3 List of Abbreviations ............................................................................................................................ 5 1. Introduction ............................................................................................................................. 7 1.1 Preface .......................................................................................................................... 7 1.2 Purpose of the analyses ................................................................................................... 8 2 Study Objectives and Endpoints ................................................................................................. 8 2.1 Study Objectives ............................................................................................................. 8 3 Study Methods ....................................................................................................................... 10 3.1 General Study Design and Plan for Phase 1 ...................................................................... 10 3.2 General Study Design and Plan for Phase 2 ...................................................................... 10 3.3 Inclusion-Exclusion Criteria and General Study Population .................................................. 11 3.4 Randomisation and Blinding ............................................................................................ 13 3.5 Study Variables ............................................................................................................. 14 4 Sample Size .......................................................................................................................... 14 5 Statistical Considerations ........................................................................................................ 15 5.1 General Principles ......................................................................................................... 15 5.2 Analysis Populations ...................................................................................................... 15 5.2.1 Phase 1 .............................................................................................................................. 15 5.2.2 Phase 2 .............................................................................................................................. 15 5.3 Covariates and Subgroups .............................................................................................. 16 5.4 Interim Analyses and Data Monitoring .............................................................................. 16 5.5 Multiple Testing ............................................................................................................. 17 6 Summary of Study Data .......................................................................................................... 17 6.1 Subject Disposition ........................................................................................................ 17 Heat Biologics, Inc. Protocol HS410-101 HS410-101 SAP version 1.0 Page 4 of 25 6.2 Protocol Deviations ........................................................................................................ 17 6.3 Demographic and Baseline Variables ...............................................................................