CTI Announces New Data Presented at EHA 2013 Congress Demonstrating the Safety and Tolerability Profile of Pacritinib in

CTI Announces New Data Presented at EHA 2013 Congress Demonstrating the Safety
    and Tolerability Profile of Pacritinib in Patients with Myelofibrosis

- Pooled Analysis from Four Phase 1 and Phase 2 Clinical Studies Demonstrates
Persistence of Treatment -

- PERSIST-1 Phase 3 Study Currently Enrolling -

PR Newswire

SEATTLE, June 17, 2013

SEATTLE, June 17, 2013 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ
and MTA: CTIC) today announced results from a pooled analysis of data from
completed Phase 1 and 2 studies of pacritinib, an oral JAK2/FLT3 inhibitor,
demonstrating the safety and tolerability profile of pacritinib in patients
with myelofibrosis. An integrated safety analysis of four completed Phase 1
and 2 studies totaled 191 patients who were treated with pacritinib for
myeloid, primarily myelofibrosis, or lymphoid malignancies to quantify
clinical toxicities, with a focus on hematologic effects. Other JAK2
inhibitors have generally been associated with increases in anemia and
thrombocytopenia but this was not observed with pacritinib. This integrated
safety data analysis showed that, regardless of initial platelet counts,
pacritinib causes minimal further marrow suppression. Even patients with
initial platelet counts <50,000/µL, a high-risk population, tolerated therapy,
maintained stable blood and platelet counts and did not require dose
reductions for thrombocytopenia. Grade 1 or 2 gastrointestinal events,
particularly diarrhea, were the most common adverse events and may be
controlled by early administration of standard anti-diarrheal agents. The
analysis was presented during a poster session at the 18^th Congress of the
European Hematology Association (EHA) held June 13-16, 2013 in Stockholm,

Pacritinib is currently being evaluated in a randomized Phase 3 clinical
trial, known as PERSIST-1, in patients with myelofibrosis. Because of
pacritinib's relative lack of bone marrow suppression, there are no study
entry restrictions due to thrombocytopenia or anemia and patients with
platelet and red blood cell transfusion dependence are allowed to enroll in
the ongoing PERSIST-1 trial. More details on this study can be found at
www.clinicaltrials.gov. Pacritinib has orphan drug designation in the United
States andEurope.

Abstract #P278: Safety Overview of Phase 1-2 Studies of Pacritinib, a
Non-Myelosuppressive JAK2/FLT3 Inhibitor, in Patients with Hematological
Malignancies. Poster session, Friday, June 14, 5:45 to 7:00 p.m. CEST.

"The use of JAK2 inhibitors to treat myelofibrosis has been a breakthrough for
patients with myelofibrosis; however, there still exists a significant unmet
need for less myelosuppressive agents given the nature of this disorder," said
Srdan Verstovsek, M.D., Ph.D., Professor, Leukemia Department, Division of
Cancer Medicine, Chief, Section for Myeloproliferative Neoplasms, Leukemia
Department, and Director, Clinical Research Center for MPNs at the University
of Texas MD Anderson Cancer Center. "This pooled safety analysis supports that
pacritinib is well-tolerated with limited hematologic side effects that would
allow it to be potentially used across all myelofibrosis patients,
particularly in those with low blood cell count."

Integrated Safety Analysis Results

A review of the safety database from four clinical studies included a Phase
1/2 study in advanced myeloid malignancies, a Phase 1 and Phase 2 study in
advanced lymphoid malignancies, and a Phase 1/2 study in myelofibrosis. A
total of 191 patients were treated with pacritinib: 129 with advanced myeloid
malignancies, including 122 patients with myelofibrosis and 7 patients with
acute myeloid leukemia; and 62 patients with advanced lymphoid malignancies,
including 38 patients with non-Hodgkin lymphoma and 24 patients with Hodgkin
lymphoma. Of the patients with myeloid disorders, 44 percent had baseline
platelet counts <100,000/µl. Pacritinib was dosed from 100 to 600 mg daily
during Phase 1 and 400 mg during Phase 2. One hundred and forty-six patients
were dosed at or greater than 400 mg daily. The median dose delivered was 98
percent of intended. The median treatment duration was 306 days (range 2-1210)
for those with myeloid disorders and 90.5 days (range 1-631) for lymphoid

Hematologic Safety is summarized in the table below.

Safety population (n=189) Hb shift from baseline to Platelet shift from
                          last value                baseline to last value
(>1 post-baseline value)
No shift                  101(53.4%)                108 (57.1%)
Cytopenia Improvement
1 grade improvement       28 (14.8%)                17 (9%)
2-4 grade improvement     6 (3.2%)                  2 (1.1%)
Cytopenia Decline
1-2 grade decline         51 (27%)                  52 (27.5%)
3-4 grade decline         1 (0.5%)                  8 (4.2%)
Note: 2 patients did not have Common Terminology Criteria (CTC grades) at
baseline or post-baseline due to missing laboratory normal ranges.

Most patients had no decline in hemoglobin or platelet count during the
studies. Of the 30 patients with myeloid disorder with baseline platelet
counts <50,000/µL from Phase 1 and 2 studies, the median decline in platelet
count observed at the end of study was 3,000/µL. In the 11 patients with
myelofibrosis with baseline platelet counts <50,000/µL enrolled in Phase 2
studies, no dose reduction were required for worsening thrombocytopenia.

The most common adverse events were gastrointestinal, particularly diarrhea,
most of which were grade 1 or 2. Per the protocols, anti-diarrheal prophylaxis
was not used routinely in these early studies; however, anecdotal data from
treating physicians where used suggests toxicity is readily controlled with
early administration of standard anti-diarrheal agents. Time to onset of
diarrhea was ≤30 days in 89 percent of those affected but rarely caused drug
discontinuation (1%). The most common serious adverse events reported (≥2
percent) included pneumonia (4.7 percent) and anemia (3.1 percent).

"Myelofibrosis is a chronic disease which will require prolonged dosing
potentially for years if we are to attempt modifying the disease and its
natural history," said Steven Benner, M.D., M.H.S., Chief Medical Officer at
CTI. "We believe this analysis shows that pacritinib is well-tolerated and
could potentially serve to treat these patients over an extended period of

In addition to detailed safety results, pharmacokinetic (PK)/pharmacodynamic
(PD) data were presented at the conference.

Abstract #P983: Characterization of the Pharmacokinetic and Pharmacodynamic
Properties of Pacritinib, a Novel Oral JAK2/FLT3 Inhibitor, in Patients with
Myelofibrosis, AML and Lymphoma. Poster session, Saturday, June 15, 5:45 to
7:00 p.m. CEST.

Two single-dose PK studies were conducted in healthy volunteers to assess the
effect of food and the inter- and intra-individual variability of pacritinib.
Pooled efficacy data from completed Phase 1/2 studies with patients treated up
to 600 mg daily were utilized to construct the exposure-response relationship
for the clinical response of pacritinib in myelofibrosis. With pacritinib at
a100 mg daily dose, mean steady-state plasma levels exceed the in vitro IC[50]
values for inhibition of the targeted kinases (JAK2/FLT3). A total of 26 out
of 65 (40 percent) myelofibrosis patients that received the 400 mg daily dose
regimen of pacritinib achieved ≥ 50 percent reduction in spleen size by
physical exam assessed through 24 weeks. PK assessments showed slow absorption
and dose-related increases in systemic exposure demonstrating a long
elimination half-life supporting a daily regimen of pacritinib. Comparison of
drug concentrations on days 1 and 15 showed a 1.5-to 2-fold increase in
exposure at steady-state. There was only minimal increase in systemic exposure
at doses beyond 400 mg daily suggesting involvement of a saturable process in
oral absorption of pacritinib. There is no significant effect of food on
pacritinib PK allowing pacritinib to be orally administered without regard to
timing of meals. In summary, pacritinib's exposure-response relationship
supports selection of the 400 mg daily regimen of pacritinib in the ongoing
Phase 3 pivotal trials.

About Myelofibrosis

Myelofibrosis is classified as a myeloproliferative neoplasm and is a chronic
bone marrow disorder. Myelofibrosis is caused by the accumulation of malignant
bone marrow cells that triggers an inflammatory response, scarring the bone
marrow and limiting its ability to produce red blood cells prompting the
spleen and liver to take over this function. Symptoms that arise from this
disease include enlargement of the spleen, anemia, extreme fatigue and pain.
It is estimated that the prevalence of myelofibrosis is approximately 30,000
in the United States.^1 ^

About Pacritinib

Pacritinib is an oral, once-a-day, tyrosine kinase inhibitor (TKI) with dual
activity against JAK2 and FLT3.The JAK family of enzymes are a central
component in signal transduction pathways, which are critical to normal blood
cell growth and development as well as inflammatory cytokine expression and
immune responses. Mutations in these kinases have been shown to be directly
related to the development of a variety of blood related cancers including
myeloproliferative neoplasms, leukemia and lymphoma. Pacritinib may offer an
advantage over other JAK inhibitors through effective treatment of symptoms
while having less treatment-emergent thrombocytopenia and anemia than has been
seen in currently approved and in-development JAK inhibitors.

About Cell Therapeutics, Inc.

Cell Therapeutics (NASDAQ and MTA: CTIC) is a biopharmaceutical company
committed to the development and commercialization of an integrated portfolio
of oncology products aimed at making cancer more treatable. CTI is
headquartered in Seattle, WA. For additional information and to sign up for
email alerts and get RSS feeds, please visit www.CellTherapeutics.com.

Safe Harbor Statement

This press release includes forward-looking statements that involve a number
of risks and uncertainties the outcome of which could materially and/or
adversely affect actual future results and the market price of CTI's
securities. Specifically, the risks and uncertainties that could affect the
development of pacritinib include risks associated with preclinical and
clinical developments in the biopharmaceutical industry in general, and with
pacritinib in particular, including, without limitation, the potential failure
of pacritinib to prove safe and effective for the treatment of patients with
myelofibrosis, either alone or in combination regimens, as determined by the
U.S. Food and Drug Administration and/or the European Medicines Agency; that
pacritinib may not satisfy a medical need not currently addressed with
existing non-selective JAK1/JAK2 inhibitors; that adverse events from
treatment with pacritinib may not be controllable; that the PERSIST-1 clinical
trial of pacritinib may not occur as planned; that 270 patients may not enroll
in the PERSIST-1 clinical trial; that the second Phase 3 clinical trial of
pacritinib may not occur as planned; that CTI may not be able to successfully
implement its plans, strategies and objectives related to the development of
pacritinib; that CTI may not be able to continue to raise capital as needed to
fund its operations and other risks, including, without limitation,
competitive factors, technological developments, costs of developing,
producing and selling PIXUVRI, pacritinib and CTI's other product candidates;
and the risk factors listed or described from time to time in CTI's filings
with the Securities and Exchange Commission including, without limitation,
CTI's most recent filings on Forms 10-K, 10-Q and 8-K. Except as may be
required by law, CTI does not intend to update or alter its forward-looking
statements whether as a result of new information, future events, or


1.MPN Research Foundation. Available at
    http://www.mpnresearchfoundation.org/Primary-Myelofibrosis. Accessed May


CTI Media and Investor Contacts:

Monique Greer
+1 206.272.4343

Ed Bell
+1 206.282.7100

In Europe
CTI Life Sciences Limited, Milan Branch

Laura Villa
E: CTI_EUInvestors@CTI-Lifesciences.com
T: +39 02 89659700

SOURCE Cell Therapeutics, Inc.

Website: http://www.celltherapeutics.com
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