Arrowhead Research’s top official this week announced that the company has shifted its research and development focus entirely onto RNAi drugs enabled by its dynamic polyconjugate, or DPC, delivery technology.
As part of the change, Arrowhead CEO Christopher Anzalone said that the firm has dropped development of its phase I cancer drug CALAA-01, which had a promising start as the first formulated siRNA drug to enter human testing but faltered in the clinic.
Though it was originally a nanotechnology company with subsidiaries in the life sciences, electronics, and energy fields, Arrowhead began exploring the RNAi field in 2005 when it established Calando Pharmaceuticals (GSN 2/25/2005).
Calando’s efforts centered on a delivery approach called Rondel, which was licensed from the California Institute of Technology and is based on cyclodextrin-based polymer nanoparticles. By 2010, the first drug incorporating the Rondel technology, CALAA-01, had advanced into phase I testing and proved capable of knocking down its target in tumors via RNAi (GSN 3/25/2010).
However, adverse events were observed among some patients in that study, and in 2011 Arrowhead announced a phase Ib trial that would test whether a pretreatment regimen could avoid such side effects. Around that time, Arrowhead also inked a deal acquiring the RNA drug assets of Roche as it shed non-biopharmaceutical operations and programs (GSN 10/27/2011).
As the Roche assets — which included the DPC technology and a fledgling hepatitis B program that has since yielded the phase I candidate ARC-520 — became the focus of Arrowhead’s efforts, the company grew tightlipped on CALAA-01 and the Rondel system, raising questions about their future.
But this week, Anzalone put those questions to rest, stating during a conference call held to discuss the company’s fiscal third quarter that the company has officially become a pure-play RNAi drug developer focused exclusively on the DPC technology.
“As our DPC platform continued to develop and we pushed ARC-520 toward the clinic, it became clear that these would be our primary near- and long-term value drivers,” he said during the call. “As such, we have lined up our resources behind them and our focus is entirely on pushing ARC-520 through the clinic and developing additional DPC-enabled RNAi therapeutics.”
“We have decided not to pursue additional candidates based on the Rondel delivery platform,” he added, noting that related intellectual property and licenses have been returned to CalTech. “We have also decided not to advance the CALAA-01 candidate into phase II.”
With that decision, ARC-520 has become Arrowhead’s flagship product candidate. The firm expects that data from the ongoing phase I trial, which is testing single, escalating doses of the drug in healthy volunteers, will be available around the end of the year, setting the stage for a phase IIa trial examining single doses in chronic HBV patients in Hong Kong in early 2014. A multi-dose phase IIb trial is planned for the second half of next year.
Elsewhere in Arrowhead’s pipeline are programs looking at intravenously administered therapies for other liver indications — programs that could use the same DPC formulation as ARC-520 and therefore be “straightforward to develop and substantially de-risked, particularly once we have human safety data later this year from ARC-520,” Anzalone said.
He noted that Arrowhead also continues to evaluate subcutaneously administered DPC drugs for liver diseases, pointing to its report last year of non-human primate data indicating that the delivery technology is as effective through this route of administration as it is when used intravenously (GSN 11/08/2012).
Meanwhile, preliminary work is ongoing on programs going after extrahepatic targets in indications such as oncology, he said, adding that a new clinical candidate is expected to be unveiled next year.
As a result of its new focus, Arrowhead has also decided to end its efforts to apply its peptide-based delivery technology, picked up through the 2012 acquisition of Alvos Therapeutics, to small-molecule drugs.
Going forward, he said, Arrowhead will only use the peptides to enhance DPCs for RNAi drugs, although he added that it would still consider partnering the delivery technology in non-RNAi areas through partnerships such as its ongoing alliance with Shire.
For the three-month period ended June 30, Arrowhead reported a net loss of $6.1 million, or $0.23 a share, compared with a year-ago loss of $8 million, or $0.71 a share.
Operating expenses in the quarter were $6.4 million, down from $6.9 million in the same period last year, reflecting a sharp drop in general and administrative expenses to $900,000 from $3.1 million that more than offset a rise in R&D spending to $1.8 million from $1.2 million.
At the end of the quarter, Arrowhead had cash and short-term investments totaling $33.1 million, due largely to the completion of a $36 million stock offering in May.