M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer

Part A was an open-label, multiple ascending dose patient study of necuparanib given first as
a single dose and then daily in combination with the nab-paclitaxel and gemcitabine regimen.
It was conducted to evaluate the safety and tolerability of necuparanib alone and in
combination with nab-paclitaxel and gemcitabine and to recommend a necuparanib dose regimen
for subsequent evaluation in Part B. Part B is a randomized, double-blind study investigating
the antitumor activity of necuparanib in combination with nab-paclitaxel and gemcitabine
compared with nab-paclitaxel, gemcitabine, and placebo. In both Parts A and B, a treatment
period consists of one 28-day cycle. The Study Patient and Investigator can decide to
continue with additional 28-day cycles according to the patient's status at the end of each
28-day cycle. Part A has completed enrollment and Part B is currently open.

Part A - Primary Objectives:

- To evaluate the safety and tolerability of necuparanib in combination with
nab-paclitaxel and gemcitabine.

- To determine the dose of necuparanib to be carried forward into Part B.

Part B - Primary Objective:

To evaluate overall survival in patients treated with necuparanib + nab-paclitaxel +
gemcitabine compared with placebo + nab-paclitaxel + gemcitabine.

Inclusion Criteria:

- Age of 18 years or older

- Confirmed pancreatic ductal adenocarcinoma

- Metastatic disease as documented by CT scan or MRI (locally advanced disease only NOT
eligible)

- At least 1 site of disease measurable by RECIST ver1.1

- ECOG performance status of 0 to 1

- Adequate bone marrow, renal capacity and hepatic function

- Willing to administer daily subcutaneous injections at home

Exclusion Criteria:

- Any prior radiotherapy, chemotherapy, surgery, or investigational therapy for adjuvant
or metastatic pancreatic cancer

- History of suspected history, or presence of heparin induced toxicity (w/ or w/o
thrombosis)

- History of unexplained bleeding episodes within 3 months of M402 dosing

- Received thrombolytic agents w/in the previous month

- Had full-dose anticoagulation with heparin, enoxaparin, dalteparin, other LMWH, a/or
other anticoagulants w/in 90 days before first dose of M402

- High cardiovascular risk, including but not limited to, recent coronary stenting or
myocardial infarction in the past year

- Major trauma or surgery w/in prior 4 weeks