First in Human Phase1/2a Clinical Trial of Anti-PAUF Monoclonal Antibody PBP1510 in Patients with Pancreatic Cancer

Inclusion Criteria:

Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) must meet all of the following inclusion criteria:

1. Adults ≥ 18 years of age (or the legal age of majority in the country ofrecruitment) at the time consent is obtained.

2. Patient should understand, voluntarily sign, and date the written consent form priorto any protocol-specific procedures.

3. Performance Status score less than or equal to 1 according to the EasternCooperative Oncology Group (ECOG) scale.

4. Have histological or cytological evidence of a diagnosis of pancreatic cancer thatis advanced and/or metastatic.

5. Have a life expectancy of ≥ 3 months.

6. No other malignancy present that would interfere with the current intervention.

7. Prior radiation therapy for treatment of cancer is allowed to < 25% of the bonemarrow, and patients must have recovered from the acute toxic effects of theirtreatment prior to study enrolment. Prior radiotherapy must be completed at least 4weeks before the first dose of study treatment.

8. At least one measurable lesion as per RECIST v1.1

9. Adequate baseline organ function defined as: ANC ≥ 1.5 × 10^9 /L; Haemoglobin ≥ 9 g/dL; Platelets ≥ 100 × 10^9 /L; Totalbilirubin ≤ 2 × ULN (≤ 3 x ULN for patients with biliary stenting and patients withGilbert's syndrome); AST and ALT < 3 x ULN (≤ 5 x ULN for patients with hepaticmetastases); Serum creatinine OR creatinine clearance (as determined by theCockcroft Gault formula) OR eGFR based on MDRD ≤ 1.5 x ULN OR ≥ 50 mL/min OR ≥ 50mL/min/1.73 m^2; LVEF ≥ 50% by ECHO or MUGA; QTc ≤ 470 ms

10. Female patients of nonchildbearing potential must meet at least 1 of the followingcriteria: have undergone a documented hysterectomy, and/or bilateral oophorectomy;have medically confirmed ovarian failure or achieved postmenopausal status. Apostmenopausal state is defined as cessation of regular menses for at least 12consecutive months with no alternative pathological or physiological cause and havea follicle stimulating hormone (FSH) level confirming the postmenopausal state inwomen not using hormonal contraception or hormonal replacement therapy. Femalepatients of childbearing potential must have a negative serum pregnancy test within 28 days prior to and negative urine pregnancy test just prior to the first dose ofPBP1510 and agree to use effective contraception, in accordance with therecommendations of the Clinical Trials Facilitation and Coordination Group (CTFG)from study entry and until for at least 6 months after the last dose of PBP1510.

11. For women of childbearing potential and men with partners of childbearing potential,agreement (by patient and/or partner) to use two effective forms of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, orcontraceptive hormone implants) from study entry and until for at least 6 monthsafter the last dose of PBP1510. Investigator or his/her representative should discuss acceptable pregnancyprevention method(s) with the patients. Highly effective methods of birth controlinclude those that result in a low failure rate (i.e., less than 1% per year) whenused consistently and correctly, such as implants, injectables, combined oralcontraceptives, levonorgestrel-releasing intrauterine system, intra-uterine devices (IUDs), and true sexual abstinence.

12. Patients must be willing and able to comply with scheduled visits, treatment plan,study restrictions, laboratory tests, contraceptive guidelines, and other studyprocedures. Patients enrolling into Part 1 (Phase 1) of the study must also meet the followinginclusion criteria:

13. Monotherapy and combination cohorts: advanced/metastatic pancreatic cancer patientswhose tumours have progressed after at least one prior line of standardchemotherapy. Patients enrolling into Part 2 (Phase 2a) of the study must also meet the followinginclusion criteria:

14. Advanced/metastatic pancreatic cancer patients whose tumours have progressed afterone prior line of standard chemotherapy.

Exclusion Criteria:

Patients enrolling into Part 1 (Phase 1), or Part 2 (Phase 2a) will be excluded if any of the following criteria apply:

1. Patients who have known brain metastases will be excluded from the study. However, apatient may be included in the study, if has been previously treated for brainmetastasis, the disease is well controlled for at least 3 months, and the patient isoff steroids.

2. Patients who have undergone a major surgery within 4 weeks prior to the start ofPBP1510 administration, other than endoscopic/radiation procedures, bypass surgery (i.e., gastrojejunostomy), laparoscopy, port placement or a diagnostic surgery (i.e., surgery done to obtain a diagnostic biopsy, without removal of an organ), aslong as the patient has recovered from these minor surgical procedures.

3. Patients who have active, uncontrolled bacterial, viral, or fungal infection(s)requiring systemic therapy, e.g., an active opportunistic infection withmycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii (P. carinii), orother microorganisms that is under treatment with myelotoxic drugs.

4. Patient has a known history of human immunodeficiency virus (HIV; HIV 1/2antibodies).

5. Patient has known history of or currently active hepatitis B (e.g., hepatitis Bantigen [HBsAg] reactive), hepatitis C (e.g., HCV RNA [qualitative] is detected) orsyphilis [Venereal Disease Research Laboratory (VDRL) to detect antibodies inblood]).

6. Patient has impaired cardiac function and uncontrolled cardiac diseases/hypertensionthat are deemed clinically significant by the Investigator and which couldcompromise the patient's safety or the study data integrity.

7. Patient has serious psychiatric disorders, which could compromise the patient'ssafety or the study data integrity.

8. Any other malignancy from which the patient has been disease-free for less than 5years, except for adequately treated and cured basal or squamous cell skin cancer.

9. Patients who are enrolled in any other therapeutic clinical trial.

10. Patients currently receiving radiation therapy or those having received radiationwithin 4 weeks prior to study entry.

11. Patients having received investigational anti-cancer drug within 28 days (or 5half-lives, whichever is longer) preceding the first dose of PBP1510 or chemotherapywithin the last 4 weeks prior to the first dose of PBP1510.

12. Patients with known allergy or hypersensitivity to components of the PBP1510formulation including the excipients and history of hypersensitivity to Chinesehamster ovary cell products or other recombinant human or humanized antibodies.

13. Patients who are pregnant, or breast feeding.

14. Patients who are unwilling or unable to comply with study procedures.

15. Patients who are not eligible to participate in this study, as judged byInvestigators.

16. A history of allergic reactions attributed to gemcitabine or compounds of similarchemical composition to gemcitabine and/or previous treatment discontinuation due togemcitabine toxicity.

Note: Patients with previous exposure to gemcitabine should not be excluded from the study.