CTIC - Cell Therapeutics Announces Results from Preclinical Study of Pixantrone (PIXUVRI®) Presented at the AACR-NCI-EORTC Meeting
SEATTLE, Oct. 21, 2013 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) today announced the presentation of findings from a preclinical study of PIXUVRI® (pixantrone) that suggest its mechanism of inducing tumor cell death is novel and distinct from that of anthracyclines such as doxorubicin. PIXUVRI is a first-in-class aza-anthracenedione with unique structural and physiochemical properties that is currently approved in the European Union for use as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. The study results were presented by Neil Beeharry, Ph.D., at the Fox Chase Cancer Center during a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held October 19-23, 2013 in Boston, MA.
"The study results suggest that PIXUVRI is unique in its mechanism for inducing tumor cell death, thereby supporting the thesis that it is the first approved drug in a new class of anti-cancer agents. PIXUVRI's mechanism of action is differentiated from the cytotoxic action induced by anthracyclines and could be the basis for the efficacy and safety profile of the drug," stated Dr. Beeharry.
The study assessed the mechanism of tumor cell killing induced by PIXUVRI in a variety of cancer cell lines. Specifically, the study assessed the impact PIXUVRI had on cell proliferation and time to cell death, the cell cycle, DNA damage response and longer term effects on cell division. Unlike anthracyclines -- which kill both normal and cancer cells with short-term exposure -- PIXUVRI had minimal short-term effects on cell survival, but probably through formation of stable DNA adducts, caused delayed but efficient tumor cell death. This effect was not dependent on the presence of the p53 gene, a gene associated with recognition of chromosomal damage and apoptosis. Loss of p53 was only associated with a further delay in cell death with longer exposure to PIXUVRI. The authors concluded that PIXUVRI appears to be impairing chromosomal segregation during mitosis, thereby generating loss of genetic material in daughter cells, an abnormality, which is ultimately lethal, and that PIXUVRI would likely be effective in cells resistant to other cytotoxic agents such as doxorubicin. The authors are pursuing leads to further understand the exact mechanism of action.
The full poster presentation is available online at www.celltherapeutics.com/publications.
About PIXUVRI (pixantrone)
PIXUVRI is a novel aza-anthracenedione with unique structural and physiochemical 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.
In May 2012, the European Commission (EC) granted conditional marketing authorization for PIXUVRI as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive NHL. The benefit of PIXUVRI 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. The SmPC is available at www.pixuvri.eu.
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 NHL. PIXUVRI does not have marketing approval in the United States.
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 www.CellTherapeutics.com.
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements are subject to a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results and the trading price of CTI's securities. Such statements include, but are not limited to, statements regarding expectations with respect to the development of the Company and its product and product candidate portfolio, that PIXUVRI is unique in its mechanism for inducing tumor cell death, thereby supporting the thesis that it is part of a new class of anti-cancer agents and readily differentiated from the mechanism of action associated with anthracyclines, and that PIXUVRI may cause delayed but efficient tumor cell death probably through formation of stable DNA adducts. Risks that contribute to the uncertain nature of the forward-looking statements include, among others, risks that PIXUVRI may fail to prove safe and effective for the treatment of relapsed or refractory NHL and/or other tumors; that results in future studies or actual results of PIXUVRI may differ from the results of past studies; 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 may not obtain favorable reimbursement or pricing determinations for PIXUVRI in certain markets in the E.U. as planned, and risks associated with the biopharmaceutical industry in general and with CTI and its product and product candidate portfolio in particular including, among others, risks associated with the following: that CTI cannot predict or guarantee the pace or geography of enrollment of its clinical trials, that the second Phase 3 clinical trial of pacritinib will not occur as planned, that CTI may not obtain favorable determinations by other regulatory, patent and administrative governmental authorities, that CTI may experience delays in the commencement of preclinical and clinical studies, risks related to the costs of developing, producing and selling PIXUVRI, pacritinib, and CTI's other product candidates, and other risks, including, without limitation, competitive factors, technological developments, that CTI's operating expenses continue to exceed its net revenues, that CTI may not be able to sustain its current cost controls or further reduce its operating expenses, that CTI may not achieve previously announced goals and objectives as or when projected, that CTI's average net operating burn rate may increase, that CTI will continue to need to raise capital to fund its operating expenses, but may not be able to raise sufficient amounts to fund its continued operation as well as other risks listed or described from time to time in CTI's most recent filings with the Securities and Exchange Commission on Forms 10-K, 10-Q and 8-K. Except as required by law, CTI does not intend to update any of the statements in this press release upon further developments.
PIXUVRI is a registered trademark of Cell Therapeutics, Inc.
Contacts:
Monique Greer
+1 206-272-4343
mgreer@ctiseattle.com
Ed Bell
+1 206-282-7100
ebell@ctiseattle.com
In Europe:
CTI Life Sciences Limited, Milan Branch
Laura Villa
+39 02 89659706
lvilla@cti-lifesciences.com
CTI_EUInvestors@CTI-Lifesciences.com
SEATTLE, Oct. 21, 2013 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) today announced the presentation of findings from a preclinical study of PIXUVRI® (pixantrone) that suggest its mechanism of inducing tumor cell death is novel and distinct from that of anthracyclines such as doxorubicin. PIXUVRI is a first-in-class aza-anthracenedione with unique structural and physiochemical properties that is currently approved in the European Union for use as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. The study results were presented by Neil Beeharry, Ph.D., at the Fox Chase Cancer Center during a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held October 19-23, 2013 in Boston, MA.
"The study results suggest that PIXUVRI is unique in its mechanism for inducing tumor cell death, thereby supporting the thesis that it is the first approved drug in a new class of anti-cancer agents. PIXUVRI's mechanism of action is differentiated from the cytotoxic action induced by anthracyclines and could be the basis for the efficacy and safety profile of the drug," stated Dr. Beeharry.
The study assessed the mechanism of tumor cell killing induced by PIXUVRI in a variety of cancer cell lines. Specifically, the study assessed the impact PIXUVRI had on cell proliferation and time to cell death, the cell cycle, DNA damage response and longer term effects on cell division. Unlike anthracyclines -- which kill both normal and cancer cells with short-term exposure -- PIXUVRI had minimal short-term effects on cell survival, but probably through formation of stable DNA adducts, caused delayed but efficient tumor cell death. This effect was not dependent on the presence of the p53 gene, a gene associated with recognition of chromosomal damage and apoptosis. Loss of p53 was only associated with a further delay in cell death with longer exposure to PIXUVRI. The authors concluded that PIXUVRI appears to be impairing chromosomal segregation during mitosis, thereby generating loss of genetic material in daughter cells, an abnormality, which is ultimately lethal, and that PIXUVRI would likely be effective in cells resistant to other cytotoxic agents such as doxorubicin. The authors are pursuing leads to further understand the exact mechanism of action.
The full poster presentation is available online at www.celltherapeutics.com/publications.
About PIXUVRI (pixantrone)
PIXUVRI is a novel aza-anthracenedione with unique structural and physiochemical 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.
In May 2012, the European Commission (EC) granted conditional marketing authorization for PIXUVRI as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive NHL. The benefit of PIXUVRI 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. The SmPC is available at www.pixuvri.eu.
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 NHL. PIXUVRI does not have marketing approval in the United States.
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 www.CellTherapeutics.com.
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements are subject to a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results and the trading price of CTI's securities. Such statements include, but are not limited to, statements regarding expectations with respect to the development of the Company and its product and product candidate portfolio, that PIXUVRI is unique in its mechanism for inducing tumor cell death, thereby supporting the thesis that it is part of a new class of anti-cancer agents and readily differentiated from the mechanism of action associated with anthracyclines, and that PIXUVRI may cause delayed but efficient tumor cell death probably through formation of stable DNA adducts. Risks that contribute to the uncertain nature of the forward-looking statements include, among others, risks that PIXUVRI may fail to prove safe and effective for the treatment of relapsed or refractory NHL and/or other tumors; that results in future studies or actual results of PIXUVRI may differ from the results of past studies; 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 may not obtain favorable reimbursement or pricing determinations for PIXUVRI in certain markets in the E.U. as planned, and risks associated with the biopharmaceutical industry in general and with CTI and its product and product candidate portfolio in particular including, among others, risks associated with the following: that CTI cannot predict or guarantee the pace or geography of enrollment of its clinical trials, that the second Phase 3 clinical trial of pacritinib will not occur as planned, that CTI may not obtain favorable determinations by other regulatory, patent and administrative governmental authorities, that CTI may experience delays in the commencement of preclinical and clinical studies, risks related to the costs of developing, producing and selling PIXUVRI, pacritinib, and CTI's other product candidates, and other risks, including, without limitation, competitive factors, technological developments, that CTI's operating expenses continue to exceed its net revenues, that CTI may not be able to sustain its current cost controls or further reduce its operating expenses, that CTI may not achieve previously announced goals and objectives as or when projected, that CTI's average net operating burn rate may increase, that CTI will continue to need to raise capital to fund its operating expenses, but may not be able to raise sufficient amounts to fund its continued operation as well as other risks listed or described from time to time in CTI's most recent filings with the Securities and Exchange Commission on Forms 10-K, 10-Q and 8-K. Except as required by law, CTI does not intend to update any of the statements in this press release upon further developments.
PIXUVRI is a registered trademark of Cell Therapeutics, Inc.
Contacts:
Monique Greer
+1 206-272-4343
mgreer@ctiseattle.com
Ed Bell
+1 206-282-7100
ebell@ctiseattle.com
In Europe:
CTI Life Sciences Limited, Milan Branch
Laura Villa
+39 02 89659706
lvilla@cti-lifesciences.com
CTI_EUInvestors@CTI-Lifesciences.com
