Cell Therapeutics' Highly Selective Oral JAK 2 Inhibitor, Pacritinib, Demonstrates Encouraging Anti-tumor Activity in Patients with Relapsed/Refractory Lymphoma

SEATTLE, Sept. 24, 2012 /PRNewswire/ -- Cell Therapeutics, Inc. ("CTI") (Nasdaq and MTA: CTIC) announced today that the phase 1 study data of its highly selective oral JAK2 inhibitor pacritinib, or SB1518, showed encouraging anti-tumor activity and good tolerability in 34 patients with relapsed/refractory lymphoma.  The results were published online in the Journal of Clinical Oncology in September, 2012.

Thirty-four patients received daily oral doses of pacritinib ranging from 100mg to 600mg. The maximal tolerated dose was not reached. Median time on study was 88 days (range of one to 574 days) with six patients on pacritinib for longer than six months. Seventeen of the 34 patients (50%) had measurable decreases in target tumor measurements ranging from 4% to 70% shrinkage. Partial remissions were noted in three patients (mantle cell (2), indolent lymphoma (1)) while 15 patients had stable disease. Median progression free and overall survival was 120 and 130 days, respectively.  Gastrointestinal (GI) side effects were most frequent and mild to moderate (grade 1-2) with no patient reporting severe (grade 3-4) GI side effects even at the 600mg dose level. Cytopenias were infrequent and modest (less than 15% all grades).

"While it is becoming increasingly accepted that activating mutations in JAK2 and FLT3 play an important role in a majority of patients with acute myeloid leukemia, this phase 1 study suggests the potential therapeutic value of targeting the JAK2 pathway in lymphomas with encouraging single agent activity demonstrated despite the extensive degree of prior therapy and refractory nature of the disease among the patients who were enrolled in this trial," noted Steven E. Benner, M.D., M.H.S., Chief Medical Officer of CTI.

About the Phase 1 Study

The primary objective was a dose finding, pharmacokinetic/pharmacodynamics study of oral pacritinib in patients with relapsed lymphoma.  

The study enrolled 35 patients with relapsed or refractory Hodgkin's or non-Hodgkin's lymphoma of any type except Burkitt's or CNS lymphoma. Patients had relapsed following a median of five prior therapies (range 2-15); 44% had failed prior stem cell transplant and 52% were rituximab refractory.

Thirty-four patients received daily doses of pacritinib for a 28-day each cycle of doses ranging from 100 to 600 mg/day. The maximum tolerated dose was not reached. Pacritinib inhibited JAK2 signaling at all dosing levels and FLT-3 inhibition were seen in most patients. The median time on study drug was 88 days (range of one to574) with six patients on pacritinib for longer than six months and 17 patients for longer than three months. There were three partial responses (greater than or equal to 300 mg/d) (2 mantle cell; 1 indolent NHL); 15 patients achieved stable disease. Seven of 13 patients with stable disease had tumor reductions ranging from 4% to 46% of baseline target lesions. Treatment was well tolerated, with mostly grade 1-2 toxicities. Gastrointestinal toxicities were the most frequent (32%) with no grade 3-4 side effects reported even among the 12 patients treated at the highest dose (600mg/d). Cytopenias were infrequent and modest supporting the lack of myelosupression with pacritinib therapy even among a patient population with poor baseline marrow reserve. The authors concluded, "collectively our data demonstrate that SB1518 is well tolerated in patients with relapsed lymphoma and has promising activity. The data warrant further efficacy studies of JAK/STAT pathway inhibitors either alone or in combination regimens."

The publication by Younes, et al. titled "Phase I Study of a Novel Oral Janus Kinase 2 Inhibitor, SB1518, in Patients with Relapsed Lymphoma: Evidence of Clinical and Biologic Activity in Multiple Lymphoma Subtypes," is available at http://jco.ascopubs.org/content/early/recent.

About Janus Associated Kinase (JAK)

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. When dysregulated by activating mutations, uncontrolled blood cell growth can occur accompanied by inflammation and immune system activation contributing to disease manifestations in MPN.  Autoimmune diseases such as psoriasis and rheumatoid arthritis also have activation of this pathway and JAK inhibitors are in development for these disorders.

About FMS- Like Tyrosine Kinase (FLT-3)

Normal expression of FLT3 is restricted to haemopoietic progenitor cells in the bone marrow, thymus and lymph nodes, but is also found on other tissues such as placenta, brain, cerebellum and gonads. Aberrantly expressed FLT3 is observed at high levels in a spectrum of hematologic malignancies including 70% to 100% of AML (Acute Myelogenous Leukemia), B-precursor cell ALL (Acute Lymphoblastic Leukemia), a fraction of T-Cell ALL, and CML (Chronic Myelogenous Leukemia).

About Pacritinib

Pacritinib is an oral, once a day, tyrosine kinase inhibitor (TKI) with dual activity against JAK2 and FLT3. Mutations in these kinases have been shown to be directly related to the development of a variety of blood related cancers including Myeloproliferative disorders ("MPD"), leukemia and lymphoma. Pacritinib has demonstrated encouraging results in phase 1 and 2 studies for patients with myelofibrosis and a phase 3 study is planned in this disease. 

FLT3 is a commonly mutated gene found in acute myeloid leukemia ("AML") patients and its activating mutations have been proven to be a negative prognostic marker for clinical outcome suggesting a possible future role for treatment of AML.

About Lymphoma

Lymphoma is a cancer of the white blood cells, namely lymphocytes, which constitute the lymphatic system. Lymphoma occurs when lymphocytes grow abnormally. The two main types of lymphoma are Hodgkin lymphoma and non- Hodgkin lymphoma. Lymphoma is the most common blood cancer.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.

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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 relapsed/refractory lymphoma or primary MF or MF secondary to other MPNs, either alone or in combination regimens, as determined by the U.S. Food and Drug Administration (the "FDA") and/or the European Medicines Agency (the "EMA"), that pacritinib may not satisfy a medical need not currently addressed with existing non-selective JAK1/JAK2 inhibitors, that the phase III study of pacritinib may not occur as planned, that the projected benefits of the acquisition of pacritinib may not materialize as expected, that CTI may not be able to successfully implement its plans, strategies and objectives related to the acquisition and development of pacritinib, CTI's ability to continue to raise capital as needed to fund its operations, competitive factors, technological developments, costs of developing, producing and selling CTI's 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 otherwise.

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