MONTREAL--(Marketwire - January 08, 2009) - TOPIGEN Pharmaceuticals Inc., a clinical-stage
biopharmaceutical company focused on innovative respiratory therapeutics,
today announced results of a Phase 2 14-day study of inhalable TPI ASM8 in
patients with asthma. TPI ASM8 utilizes TOPIGEN's proprietary
oligonucleotide technology and is unique because it inhibits multiple
targets associated with inflammation in asthma potentially enabling
broader, but more specific, pharmacological activity with limited systemic
availability and a favorable safety profile.
Following a controlled allergen challenge in patients with mild asthma, TPI
ASM8 did not demonstrate statistical significance in the primary efficacy
endpoint -- late asthmatic response. However, trends were observed on other
endpoints that are consistent with statistically significant results
observed in an earlier Phase 2 study. In addition, TPI ASM8 continues to
demonstrate a favorable safety and pharmacokinetic profile consistent with
all prior studies. TOPIGEN plans to continue Phase 2 clinical development
of TPI ASM8 with the initiation of a further trial in patients with asthma
and additional toxicology studies to support longer-term trials and
regulatory agency review.
"We believe that TPI ASM8 has a very compelling clinical profile for the
treatment of moderate to severe asthma," said Mark Parry-Billings, Ph.D.,
Chief Executive Officer of TOPIGEN. "As an inhalable candidate with a well
established safety profile, TPI ASM8 offers a significant advantage over
other treatments in development for this patient population -- primarily
injectable monoclonal antibodies. Importantly, TPI ASM8 inhibits multiple
key inflammatory targets which are increasingly the focus of large pharma
drug development pipelines. We plan to expand the TPI ASM8 program with the
initiation of additional dose-finding studies in the first half of 2009 and
we are optimistic that we will be able to define the potential role TPI
ASM8 can play in providing much needed treatment options for patients with
moderate to severe asthma who do not respond adequately to the current
standard of care."
The Phase 2 14-day trial was a randomized, crossover, placebo-controlled
allergen challenge study designed to evaluate the effect of TPI ASM8 in
patients with asthma. Primary endpoints were safety and late asthmatic
response and secondary endpoints included target mRNA knockdown, early
asthmatic response and sputum eosinophils. Eosinophils are cells that are
recognized as key contributors to the inflammation and airway destruction
in all grades of asthma and other allergic diseases.
Eighteen patients enrolled in the study received TPI ASM8. A difference
versus placebo in late asthmatic response was not seen and while TPI ASM8
attenuated the rise in sputum eosinophils post allergen challenge by 50%,
this difference in comparison to placebo did not achieve statistical
significance. TOPIGEN believes that a blunted and variable response to
allergen challenge may have impacted the ability to discriminate a
treatment effect. TPI ASM8 continued to generate a positive safety profile
and was well tolerated with no reported serious adverse events.
Earlier this year, statistically significant positive results from a Phase
2 three-day allergen challenge study of TPI ASM8 were published in the
American Journal of Respiratory and Critical Care Medicine. TPI ASM8, at
low lung doses, had a significant effect on the late and early asthmatic
response and attenuated the rise in sputum eosinophils by 54%, a difference
that was statistically significant. Target mRNA was knocked down
approximately five fold and was also statistically significant. The drug
was shown to be safe and well-tolerated and systemic exposure was minimal
following once daily inhalation.
About Inhaled TPI ASM8
TPI ASM8 is based on TOPIGEN's proprietary oligonucleotide technology and
is designed specifically to reduce the recruitment and persistence of
chronic inflammatory cells and their associated release of cytokines -- all
key components underlying the cause of the disease. TOPIGEN's
oligonucleotides are distinct from other oligonucleotide approaches in that
they are designed specifically to be nonimmunostimulatory. TPI ASM8 targets
two distinct cellular pathways involved in allergic airway inflammation by
inhibiting the recruitment of allergic inflammatory cells, via an effect on
the CCR3 receptor and by reducing the persistence of allergic inflammatory
cells via interference with the common beta sub-unit for the receptors of
interleukin IL-3, IL-5 and GM-CSF. This pioneering multi-targeted approach
of blocking the synthesis of specific receptors with RNA-silencing
technology is expected to have advantages over current medications by
providing broader, but specific, pharmacological activity with limited
systemic availability, in a convenient, inhaled formulation.
About Asthma
Asthma is a chronic inflammatory disease of the airways in which many cells
and cellular elements play a role -- in particular, eosinophils, mast cells
and T-lymphocytes. In susceptible individuals, this inflammation causes
recurrent episodes of wheezing, breathlessness, chest tightness and
coughing, particularly at night and/or in the early morning. The
inflammation also causes an associated increase in the airway
hyperresponsiveness to a variety of stimuli. Symptoms are usually
associated with widespread, but variable airflow obstruction that is at
least partly reversible with treatment.
About TOPIGEN
TOPIGEN Pharmaceuticals is developing a clinical pipeline of innovative
therapeutics for respiratory diseases, including asthma and COPD. The
Company's unique, multi-targeted oligonucleotide product candidates have
compelling therapeutic profiles that address major unmet medical needs.
TOPIGEN's business strategy is to advance products through clinical proof
of concept and out-license to partners for commercialization.
www.topigen.com
