1. Smallpox vaccine in combination with ST-246 Robert Jordan, Ph.D. SIGA Technologies, Inc FDA – Public HearingMay 17, 2007

2. Smallpox Deployment Scenario ACAM-2000 ST-246 MVA Exposure Incubation Rash……………Death Fever ~ 14 days ~ 3 days ~ 21 days Sentinel Case Golden HoursST-246

3. ST-246 Progress to Date ST-246 is a potent, non-toxic and specific inhibitor of orthopoxvirus replication ST-246 is effective in multiple rodent challenge models against orthopoxvirus induced pathogenesis and/or disease ST-246 is effective against monkeypox and variola virus in a non-human primate model of orthopoxvirus disease ST-246 is orally bioavailable with excellent PK parameters ST-246 IND approved, Fast-Track status granted Orphan Drug Designation for prevention and treatment of smallpox approved Human clinical studies with ST-246 are underway ST-246

4. ST-246 Target is F13L Systemic Spread Disease Cell-to-Cell Spread Local Infection Replication & Assembly Immature Virus (IV) Intracellular Mature Virus (IMV) Extracellular Enveloped Virus (EEV) F13L No Disease* ST-246 TGNPM *Animals infected in presence of ST-246 develop a protective immune response

5. I.N. vaccinia virus challenge in mice Dose optimization No drugST-246

6. ST-246 protects animals from all orthopoxvirus pathogens tested (VV, CPX, ECTV, RPV, MPX, VaV) Addition of ST-246 up to 72h post infection protects animals from disease & death ST-246 reduces viral replication in lung by 6 logs ST-246 treatment in combination with Dryvax elicits a protective immune response. Animal Efficacy Highlights

7. Prophylaxis - Prevent disease in non-vaccinated individuals Post-exposure Prophylaxis - Treat non-symptomatic individuals previously exposed to smallpox Therapeutic – Treat individuals exhibiting smallpox disease symptoms Adjunct to Vaccination  Use in combination with vaccines to prevent smallpox disease  Prevent vaccine-related complications  Prevent disease in those populations unable to be vaccinated Uses for the ST-246 Smallpox Antiviral

8. Dryvax Dermal Challenge/Vehicle Treatment

9. Dryvax Dermal Challenge/SIGA-246 Treatment

10. Cytokine Release Assay Acute Response Memory Response

11. Anti-Vaccinia IgG Acute Response Memory Response

12. ST-246/Dryvax Conclusions Vaccine/ST-246 combination elicits enhanced IFN-gamma responses (primarily attributable to CD8 T cells) at both acute and memory phases of the immune response Vaccine/ST-246 combination elicits equivalent proliferative and humoral responses Vaccine/ST-246 combination elicits equivalent protective immunity ST-246 in combination with a smallpox vaccine could protect individuals from severe disease prior to development of protective immunity