1. Study 38.2: Experimental Design and Summary

2. Study 38.2: Experimental Design Day 0 7B2-AAA I.V. infusion 50 mg/kg Day -6 Pre-bleed and rectal biopsies 12 h Rectal biopsies 52 h 7B2-AAA I.V. infusion 50 mg/kg 60 h Rectal biopsies

3. Study 38.2: Details Monkey IDs: 5105, 5100, 5109, 5104 All monkeys SIV-negative and non-immunized prior to study Intravenous infusion of 7B2-AAA, a non- neutralizing mAb against the gp41 immunodominant epitope; 50 mg/kg 2X at 0 and 52 hours. Timing was determined based on a previous pharmacokinetic study. Rectal biopsies obtained pre and then 8 or 12 hours post each infusion. RNA was isolated from the rectal mucosa for microarray analysis.

4. Study 38.2: Objectives Global microarray analysis to determine differential expression patterns following the infusion of 7B2-AAA. We are looking for the upregulation/downregulation of any genes of interest—no underlying hypothesis.

5. Cytokine kinetics from rectal wecks taken in NHP 38.2

6. CytokinePlasmaRectal Weck G-CSF GM-CSF IFNg IL-10 IL-12/23(p40)X IL-13 IL-15X IL-17 IL-18XX IL-1bXX IL-1raXX IL-2 IL-4 IL-5 IL-6 IL-8XX MCP-1XX MIP-1a MIP-1b TGFaXX TNFa VEGF sCD40LX 7B2 NHP PK study Cytokine Elevations

7. IL-1b Kinetics in Rectal Wecks

8. IL-18 Kinetics in Rectal Wecks

9. IL-1ra Kinetics in Rectal Wecks

10. IL-8 Kinetics in Rectal Wecks

11. TGFa Kinetics in Rectal Wecks

12. MCP-1 Kinetics in Rectal Wecks

13. Quality Control of Arrays No Sample outliers found. Distributions of expression values consistent

14. Exploratory Analysis Unsupervised analysis results in Samples grouping by Donor. Will provide a report (Part B), with analysis blocked by donor.

15. Differentical Gene Expresion Hour 60 most DEG, h12 looks more like preInfusion. h60 vs pre on the left, F test on right

16. Gene Set Enrichment analysis h12 vs preInfusion h12, TGF-beta, IL-22 pathways. 39 pathways enriched, non meet significance.

17. Gene Set Encichment h60 vs Preinfustion 120 pathways enriched; predominantly signally pathways responding, top genes presented here. Please see table in report. Many cytokine and Chemokines have beeen affected. 3 pathways meet significance. Will see if this signal gets clearer with Analysis part B, bloc by donor