A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer

Inclusion Criteria:

1. A diagnosis of advanced and unresectable or metastatic pancreatic adenocarcinomaconfirmed by:

2. Histopathology from primary tumor in pancreas, OR

3. Histopathology from a non-pancreatic lesion in the presence of a mass in thepancreas consistent with pancreatic adenocarcinoma or a medically documentedhistory of pancreatic adenocarcinoma.

4. Measurable disease per RECIST v.1.1

5. Male or non-pregnant, non-lactating female, ≥18 years or age

6. If a female patient is of child-bearing potential, as evidenced by menstrualperiods, she must have a negative serum pregnancy test (beta-human chorionicgonadotropin [β- hCG]) documented prior to the first administration of studdrugs

7. Female patients of childbearing age and women < 12 months since the onset ofmenopause must agree to use acceptable contraceptive methods for the durationof the study and 9 months following the last injection of OT-101.

8. Male patients must use effective contraception for a duration of 6 months afterthe final dose, as per the prescribing information for oxaliplatin.

9. Provide signed written informed consent

10. Eastern Cooperative Group (ECOG) Performance Status (PS) score of 0-1

11. Willingness and ability to comply with study requirements

12. Patient has adequate organ function by the following laboratory assessments atbaseline(obtained ≤28 days prior to Randomization): Hematologic

• Platelets ≥100×109/L

• Hemoglobin ≥9.0 g/dL

• Absolute Neutrophil Count (ANC) ≥1.5×109/L

• Patient has acceptable coagulation values obtained ≤28 days prior toRandomization as demonstrated by prothrombin time (PT) or internationalnormalized ratio (INR) and partial thromboplastin time (PTT) ≤1.5× upper limitof normal (ULN) (if on Coumadin, patient must be changed to LMWH or on FactorII or Xa anticoagulant with a t½ of less than 24 hours Hepatic

• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤3×ULN (if livermetastases are present, ≤5×ULN)

• Alkaline phosphatase ≤2.0×ULN (if liver metastases are present, ≤5×ULN)

• Total bilirubin ≤2.0×ULN (in patients with Gilbert's Syndrome total bilirubin <or = 2.5xULN) Renal

• Calculated creatinine clearance ≥50 mL/min. Actual body weight should be usedfor calculating creatinine clearance (e.g., using the Modification of Diet inRenal Disease [MDRD] formula. For patients with a body mass index (BMI) >30kg/m2, lean body weight should be used instead

8. Patient must have a life expectancy of ≥3 months in the opinion of the Investigator

Exclusion Criteria:

1. Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (ie,lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, orcystadenocarcinoma

2. Patient has experienced a decrease in ECOG PS between Screening visit and within 72hours prior to Randomization

3. Patient on Coumadin and not willing to change to LMWH or oral Factor II or Xainhibitor with t½ of less than 24 hours

4. History of prior malignancy, except for adequately treated in situ cancer, basalcell, squamous cell skin cancer, or other cancers (eg, breast and prostate) forwhich the patient has been disease-free for at least 3 years. Patients with priorcancer that is adequately controlled per the judgement of the Investigator will notbe excluded from the study

5. Any serious medical condition, laboratory abnormality, psychiatric illness, orcomorbidity that, in the judgment of the Investigator, would make the patientinappropriate for the study

6. Patients with abnormal electrocardiogram (ECG) at baseline (QT or QTc interval >470ms) will be excluded from this study. The eligibility of patients with ventricularpacemakers for whom the QT interval may not be accurately measurable will bedetermined on a case-by-case basis by the Sponsor's medical representative inconsultation with the principal investigator.

7. Serious systemic fungal, bacterial, viral, or other infection that is not controlledor requires intravenous antibiotics

8. Known history of positivity (regardless of immune status) for human immunodeficiencyvirus(HIV)

9. Known history of chronic active or active viral hepatitis A, B, or C infection

10. Clinically significant bleeding within 2 weeks prior to Randomization (eg,gastrointestinal[GI] bleeding or intracranial hemorrhage)

11. Pregnant or lactating women

12. Myocardial infarction, coronary bypass surgery, or arterial thromboembolic eventswithin the last 6 months prior to Randomization, symptomatic congestive heartfailure (New York Heart Association Classification >Class II, unstable angina, orunstable cardiac arrhythmia requiring medication

13. Clinically significant ascites defined as requiring ≥1 paracentesis every 2 weeks

14. Major surgery, defined as any surgical procedure that involves general anesthesiaand a significant incision (ie, larger than what is required for placement ofcentral venous access, percutaneous feeding tube, or biopsy) within 28 days prior toRandomization or anticipated surgery during the study period

15. Prior history of receiving immune checkpoint inhibitors (anti-CTLA4, anti-PD1,anti-PD-L1)

16. Peripheral neuropathy (>Grade 1)

17. Known history of dihydropyrimidine dehydrogenase deficiency (DPD) -Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in thecatabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are atrisk of developing severe 5-FU-associated toxicity

18. History or risk of autoimmune disease, including but not limited to systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosisassociated with antiphospholipid syndrome, Wegner´s granulomatosis, Sjogren´ssyndrome, Bell´s palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, orglomerulonephritis, except for psoriasis not requiring systemic therapy, vitiligo oralopecia areata, or hypothyroidism

19. Patients receiving any of the following medications are not eligible for study:

20. Investigational agents other than the protocol drugs

21. Anti-coagulants (except for heparin to maintain the patency of central venouscatheters)

22. Non-steroidal anti-inflammatory drugs

23. Clopidogrel (Plavix), dipyridamole (Persantine), or any other drug thatinhibits platelet functions

24. Patients on greater than 2 mg dexamethasone, 10 mg Prednisone or or equivalentdose in alternate corticosteroid daily or actively undergoing corticosteroiddose escalation are NOT eligible

25. History of allergic reactions or known hypersensitivity to compounds of similarchemical or biologic composition to OT-101 such as anti-sense oligonucleotides orsiRNA

26. Patients who are unable to return for follow-up visits or obtain follow-up studiesrequired to assess toxicity to therapy. Telemedicine visits are acceptable

27. Not willing and able to comply with study requirements including protocol mandatedprocedures and visits

28. Other contraindications as defined in the product label of the components of themFOLFIRINOX treatment regimen

29. Participation in another investigational clinical trial within 30 days of receivingthe last dose of investigational study drug

30. Clinically significant psychiatric disorders, legal incapacity or limited legalcapacity

31. Patients with a primary immunodeficiency

32. Patients with active central nervous system (CNS) metastases. (Patients withadequately treated CNS metastases who are clinically stable for at least 6 weeksafter discontinuation of corticosteroids may be eligible for enrollment with theapproval of the Sponsor's medical representative and the principal investigator)