Filing
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) April
19, 2005
ADVENTRX
Pharmaceuticals, Inc.
(Exact
name of registrant as specified in its charter)
Delaware
(State or
other jurisdiction of incorporation)
|
001-32157
(Commission
File Number) |
84-1318182
(IRS
Employer Identification No.) |
6725
Mesa Ridge Road, Suite 100
San
Diego, California 92121
(Address
of principal executive offices) (Zip Code)
(858)
552-0866
(Company’s
telephone number, including area code)
Item
8.01. Other Events.
On April
19, 2005, the Company announced that it presented CoFactor toxicity and
pharmacodynamics data from its Phase II clinical trial in metastatic colorectal
cancer. In addition, the Company announced that it presented enhanced antitumor
activity and lower systemic toxicity with CoFactor combination therapies in
preclinical models for colorectal and pancreatic cancer.
The press
releases issued by the Company on April 19, 2005 with respect to these matters
are included with this report as exhibits.
Item
9.01. Financial Statements and Exhibits.
| (99) |
©The
exhibit list required by this item is incorporated by reference to the
Exhibit Index filed as part of this report. |
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.
|
ADVENTRX
Pharmaceuticals, Inc. | ||
|
By: |
/s/ Carrie E. Carlander | |
|
Name:
Carrie E. Carlander | ||
|
Title:
Chief Financial Officer, Vice President, Finance, and
Treasurer
April
19, 2005 | ||
EXHIBIT
INDEX
|
Exhibit
|
Description
|
|
99.1
|
Press
Release of the Company dated April 19, 2005.
|
|
99.2
|
Press
Release of the Company dated April 19, 2005
|
Exhibit
99.1
ADVENTRX
PRESENTS COFACTOR TOXICITY AND PHARMACODYNAMICS DATA FROM PHASE II
TRIAL
SAN
DIEGO - April 19, 2005 -
ADVENTRX Pharmaceuticals, Inc. (Amex: ANX) today announced that it presented
CoFactor™ toxicity and pharmacodynamics data collected from the Company’s
ongoing CoFactor Phase II clinical trial in metastatic colorectal cancer. This
data suggests that there is negligible risk of toxicity.
C. Paul
Spears, M.D., co-inventor of CoFactor, investigator in the COFU trial and lead
author on the study, presented the results during the 96th Annual
Meeting of the American Association for Cancer Research (AACR) in Anaheim,
Calif.
Use of
5,10-methylene-tetrahydrofolate
([6R,S]-5,10-methylene-tetrahydropteroyl-monogluta-ate, CH2FH4) for
promotion of 5-fluorouracil (5-FU) metabolite fluorodeoxyuridylate inhibition of
thymidylate synthase has been promising for parameters of efficacy in solid
tumors, with less toxicity than by use of leucovorin. CH2FH4 in
dilute aqueous solution potentially could form formaldehyde (CHO) intermediates
through kinetic dissociation of the methyene unit. Formation of CHO in
vivo could be
toxic, as in methanol metabolism. Formic acid is an end-metabolite of CHO and a
marker for CHO toxicity.
Addition
of CH2FH4
(CoFactor TM), 60
mg/m2
, bolus
i.v., to i.v. weekly 5-FU, 450 mg/m2, was
carried out in a Phase II trial in colon cancer patients as initial treatment of
metastatic disease. Urinary formic acid levels were determined by ion
chromatography at baseline, and at 2, 6, and 24 h after 5-FU/ CH2FH4, in the
first 16 patients. This was repeated weekly for 6 weeks of the first cycle.
Clinical markers related to CH2FH4
metabolism also included blood levels of B12, homocysteine, and RBC
folate.
Normal
urinary formic acid levels are 5 µg/mL (range, 0 - 12). Baseline pre-dose formic
acid values of the first 16 patients on weekly 5-FU/ CH2FH4 showed a
mean of 3.7 µg/mL (SD 6.14) and median value of 2.0 µg/mL (range, 0 - 26). The
average value at 2 h was 2.0 (SD 1.32) and at 24 hours, 1.7 µg/mL (median 1.9
and 2.0 respectively, range 0 - 5.3 for 2 h, 0 - 3.0 for 24 h).
Baseline
pre-dose RBC folate levels (by methotrexate competition) were 585, 573, and 442
ng/mL in the first three patients of study. Sustained increases to 1689, 1334,
and 862 ng/mL, respectively, after weekly 5-FU/ CH2FH4 were
noted.
Results
of homocysteine levels in serum in 24 patients are available. Baseline mean
pre-dose levels were 9.55 (SD 2.71) µM, with no change at week two or later
post-dosing, 9.75 (SD 2.25) µM. However, one patient with a baseline
homocysteine value of 14.2 showed a drop to 4.3 µM.
In
conclusion, the metabolism of i.v. CH2FH4 at 60
mg/m2, which
results in marked RBC folate pool expansion, not only results in no immediate or
delayed formic acid excretion, but may be associated with a decrease in urinary
formate. This is consistent with the established use of reduced folates for
treatment of methanol/CHO toxicity. CH2FH4 may bind
additional moles of CHO, or this may occur through FH4 its
major metabolite.
“This
study demonstrates that the simple, rapid administration of CoFactor shows
direct and sustained expansion of folate pools without concomitant toxicity,”
said Joan M. Robbins, Ph.D., ADVENTRX chief technical officer and co-author of
the study. “We continue to be encouraged by the safety profile for
CoFactor.”
This
abstract “Pharmacodynamics of weekly intravenous
methylene-tetrahydrofolate/5-fluorouracil on formic acid, RBC folate, and
homocysteine levels in patients with metastatic colon cancer” is
available via the Company’s Web site at www.adventrx.com.
ADVENTRX
has filed for clearance to initiate a Phase III trial in the US and recently
received clearance in the UK to begin an international Phase IIb trial with
CoFactor in metastatic colorectal cancer and intends to file in the first half
of this year for clearance to initiate an EU-based Phase III study in pancreatic
cancer.
About
CoFactor
CoFactor
is a folate-based biomodulator drug developed to enhance the activity of the
widely used cancer chemotherapeutic, 5-FU. Clinical data from previous clinical
trials in Europe have demonstrated clinical benefit and improved overall median
survival in patients with advanced tumors, including colorectal, pancreatic and
breast. CoFactor creates more stable binding, compared to leucovorin, of the
active form of 5-FU, FdUMP, to the target enzyme, thymidylate synthase (TS).
CoFactor bypasses the chemical pathway required by leucovorin to deliver the
active form of folate to allow 5-FU to work more effectively. This improves 5-FU
performance and lowers toxicity. ADVENTRX is the exclusive licensee of this
compound. More information on CoFactor can be found at http://www.adventrx.com/products/antic_cofactor.htm.
About
ADVENTRX
ADVENTRX
Pharmaceuticals is a biopharmaceutical research and development company focused
on introducing new technologies for anticancer and antiviral treatments that
improve the performance of existing drugs and address significant problems such
as drug metabolism, bioavailability and resistance. More information can be
found on the Company's Web site at www.adventrx.com.
Forward
Looking Statement
This
press release contains forward-looking statements within the meaning of the
"safe harbor" provisions of the Private Securities Litigation Reform Act of
1995. Such statements are made based on management's current expectations and
beliefs. Actual results may vary from those currently anticipated based upon a
number of factors, including uncertainties inherent in the drug development
process, the timing and success of clinical trials, the validity of research
results, and the receipt of necessary approvals from the FDA and other
regulatory agencies. For a discussion of such risks and uncertainties, which
could cause actual results to differ from those contained in the forward-looking
statements, see “Risk Factors” in the Company’s last quarterly report on Form
10-QSB, as well as other reports that the Company files from time to time with
the Securities and Exchange Commission. All forward-looking statements are
qualified in their entirety by this cautionary statement. The Company undertakes
no obligation to release publicly any revisions, which may be made to reflect
events or circumstances after the date hereof.
| Contact: | Investor Contact: |
| ADVENTRX Pharmaceuticals | Lippert, Heilshorn & Associates |
| Andrea Lynn | Jody Cain (jcain@lhai.com) |
| 858-552-0866 | Brandi Floberg (bfloberg@lhai.com) |
| 310-691-7100 | |
| Media Contact | |
| Lippert Heilshorn & Associates | |
| Mark Stuart (mstuart@lhai.com) | |
| 310-691-7116 |
Exhibit
99.2
ADVENTRX
PRESENTS ENHANCED ANTITUMOR ACTIVITY AND LOWER SYSTEMIC TOXICITY
WITH
COFACTOR COMBINATION THERAPIES IN PRECLINICAL MODELS
SAN
DIEGO - April 19, 2005 -
ADVENTRX Pharmaceuticals, Inc. (Amex: ANX) today announced that it presented
preclinical results that demonstrated CoFactor™ plus 5-fluorouracil (5-FU) used
in combination with various other anticancer treatments enhanced antitumor
activity and reduced systemic toxicity in mouse models for colorectal and
pancreatic cancer.
Mark
Cantwell, Ph.D., ADVENTRX director of preclinical programs, presented the
results during the 96th Annual
Meeting of the American Association for Cancer Research (AACR) in Anaheim,
Calif.
Using
in
vivo human
tumor xenotransplant mouse models for colorectal and pancreatic cancer, the
antitumor efficacy of 5-FU/CoFactor in combination with CPT-11, oxaliplatin,
anti-VEGF antibody, and gemcitabine, CoFactor-containing combination regimens
induced either equivalent or better antitumor responses, as noted by slower
tumor growth and increased mouse survival, compared with leucovorin-containing
combinations for all drug types tested.
In an
in
vivo Balb/c
systemic toxicity model, 5-FU/CoFactor induced less systemic toxicity than
5-FU/LV either alone or in combination drug regimens. Lower hematological
toxicity was observed including less thrombocytopenia, neutropenia and
lymphopenia. Furthermore, weight loss, a common side-effect associated with
5-FU/LV-based treatments, was quantitatively less severe with drug treatments
containing CoFactor. For example, while 5-FU/LV/gemcitabine induced >25%
weight loss in 91% of mice, significantly less (p < 0.05, Fisher’s exact
test) mice treated with 5-FU/CoFactor/gemcitabine (33% of mice) had this level
of weight loss.
“This
data suggests CoFactor increases the therapeutic index of 5-FU-based regimens in
combination with a broad range of cytotoxic drugs,” said Joan M. Robbins, Ph.D.,
ADVENTRX chief technical officer and co-author of the study. “As such, CoFactor
might be a valuable replacement for leucovorin in combination regimens because
of its enhanced antitumor activity with lower associated systemic toxicity.”
This
abstract “5,10-methylenetetrahydrofolate/5-fluorouracil
combination therapy shows enhanced antitumor activity and lower systemic
toxicity with a broad range of cytotoxic drugs” is
available via the Company’s Web site at www.adventrx.com.
ADVENTRX
has filed for clearance to initiate a Phase III trial in the US and recently
received clearance in the UK to begin an international Phase IIb trial with
CoFactor in metastatic colorectal cancer and plans to file in the first half of
this year for clearance to initiate an EU-based Phase III study in pancreatic
cancer.
About
CoFactor
CoFactor
is a folate-based biomodulator drug developed to enhance the activity of the
widely used cancer chemotherapeutic, 5-FU. Clinical data from previous clinical
trials in Europe have demonstrated clinical benefit and improved overall median
survival in patients with advanced tumors, including colorectal, pancreatic and
breast. CoFactor creates more stable binding, compared to leucovorin, of the
active form of 5-FU, FdUMP, to the target enzyme, thymidylate synthase (TS).
CoFactor bypasses the chemical pathway required by leucovorin to deliver the
active form of folate to allow 5-FU to work more effectively. This improves 5-FU
performance and lowers toxicity. ADVENTRX is the exclusive licensee of this
compound. More information on CoFactor can be found at http://www.adventrx.com/products/antic_cofactor.htm.
About
ADVENTRX
ADVENTRX
Pharmaceuticals is a biopharmaceutical research and development company focused
on introducing new technologies for anticancer and antiviral treatments that
improve the performance of existing drugs and address significant problems such
as drug metabolism, bioavailability and resistance. More information can be
found on the Company's Web site at www.adventrx.com.
Forward
Looking Statement
This
press release contains forward-looking statements within the meaning of the
"safe harbor" provisions of the Private Securities Litigation Reform Act of
1995. Such statements are made based on management's current expectations and
beliefs. Actual results may vary from those currently anticipated based upon a
number of factors, including uncertainties inherent in the drug development
process, the timing and success of clinical trials, the validity of research
results, and the receipt of necessary approvals from the FDA and other
regulatory agencies. For a discussion of such risks and uncertainties, which
could cause actual results to differ from those contained in the forward-looking
statements, see “Risk Factors” in the Company’s last quarterly report on Form
10-QSB, as well as other reports that the Company files from time to time with
the Securities and Exchange Commission. All forward-looking statements are
qualified in their entirety by this cautionary statement. The Company undertakes
no obligation to release publicly any revisions, which may be made to reflect
events or circumstances after the date hereof.
| Contact: | Investor Contact: |
| ADVENTRX Pharmaceuticals | Lippert, Heilshorn & Associates |
| Andrea Lynn | Jody Cain (jcain@lhai.com) |
| 858-552-0866 | Brandi Floberg (bfloberg@lhai.com) |
| 310-691-7100 | |
| Media Contact | |
| Lippert Heilshorn & Associates | |
| Mark Stuart (mstuart@lhai.com) | |
| 310-691-7116 |
Email Alerts
Enter your e-mail address to receive alerts whenever certain new company information is posted to this site