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Arrowhead Aims for HBV IND in Early 2013, Releases Preclinical Data from Program

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Just months after adding a hepatitis B treatment to its pipeline, Arrowhead Research's top official this week said that the company expects the program to yield an investigational new drug application in the first half of next year.

Arrowhead, which just released its fiscal second-quarter financial results, also announced preclinical data showing that siRNAs formulated in the company's proprietary dynamic polyconjugate, or DPC, technology could significantly reduce levels of the viral RNA and DNA in animal models of the disease.

Arrowhead's HBV effort stems from the company's acquisition of Roche's RNA medicines assets late last year after the pharmaceutical giant cut all of its in-house work with the technology as part of a company-wide restructuring in 2010 (GSN 10/27/2011).

As part of the deal, Arrowhead picked up Roche's Madison, Wis., research facility, the DPC technology, and its lead HBV program.

When Arrowhead announced the new drug-development effort in February, President and CEO Christopher Anzalone said that the firm expected to have a candidate in preclinical testing by year end (GSN 2/16/2012).

“We have completed work validating the specific type of DPC, siRNA sequences, and chemical modifications we will use” for the drug, he said this week during a conference call held to discuss the second-quarter financials. As such, Arrowhead expects to file an IND to begin human testing of the HBV candidate “late in the second quarter” of 2013.

According to Anzalone, the company is considering running the phase I trial in Asia, where the disease is endemic, which would allow Arrowhead to test its compound in infected volunteers.

“Such a trial will be designed to generate an efficacy readout during phase I, enabling relatively early partnering opportunities for this candidate,” he noted.

Anzalone also said that Arrowhead aims to give its HBV program and the DPC technology a higher profile.

“Under Roche, the DPC technology was largely embargoed from publicity,” he said during this week's call. “We are committed to publishing some of these data to unveil the power and flexibility of this platform.”

Data from the HBV program is being prepared for presentation at scientific meetings, he said, while reports on the DPC approach are being submitted to peer-reviewed journals with publications expected this year.

And Arrowhead is already making good on that promise. At the European Foundation for Clinical Medicine conference in Switzerland this week, Arrowhead presented data it said supports the development of its HBV candidate as a cure, rather than a chronic treatment, for the condition.

Those data show that single doses of hepatocyte-targeted anti-HBV siRNAs, formulated with the DPC technology and systemically administered to a mouse model, resulted in a multi-log reduction of serum hepatitis B surface antigen, which is believed to impair the immune system's ability to fight the virus, and serum HBV DNA, Arrowhead said.

“Dramatic reductions in viral transcripts, viral replicative DNA intermediates, and intracellular HBV core antigen were observed in the liver after two weekly doses,” Arrowhead added. Meantime, in multi-dose studies in mice carrying a “hepatocyte-specific reporter gene fused to HBV sequences, four bi-weekly injections of anti-HBV siRNA DPCs resulted in a multi-log reduction in gene expression over 2 months without changes in toxicity markers.”

Despite its focus on its HBV candidate, Arrowhead is still pressing forward with CALAA-01, a cancer drug that incorporates the firm's Rondel cyclodextrin-based polymer delivery technology and its first clinical candidate.

After encountering certain adverse events in patients receiving high doses of the drug in a phase I trial, Arrowhead launched a phase Ib study last year to see whether those side effects can be mitigated with pre-treatment at lower doses.

Anzalone said this week that the phase Ib trial is still on track to be completed by this summer.

Fiscal Second Quarter

For the three-month period ended March 31, Arrowhead posted revenues of $31,250, compared with zero revenues in the year ago period.

Operating costs in the quarter jumped to $4.9 million from $1.8 million, reflecting the impact of the company's acquisition of Roche's Madison facility and its roughly 40 employees.

Arrowhead's net loss in the quarter surged to $5.3 million, or $0.50 per share, from $2.9 million, or $0.37 a share, the year before.

At the end of the quarter, Arrowhead had cash and cash equivalents totaling $6.3 million.

During the conference call, Anzalone declined to provide specific guidance on the company's fund-raising plans, but noted that it maintains a loan facility from Lincoln Park Capital that allows it to draw up to $15 million at its discretion over roughly the next two and a half years.

“We view that as something that gives us an awful lot of flexibility about how and when to bring in outside capital,” Anzalone noted.

“We are also actively looking to partner parts of our RNAi program,” he added. “So between the Lincoln Park facility, our partnering endeavors, and potential outside capital raise, we feel comfortable that we have access to the capital we need … to keep our programs moving forward.”

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