Preclinical gene therapy company Intrexon Corp. pulled down $25 million in a Series C1 round backed entirely by venture capital firm Third Security LLC.

The financing brings the total private equity investment in Blacksburg, Va.-based Intrexon to $32.3 million, most of it provided through funds managed by Radford, Va.-based Third Security.

Intrexon CEO Robert Beech said the funds will support the company's efforts to advance its lead gene therapy program for melanoma into clinical trials by the end of the year, pending regulatory approvals. A program in glioma is "not far behind," he said, adding that Intrexon is interesting in applying its novel gene therapy approach to other difficult-to-treat indications including prostate and other cancers, cardiac failure and progressive neural disorders such as Parkinson's disease.

Intrexon's platform represents an amalgamation of gene therapy technologies developed internally at Intrexon - previously known as Genomatix Corp. - as well as those acquired through a merger with RheoGene Inc., of Norristown, Pa. Financial terms for the merger, which was announced late last year and closed in the first quarter, were not disclosed.

Pre-merger, Intrexon focused on modulating protein-protein interactions in specific, subcellular locations. Beech explained that while small molecules and siRNA also interfere with protein-protein interactions, their "pan-cellular" effects can result in toxicity. Inhibition of a protein, such as the kinase AKT, can cause apoptosis in one location within the cell and promote survival in another location. Differentiating between those locations requires subcellular control that "must be done from the inside of the cell" through gene therapy, he said.

While Intrexon focused on the subcellular proteomics of gene programs, RheoGene was known for gene regulation and integration. Its flagship RheoSwitch Therapeutic System combines external control of gene programs through an activator drug with "the ability to use the body's natural feedback loops in the regulation of the on/off switch," Breech said. RheoGene's integrase platform allows for precise positioning of the gene programs in safe, stable and transcriptionally active locations within the genome of targeted cells.

Both companies had gene delivery programs, and Intrexon is working with both ex vivo approaches using autologous cells that are harvested and transduced outside the patient's body and then re-implanted, and in vivo delivery using nonreplicating viruses, biopolymers or biomechanical devices.

Together, those four elements - gene programs, regulation, integration and delivery - are all about "getting in place and controlling exogenous genes," Beech said.

The resulting preclinical candidates in melanoma and glioma involve "ex vivo transduction of autologous dendritic cells with an inducible gene program that is repositioned and timed in vivo to deliver the maximum immunotherapeutic response," he added.

Intrexon's merger with RheoGene grew out of a license agreement, and Intrexon still makes technology licenses outside of human therapeutic applications available through its Quadrant Biosystems division.

Beech said the $25 million Series C1 will be delivered in two tranches, the second of which is tied to undisclosed milestones. He declined to specify the amount of each tranche.

The Series C1 round follows a $5 million Series C in August 2006, a $1 million Series B1 in March 2006 and a $500,000 Series B in May 2005, all backed by Third Security's funds. An $825,000 Series A in May 2004 came from Carilion Health System, the Virginia Tech Foundation, and several angel investors.