Halozyme and Intrexon to Develop Subcutaneous Recombinant Alpha 1-Antitrypsin Replacement Therapy

Intrexon will pay Halozyme $9 million up front to leverage Halozyme’s enzyme technology in the development of a subcutaneous injectable formulation of Intrexon’s drug candidate for indications resulting from A1AT deficiency. Potential future milestone payments could reach $54 million, and Intrexon could make up to 11% in royalties.

Under the worldwide, exclusive license, Halozyme’s rHuPH20 (recombinant human hyaluronidase) will be coupled with Intrexon’s recombinant human alpha 1-antitrypsin (rHuA1AT). Intrexon will fund all development and commercialization expenses for the program, which is currently in the scale-up phase of process development.

The deal with Intrexon comes less than a month after Halozyme inked a potentially $83 million deal with ViroPharma for the use of rHuPH20 in the development of a subcutaneous formulation of the latter’s hereditary angioedema drug, Cinryze™.

Alpha 1-antitrypsin (A1AT) is a protease inhibitor made in the liver that works to protect the lungs and the liver. Deficient production of this protein is caused by a genetic defect and it can lead to chronic lung diseases such as emphysema as well as liver disease. Treatment involves replacement of the missing A1AT protein administered intravenously once weekly for most patients and it is considered lifelong therapy.

Several intravenous A1AT products have received FDA approval in the U.S. Currently the A1AT protein is gathered and processed from plasma collected from healthy human donors. Intrexon is using its synthetic DNA platform for high-level expression of recombinant A1AT. rHuA1AT provides a protective effect from inflammatory cell proteases, especially neutrophil elastase, the companies report.

"The combination of Intrexon's synthetic DNA platform for high-level A1AT production with Halozyme's subcutaneous enzyme technology may enable the first recombinant human A1AT replacement therapy with a more patient-friendly administration profile," states Gregory I. Frost, Ph.D., Halozyme's president and CEO.

Halozyme's rHuPH20 enzyme facilitates the absorption and dispersion of drugs or fluids that are injected under the skin. When injected under the skin rHuPH20 transiently generates channels in tissues underlying the outer layers of the skin to increase the absorption and spread of injected drugs.

When combined with rHuPH20, molecules as large as 200 nanometers may pass freely through the extracellular matrix, which recovers its normal density within approximately 24 hours, leading to a drug delivery platform that does not permanently alter the architecture of the skin, according to the companies.

rHuOH20 was developed on Halozyme's Enhanze™ technology, the drug delivery platform designed to increase the absorption and dispersion of biologics. Besides Intrexon and ViroPharma, the company has partnerships with Roche and Baxter to apply Enhanze to therapeutic biologics including Herceptin, MabThera, and immunoglobulin.