Phase III development of immunotherapeutic is projected to start by mid-2012.
RXi Pharmaceuticals is acquiring cancer drugs firm Apthera to get its hands on the latter’s late-stage NeuVax™ peptide immunotherapy. The stock-based acquisition deal will see Apthera stakeholders initially receive about 4.8 million shares of RXi’s common stock. Additional payments based on development and commercial milestones relating to NeuVax could also be due.
Completion of the acquisition would give RXi its first clinical-stage product. Apthera’s NeuVax is projected to move into Phase III development as an adjuvant treatment for HER2-positive breast cancer during the first half of 2012.
“The RXi-Apthera merger represents an exciting turning point in which we are advancing from being a technology platform company to a late-stage product development company aimed at blockbuster therapeutic markets,” remarks RXi director Mark Ahn, Ph.D., who will take on the role of president and CEO of the combined company. “Acquiring Apthera’s cancer vaccine product candidates builds upon the promising RNAi-based preclinical work related to cancer vaccines that we have recently been doing at RXi.
NeuVax consists of the E75 peptide derived from HER2 combined with the immune adjuvant granulocyte/ macrophage colony stimulating factor (GM-CSF). Treatment with NeuVax stimulates cytotoxic (CD8+) T cells in a highly specific manner to target cells expressing any level of HER2. The firm claims that unlike existing monoclonal antibody therapy that requires repeated and frequent intravenous infusion, NeuVax can generate continuing activation of the immune system and therapeutic levels of killer T-cells with a once-monthly intradermal dosing schedule. FDA has granted Apthera a Special Protocol Assessment for a Phase III clinical trial of NeuVax for the adjuvant breast cancer therapy indication.The cancer vaccine is in addition undergoing a Phase I/II clinical study as an adjuvant treatment of early-stage, HER2-positive prostate cancer. Phase I/II studies evaluating NeuVax in combination with Herceptin are also under way.
RXi is an RNAi therapeutics firm exploiting a technology platform that includes both RNAi compounds and delivery methods. Its rxRNA™ platform includes optimized rxRNAori and rxRNAsolo molecules based on dual or single-stranded RNAi configurations and self-delivering sd-rxRNA molecules. The firm’s delivery technologies include nanotransporters for systemic delivery of its rxRNAori and rxRNAsolo molecules, and glucan-encapsulated RNAi particles (GeRPs), which may enable rxRNAs to be delivered orally.
An IND submission for lead dermal antiscarring candidate RXI-109 is projected for the second half of 2011. RXI-109 is a self-delivering RNAi compound (sd-rxRNA™) designed to reduce the expression of connective tissue growth factor, a critical regulator of several biological pathways involved in fibrosis, RXi explains. It hopes RXI-109 will have applications in the treatment of a range of indications with a fibrotic component, including scar formation in the skin.
sd-rxRNA molecules are designed to incorporate the desired characteristics of both RNAi and antisense technologies, and not to require an additional delivery vehicle for efficient cellular uptake or tissue distribution, RXi notes. While single-stranded antisense compounds have favorable tissue distribution and cellular uptake properties, they don’t display the intracellular potency of double-stranded RNAi compounds, the firm notes. Conversely, the duplex structure and hydrophilic character of traditional RNAi compounds results in poor tissue distribution and cellular uptake.
In an attempt to combine the best properties of both technologies, sd-rxRNA molecules combine a single-stranded phosphorothioate region with a short duplex region and a variety of nuclease-stabilizing and lipophilic chemical modifications. The combination of these features allows sd-rxRNA to achieve efficient spontaneous cellular uptake and potent, long-lasting intracellular activity, RXi claims.
Data available to date suggests that efficient uptake of sd-rxRNA compounds could be possible any tissue, as long as the route of administration enables local delivery of a relatively high concentration of the compound. The drug-like properties of sd-rxRNAs, including extended circulation time and better tissue distribution, may also make them amenable for systemic delivery, the firm suggests.