Trial of NanoPac® in Subjects With Locally Advanced Pancreatic Adenocarcinoma

In this open-label, dose-escalating, Phase IIa trial, subjects with locally advanced
pancreatic adenocarcinoma will receive intratumoral (ITU) NanoPac® (Sterile Nanoparticulate
Paclitaxel) via endoscopic ultrasound-guided direct injection.

Subjects will be enrolled in sequential cohorts of NanoPac® at escalating doses, at a volume
based on up to 20% of calculated tumor volume (with a maximum injection volume of 5 mL per
subject). Each cohort will have three subjects, with cohorts enrolled sequentially starting
at the lowest concentration. Following DSMB review of the cohort data, the next cohort may
begin enrolling, an additional three subjects at the current dose may be enrolled, or if the
first dose does not provide adequate safety and tolerability the study may be halted.

The dose determined to be most suitable for further evaluation, defined as the highest dose
with an acceptable safety and tolerability profile as determined by the Data Safety
Monitoring Board (DSMB), will be the dose used in the second phase of the study which will
enroll 12 additional subjects who will receive two injections of NanoPac® at the same dose
one month apart.

Plasma samples will be taken at various time points on the day of NanoPac® injection as well
as once at each of the study visits, to characterize the pharmacokinetics (PK) of
intratumoral NanoPac®.

Subjects will be followed for three months after NanoPac® injection for safety, overall
survival (OS), progression-free survival (PFS), CA-19-9 levels, carcinoembryonic antigen
(CEA) levels, reduction in pain, and tumor response to therapy (as shown by imaging). A
follow-up visit is planned at six months after the first NanoPac® administration.

Inclusion Criteria:

- Signed informed consent;

- Age ≥18 years;

- Histologically/cytologically confirmed locally advanced pancreatic adenocarcinoma; at
least one lesion with a diameter of at least 1.5 cm but no more than 6 cm as
documented via imaging (within 6 weeks of Screening);

- Subject not a candidate for surgery;

- Completion of at least one standard of care IV chemotherapy course for subjects in the
dose escalation phase of the study. IV chemotherapy will be initiated prior to first
NanoPac injection for subjects in the second phase. Hematologic recovery must be
confirmed prior to study entry;

- Performance Status (ECOG) 0-1 at study entry;

- Life expectancy of at least 3 months;

- Adequate marrow, liver, and renal function at study entry:

- ANC ≥ 1.5 x 109/L

- Hemoglobin ≥ 9.5 grams/dL

- Platelets ≥ 75 x 109/L

- Total bilirubin ≤ 1.5x institutional ULN

- AST/ ALT ≤ 2.5x institutional ULN

- Creatinine ≤ 1.5x institutional ULN

- Effective contraception if the risk of conception exists.

Exclusion Criteria:

- Thrombotic or embolic events;

- Acute or subacute intestinal occlusion;

- History of inflammatory bowel disease;

- Known hypersensitivity to study drugs;

- Known drug or alcohol abuse;

- Pregnant or breastfeeding women;

- Previous or concurrent history of non-pancreatic malignancy except for non-melanoma
skin cancer.