Alpha-1 Disease

Alpha-1 Disease

The Alpha-1 Project

Inhibrx’s AAT-Fc has the potential to benefit Alpha-1 Disease patients through improved efficacy and less frequency dosing. This therapeutic is supported by the Alpha-1 Project and is expected to initiate clinical studies in 2017.

Genetic emphysema is caused by a deficiency in Alpha-1 antitrypsin (AAT), a protein that protects tissues such as lung from the destructive enzymes of inflammatory cells. In people who have AAT deficiencies, these inflammatory enzymes cause excessive breakdown of lung tissue, resulting in emphysema – also a key feature of a syndrome known as COPD (chronic obstructive pulmonary disease). Recent studies show augmentation therapy with plasma derived AAT protein is effective in slowing the progression of lung destruction in patients with Alpha-1.

Inhibrx developed a fully active recombinant AAT IgG Fc fusion protein engineered to eliminate inactivation by oxidation and further extend half-life. In animal studies, this therapeutic injected intravenously reached the lung and significantly inhibited neutrophil elastase activity.

Sensitive ex vivo immunogenicity testing indicate a lower risk of immunogenicity with Inhibrx’s AAT-Fc therapeutic compared to plasma derived AAT. Plasma derived products are produced from pooled donor plasma, wherein allelic variation can introduce multiple protein species into the final product, thereby enhancing the risk of immunogenicity. Recombinant proteins are derived from clonal genetic material enabling the production of homogenous therapeutic protein products.

Inhibrx’s AAT-Fc therapeutic is manufactured in mammalian cells, the industry standard for commercial therapeutic antibody and Fc fusion protein production. Cell line development data indicate this therapeutic is a high yielding protein that is easily scalable and will have superior manufacturing economics.