RNAi drugs are beginning to gain traction in clinical stages, with Alnylam ($ALNY) leading the way, but companies such as Arrowhead Research ($ARWR) out of Pasadena, CA, are also looking to create genetic treatments out of the hard-to-deliver material. This week, the company announced the completion of its enrollment for a Phase I RNAi-based hepatitis B (HBV) trial as well as a planned $60 million private offering.
Arrowhead's lead candidate ARC-520 uses the company's own delivery vehicle called Dynamic Polyconjugates (DPCs), Vince Anzalone, the company's director of finance and investor relations, told FierceDrugDelivery in an email. The polymer-based system stands apart from other RNA delivery platforms in its ability to induce endosomal escape, Anzalone said. This method of releasing the genetic material into the cell is enabled by a "masking" and "unmasking" process, allowing the RNA to enter the cell unharmed through a harsh external environment into the cytoplasm, where the specific siRNA strands can silence the expression of the target gene, he said.
"RNAi in general, and the siRNAs in ARC-520 specifically, act in a fundamentally different way than current HBV treatments," Anzalone said. "These siRNAs intervene at the point of DNA transcription, upstream of where nucleotide and nucleoside analogues act, and have been shown to deeply knock down all HBV gene products, including proteins and the viral intermediates necessary to produce viral DNA. Many experts in the field believe that knocking down key viral antigens (s-antigen in particular) may revive the host adaptive immune response and potentially achieve a functional cure."
The Phase I trial is designed to characterize the safety profile of ARC-520. Arrowhead is also preparing a Phase IIa efficacy study in HBV patients in Hong Kong and plans to file within the next few months for approval to begin the study.
The company is also planning a $60 million private offering of 3,071,000 shares of common stock and 46,000 shares of preferred stock priced at $5.86, to close around Oct. 11. Arrowhead did not disclose individual investors.
"We plan to use the proceeds from the offering to fund clinical development of ARC-520 through the upcoming Phase 2a study, which we believe will be complete in the first half of 2014 and a multi-national Phase 2b study planned for the second half of 2014," Anzalone said. "Funds will also be used to get to clinical proof of concept for two additional RNAi therapeutics, and to build out our pre-clinical pipeline."
- here's the ARC-520 release
- and the private offering release