A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome (MDS)

The study is a nonrandomized open-label treatment with varying doses of cenersen by
intravenous administration to:

Primary

*To assess the safety profile and dose limiting toxicities (DLT) of cenersen for each of
three increasing dose levels as stipulated by the protocol in patients with lower risk MDS
defined as low or intermediate-1 risk by IPSS.

Secondary

- To determine the lowest pharmacologically active exposure from among three increasing
dose levels as stipulated by the protocol that exhibits the desired activity on
erythropoiesis after evaluation of all dose levels, and

- To determine if intermittent treatment with cenersen will reduce transfusion
requirements for patients with lower risk MDS.

Inclusion Criteria:

- Must have histologically or cytologically confirmed diagnosis of MDS according to WHO
classification that meets IPSS low to intermediate-1 risk criteria.

- For patients with del(5q) MDS, documented del(5q) MDS by metaphase cytogenetics or
FISH analysis with up to 1 additional cytogenetic abnormality other than 1 involving
chromosome 7 or chromosome 17.

- Demonstrated refractoriness or intolerance to standard approved therapy (lenalidomide
in del(5q) MDS patients & azanucleosides in non-del(5q)patients).

- Recovered from acute toxicities of other treatments (≤ Grade 2). All other MDS
treatments discontinued at least 4 weeks prior to treatment except epoetin alpha
(Procrit) 2 weeks.

- Ability to understand & willingness to sign a written informed consent document.

- Age ≥ 18 years at time of signing informed consent form.

- ECOG performance status ≤2.

- Life expectancy >4 weeks following initiation.

- Must meet following requirements:

- total bilirubin: ≤2 x upper normal limit (UNL) (patients with Gilbert's disease
are eligible, hyperbilirubinemia is intermittent & indirect)

- AST(SGOT)/ALT(SGPT): ≤3 x UNL

- creatinine: ≤2 x UNL

- <1% peripheral blood blasts.

- <10% bone marrow blasts.

- Medical history of RBC transfusion dependent anemia ≥4 units of RBCs during the 16
weeks prior to admin of study drug & ≥2 units of RBCs over prior 8 weeks (day -56 to
day 1 prior to treatment; baseline period) for documented Hgb of ≤ 9g/dL (during
baseline). Didn't have a 56 day RBC transfusion-free period during 16 weeks prior to
administration of study drug.

- Teratogenic effects of cenersen are unknown, women of child-bearing potential & men
must agree to use adequate contraception prior to study entry & for the duration of
study participation.

Exclusion Criteria:

- Receiving MDS treatment except blood transfusion and/or iron chelation within 4 weeks
prior to entering study or no recovery from adverse events due to agents administered
more than 4 weeks earlier.

- no current or prior use of investigational agents within 4 weeks of study entry.

- Known history of malignancy diagnosed within 2 years other than non-melanoma skin
cancer.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cenersen.

- exclude use of acetaminophen or acetaminophen-containing medications from 1 day
before to 1 day after completion of treatment. The active metabolite of
acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), is known to block effects of
cenersen & use of acetaminophen during treatment with study regimen has been
associated with a failure to achieve a response in a past clinical trial of cenersen.

- Uncontrolled intercurrent illness that would limit compliance with study
requirements.

- Pregnant women are excluded from this study. Breastfeeding should be discontinued if
the mother is treated with cenersen

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
unknown potential for interactions with cenersen.

- Any condition, including presence of laboratory abnormalities, which places subject
at unacceptable risk if s/he were to participate in study or confounds ability to
interpret data from study according to investigator assessment.

- Therapy related MDS.

- Clinically significant anemia according to investigator's assessment due to factors
such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or
gastrointestinal bleeding.

- Received hematopoietic growth factors within specified limits prior to treatment (2
weeks for epoetin alpha (Procrit) & 4 weeks for darbepoetin alpha (Aranesp)).

- Active hepatitis B or C or other active liver disease.

- Chronic use (>2 weeks) of greater than physiologic doses of corticosteroid agent
(dose equivalent to ≥10mg of prednisone) within 28 days of 1st day of study drug
treatment & during treatment