Pipex Pharmaceuticals, Inc. (AMEX: PP), a specialty pharmaceutical
company developing innovative late-stage drug candidates for the
treatment of central nervous system and autoimmune diseases, today
announced that it has acquired an oral, once-daily candidate for
the treatment of rheumatoid arthritis (RA) which has completed a
160 patient, multi-center, double-blind, randomized,
placebo-controlled Phase II clinical trial for the treatment of
rheumatoid arthritis (RA). Rheumatoid arthritis is an autoimmune
disease which affects approximately 20 million people worldwide.
Oral dnaJP1 has been developed using computer-aided, rational
drug design techniques which resulted in a short synthetic peptide
derived from a heat shock protein dnaJ. Heat shock proteins and
dnaJ are upregulated during cellular stress, including inflammation
and autoimmune diseases. Heat shock protein responses have been
found in several other autoimmune diseases other than RA, including
Juvenile idiopathic arthritis (JIA), multiple sclerosis (MS) and
inflammatory bowel disease (IBD). The mechanism of action of dnaJP1
relies on selectively inducing an immune shift of a T-cell function
from inflammatory to regulatory, thus inhibiting disease-related
inflammation and inducing a tolerogenic immunologic response. Oral
dnaJP1 is a new chemical entity (NCE) which is covered by issued
U.S. and international patent filings including composition of
matter and methods of use patents. This phase II clinical program
was supported by a $5 million grant from the National Institutes of
Health (NIH).
Below is a summary of the response data from the phase II
clinical trial for oral dnaJP1 at the ACR20 endpoint along with the
percentage of ACR20 response at day 112, 140 and 168 as well as day
112, 140 and 168 and day 196 follow-up without further drug
therapy. ACR20 is a composite endpoint developed by the American
College of Rheumatology and generally accepted as an FDA approvable
scoring criteria.
Oral dnaJP1 ACR20
AUC Days 112, 140, 168
and 196 P=0.04
AUC Days 112, 140, 168 P=0.09
Consistent with the disease modifying process of active immune
tolerization, there was a progressive separation between treatment
and placebo groups for both ACR20 and ACR50 endpoints after day
112. Oral dnaJP1 treated patients achieved a 40.7% ACR20 response
at follow up versus 21.5% of placebo-treated patients (CMH test
p=0.007, GEE p < 0.001). The proportion of dnaJP1-treated
patients who achieved an ACR20 response at Days 112, 140, 168, and
follow up was significantly higher than that of placebo-treated
patients (CMH p=0.03; GEE p=0.0005). A statistically significant
difference was also seen for the AUC when more strict ACR50
criteria are applied (GEE p-value=0.02). The primary endpoint (AUC
112-140-168) found more patients succeeding on dnaJP1 (p=0.09 by
CMH and p=0.04 by adjusted GEE). GEE analysis was employed to
correct for intercenter variability and this was possible as
randomization occurred per center. Patients in this study were
permitted to be on currently available standard background
therapies, including HCQ, corticosteroids, sulfasalazine,
analgesics, NSAIDS, but not on disease modifying agents or
biologics.
From an immunologic standpoint, oral dnaJP1 also demonstrated an
80% reduction in the production in-vitro of TNF-alpha by T cells (p
< 0.007), a hallmark cytokine of inflammation. Additionally,
oral dnaJP1 treated patients demonstrated an increase in
tolerogenic cytokines and immune response genes, including IL-10
and FoxP3 production.
In combination with low dose etanercept (Enbrel�), an animal
equivalent of dnaJP1 has also demonstrated a significant reduction
of mean arthritis scores was achieved on day 23 (p=0.0004) as
compared to placebo in preclinical animal models. Additionally,
oral dnaJP1 and single low dose Etanercept combination therapy led
to a significant improvement of the histological score in the
joints (p=0.014 vs. untreated). Lastly, combination therapy of
etanercept and oral dnaJP1 led to an antigen specific increase of
tolerogenic cytokines, including IL-10 and IL-4 production and up
regulation of CTLA-4 expression.
Dr. Salvatore Albani, Chairman of the Arizona Arthritis Center
at the University of Arizona and inventor of this program,
commented, "Due to its oral activity and plausible long term
durable response rate seen in RA patients in the initial
multi-center, placebo controlled Phase II clinical trial, oral
dnaJP1 may have an important clinical advantage over current
injectable RA treatments which have significant toxicities. Our
preliminary studies also strongly suggest that the mechanism of
action of dnaJP1 is complementary to current biologics, thus
providing the opportunity to develop combination therapies which
may improve currently used regimens. The long term statistically
significant improvement in clinical scores as seen by ACR20 and
ACR50 following cessation of drug therapy further suggests that
this technology may be inducing a tolerogenic response."
Nicholas Stergis, Pipex's Chief Executive Officer, stated, "We
are pleased to have broadened our therapeutic pipeline of products
with the acquisition of this innovative program. Oral dnaJP1
certainly complements our existing clinical stage immunology
programs which include TRIMESTA, our oral phase II/III clinical
program in multiple sclerosis and our CD4 inhibitor technology. We
have been equally impressed with the rigor and quality of the
scientific data, along with the level of grant funding this program
has received over the years from the NIH. We look forward to
reporting additional clinical data from this study later this
year."
About Oral dnaJP1
Oral dnaJP1 is a once-daily epitope specific immunotherapy for
rheumatoid arthritis (RA) patients. Oral dnaJP1 is a heat shock
protein (hsp)-derived peptide which was previously identified as a
contributor of T cell mediated inflammation in RA. Immune responses
to hsp are often found at sites of inflammation and have an
initially amplifying effect that needs to be downregulated to
prevent tissue damage. The mechanisms for this regulation involve T
cells with regulatory function that are specific for hsp-derived
antigens. This regulatory function is one of the key components of
a "molecular dimmer" whose physiologic function is to modulate
inflammation independently from its trigger. This function is
impaired in autoimmunity and could be restored for therapeutic
purposes.
Oral dnaJP1 contains the five amino acid cassette present on
most of the HLA class II alleles associated with RA. In preclinical
work, the most relevant epitope was mapped and showed its
contribution to pro-inflammatory T cell responses in vitro in
patients with active RA. These data led to the hypothesis that the
sequences shared between immunologically relevant self and foreign
proteins (HLA and hsp) would affect thymic selection and peripheral
activation of potentially pathogenic T cells at different stages
(multistep molecular mimicry hypothesis, Nature Medicine 1995).
The mechanistic hypothesis is that mucosal tolerization to
dnaJP1 could determine immune tolerization primarily of T cells and
secondarily of APC. The effects of immune tolerance are initially
peptide-specific but affect secondarily non-epitope specific
pathways. Immune tolerance could translate into clinical
benefit.
The phase II clinical trial enrolled 160 patients with RA in 11
centers nationwide, including University of California, San Diego
(UCSD), Standard University, Mayo Clinic, Virginia Mason
University, Instituto Mexico, Del Serguo, University of Arizona,
John Hopkins University and University of California, Irvine.
Patients in the oral dnaJP1 arm of the trial received 25 mg of oral
dnaJP1 daily for six months with a one month follow up.
Through a majority-owned subsidiary, Pipex has an exclusive
worldwide license to issued U.S. patents and pending international
patents relating to composition of matter, along with methods of
use.
About Rheumatoid Arthritis
Rheumatoid arthritis is a chronic inflammatory disease that
leads to pain, stiffness, swelling and limitation in the motion and
function of multiple joints. If left untreated, rheumatoid
arthritis can produce serious destruction of joints that frequently
leads to permanent disability. Though the joints are the principal
body part affected by rheumatoid arthritis, inflammation can
develop in other organs as well. The disease currently affects over
two million Americans, almost 1% of the population, and is two to
three times more prevalent in women. Onset can occur at any point
in life but is most frequent in the fourth and fifth decades of
life, with most patients developing the disease between the ages of
35 and 50. Over 20 million people suffer from rheumatoid arthritis
worldwide and the global market is estimated at over $6.3 billion.
DMARDs, including biologics, accounted for nearly $5.0 billion of
that figure.
About Pipex Pharmaceuticals, Inc.
Pipex Pharmaceuticals, Inc. ("Pipex") is a specialty
pharmaceutical company that is developing proprietary, late-stage
drug candidates for the treatment of central nervous system and
autoimmune diseases. Pipex's strategy is to exclusively in-license
clinical-stage drug candidates for the treatment of unmet medical
diseases. Pipex is focused on developing products to treat, Dry
Age-Related Macular Degeneration (AMD), Multiple Sclerosis (MS),
Rheumatoid Arthritis (RA) and Fibromyalgia. For further information
please visit www.pipexinc.com.
This press release contains forward-looking statements, within
the meaning of Section 21E of the Securities Exchange Act of 1934,
that reflect Pipex Pharmaceuticals, Inc.'s current expectations
about its future results, performance, prospects and opportunities,
including statements regarding Oral dnaJP1 having an important
clinical advantage over current injectable RA treatments, Oral
dnaJP1 inducing a toleragenic response, and reporting additional
data from the study later this year. Where possible, Pipex has
tried to identify these forward-looking statements by using words
such as "anticipates," "believes," "intends," or similar
expressions. These statements are subject to a number of risks,
uncertainties and other factors that could cause actual events or
results in future periods to differ materially from what is
expressed in, or implied by, these statements including the risks
set forth in our Form 10-Q for our fiscal quarter ended June 30,
2008 and other filings with the Securities and Exchange Commission.
We cannot assure you that we will be able to successfully develop
or commercialize products based on our technologies, particularly
in light of the significant uncertainty inherent in developing,
manufacturing and conducting preclinical and clinical trials of new
pharmaceuticals, and obtaining regulatory approvals, that our
technologies will prove to be safe and effective, that our cash
expenditures will not exceed projected levels, that we will be able
to obtain future financing or funds when needed, that product
development and commercialization efforts will not be reduced or
discontinued due to difficulties or delays in clinical trials or
due to lack of progress or positive results from research and
development efforts, that we will be able to successfully obtain
any further grants and awards, maintain our existing grants which
are subject to performance, that we will be able to patent,
register or protect our technology from challenge and products from
competition or maintain or expand our license agreements with our
current licensors, or that our business strategy will be
successful. All forward-looking statements made in this press
release are made as of the date hereof, and Pipex assumes no
obligation to update the forward-looking statements included in
this news release whether as a result of new information, future
events, or otherwise.
Enbrel� is a registered trademark of Wyeth and Amgen, Inc.
For Further Information Contact: Nicholas Stergis Chief
Executive Officer (734) 332-7800 Thomas Redington Investor
Relations Redington, Inc. (203) 222-7399
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