| We are developing a portfolio of AAV-based products that have the potential to address some of today’s most intractable health problems. Our lead proprietary program is being developed for the treatment of inflammatory arthritis. We also have partnered programs addressing HIV/AIDS, congestive heart failure and Huntington’s disease. We are pleased of the progress that was made in each of these programs in 2006.
tgAAC94
Indication: Inflammatory arthritis
Development Stage: Phase I/II
Description
An adeno-associated viral (AAV) vector that delivers a DNA sequence that encodes a soluble form of the receptor for TNF-α (TNFR). Soluble TNFR inhibits TNF-α, a potent proinflammatory cytokine that plays a major role in inflammatory arthritis.
Designed for local administration into inflamed joints of patients who, despite being treated with systemic TNF-α antagonists, have one or more joints that continue to be inflamed.
Clinical Need
There are 2-3 million people in the United States alone living with inflammatory arthritis, including rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.
Inflammatory arthritis leads to significant morbidity, loss of productivity and healthcare spending. Costs in 1997, the most recent year for which data are available were $86.2 billion.
It is estimated that up to 40 percent of patients with rheumatoid arthritis have only partial responses to TNF-α inhibitor drugs.
2006 Achievements
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Received FDA approval to expand the Phase I clinical protocol of tgAAC94 in patients with inflammatory arthritis to include a higher dose and a greater number of patients, resulting in a change in the designated development status of the trial to a Phase I/II; |
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Reported encouraging interim results of the tgAAC94 Phase I/II clinical trial at three scientific conferences, demonstrating favorable safety and toxicity profiles and trends toward improvement in signs and symptoms of the disease; |
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Presented preclinical data demonstrating that delivery of the gene that encodes soluble TNFR with a vector based on AAV serotype 1 (AAV1) resulted in potent anti-inflammatory effects. While tgAAC94, which is based on AAV2, has been optimized for intra-articular administration, an AAV1 vector may allow for intramuscular delivery of soluble TNFR. |
2007 Objectives
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Complete enrollment of 120 patients with inflammatory arthritis in the Phase I/II clinical trial; |
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Present additional interim safety and efficacy data at multiple scientific conferences. |
tgAAC09
Indication: HIV/AIDS
Development Stage: Phase II
Partners: International AIDS Vaccine Initiative, Columbus Children's Research Institute and Children’s Hospital of Philadelphia. Description
An AAV-based vaccine used to deliver HIV antigens that are intended to stimulate the immune system and fight against HIV infection.
Intended as a prophylactic vaccine candidate designed to protect against HIV infection in HIV negative individuals and/or prevent progression to AIDS in people who become infected with HIV.
Clinical Need
An estimated 40 million people worldwide are living with HIV infections, nearly all of who are expected to experience life-threatening HIV-related complications within the next two decades.
The worldwide incidence of HIV/AIDS continues to increase.
There are more than 25 million HIV-positive people in sub-Saharan Africa, most of whom have limited access to health care.
Cases of HIV/AIDS are also increasing in most developed nations as well, even when access to diagnosis and treatment is more readily available.
2006 Achievements
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Reported results of the Phase I clinical trial of tgAAC09, an investigational HIV/AIDS vaccine candidate for the developing world, demonstrating no safety concerns and modest immunogenic responses; |
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Expanded the Phase II HIV/AIDS vaccine clinical studies underway in Southern Africa to include Uganda and Zambia; |
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Revised the collaboration and license agreement with the IAVI, Children's Hospital of Philadelphia and Columbus Children's Research Institute in support of the development and commercialization of HIV/AIDS vaccines for the developing world. |
2007 Objectives
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Report Phase II clinical data from the ongoing trials of tgAAC09; |
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Continue preclinical evaluation of a variety of vaccine candidates for use in the
developed world. |
MYDICAR™ (AAV1/SERCA2a)
Indication: Congestive heart failure
Development Stage: Preclinical
Partner: Celladon Corporation
Description
MYDICAR utilizes an AAV1 vector to deliver the SERCA2a gene to heart muscle tissue. Previous studies have shown that SERCA2a activity is decreased in heart tissue obtained from heart failure patients and that delivery of the SERCA2a gene can improve cardiac contractility in animal models of heart failure.
Clinical Need
Five million people in the United States alone have heart failure, and another 550,000 new cases are diagnosed each year.
Congestive heart failure contributes to or causes about 300,000 deaths annually.
There is no cure for CHF.
2006 Achievements
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Conducted preclinical studies in support of filing an Investigational New Drug (IND) application with the FDA; |
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Presented data from a preclinical study conducted in a sheep model designed to have a reduction in heart function similar to that found in patients with Class 3 heart failure; |
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Compared with control animals, six treated sheep showed significant improvement in heart function and contractility; |
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At one month after treatment, average heart function in treated sheep improved, while average function in control animals declined. |
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2007 Objectives
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Initiate a Phase I trial of MYDICAR in patients with cardiomyopathy and symptoms of heart failure. |
AAV-HDsiRNA
Indication: Huntington’s disease
Development Stage: Preclinical
Partner: Sirna/Merck
Description
An AAV vector that delivers a short interfering RNA (siRNA) and is designed to inhibit the activity of the gene that causes Huntington’s disease.
Clinical Need
Huntington's disease is a devastating, inherited, degenerative brain disorder that is progressive and always fatal.
The disease affects more than 30,000 people in the United States, with another 150,000 at risk of inheriting the deadly gene.
There is no effective treatment or cure for Huntington’s disease.
2006 Achievements
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Reported encouraging data from a preclinical study of an AAV-HDsiRNA construct in a mouse model of Huntington’s disease. |
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Injection of AAV-HDsiRNA into the brains of 5-week old mice did not negatively impact weight gain or a measurement of motor coordination. |
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At 13 weeks of age, treated mice did not exhibit hind limb clasping, an indicator of neurological dysfunction.
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2007 Objectives
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Work with Sirna/Merck to identify a therapeutic construct; |
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Conduct preclinical studies of the selected construct to support an IND filing in the first half of 2008. |
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