With its lead gene therapy candidate for HIV in Phase II trials, Virxsys Corp. gained access to RNA-based preclinical assets and core technology through the acquisition of Intronn Inc.

"Virxsys is a delivery company - we just didn't have enough payloads," Virxsys President and CEO Riku Rautsola said. The acquisition of Intronn provides mRNA payloads that can be delivered using Virxsys' lentiviral vector-based gene therapy approach, he added.

The two privately held companies declined to specify terms of the deal, except to say it was an all-stock transaction. Employees from Raleigh, N.C.-based Intronn will be integrated into Virxsys' Gaithersburg, Md., headquarters.

For Virxsys, the near-term focus will remain on lead candidate VRX496, a gene therapy for HIV that delivers an antisense sequence targeting the HIV envelope protein within a lentiviral vector. The vector is inserted into CD4 T cells extracted from the patient, which are then reinfused.

In a Phase I study, VRX496 decreased viral load and was well tolerated, and preliminary Phase II data confirmed previous safety findings. The drug is being studied in a Phase II trial evaluating bolus doses in patients who have failed other HIV drugs, which Rautsola said should result in some data in the first quarter of 2008. An investigator-initiated Phase I/II trial evaluating the transfer of patients to VRX496 who have stabilized on other HIV drugs also is ongoing, and a Phase II trial in treatment-naïve HIV patients is due to start in the next six to eight weeks.

"We're trying to decide on the optimum dose and patient population to move into Phase III," Rautsola said. He also noted that while other companies produce research-grade lentiviral vectors, VRX496 is the only lentiviral gene therapy approach being studied in FDA-sanctioned clinical trials.

Lentiviruses are a subclass of retroviruses and may offer advantages over the adenoviral (AV) and adeno-associated viral (AAV) vectors often used in gene therapy. Lentiviral vectors have longer exposure and better cell penetration, Rautsola said, as well as the potential for increased safety.

"A big drawback of AV and AAV is they usually have immunogenicity problems," Rautsola said. He added that while retroviruses can be associated with carcinogenicity, the HIV-derived lentiviral vectors, such as those used by Virxsys, are not carcinogenic. The company has seen no serious side effects in 50 patients treated over several years.

The high-profile death of young gene therapy patient Jesse Gelsinger in 1999, which resulted in a flurry of negative media coverage, came after he was treated with an AV construct. Safety concerns also have plagued retroviral gene therapy trials in France, and most recently, an AAV trial conducted by Targeted Genetics Corp. However, a panel of federal experts agreed last week that more data were needed to determine whether the July death of a woman in the Targeted Genetics trial was attributable to the gene therapy or to other factors. (See BioWorld Today, Oct. 14, 1999; July 30, 2007; and Sep. 18, 2007.)

Beyond VRX496, Virxsys is integrating its preclinical programs with those acquired from Intronn. Both companies had early stage programs for hemophilia and cholesterol, and Virxsys also was working on an HIV therapeutic vaccine. Moving forward, cancer is also an area of interest to the company.

Intronn's RNA programs are based on its spliceosome-mediated RNA trans-splicing (SMaRT) technology. While many RNA companies use RNAi to block certain genes, Intronn's approach uses mRNA, which will be delivered using Virxsys' lentiviral vectors, to insert new sequences into a gene that have the potential to repair mutations or alter gene expression.

Rautsola said Virxsys already has done studies under a nondisclosure agreement that combined Intronn's RNA with Virxsys' lentiviral delivery.

Another company seeking to deliver RNA with gene therapy is Tacere Therapeutics Inc. The company expects to start clinical trials late next year with lead product TT-033, a combination of three short-hairpin RNAs (shRNAs) delivered within an AAV protein coat to three separate regions of the hepatitis C virus. (See BioWorld Today, July 24, 2007.)