Using a major scientific meeting as its stage, VasGene Therapeutics Inc. stepped forward and introduced a broad audience to its cancer technology.

The Los Angeles-based firm has pushed a next-generation inhibitor of vascular endothelial growth factor (VEGF) into initial clinical studies, with promising safety and early efficacy data seen thus far. VasGene reported its findings last week at the American Society of Hematology meeting in San Diego.

Called Veglin (VEGF-AS), its lead antisense product employs a three-prong approach to inhibiting tumor growth by targeting VEGF's A, C and D isoforms. VEGF A is associated with angiogenesis and blood vessels, while VEGF C and D are associated with lymphangiogenesis and lymph vessels.

Company founder Parkash Gill discovered the compound as part of his research as a medical professor at the Norris Cancer Center, part of the University of Southern California's Keck School of Medicine.

"We applied an approach of using antisense fragments to target the messenger RNA for the gene that degrades the message, so protein is not produced," Gill told BioWorld Today. "When we did that, there was a very significant effect on tumor cells - they were not dividing in vitro. So after testing a few of these molecules, we picked a couple and tested them in an in vivo model with a particular tumor in immunodeficient mice and treated them with the compound. And sure enough, it reduced the rate of tumor growth."

He said VasGene's approach not only targets blood vessel growth, but also tumor cells, increasing the likelihood of an antiangiogenic product's effectiveness as a monotherapy. Though prior preclinical findings on the compound have recently been published by various other researchers, Gill said the results presented last week marked the first public disclosure of clinical data among peers.

Principal investigator Alexandra Levine of the Norris Cancer Center outlined Phase I data that pointed to Veglin's safety in a number of cancers and HIV-related malignancies through eight escalating dose levels, ranging from 15 mg/m2 to 85 mg/m2. There was no evidence of hypertension or other side effects seen with other VEGF antagonists.

Used as a single agent, Veglin also demonstrated evidence of tumor response following one or two cycles of therapy in some of the trial's 26 patients, who had diseases such as lymphoma, AIDS-Kaposi's sarcoma, renal-cell carcinoma, sarcoma, colon and lung cancer, as well as other malignancies.

"We know that we have not observed any [cardiovascular or blood loss] side effects," Gill said, noting the product's differentiation from Avastin, the antibody-based anti-VEGF compound in development by South San Francisco-based Genentech Inc. He added that Veglin lacks the immune system stimulation seen with other antisense products. "It is clear that nearly all other compounds in development are targeting one protein of VEGF, but our compound also inhibits VEGF C," he said.

He said that allows Veglin to target a broader category of VEGF proteins than other competing development-stage products, though he acknowledged the skepticism associated with antisense drugs. The company expects to begin Phase II trials of Veglin as monotherapy and combination therapy during the first quarter of next year.

The drug candidate's early development was supported by VasGene's first round of venture capital financing, worth $4.5 million. Closed in the spring of 2002, the funds also were used to secure lab and office space for the nascent company. Gill said another funding round is scheduled for next year, with a commitment already secured from Philadelphia-based RAM Capital LLC, VasGene's primary investor to date.

A pair of preclinical programs is further down the development path.

Ephrin, a B2/EphB4 antagonist, is designed to prevent angiogenesis in eye diseases by inhibiting growth of tumors and constricting their blood supply. The product's underlying technology, which also has applications in cancer, is licensed from the California Institute of Technology in Pasadena. Its VAS012 small molecule belongs to a new class of anticancer agents designed to be cytotoxic to proliferating endothelial cells.

Gill said the majority of VasGene's staff includes researchers, with consultants employed on a part-time basis to provide safety and regulatory support. The company is positioned to carry on research activities on its own, but going forward, product development likely would include partnering plans for the ocular product and perhaps the others as well.

Gill, who said he has played a research role in developing three FDA-approved products, sees VasGene as well positioned for continued growth.