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CT TG01 -01 Version v10.0 27 June 2018 Confidential 9 / 87 Abbreviations Abbr eviation Term AE Adverse event ALT Alanine aminotransferase ASCI antigen - specific cancer immunotherap y AST Aspartate aminotransferase BUN Blood urea nitrogen CK Creatinine kinase CRF Case report form CRA Clinical Research Associate CR Complete re sponse CT Computed tomography CTC Common toxicity criteria CTCAE Common terminology criteria for adver se events DC Dend ritic cell DFS Disease free survival DTH Delayed -type hypersensitivity ECG Electrocardiogram ECOG Eastern Cooperative Oncology Group GCP Good clinical practice GM-CSF Granulocyte macrophage colony stimulating factor GMP Good manufacturing practice hENT1 Human e quilibrative nucleoside t ransporter 1 HLA Human leucocyte antigene IB Investigator’s Brochure ICH International Conference on Harmonisation IEC Independent Ethics Committee INR International normalised ratio IRB Institutional r eview board ITT Intention- to-treat iv Intravenous kg Kilogram(s) CT TG01 -01 Version v10.0 27 June 2018 Confidential 10 / 87 Abbr eviation Term KRAS Kirsten rat sarcoma viral oncogene homolog L Litre LDH Lactate deh ydrogenase LPLV Last patient Last visit mg Milligram(s) mL Millilitre mm Millimetre(s) μM Micromolar NCI National Cancer Institute OS Overall survival PBMC Peripheral blood mononuclear cell PD Progressive disease PI Principal investigator PR Partial response PS Performance status PTT Prothrombin time PV Pharmacovigilance QoL Quali ty of life RAS Rat sarcoma RBC Red blood c ells SAE Serious adverse event SD Stable disease SGOT Serum glutamic oxaloacetic transaminase SGPT Serum glutamic py ruvic transaminase SOC Standard of care TAA Tumour associated antigen UNL Upper normal l imit WBC White blood c ells 5-FU 5-Fluorouracil CT TG01 -01 Version v10.0 27 June 2018 Confidential 11 / 87 1. SYNOPSIS Title of Trial: A Phase I/II Trial of TG01 and Gemcitabine as Adjuvant Therapy for Treating Patients wi th Resect ed Adenocarcinoma of the Pancreas Trial Number: CT TG01 -01 Sponsor: Targovax AS A Trial Physician: Trial Centres: 4-5 centre s located in Norway , UK and Spain Estimated Trial Dura tion: Phase I and Phase II part (main and concomitant group) : 104 weeks enrolment 104 weeks treatment Duration: 5 years and 4 months Survival follow -up un til end of life. Phase II (modified vaccination group) : 48 weeks enrolment 104 weeks treatment Durat ion: 2 years and 11 months Survival follow -up until end of life. Total study duration : 5 years and 4 months Trial Phase: Phase I /II Trial Objectives: 1. To assess the safety of GM-CSF/TG01 vaccination and adjuvant chemotherapy 2. To assess the immune resp onse to GM-CSF/TG01 and the effect of adjuvant chemotherapy in patients receiving GM-CSF/TG01 after primary resection of pancreatic adenocarcinoma 3. To assess at 2 years the clinical efficacy of GM -CSF/TG01 in patients with resected pancreatic cancer 4. To ass ess the relationship of KRAS status to recurrence 5. To monitor CA19-9 levels Trial Design: Phase I Part Up to 12 patients will be assessed for safety and t he effect of Gemcitabine on immune response. Initially, 6 patients will be treated with GM -CSF/TG01 within 1 -8 weeks after surgery and when these 6 patients have reached week 11 : • If 0/6 patients have an immune response and/or >3/6 patients have a DLT the study will be terminated • If 1-3/6 patients have an immune response and/or 3/6 patients have a DLT a further 6 patients will be enrolled CT TG01 -01 Version v10.0 27 June 2018 Confidential 12 / 87 • If ≥ 4/6 patients have an immune response and ≤2/6 patients have a DLT then phase II study will be initiated If the phase I enrolment is expanded to 12 patients then at week 11: • If <4/12 patients have an immune response and/or >4/12 patients have a DLT the s tudy will be terminated • If ≥4/12 patients have an immune response and ≤4/12 patients have a DLT, phase II will be initiated The Phase II part of the study will therefore be initiated if: o ≥4/6 patients have an immune response and ≤2/6 patients have a DLT o r o ≥4/12 patients have an immune response and ≤4/12 patients have a DLT Patients who are withdrawn for reasons other than toxicity may be replaced if they received less than 4 weeks of vaccination and have not starte d Gemcitabine Phase II Part A further 18-25 patients treated with GM -CSF/TG01 + gemcitabine will be added in the P hase II part of the study to provide a total of up to 30 patients in the study as a whole. These patients will follow the same schedule of a ssessment as in the Phase I part (Table 1) and will constitute the main group. Vaccination should be initiated as soon as possible after surgery. Should for medical or other reasons, a patient be unable to start Gemcitabine either within the 12 week window or at all, vaccination s will be contin ued. In exceptional circumstance, due to medical reasons, where vaccination cannot be started soon after surgery, a maximum of 6 patients can start vaccination at the same time as chemotherapy (Table 2) . These patien ts will constitute the concomitant grou p. Patients who are withdrawn for reasons other than toxicity may be replaced if they received less than 4 weeks of vaccination and have not started gemcitabine. The above Phase II part has established a vaccination protocol that provides a positive immu ne response. A new cohort with up to 13 patients is to be enrolled to test if a modified schedule of administration of GM -CSF/ TG01 can induce and maintain the same immune response and reduce the severity of or avoid s ide effects related to allergic reactio ns (Table 3). These patients will constitute the modified vaccination group. Phase I and Phase II P arts Patients will receive GM- CSF followed by TG01, 10-15 minutes later. Between 3-7 weeks after GM -CSF/TG01 inject ions have started, patients will also receive Gemcitabine on the same day and after TG01 administration. The patients will all be assessed for safety and immune responses by week 11 a fter receiving at least 1 cycle of gemcitabine treatment . In the Phase I I part , vaccination will start CT TG01 -01 Version v10.0 27 June 2018 Confidential 13 / 87 as soon as the vaccination schedule can be adhered to and gemcitabine (or 5FU/Leucovorin as per protocol in case of impaired l iver function) will be started at least 3 weeks later and where possible within 12 weeks from surge ry (main group). Patients for whom chemotherapy timing cannot be assured will start vaccination as soon as the vaccination schedule can be adhered to and will receive chemotherapy or not according to their needs. Patients, who for medical reasons, cannot s tart vaccination early may start this a t the same time as chemotherapy to the limit of 6 patients (concomitant group). Treatment will be interrupted in any individual patient in case of unacceptable toxicity. If the toxicity is considered to be due to ge mcitabine alone then immunisation with GM -CSF/TG01 will be continued. With the exception of patients who have received less than 4 weeks of immunisation with GM - CSF/TG01 and no gemcitabine , all patients will complete the study follow up (even if withdrawn from therapy) unless they withdraw consent . After completion of the gemcitabine treatment , patients who are recurrence- free (with or without a detected immune response ) will continue to receive GM- CSF/TG01 every 4 weeks until 52 weeks, then every 12 weeks until 2 years or until withdrawal of consent or toxicity whichever is the earliest . Patients who recur during the study and had a positive immune response during the study treatment period should continue to receive GM -CSF/TG01 every 4 weeks until 52 weeks, then every 12 weeks until 2 years or until withdrawal of consent or toxicity whichever is the earliest. Patients who recur and haven’t had a positive immune response during the study treatment period will be withdrawn . The same applies to patients wh o never start chemotherapy. For all patients , where possible , a survival follow -up will continue to be performed every 6 months after the initial 2 years of study period and until the last remaining patient in the modified cohort reaches the 2 years study period or withdraws consent or experie nces toxicity, whichever is the earliest. Thereafter, a survival follow -up will continue to be performed approximately every 12 months until end of life. Modified vaccination group Patients will start vaccination as soon as possible after surgery. P atient s will receive GM- CSF followed by TG01 15-20 minutes later. Gemcitabine will commence preferably at least 3 weeks later and vaccination will be put on hold until chemotherapy completion . In the event that chemotherapy cannot be started patients should continue to be vaccinated 4- weekly . After completion of the gemcitabine treatment, patients who are recurrence -free (with or without a detected immune response) will continue to receive 4-weekly GM-CSF/TG01 (plus one vaccination at week 5 post -chemotherapy) until week 52 then every 12 weeks until 2 years or until withdrawal of consent or toxicity whichever is the earliest. Patients who recur during the study and had a positive immune response during the study treatment pe riod should continue to receive 4- weekl y GM-CSF/TG01 (plus one vaccination at week 5 post -chemotherapy) until week 52 then every 12 weeks until 2 years , until withdrawal of consent or toxicity CT TG01 -01 Version v10.0 27 June 2018 Confidential 14 / 87 whichever is the earliest. Patients who recur and haven’t had a positive immune response during the study treatment period will be withdrawn. Where possible, a survival follow -up will continue to be performe d every 6 months after the initial 2 years of study period and until the last remaining patient in the modified cohort reaches the 2 years study period or withdraws consent or experiences toxicity, whichever is the earliest. Thereafter, a survival follow -up will continue to be performed approximately every 12 months until end of life. The efficiency of this modified vaccination group will be assessed aft er 6 patients have data for DTH assessments after 8 weeks. The cohort will continue if the tolerability is acceptable and there are at least 4/6 patients with a positive immune response by week 8. If <4/6 patients hav e an acceptable immune response, the ne xt patients will revert to the previous induction schedule of 3 vaccinations in the first week. Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas 2. Stage I or II disease (clinical stage T1 -3, N0-1, M0 by AJCC staging criteria).