THE WORLD ALLERGY ORGANIZATION SUBCUTANEOUS IMMUNOTHERAPY SYSTEMIC REACTION GRADING SYSTEM .................................................................................................81 LIST OF TABLES Table 1. Synthetic Peptide Sequences ..................................................................................20 Table 2. Local Reaction Assessment Scale ..........................................................................44 LIST OF FIGURES Figure 1. Cancer Testis Antigens Targeted by PolyPEPI1018 .............................................21 Figure 2. Mechanism of Action of Precision PolyPEPI1018 CRC Vaccine .........................22 Figure 3. Study Design Schema ............................................................................................30 Figure 4. Distribution of the Expected Number of Positive Tests ........................................67 Figure 5. Expected Distribution of Probabilities Having a Given Number of Subjects with Positive Immune Response for Two or More Antigens ................................68 Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 16 of 81 CONFIDENTIAL LIST OF ABBREVIATION S AND DEFINITIONS OF TERMS Abbreviation Definition AE adverse event ALAT alanine amino transferase ASAT aspartate amino transferase CA 19-9 cancer antigen CDx companion diagnostic CEA carcinoembryonic antigen CNS central nervous system CPI checkpoint inhibitors CRC colorectal cancer CRF case report form CTA cancer testis antigen CTCAE Common Terminology Criteria for Adverse Events CTL cytotoxic T lymphocyte EC Ethics Committee ECG electrocardiogram ECOG Eastern Cooperative Oncology Group eCRF electronic case report form EGFR epidermal growth factor receptor ELISPOT Enzyme-Linked ImmunoSpot EU European Union 5FU 5-fluorouracil FDA Food and Drug Administration GCP Good Clinical Practice GMP Good Manufacturing Practice hCG human chorionic gonadotropin HLA human leukocyte antigen ICF informed consent form ICH International Council for Harmonisation IEC Independent Ethics Committees IFN interferon IHC immunohistochemistry IP investigational product IRB Institutional Review Boards mCRC metastatic colorectal cancer MedDRA Medical Dictionary for Regulatory Activities Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 17 of 81 CONFIDENTIAL MEK MAPK/ERK kinase MSI-H high microsatellite instability NCI-CTCAE National Cancer Institute -Common Terminology Criteria for Adverse Events NMC non-medical complaint ORR overall response rate PBMC peripheral blood mononuclear cells PEPI personal epitope PHPC Precursors with High Proliferation Capacity PR partial response RAS Rat Sarcoma Viral Oncogene Homolog RECIST Response Evaluation Criteria in Solid Tumors RSI Reference Safety Information SAE serious adverse event SAER SAE report SAS Safety Analysis Set SC subcutaneous(ly) SIC subject identification code SoA Schedule of Study Assessments SOC system organ class SUSAR suspected unexpected serious adverse reaction TEAE treatment -emergent adverse event TIL tumor ‐infiltrating lymphocyte ULN upper limit of normal US United States WT wildtype Treos Bio ZRT OBERTO -101 Amendment 3 Product: PolyPEPI 1018 Colorectal Cancer Vaccine Page 18 of 81 CONFIDENTIAL 1 BACKGROUND INFORMATI ON 1.1 Colorectal Cancer Background Colorectal cancer is a leading cause of cancer -related mortality worldwide. In the European Union (EU-28) and the World H ealth Organization Europe Region, t he mean mortality rates per 100,000 population are respectively 15.2 and 15.7 for men and 9.0 and 9.7 for women (Ferlay 2015).