS The phase IIB study is supported in part by a grant from the Research Council of Norway GLOBVAC program

NAPWA’s Treatment Horizons: Pathways to a Functional Cure IAS 2011, Rome, Italy 19th July 2011