A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer

In the setting of refractory, metastatic disease a complete resolution of tumor burden is not
a reasonable expectation. Instead, the primary goal of anti-tumor therapy at this stage is to
eliminate or reduce the symptomatic effects of the tumor, while trying to prolong survival
for as long as possible. Due to treatment related morbidity however, few treatment modalities
are ideal for this objective. Even with the most recent targeted agents (such as multi-kinase
inhibitors), drug related toxicities frequently lead to relatively short treatment durations.
With discontinuation of therapy, disease progression is uncontrolled and prognosis is poor.

New agents that control disease progression—while improving tumor-related symptoms, rather
than causing significant therapy related morbidity—are vitally needed to treat patients with
advanced cancer, including those with colorectal cancer. An approach has been taken to
develop such an agent using a monoclonal antibody to block the chronic inflammation involved
in both malignant disease progression and constitutional symptoms.

Xilonix™ is expected to inhibit tumor growth and metastasis by interrupting crucial signals
that drive angiogenesis and invasiveness. The antibody therapy may also block tumor
microenvironment infiltration by leukocytes (such as myeloid suppressor cells) that suppress
antitumor immunity, enabling better host immune control of the disease. In addition to local
effects on the tumor, Xilonix™ is expected to work systemically to correct the metabolic
dysregulation, fatigue and anxiety mediated by chronic inflammatory signaling to the central
nervous system.

Inclusion Criteria:

1. Subjects with pathologically confirmed colorectal carcinoma that is metastatic or
unresectable and which is refractory to standard therapy. To be considered refractory,
a subject must have experienced progression (or intolerance) after treatment with
standard approved regimens including, oxaliplatin, irinotecan flouropyrimidine,
bevacizumab, and cetuximab or panitumumab if KRAS wildtype.

2. Subjects will not be treated with any radiation, chemotherapy, or investigational
agents while enrolled in this protocol.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2.

4. At least 2 weeks since the last previous cancer treatment including: chemotherapy,
radiation therapy, immunotherapy, surgery, hormonal therapy, or targeted biologics.

5. Age ≥ 18 years, male or female subjects.

6. Serum potassium and magnesium levels within institutional normal limits. Total serum
calcium or ionized calcium level must be greater than or equal to the lower limit of
normal.

7. Adequate renal function, defined by serum creatinine ≤ 1.5 x ULN.

8. Adequate hepatic function

9. Adequate bone marrow function

10. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at
Screening.

11. Signed and dated institutional review board (IRB)-approved informed consent before any
protocol-specific screening procedures are performed.

12. Patients enrolled must, in the Investigator's judgment, be healthy enough to stay on
the clinical trial for three months.

Exclusion Criteria:

1. Mechanical obstruction that would prevent adequate oral nutritional intake.

2. Serious uncontrolled medical disorder, or active infection, that would impair the
ability of the patient to receive protocol therapy.

3. Uncontrolled or significant cardiovascular disease, including:

4. Dementia or altered mental status that would prohibit the understanding or rendering
of informed consent.

5. Subjects who have not recovered from the adverse effects of prior therapy at the time
of enrollment to ≤ grade 1; excluding alopecia and grade 2 neuropathy.

6. Immunocompromised subjects, including subjects known to be infected with human
immunodeficiency virus (HIV).

7. Known hepatitis B surface antigen and/or positive hepatitis C antibody and presence of
hepatitis C RNA.

8. History of tuberculosis (latent or active) or positive Interferon-gamma release assay
(IGRA).

9. Receipt of a live (attenuated) vaccine within 1 month prior to Screening

10. Subjects with history of hypersensitivity to compounds of similar chemical or biologic
composition of XILONIX™.

11. Women who are pregnant or breastfeeding.

12. WOCBP or men whose sexual partners are WOCBP who are unwilling or unable to use an
acceptable method of contraception for at least 1 month prior to study entry, for the
duration of the study, and for at least 3 months after the last dose of study
medication.

13. Weight loss >20% in the previous 6 months.