UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): June 7, 2004
ENZON PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
Delaware 0-12957 22-2372868
(State or other jurisdiction of (Commission (IRS Employer
incorporation) File Number) Identification)
685 Route 202/206, Bridgewater, New Jersey 08807
(Address of principal executive offices) (Zip Code)
(Registrant's telephone number, including area code: (908) 541-8600
- --------------------------------------------------------------------------------
(Former name or former address, if changed since last report)
Item 5. Other Events
Press Release by Enzon Pharmaceuticals
On June 7, 2004, Enzon Pharmaceuticals, Inc. (NASDAQ:ENZN) provided a summary of
clinical advancements at the 40th Annual Meeting of the American Society of
Clinical Oncology (ASCO) in New Orleans, Louisiana. Poster presentations
included follow-up results from a Phase 2 study that demonstrated the promise of
Onco TCS (vincristine sulfate liposomes injection) in combination therapy for
the first-line treatment of aggressive non-Hodgkin's lymphoma (NHL). Also
presented were results from a Phase 2 study for Pegamotecan, a novel pegylated
camptothecin conjugate, for the treatment of gastric and gastroesophageal
cancers and results from a National Cancer Institute (NCI) Phase 1 study for
SS1P, a recombinant immunotoxin under investigation as a potential therapy for
mesothelin-expressing cancers, (e.g. mesothelioma, ovarian cancer, and
pancreatic cancer). Investigators from each of the studies presented the data
from their respective trials during the ASCO meeting, June 5 through June 7,
2004. Key highlights from the presentations have been included below.
Onco TCS
Investigators presented follow-up results of a Phase 2 clinical trial, which
demonstrated the potential of Onco TCS as part of a combination regimen in the
first-line treatment of aggressive NHL. The study is being sponsored by Enzon
and its partner Inex Pharmaceuticals Corporation (TSX: IEX). Results were
released from 68 evaluable patients in a Phase 2 open-label study conducted at
the University of Texas M.D. Anderson Cancer Center in Houston, Texas in which
Onco TCS was used in combination with cyclophosphamide, doxorubicin
hydrochloride, and prednisone. Rituxan(R) was also administered to those
patients with B-cell lymphoma.
Key findings from the study were as follows:
o Sixty-three patients, (93%) of patients, responded to the therapy.
Sixty-two patients had their tumors completely eliminated for a
complete response rate of 91% and one patient's tumor volume
decreased by more than 50% for a partial response rate of 1% and an
overall response rate of 93%.
o Of the 68 patients, 37 patients were over the age of 60 years and
91% of these patients were complete responders. In the 31 patients
under the age of 60 years, 90% were complete responders and 3% were
partial responders. Treatment was well tolerated by both groups with
only 6% of patients withdrawing during the trial from adverse
events.
o 88% of courses were delivered at full dose with no dose capping.
Adverse events observed were consistent with those seen with the
standard first-line chemotherapy combination (neurotoxicity, anemia,
neutropenia and thrombocytopenia).
o Investigators also presented positive patient survival data. At a
median follow-up of 22 months, median progression-free survival and
median overall survival were not yet reached. Overall survival was
99% (1 death) and progression-free survival was 87% (9 relapses).
Progression-free survival for the elderly patient group was 86% (5
relapses) and 87% for the younger patient group (4 relapses).
o Based on these data the investigators concluded that Onco TCS may
represent an important new drug when used in combination for
aggressive NHL.
One-year interim results of this study were released in December 2002 at the
American Society of Hematology (ASH) meeting and provided the initial analysis
of the data. The ASCO results provide data analysis after a longer period of
follow-up.
The current standard first-line treatment for the aggressive form of NHL is the
CHOP chemotherapy combination, comprising the drugs cyclophosphamide,
doxorubicin hydrochloride, Oncovin(R) (vincristine) and prednisone. In this
open-label Phase 2 clinical trial the Oncovin(R) (vincristine) component is
substituted with Onco TCS, which is vincristine encapsulated in Inex's
proprietary sphingosomal drug delivery technology. Patients diagnosed with
B-cell lymphoma also received Rituxan(R) (rituximab), a monoclonal antibody.
In addition to the Phase 2, first-line study, investigators also presented a
pharmacokinetics study of Onco TCS in Patients with Metastatic Melanoma. The
data presented supported the extended release formulation and longer circulation
half-life of Onco TCS compared to vincristine.
Pegamotecan
Results were presented from a Phase 2 study in which Pegamotecan was evaluated
as a single-agent treatment for gastric and gastroesophageal junction cancers.
Thirty-five patients with gastric and gastroesophageal junction cancers were
treated: 28 patients were treatment naive and seven patients had received one
prior chemotherapy regimen. The primary endpoint for the study was response rate
with the criteria for moving forward being at least 5 responses.
Key findings from the study were as follows:
o Nineteen (19) of the 35 patients (54%) experienced a response or
stabilization of disease. Five patients (14%) achieved a partial
response and 14 patients (40%) experienced stable disease.
o Pegamotecan showed promising activity based on time to response and
duration of response. For those patients that achieved a partial
response, the median time to response was 46 days, with a range of
40 days to 124 days, and the median duration of response was 127
days, with a range of 108 days to 208 days.
o Pegamotecan appeared to be well tolerated for a cytotoxic agent.
Grade 4 toxicities occurred in 23% of patients, the most common
being granulocytopenia, neutropenia and anorexia. The most common
adverse events were nausea and vomiting. Patients were not
pre-treated in the study and future studies will attempt to control
nausea and vomiting with prophylactic use of anti-emetics.
o Based on these data, the investigators concluded that Pegamotecan
may be a promising treatment for patients with gastric and
gastroesophageal cancers.
SS1P
The National Cancer Institute (NCI) presented results of a multi-center Phase 1
study of SS1P as a targeted therapy of mesothelin-expressing cancers. The
primary objective of the study was to determine the toxicities and maximum
tolerated dose of SS1P. Secondary objectives were to determine the
pharmacokinetics and immunogenicity and observe any anti-tumor activity.
Twenty-three patients with mesothelin-expressing mesotheliomas, ovarian cancer,
or pancreatic cancer were treated. All of the patients had failed a first-line
therapy.
SS1P was administered intraveneously over 30 minutes every other day for 6 or 3
doses. The maximum tolerated dose for the 6 dose schedule was determined. All
dose-limiting toxicities were observed during the second week of treatment.
Therefore, the study protocol was amended so that SS1P was administered every
other day for a total of 3 doses in one week. Dose escalation is ongoing to
determine the maximum tolerated dose for the 3 dose schedule.
Key findings from the study were as follows:
o Of 22 evaluable patients, a response or stabilization of the disease
was achieved in 14 patients or 64%.
o Clinical benefit was observed in several patients including complete
resolution of abdominal and pelvic ascites.
o Based upon these data, investigators concluded that SS1P shows
evidence of anti-tumor activity. Enzon and the NCI are planning
additional studies in patients with mesothelin-expressing cancers.
About Onco TCS
Onco TCS is a proprietary drug comprised of the widely used off-patent
anticancer drug vincristine encapsulated in INEX's sphingosomal drug delivery
technology. INEX's technology is designed to provide prolonged blood
circulation, tumor accumulation and extended drug release at the cancer site.
These characteristics are intended to increase the effectiveness and reduce the
adverse effects of the encapsulated drug.
In May 2004, Enzon and Inex announced that the U.S. Food and Drug Administration
(FDA) had accepted the New Drug Application (NDA) for Onco TCS (vincristine
sulfate liposomes injection). The FDA has established a target date of January
15, 2005 for completion of review of the Onco TCS NDA. The NDA is seeking
marketing approval for Onco TCS as a single-agent treatment for patients with
relapsed aggressive non-Hodgkin's lymphoma (NHL) previously treated with at
least two combination chemotherapy regimens.
In addition to the lead indication, relapsed aggressive NHL, Enzon and INEX
intend to develop Onco TCS for use as a single-agent therapy or in combination
therapy for several cancers in which vincristine is now used.
In January 2004, Enzon and INEX announced a strategic partnership to develop and
commercialize Onco TCS. Under the terms of the agreement, Enzon has the
exclusive North American commercialization rights for Onco TCS for all
indications, subject to certain co-promotion rights of INEX. INEX retains
commercialization rights outside North America.
About Pegamotecan
Pegamotecan is a polyethylene glycol (PEG)-enhanced version of camptothecin, a
small molecule that is a potent anti-cancer compound in the class of
topoisomerase I inhibitors. Using its proprietary PEG technology, Enzon designed
Pegamotecan to improve solubility, extend the circulating half-life, and enable
preferential accumulation at tumor sites. Due to the increased molecular size of
Pegamotecan compared to native camptothecin, it appears that Pegamotecan
passively targets certain tumors due to their enhanced vascular permeability,
thereby attaining enhanced permeation and retention within these tumors (EPR
effect).
In January 2004, patient dosing was initiated in a pivotal clinical trial
designed to evaluate Pegamotecan as single-agent therapy for the treatment of
gastric and gastroesophageal junction cancers in patients who had received prior
chemotherapy. Enzon is focusing its development program for Pegamotecan on
second-line therapy for gastric and gastroesophageal junction cancers, as there
are no single-agent drug approvals for this indication. The Company believes
that Pegamotecan may be eligible for accelerated approval under Subpart H of the
Food and Drug Act for the treatment of these cancers.
About SS1P
SS1P is a fusion protein consisting of a disulfide linked antibody fragment
linked to domains II and III of Pseudomonas exotoxin A. The antibody fragment
targets mesothelin, a cell surface antigen overexpressed in mesothelioma,
ovarian and pancreatic cancers. Importantly, mesothelin is not expressed in
normal pancreas, pancreatitis (inflammation of the pancreas), or benign
pancreatic adenoma.
In November 2003, Enzon announced a Collaborative Research and Development
Agreement (CRADA) with the National Institutes of Health (NIH). The development
program will center on the recombinant immunotoxin SS1P. Enzon and the NCI plan
to begin a Phase 2 clinical trial around the end of 2004.
About Enzon
Enzon Pharmaceuticals is a biopharmaceutical company dedicated to the discovery,
development and commercialization of therapeutics to treat life-threatening
diseases. The Company has developed or acquired a number of marketed products,
including PEG-INTRON(R), marketed by Schering-Plough, and ABELCET(R),
ONCASPAR(R), ADAGEN(R), and DEPOCYT(R), marketed in North America by Enzon's
specialized sales force. Enzon's science-focused strategy includes an extensive
drug development program that leverages the Company's macromolecular engineering
technology platforms, including PEG modification and single-chain antibody
(SCA(R)) technologies. Internal research and development efforts are
complemented by strategic transactions that provide access to additional
products and technologies. Enzon has several drug candidates in various stages
of development, independently and with partners, including Onco TCS, for which a
U.S. marketing application is currently being reviewed by the FDA for the
treatment of relapsed aggressive non-Hodgkin's lymphoma. Further information
about Enzon and this press release can be found on the Company's web site at
www.enzon.com.
There are forward-looking statements contained herein that are not based on
historical fact, including without limitation statements containing the words
"believes," "may," "plans," "will," "estimates," "continue," "anticipates,"
"intends," "expects," and similar expressions. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause
actual results, events or developments to be materially different from the
future results, events or developments discussed above. Such factors include the
risk that Onco TCS may not receive regulatory approval from the FDA under
Subpart H of the Food and Drug Act and the fact that any such approval, if
granted, will include post approval commitments, the risks that Pegamotecan and
SS1P will not successfully progress through their clinical studies,
as well as those described in Enzon's Form 10-K and Forms 10-Q on file with the
SEC, such as Enzon's ability to successfully launch and market Onco TCS, Enzon's
ability to sustain profitability, and positive cash flow; risks in obtaining and
maintaining regulatory approval for indications and expanded indications for
Enzon's products; market acceptance of and continuing demand for Enzon's
products; timing and results of clinical trials, including, without limitation,
the ongoing clinical trials of Pegamotecan for the treatment of gastric and
gastroesophageal cancers and SS1P for the treatment of mesotheliomas, ovarian
cancer, or pancreatic cancer; the risk that the FDA may not deem Pegamotecan
eligible for accelerated approval under Subpart H of the Food and Drug Act; and
the impact of competitive products and pricing. These factors should be
considered carefully and readers are cautioned not to place undue reliance on
such forward-looking statements. All information in this press release is as of
June 7, 2004 and the Company undertakes no duty to update this information.
Joint Press Release by Enzon Pharmaceuticals and Inex Pharmaceuticals
On June 7, 2004, Enzon Pharmaceuticals Inc. ("Enzon"; NASDAQ: ENZN) and Inex
Pharmaceuticals Corporation ("INEX"; TSX: IEX) released follow-up results from a
phase II clinical trial that indicate Onco TCS (vincristine sulfate liposomes
injection) has potential to be used in combination with other cancer drugs for
the first-line treatment of patients with aggressive non-Hodgkin's lymphoma
(NHL).
The follow-up results were reported at the Annual Meeting of the American
Society of Clinical Oncology (ASCO) in New Orleans, Louisiana. One-year interim
results were released in December 2002 at the American Society of Hematology
meeting and provided the initial data analysis. The ASCO results provide data
analysis after a longer period of follow-up.
Follow-up results were released from 68 evaluable patients in a phase II
open-label clinical trial conducted at The University of Texas M. D. Anderson
Cancer Center in Houston, Texas in which Onco TCS was used as part of a
combination regimen in the first-line treatment of aggressive NHL. Sixty-three
patients, or 93% of patients, responded to the therapy. Sixty-two patients had
their tumors completely eliminated for a complete response rate of 91% and one
patient's tumor volume decreased by more than 50% for a partial response rate of
1% and an overall response rate of 93%.
Of the 68 patients, 37 patients were over the age of 60 years and 91% of these
patients were complete responders. In the 31 patients under the age of 60 years,
90% were complete responders and 3% were partial responders. Treatment was well
tolerated by both groups with only 6% of patients withdrawing from treatment due
to adverse events.
Investigators also presented positive patient survival data. At a median
follow-up of 22 months, median progression-free survival and median overall
survival had not yet been reached. Overall survival was 99% (one death) and
progression-free survival was 87% (nine relapses). Progression-free survival for
the elderly patient group was 86% (five relapses) and 87% for the younger
patient group (four relapses).
In December 2002, INEX reported at the ASH annual meeting that at a median
follow-up of 12 months after treatment, progression free survival for the
elderly group was 89% (four relapses) and 94% for the younger patient group (two
relapses). Therefore, the progression free survival at a median of 22 months
presented today at ASCO compares favorably with the previously reported results.
The current standard first-line treatment for the aggressive form of NHL is the
CHOP chemotherapy combination, comprising the drugs cyclophosphamide,
doxorubicin hydrochloride, Oncovin(R) (vincristine) and prednisone. This phase
II trial treated patients with CHOP in which the Oncovin(R) (vincristine)
component was substituted with Onco TCS. Patients diagnosed with B-cell lymphoma
also received Rituxan(R) (rituximab).
In addition to the first-line lymphoma study, data were also presented at ASCO
on an Onco TCS pharmacokinetics trial in patients with metastatic melanoma. The
data presented supports the extended release formulation and longer circulation
half-life of Onco TCS compared to vincristine.
About Onco TCS
Onco TCS is a proprietary drug comprised of the widely used off-patent
anticancer drug vincristine encapsulated in INEX's sphingosomal drug delivery
technology. This technology provides prolonged blood circulation, tumor
accumulation and extended drug release at the cancer site. These characteristics
are designed to increase the effectiveness and reduce the side effects of the
encapsulated drug.
About Non-Hodgkin's Lymphoma (NHL)
NHL is the fifth-leading cause of cancer deaths in the United States (19,400
estimated in 2004) and the sixth-leading cause of cancer deaths in Canada (2,900
estimated in 2004), according to estimates of the American Cancer Society and
the Canadian Cancer Society. Approximately 53,400 and 6,400 new cases were
diagnosed in the U.S. and Canada respectively in 2003.
About INEX
INEX is a Canadian biopharmaceutical company developing and commercializing
proprietary drugs and drug delivery systems to improve the treatment of cancer.
Further information about INEX and this press release can be found at
www.inexpharm.com.
About Enzon
Enzon Pharmaceuticals is a biopharmaceutical company dedicated to the discovery,
development and commercialization of therapeutics to treat life-threatening
diseases. Further information about Enzon and this press release can be found at
www.enzon.com.
There are forward-looking statements contained herein that are not based on
historical fact, including without limitation statements containing the words
"believes," "may," "plans," "will," "estimate," "continue," "anticipates,"
"intends," "expects," and similar expressions. Such forward looking statements
involve known and unknown risks, uncertainties and other factors that may cause
actual results, events or developments to be materially different from
future results, events or developments described in the forward looking
statements. Such factors include the risk that Onco TCS may not receive
regulatory approval from the FDA under Subpart H of the Food and Drug Act and
the fact that any such approval, if granted, will include post approval
commitments, as well as those described in Enzon's Form 10-K and Forms 10-Q on
file with the SEC and INEX's publicly filed periodic reports and others, such
as, (i) as to Enzon, Enzon's ability to successfully launch and market Onco TCS,
Enzon's ability to sustain profitability, and positive cash flow; risks in
obtaining and maintaining regulatory approval for indications and expanded
indications for Enzon's products; market acceptance of and continuing demand for
Enzon's products; timing and results of clinical trials and the impact of
competitive products and pricing and (ii) as to INEX, INEX's stage of
development, lack of product revenues, additional capital requirements, risks
associated with the completion of clinical trials and obtaining regulatory
approval to market INEX's products, risks associated with the failure to secure
all necessary intellectual property from third parties, the ability to protect
its intellectual property and dependence on collaborative partners. These
factors should be considered carefully and readers are cautioned not to place
undue reliance on such forward-looking statements. All information in this press
release is as of June 7, 2004, and Enzon and INEX undertake no duty to update
this information.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
Dated: June 8, 2004
By: /s/ Kenneth J. Zuerblis
------------------------------------
Kenneth J. Zuerblis
Vice President, Finance and
Chief Financial Officer
Exhibit 99.1
ENZON
PHARMACEUTICALS For Immediate Release
================================================================================
PRESS RELEASE Contact: Susan M. Mesco
Director, Investor Relations
(908)541-8777
Euro RSCG Life NRP
Mark R. Vincent, Media Relations
(212)845-4239
ENZON PROVIDES CLINICAL UPDATES ON THREE ONCOLOGY CANDIDATES
AT ANNUAL MEETING OF AMERICAN SOCIETY OF CLINICAL ONCOLOGY
-Onco TCS Demonstrates Potential in the First-Line Setting for NHL-
-Pegamotecan Phase 2 Study Meets Primary Endpoint-
-SS1P Phase 1 Study Shows Evidence of Anti-tumor Activity and Clinical Benefit-
Bridgewater, NJ - June 7, 2004 - Enzon Pharmaceuticals, Inc. (NASDAQ:ENZN)
today provided a summary of clinical advancements at the 40th Annual Meeting of
the American Society of Clinical Oncology (ASCO) in New Orleans, Louisiana.
Poster presentations included follow-up results from a Phase 2 study that
demonstrated the promise of Onco TCS (vincristine sulfate liposomes injection)
in combination therapy for the first-line treatment of aggressive non-Hodgkin's
lymphoma (NHL). Also presented were results from a Phase 2 study for
Pegamotecan, a novel pegylated camptothecin conjugate, for the treatment of
gastric and gastroesophageal cancers and results from a National Cancer
Institute (NCI) Phase 1 study for SS1P, a recombinant immunotoxin under
investigation as a potential therapy for mesothelin-expressing cancers, (e.g.
mesothelioma, ovarian cancer, and pancreatic cancer). Investigators from each of
the studies presented the data from their respective trials during the ASCO
meeting, June 5 through June 7, 2004. Key highlights from the presentations have
been included below.
"Enzon is continuing to make significant progress in advancing its
clinical pipeline of oncology drug candidates. The multiple presentations at
this year's ASCO meeting exemplifies our team's ability to successfully execute
Enzon's strategy and further underscores our commitment to expand and advance
our clinical pipeline," stated Uli Grau, Ph.D., Enzon's Chief Scientific
Officer.
-more-
ASCO 2004/ page 2
Onco TCS
Investigators presented follow-up results of a Phase 2 clinical trial,
which demonstrated the potential of Onco TCS as part of a combination regimen in
the first-line treatment of aggressive NHL. The study is being sponsored by
Enzon and its partner Inex Pharmaceuticals Corporation (TSX: IEX). Results were
released from 68 evaluable patients in a Phase 2 open-label study conducted at
the University of Texas M.D. Anderson Cancer Center in Houston, Texas in which
Onco TCS was used in combination with cyclophosphamide, doxorubicin
hydrochloride, and prednisone. Rituxan(R) was also administered to those
patients with B-cell lymphoma.
Key findings from the study were as follows:
o Sixty-three patients, (93%) of patients, responded to the therapy.
Sixty-two patients had their tumors completely eliminated for a
complete response rate of 91% and one patient's tumor volume
decreased by more than 50% for a partial response rate of 1% and an
overall response rate of 93%.
o Of the 68 patients, 37 patients were over the age of 60 years and
91% of these patients were complete responders. In the 31 patients
under the age of 60 years, 90% were complete responders and 3% were
partial responders. Treatment was well tolerated by both groups with
only 6% of patients withdrawing during the trial from adverse
events.
o 88% of courses were delivered at full dose with no dose capping.
Adverse events observed were consistent with those seen with the
standard first-line chemotherapy combination (neurotoxicity, anemia,
neutropenia and thrombocytopenia).
o Investigators also presented positive patient survival data. At a
median follow-up of 22 months, median progression-free survival and
median overall survival were not yet reached. Overall survival was
99% (1 death) and progression-free survival was 87% (9 relapses).
Progression-free survival for the elderly patient group was 86% (5
relapses) and 87% for the younger patient group (4 relapses).
o Based on these data the investigators concluded that Onco TCS may
represent an important new drug when used in combination for
aggressive NHL.
-more-
ASCO 2004/ page 3
One-year interim results of this study were released in December 2002 at
the American Society of Hematology (ASH) meeting and provided the initial
analysis of the data. The ASCO results provide data analysis after a longer
period of follow-up.
The current standard first-line treatment for the aggressive form of NHL
is the CHOP chemotherapy combination, comprising the drugs cyclophosphamide,
doxorubicin hydrochloride, Oncovin(R) (vincristine) and prednisone. In this
open-label Phase 2 clinical trial the Oncovin(R) (vincristine) component is
substituted with Onco TCS, which is vincristine encapsulated in Inex's
proprietary sphingosomal drug delivery technology. Patients diagnosed with
B-cell lymphoma also received Rituxan(R) (rituximab), a monoclonal antibody.
In addition to the Phase 2, first-line study, investigators also presented
a pharmacokinetics study of Onco TCS in Patients with Metastatic Melanoma. The
data presented supported the extended release formulation and longer circulation
half-life of Onco TCS compared to vincristine.
Pegamotecan
Results were presented from a Phase 2 study in which Pegamotecan was
evaluated as a single-agent treatment for gastric and gastroesophageal junction
cancers. Thirty-five patients with gastric and gastroesophageal junction cancers
were treated: 28 patients were treatment naive and seven patients had received
one prior chemotherapy regimen. The primary endpoint for the study was response
rate with the criteria for moving forward being at least 5 responses. Key
findings from the study were as follows:
o Nineteen (19) of the 35 patients (54%) experienced a response or
stabilization of disease. Five patients (14%) achieved a partial
response and 14 patients (40%) experienced stable disease.
o Pegamotecan showed promising activity based on time to response and
duration of response. For those patients that achieved a partial
response, the median time to response was 46 days, with a range of
40 days to 124 days, and the median duration of response was 127
days, with a range of 108 days to 208 days.
o Pegamotecan appeared to be well tolerated for a cytotoxic agent.
Grade 4 toxicities
-more-
ASCO 2004/ page 4
occurred in 23% of patients, the most common being granulocytopenia,
neutropenia and anorexia. The most common adverse events were nausea
and vomiting. Patients were not pre-treated in the study and future
studies will attempt to control nausea and vomiting with
prophylactic use of anti-emetics.
o Based on these data, the investigators concluded that Pegamotecan
may be a promising treatment for patients with gastric and
gastroesophageal cancers.
SS1P
The National Cancer Institute (NCI) presented results of a multi-center
Phase 1 study of SS1P as a targeted therapy of mesothelin-expressing cancers.
The primary objective of the study was to determine the toxicities and maximum
tolerated dose of SS1P. Secondary objectives were to determine the
pharmacokinetics and immunogenicity and observe any anti-tumor activity.
Twenty-three patients with mesothelin-expressing mesotheliomas, ovarian cancer,
or pancreatic cancer were treated. All of the patients had failed a first-line
therapy.
SS1P was administered intraveneously over 30 minutes every other day for 6
or 3 doses. The maximum tolerated dose for the 6 dose schedule was determined.
All dose-limiting toxicities were observed during the second week of treatment.
Therefore, the study protocol was amended so that SS1P was administered every
other day for a total of 3 doses in one week. Dose escalation is ongoing to
determine the maximum tolerated dose for the 3 dose schedule. Key findings from
the study were as follows:
o Of 22 evaluable patients, a response or stabilization of the disease
was achieved in 14 patients or 64%.
o Clinical benefit was observed in several patients including complete
resolution of abdominal and pelvic ascites.
o Based upon these data, investigators concluded that SS1P shows
evidence of anti-tumor activity. Enzon and the NCI are planning
additional studies in patients with mesothelin-expressing cancers.
About Onco TCS
Onco TCS is a proprietary drug comprised of the widely used off-patent
anticancer drug
-more-
ASCO 2004/ page 5
vincristine encapsulated in INEX's sphingosomal drug delivery technology. INEX's
technology is designed to provide prolonged blood circulation, tumor
accumulation and extended drug release at the cancer site. These characteristics
are intended to increase the effectiveness and reduce the adverse effects of the
encapsulated drug.
In May 2004, Enzon and Inex announced that the U.S. Food and Drug
Administration (FDA) had accepted the New Drug Application (NDA) for Onco TCS
(vincristine sulfate liposomes injection). The FDA has established a target date
of January 15, 2005 for completion of review of the Onco TCS NDA. The NDA is
seeking marketing approval for Onco TCS as a single-agent treatment for patients
with relapsed aggressive non-Hodgkin's lymphoma (NHL) previously treated with at
least two combination chemotherapy regimens.
In addition to the lead indication, relapsed aggressive NHL, Enzon and
INEX intend to develop Onco TCS for use as a single-agent therapy or in
combination therapy for several cancers in which vincristine is now used.
In January 2004, Enzon and INEX announced a strategic partnership to
develop and commercialize Onco TCS. Under the terms of the agreement, Enzon has
the exclusive North American commercialization rights for Onco TCS for all
indications, subject to certain co-promotion rights of INEX. INEX retains
commercialization rights outside North America.
About Pegamotecan
Pegamotecan is a polyethylene glycol (PEG)-enhanced version of
camptothecin, a small molecule that is a potent anti-cancer compound in the
class of topoisomerase I inhibitors. Using its proprietary PEG technology, Enzon
designed Pegamotecan to improve solubility, extend the circulating half-life,
and enable preferential accumulation at tumor sites. Due to the increased
molecular size of Pegamotecan compared to native camptothecin, it appears that
Pegamotecan passively targets certain tumors due to their enhanced vascular
permeability, thereby attaining enhanced permeation and retention within these
tumors (EPR effect).
In January 2004, patient dosing was initiated in a pivotal clinical trial
designed to evaluate Pegamotecan as single-agent therapy for the treatment of
gastric and gastroesophageal junction cancers in patients who had received prior
chemotherapy. Enzon is focusing its
-more-
ASCO 2004/ page 6
development program for Pegamotecan on second-line therapy for gastric and
gastroesophageal junction cancers, as there are no single-agent drug approvals
for this indication. The Company believes that Pegamotecan may be eligible for
accelerated approval under Subpart H of the Food and Drug Act for the treatment
of these cancers.
About SS1P
SS1P is a fusion protein consisting of a disulfide linked antibody
fragment linked to domains II and III of Pseudomonas exotoxin A. The antibody
fragment targets mesothelin, a cell surface antigen overexpressed in
mesothelioma, ovarian and pancreatic cancers. Importantly, mesothelin is not
expressed in normal pancreas, pancreatitis (inflammation of the pancreas), or
benign pancreatic adenoma.
In November 2003, Enzon announced a Collaborative Research and Development
Agreement (CRADA) with the National Institutes of Health (NIH). The development
program will center on the recombinant immunotoxin SS1P. Enzon and the NCI plan
to begin a Phase 2 clinical trial around the end of 2004.
About Enzon
Enzon Pharmaceuticals is a biopharmaceutical company dedicated to the discovery,
development and commercialization of therapeutics to treat life-threatening
diseases. The Company has developed or acquired a number of marketed products,
including PEG-INTRON(R), marketed by Schering-Plough, and ABELCET(R),
ONCASPAR(R), ADAGEN(R), and DEPOCYT(R), marketed in North America by Enzon's
specialized sales force. Enzon's science-focused strategy includes an extensive
drug development program that leverages the Company's macromolecular engineering
technology platforms, including PEG modification and single-chain antibody
(SCA(R)) technologies. Internal research and development efforts are
complemented by strategic transactions that provide access to additional
products and technologies. Enzon has several drug candidates in various stages
of development, independently and with partners, including Onco TCS, for which a
U.S. marketing application is currently being reviewed by the FDA for the
treatment of relapsed aggressive non-Hodgkin's lymphoma. Further information
about Enzon and this press release can be found on the Company's web site at
www.enzon.com.
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ASCO 2004/ page 7
There are forward-looking statements contained herein that are not based on
historical fact, including without limitation statements containing the words
"believes," "may," "plans," "will," "estimates," "continue," "anticipates,"
"intends," "expects," and similar expressions. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause
actual results, events or developments to be materially different from the
future results, events or developments discussed above. Such factors include the
risk that Onco TCS may not receive regulatory approval from the FDA under
Subpart H of the Food and Drug Act and the fact that any such approval, if
granted, will include post approval commitments, the risks that Pegamotecan and
SS1P will not successfully progress through their clinical studies, as well as
those described in Enzon's Form 10-K and Forms 10-Q on file with the SEC, such
as Enzon's ability to successfully launch and market Onco TCS, Enzon's ability
to sustain profitability, and positive cash flow; risks in obtaining and
maintaining regulatory approval for indications and expanded indications for
Enzon's products; market acceptance of and continuing demand for Enzon's
products; timing and results of clinical trials, including, without limitation,
the ongoing clinical trials of Pegamotecan for the treatment of gastric and
gastroesophageal cancers and SS1P for the treatment of mesotheliomas, ovarian
cancer, or pancreatic cancer; the risk that the FDA may not deem Pegamotecan
eligible for accelerated approval under Subpart H of the Food and Drug Act; and
the impact of competitive products and pricing. These factors should be
considered carefully and readers are cautioned not to place undue reliance on
such forward-looking statements. All information in this press release is as of
June 7, 2004 and the Company undertakes no duty to update this information.
Exhibit 99.2
ENZON
PHARMACEUTICALS For Immediate Release
================================================================================
PRESS RELEASE
Contact: Susan Mesco
Director, Investor Relations
908-541-8678
Euro RSCG Life NRP
Mark R. Vincent, Media Relations
212-845-4239
ENZON AND INEX PRESENT PROMISING FOLLOW-UP DATA AT AMERICAN
SOCIETY OF CLINICAL ONCOLOGY SHOWING ONCO TCS
POTENTIAL IN FIRST-LINE LYMPHOMA
BRIDGEWATER, NJ - June 7, 2004 - Enzon Pharmaceuticals Inc. ("Enzon";
NASDAQ: ENZN) and Inex Pharmaceuticals Corporation ("INEX"; TSX: IEX) today
released follow-up results from a phase II clinical trial that indicate Onco TCS
(vincristine sulfate liposomes injection) has potential to be used in
combination with other cancer drugs for the first-line treatment of patients
with aggressive non-Hodgkin's lymphoma (NHL).
The follow-up results were reported at the Annual Meeting of the American
Society of Clinical Oncology (ASCO) in New Orleans, Louisiana. One-year interim
results were released in December 2002 at the American Society of Hematology
meeting and provided the initial data analysis. The ASCO results provide data
analysis after a longer period of follow-up.
David Main, President and CEO of INEX, said the follow-up results are very
encouraging. "These data support the commercial strategy of seeking marketing
approval for Onco TCS as a treatment for relapsed aggressive NHL, as well as our
goal to continue to expand its potential in additional indications including
first-line aggressive NHL. Importantly, after 22 months, patient survival data
continues to support our positive expectations for this product in the first
line setting."
Follow-up results were released from 68 evaluable patients in a phase II
open-label clinical trial conducted at The University of Texas M. D. Anderson
Cancer Center in Houston,
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ASCO 2004 Joint/ page 2
Texas in which Onco TCS was used as part of a combination regimen in the
first-line treatment of aggressive NHL. Sixty-three patients, or 93% of
patients, responded to the therapy. Sixty-two patients had their tumors
completely eliminated for a complete response rate of 91% and one patient's
tumor volume decreased by more than 50% for a partial response rate of 1% and an
overall response rate of 93%.
Of the 68 patients, 37 patients were over the age of 60 years and
91% of these patients were complete responders. In the 31 patients under the age
of 60 years, 90% were complete responders and 3% were partial responders.
Treatment was well tolerated by both groups with only 6% of patients withdrawing
from treatment due to adverse events.
Investigators also presented positive patient survival data. At a median
follow-up of 22 months, median progression-free survival and median overall
survival had not yet been reached. Overall survival was 99% (one death) and
progression-free survival was 87% (nine relapses). Progression-free survival for
the elderly patient group was 86% (five relapses) and 87% for the younger
patient group (four relapses).
In December 2002, INEX reported at the ASH annual meeting that at a median
follow-up of 12 months after treatment, progression free survival for the
elderly group was 89% (four relapses) and 94% for the younger patient group (two
relapses). Therefore, the progression free survival at a median of 22 months
presented today at ASCO compares favorably with the previously reported results.
Arthur Higgins, Enzon's chairman, said, "These results continue to
demonstrate the excellent potential for Onco TCS as part of first-line
combination therapy for aggressive NHL. The rate and duration of response in the
context of the therapy being very well tolerated is especially important for
elderly patients. Further, these data are particularly encouraging when reviewed
in the context of published studies for CHOP and CHOP plus Rituximab."
The current standard first-line treatment for the aggressive form of NHL
is the CHOP chemotherapy combination, comprising the drugs cyclophosphamide,
doxorubicin hydrochloride, Oncovin(R) (vincristine) and prednisone. This phase
II trial treated patients with CHOP in which the Oncovin(R) (vincristine)
component was substituted with Onco TCS. Patients diagnosed with B-cell lymphoma
also received Rituxan(R) (rituximab).
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ASCO 2004 Joint/ page 3
In addition to the first-line lymphoma study, data were also presented at
ASCO on an Onco TCS pharmacokinetics trial in patients with metastatic melanoma.
The data presented supports the extended release formulation and longer
circulation half-life of Onco TCS compared to vincristine.
About Onco TCS
Onco TCS is a proprietary drug comprised of the widely used off-patent
anticancer drug vincristine encapsulated in INEX's sphingosomal drug delivery
technology. This technology provides prolonged blood circulation, tumor
accumulation and extended drug release at the cancer site. These characteristics
are designed to increase the effectiveness and reduce the side effects of the
encapsulated drug.
About Non-Hodgkin's Lymphoma (NHL)
NHL is the fifth-leading cause of cancer deaths in the United States
(19,400 estimated in 2004) and the sixth-leading cause of cancer deaths in
Canada (2,900 estimated in 2004), according to estimates of the American Cancer
Society and the Canadian Cancer Society. Approximately 53,400 and 6,400 new
cases were diagnosed in the U.S. and Canada respectively in 2003.
About INEX
INEX is a Canadian biopharmaceutical company developing and
commercializing proprietary drugs and drug delivery systems to improve the
treatment of cancer. Further information about INEX and this press release can
be found at www.inexpharm.com.
About Enzon
Enzon Pharmaceuticals is a biopharmaceutical company dedicated to the
discovery, development and commercialization of therapeutics to treat
life-threatening diseases. Further information about Enzon and this press
release can be found at www.enzon.com.
There are forward-looking statements contained herein that are not based on
historical fact, including without limitation statements containing the words
"believes," "may," "plans,"
-more-
ASCO 2004 Joint/ page 4
"will," "estimate," "continue," "anticipates," "intends," "expects," and similar
expressions. Such forward looking statements involve known and unknown risks,
uncertainties and other factors that may cause actual results, events or
developments to be materially different from future results, events or
developments described in the forward looking statements. Such factors include
the risk that Onco TCS may not receive regulatory approval from the FDA under
Subpart H of the Food and Drug Act and the fact that any such approval, if
granted, will include post approval commitments, as well as those described in
Enzon's Form 10-K and Forms 10-Q on file with the SEC and INEX's publicly filed
periodic reports and others, such as, (i) as to Enzon, Enzon's ability to
successfully launch and market Onco TCS, Enzon's ability to sustain
profitability, and positive cash flow; risks in obtaining and maintaining
regulatory approval for indications and expanded indications for Enzon's
products; market acceptance of and continuing demand for Enzon's products;
timing and results of clinical trials and the impact of competitive products and
pricing and (ii) as to INEX, INEX's stage of development, lack of product
revenues, additional capital requirements, risks associated with the completion
of clinical trials and obtaining regulatory approval to market INEX's products,
risks associated with the failure to secure all necessary intellectual property
from third parties, the ability to protect its intellectual property and
dependence on collaborative partners. These factors should be considered
carefully and readers are cautioned not to place undue reliance on such
forward-looking statements. All information in this press release is as of June
7, 2004, and Enzon and INEX undertake no duty to update this information.