Preclinical Study Provides Potential Mechanisms for Lower Cardiotoxicity in Patients with Multiply Relapsed or Refractory

 Preclinical Study Provides Potential Mechanisms for Lower Cardiotoxicity in
 Patients with Multiply Relapsed or Refractory Aggressive B-cell NHL Treated
            with PixuvriTM Who Received Prior Doxorubicin Therapy

PR Newswire

SEATTLE, Dec. 17, 2012

SEATTLE, Dec. 17, 2012 /PRNewswire/ --Cell Therapeutics, Inc. (CTI) (Nasdaq
and MTA: CTIC) today announced the publication of results from a preclinical
study of Pixuvri^TM (pixantrone) in the The Journal of Pharmacology and
Experimental Therapeutics providing potential mechanisms for lower
cardiotoxicity in patients treated with Pixuvri who received prior
doxorubicin therapy. While CHOP-R is considered an effective therapy and is
the standard of care in first line treatment of aggressive B-cell non-Hodgkin
lymphoma (NHL), exposure to cumulative doses of doxorubicin, an anthracycline
contained in this regimen, is associated with increasing the incidence of
irreversible, severe, and symptomatic cardiac toxicity. The association with
heart damage limits the use of doxorubicin and other anthracyclines beyond
first line therapy and in patients with pre-existing cardiac disease.

Pixuvri is a novel anthracenedione that lacks the structural motifs that lead
to the formation of reactive oxygen species or long-lived hydroxyl metabolites
which are believed to be involved in cardiac damage. Although anthracycline
induced cardiotoxicity is complex and multi-factorial, this study provides
potential mechanisms by which Pixuvri avoids inducing this serious side
effect. The study by Giorgio Minotti, M.D., at the Center for Integrated
Research and Drug Sciences, University Campus Bio-Medico, Rome Italy, showed
that in a human cardiac tissue model, both untreated and pretreated with
doxorubicin, Pixuvri did not form reactive oxygen species or long lived
hydroxymetabolites. In doxorubicin pretreated cardiac samples, Pixuvri also
inhibited formation of the long-lived hydroxymetabolite of doxorubicin. These
results suggest mechanisms for the low incidence of cardiotoxicity seen in
clinical trials of Pixuvri in doxorubicin naive or pretreated patients.

"Anthracyclines are an effective therapy in aggressive B-cell NHL patients but
their use is limited due to the association with cardiac damage," said
Professor Minotti. "Cardiotoxicity complicates the clinical management of
patients who relapse after first-line therapy as second or third line
non-anthracycline chemotherapeutics might precipitate cardiotoxicity through
multiple mechanisms. These data provide a biological rationale for the safety
profile of Pixuvri and supports Pixuvri's role in treating multiply relapsed
or refractory aggressive B-cell NHL."

The publication by Salvatorelli E., et al., led by Professor Minotti G.,
titled "The novel anthracenedione, pixantrone, lacks redox activity and
inhibits doxorubicinol formation in human myocardium; Insight to explain the
cardiac safety of pixantrone in doxorubicin treated patients," is available

About Pixuvri (pixantrone)
Pixuvri is a novel aza-anthracenedione with unique structural and
physio-chemical properties. Unlike related compounds,Pixuvri forms stable DNA
adducts and in preclinical models has superior anti-lymphoma activity compared
to related compounds. Pixuvri was structurally designed so that it cannot bind
iron and perpetuate oxygen radical production or form a long-lived hydroxyl
metabolite -- both of which are the putative mechanisms for anthracycline
induced acute and chronic cardiotoxicity. These novel pharmacologic properties
allow Pixuvri to be administered to patients with near maximal lifetime
exposure to anthracyclines without unacceptable rates of cardiotoxicity.

InMay 2012, Pixuvri received conditional marketing authorization in the E.U.
as monotherapy for the treatment of adult patients with multiply relapsed or
refractory aggressiveNHL. The benefit of pixantrone treatment has not been
established in patients when used as fifth line or greater chemotherapy in
patients who are refractory to last therapy. The Summary of Product
Characteristics ("SmPC") has the full prescribing information, including the
safety and efficacy profile of Pixuvri in the approved indication. TheSmPCis

CTI is currently accruing patients into a Phase 3 trial comparing Pixuvri and
rituximab with gemcitabine and rituximab in the setting of aggressive B-cell

Pixuvri does not have marketing approval inthe United States.

About Conditional Marketing Authorization
Similar to accelerated approval regulations intheUnited States, conditional
marketing authorizations are granted in the E.U. to medicinal products with a
positive benefit/risk assessmentthat address unmet medical needs and whose
availability would result in a significant public health benefit. A
conditional marketing authorization is renewable annually. Under the
provisions of the conditional marketing authorization for Pixuvri, CTI will be
required to complete a post-marketing study aimed at confirming the clinical
benefit previously observed.

The European Medicines Agency's (the "EMA")Committee for Medicinal Products
for Human Usehas accepted PIX306, CTI's ongoing randomized controlled phase
III clinical trial, which compares Pixuvri-rituximab to gemcitabine-rituximab
in patients who have relapsed after one to three prior regimens for aggressive
B‑cellNHL and who are not eligible for autologous stem cell transplant. As a
condition of approval, CTI has agreed to have available the PIX306 clinical
trial results byJune 2015.

About Cell Therapeutics, Inc.
CTI (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

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 Pixuvri include risks associated with preclinical and clinical
developments in the biopharmaceutical industry in general and with Pixuvri in
particular including, without limitation, the potential failure of Pixuvri to
prove safe and effective for the treatment of relapsed or
refractoryNHLand/or other tumors as determined by theU.S. Food and Drug
Administration, that CTI may not market and commercialize Pixuvri in the E.U.
as planned, that results in future studies may differ,that CTI may not be able
to complete the PIX306 clinical trial of Pixuvri-rituximab compared to
gemcitabine-rituximab in patients who have relapsed after 1 to 3 prior
regimens for aggressive B cellNHL and who are not eligible for autologous
stem cell transplant byJune 2015or at all as required by the EMA or have the
results of such trial available byJune 2015or at all, that CTI may not be
able complete a post-marketing study aimed at confirming the clinical benefit
observed in the PIX301 trial, that the conditional marketing authorization for
Pixuvri may not be renewed, that CTI cannot predict or guarantee the pace or
geography of enrollment of its clinical trials or the total number of patients
enrolled, that CTI's average net operating burn rate may increase and CTI's
ability to continue to raise capital as needed to fund its operations in
general, and, including, without limitation, competitive factors,
technological developments, costs of developing, producing, and selling
Pixuvri, and the risk factors listed or described from time to time in CTI's
filings with theSecurities and Exchange Commissionincluding, without
limitation, CTI's most recent filings on Forms 10-K, 8-K, and 10-Q. 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 otherwise


Monique Greer

Ed Bell

SOURCE Cell Therapeutics, Inc.

Press spacebar to pause and continue. Press esc to stop.