VAP-1 ANTIBODY FOR INFLAMMATORY / FIBROTIC DISEASE
A key factor in establishing and maintaining chronic inflammation is the excessive accumulation of white blood cells, or leukocytes, in the tissue (e.g. surrounding joints, or in skin). Leukocytes exit the blood stream and move towards the site of inflammation through a series of processes, including attachment to specific adhesion proteins. These proteins are often expressed in response to initial inflammatory signals. Biotie has developed a fully human antibody that directly inhibits one such adhesion molecule – VAP-1. An exciting feature of VAP-1 is that its expression is thought to be upregulated only at the site of inflammation, limiting potential side effects of a product targeting this pathway.
Vascular adhesion protein-1 (VAP-1) as a therapeutic target
A key factor in establishing and maintaining chronic inflammation is the excessive accumulation of white blood cells, or leukocytes, in the tissue (e.g. surrounding joints, or in skin). Leukocytes exit the blood stream and move towards the site of inflammation through a series of processes, including attachment to specific adhesion proteins. These proteins are often expressed in response to initial inflammatory signals. VAP-1 is an adhesion molecule expressed on the endothelial lining of blood vessels. An exciting feature of VAP-1 is that its expression is thought to be upregulated only at the site of inflammation, limiting potential side effects of a product targeting this pathway.
BTT-1023 product profile
BTT-1023 is a fully human monoclonal antibody that specifically binds to VAP-1. Biotie has previously demonstrated encouraging efficacy and safety for BTT-1023 in early clinical studies in rheumatoid arthritis and psoriasis patients and in a range of preclinical models of inflammatory diseases, including COPD and certain neurological conditions. More recently, Biotie has generated new data indicating that VAP-1, in addition to its clinically demonstrated role in inflammatory diseases, has an important role in fibrotic diseases. These data, generated in part in collaboration with National Institute for Health Research Liver Biomedical Research Unit at the University of Birmingham, UK, reveal significant potential for BTT-1023 in certain niche liver inflammatory fibrotic diseases. These data will be published at upcoming scientific and medical conferences and represent potentially new and exciting development opportunities for BTT-1023 in a range of conditions.
Clinical trial status
Biotie has completed three clinical studies with its VAP-1 antibody including a single dose, placebo-controlled study in healthy volunteers and two Phase 1b trials in patients with rheumatoid arthritis and psoriasis, respectively. These trials have shown that BTT1023 is safe and generally well tolerated when administered intravenously (IV) at repeated doses of up to 8mg/kg.
Although the Phase 1b trials were not designed to enable formal statistical evaluation of efficacy, in several assessments of treatment effect in the RA trial, including Disease Activity Score based on 28 joint assessment (DAS28) criteria and American College of Rheumatology criteria (ACR), the responses observed in patients taking higher doses of BTT1023 were greater than in the placebo group, including several patients reaching an ACR50 response (a 50% reduction in their ACR score) during treatment.
In the third quarter 2010, data from the Phase 1b trial in patients with psoriasis was reported. While the efficacy signals were not as robust as in the RA trial, there were several patients on active drug that experienced an improvement in their condition. Two patients reported a transient exacerbation in their psoriasis symptoms after treatment had been completed; apart from these two cases, no serious or severe adverse events were reported.
Program status
Biotie is currently optimizing the scale-up of the manufacturing process for BTT-1023 and expects to start proof-of-concept clinical studies in selected indications in H2 2012.
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Updated April 24, 2012