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Targeted Genetics Corporation
TARGETED GENETICS PRESENTS ADDITIONAL DATA FROM ITS
INFLAMMATORY ARTHRITIS PROGRAM AT THE 13th ANNUAL
CONGRESS OF THE EUROPEAN SOCIETY OF GENE THERAPY
Results demonstrate safety and reduction of mean tenderness and swelling
scores of the treated joint; results support continued study of tgAAC94 in
conjunction with TNF-alpha antagonists in inflammatory arthritis
Seattle, WA and Prague, Czech Republic October 31, 2005 Targeted Genetics Corporation (Nasdaq:
TGEN) presents additional results from its initial Phase I clinical trial of tgAAC94 in patients
with inflammatory arthritis, in a poster session during the 13th Annual Congress of the
European Society of Gene Therapy in Prague, Czech Republic, October 29 November 1. Barrie J.
Carter, Ph.D., Executive Vice President and Chief Scientific Officer at Targeted
Genetics, is presenting the data in a poster session at the conference. This presentation
highlights data from the Phase I clinical study evaluating the safety of intra-articular injection
of two escalating dose levels of tgAAC94 in patients not on concomitant systemic TNF-alpha
The Phase I clinical trial was designed to evaluate safety of a single dose of tgAAC94 injected
locally into the arthritic joint of subjects suffering from inflammatory arthritis. Enrollment
was limited to those not currently on concomitant TNF-alpha antagonist therapies. Fifteen subjects
who enrolled in the trial were randomized to receive either one of two escalating dose levels of
tgAAC94 (n=11) or a placebo (n=4). The trial contained a placebo arm at each dose level, which was
included to assess safety and determine whether any adverse events were attributable to an
intra-articular injection itself, as opposed to an intra-articular injection of tgAAC94.
Preliminary safety data were previously reported by the Company after all subjects had been
evaluated for 4 weeks after injection. Secondary endpoints were also reported on a subset of
subjects that had completed up to eight weeks of follow-up. In those treated with tgAAC94 and
followed for up to eight weeks, there was an indication of sustained improvement in signs and
symptoms of disease in injected joints. The trial is closed for enrollment and patients will
continue to be followed for 24 weeks after injection.
All subjects have now been followed for at least 12 weeks after injection of tgAAC94 or placebo.
Data presented at this time point demonstrate that:
I am very encouraged that the results from later time points in the study continue to demonstrate
the safety of injecting tgAAC94 directly into affected joints, and the observed trends in
improvements in tenderness and swelling scores of treated joints persist, said Carter. We
believe that the data presented today support the potential of our experimental therapeutic
product, tgAAC94, to treat patients who suffer with inflammatory arthritis. We are excited to have
recently initiated our next Phase I clinical study in patients with inflammatory arthritis who have
not experienced an adequate response to anti-TNF-alpha therapy and who might have ongoing
destructive inflammation in select joints.
About the Follow-on Phase I Clinical Trial of tgAAC94
In October, 2005, Targeted Genetics initiated a follow-on Phase I clinical trial of tgAAC94
administered directly to affected joints of patients with inflammatory arthritis who may be
receiving concomitant systemic TNF-alpha antagonist therapy. The study is designed to enroll up to
40 subjects and will evaluate tgAAC94 at two dose levels in patients with rheumatoid arthritis,
psoriatic arthritis or ankylosing spondylitis and who may be receiving concomitant treatments of
anti-TNF-alpha therapy. tgAAC94 is being developed initially as a complementary therapy for
patients who may not achieve adequate relief with existing arthritis treatments or others who have
disease limited to a few joints and therefore, may not need systemic protein therapies. This
targeted, localized approach to treatment is intended to provide therapeutic benefit that will
enable patients to achieve better control and relief of the signs and symptoms of their disease.
In the first segment of the double-blind, placebo-controlled study, subjects will receive a single
intra-articular injection of tgAAC94 or placebo in the affected joint and be monitored until
swelling in the target joint reaches pre-determined criteria for re-injection. At that time, both
tgAAC94-injected subjects and those initially injected with placebo will receive a second injection
of tgAAC94 in the affected joint as part of the open-label segment of the study. The primary
endpoint of the study is to establish the safety of a higher dose and of repeat administration of
tgAAC94 into the joints of subjects with or without concomitant TNF-alpha inhibitor therapy.
Secondary endpoints include evaluation of pain, swelling, duration of response, and overall disease
activity following intra-articular administration of tgAAC94 to affected joints, as well as
molecular markers of disease. Additionally, changes in joint inflammation and joint damage will be
assessed in a subset of patients using magnetic resonance imaging.
tgAAC94 uses Targeted Genetics recombinant AAV (rAAV) vector technology and contains a gene that
encodes a soluble form of the TNF-alpha receptor (TNFR:Fc). Soluble TNFR inhibits the immune
stimulating activity of TNF-alpha. Direct injection of tgAAC94 into affected joints leads to the
localized production of soluble TNFR by the patient s joint cells. Localized production of TNFR
reduces the activity of TNF-alpha within the joint, potentially leading to a decrease in the signs
and symptoms of inflammatory disease and inhibition of joint destruction. Preclinical studies have
demonstrated the efficacy of tgAAC94 in reducing inflammation and joint damage. Data from
preclinical studies conducted in an animal model of inflammatory arthritis demonstrated that a
single injection of rAAV encoding a soluble form of the rat TNFR:Fc vector into the ankles of
arthritic rats resulted in a significant reduction in ankle and hind paw swelling as measured by
arthritis index scores.
tgAAC94 is being developed as a potential supplement to systemic anti-TNF-alpha protein therapy for
use in patients with inflammatory arthritis who have one or more joints that do not respond to
systemic protein therapy. Local administration of a DNA sequence encoding a soluble TNFR
potentially may supplement currently used drugs in a number of inflammatory conditions. In
addition, a locally administered anti-TNF-alpha therapy could also be useful in patients who have a
limited number of joints affected by inflammatory arthritis that are at a risk for progressive
joint damage but who may not require systemic therapy. The characteristics of AAV vectors make them
well suited for delivery of genetic material to joints and other organs. The Company s rAAV
technology platform is used to deliver genes and is based on AAV, a naturally-occurring virus that
has not been associated with any disease in humans.
About Targeted Genetics
Targeted Genetics Corporation is a biotechnology company committed to the development and
commercialization of innovative targeted molecular therapies for the prevention and treatment of
inflammatory arthritis and other acquired and inherited diseases with significant unmet medical
need. We use our considerable knowledge and capabilities in the development and manufacturing of
gene delivery technologies to advance a diverse product development pipeline. Our product
development efforts target inflammatory arthritis, AIDS prophylaxis, congestive heart failure,
Huntington s disease and hyperlipidemia. To learn more about Targeted Genetics, visit our website
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements regarding our intellectual property, research
programs and clinical trials, our product development and our potential development platforms
including tgAAC94 and other statements about our plans, objectives, intentions and expectations. In
particular, the statements regarding the Company s pipeline, ability to maintain patients in the
trial for follow-up and future clinical trial plans are forward-looking statements. These
statements, involve current expectations, forecasts of future events and other statements that are
not historical facts. Inaccurate assumptions and known and unknown risks and uncertainties can