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Calando Aims to Complete RNAi Phase I Trial, Ink Development Partnership by Year's End

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By Doug Macron

Arrowhead Research's CEO last week struck an optimistic note about the company's drug-development efforts by stating that its Calando Pharmaceuticals subsidiary remains on track to complete a phase I study of its siRNA-based cancer drug, and partner the program before the end of the year.

Christopher Anzalone also said Calando is advancing another RNAi candidate and building its research and development infrastructure — a notable departure from events in 2009 when Arrowhead said it was halting all preclinical work and shuttering Calando's laboratory in order to trim costs.

Anzalone made the remarks during Arrowhead's fiscal second-quarter earnings conference call.

The cancer drug, CALAA-01, comprises siRNAs against the M2 subunit of ribonucleotide reductase delivered via its proprietary Rondel cyclodextrin-based polymer technology. It became the first formulated RNAi therapeutic to enter human testing in 2008.

About a year ago, Calando hit a major milestone when it published data from the ongoing phase I study in Nature, showing that CALAA-01 could knock down its intended target mRNA and protein inside a tumor through an RNA interference mechanism when delivered intravenously (GSN 3/25/2010).

Earlier this year, however, Anzalone said that enrollment in the study was not proceeding as quickly as it had hoped, and that it was adding a third clinical site to “maximize the rate at which we are able to treat new patients” (GSN 2/17/2011).

During last week's call, he said progress has been made on the enrollment front, and that the phase I study remains on track to wrap up by the end of the year.

He said “the number of patients we're able to biopsy” is a “big contributing factor” beyond Calando's full control, and added that “we can really only tell if we're hitting delivery-efficacy endpoints if we're able to biopsy patients [before] and during treatment.

“Those are easiest to do with [the] melanoma patients” who provided the data that resulted in the Nature paper. “That is not entirely in our control, but we certainly hope we are able to bring in sufficient melanoma patients that we can biopsy and show the data we expect.”

In response to an investor's question during the conference call, Anzalone declined to provide details on the number of patients enrolled thus far in the phase I, but said that its protocols allow for up to 30.

“We are less than that, but should be in a position to talk more about this shortly when the trial is finished,” he said.

Anzalone added that Arrowhead also believes that data from the trial, which is expected to be in line with those published in the Nature paper, will be robust enough to enable the shop to sign on an industry partner by the end of the year.

“The RNAi-partnering landscape has changed over the past year, and an increased amount of clinical data is now needed,” he said. “We believe this is the result of the large number of failures in delivery, as well as a maturation of the RNAi field, which has moved the expectation of clinical data closer to that of other therapeutic classes.

“Whatever the reasons for [this] change, we believe this shift will help us in the mid- to long term," Anzalone added. "There are only a very small number of delivery technologies in the clinic now, so our relatively advanced data and well-tolerated system will compete for partnerships with a much smaller number of other technologies than even a year ago."

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However, he cautioned that “we don't control the timing of that partnership. We are certainly hopeful we can establish the type of data that we need to ink that partnership, but that is somewhat beyond our control.”

Meantime, Calando has also restarted its preclinical R&D with an eye toward “developing a follow-on candidate” to CALAA-01, Anzalone said. The company is also “building our leadership team and R&D capabilities to support the future development” of such assets, he noted.

This is in sharp contrast to events in mid-2009, when Arrowhead disclosed that it had stopped work on all drug candidates other than CALAA-01, and that it would end the clinical-development program for that drug once the phase I trial had been completed. A few months later, Arrowhead closed Calando's lab, shifting CALAA-01 development work to another of its subsidiaries (GSN 8/13/2009).

Anzalone did not provide any details on the preclinical work or the exact nature of the increased “R&D capabilities.”

Fiscal Q2

For the three-month period ended March 31, Arrowhead's net loss from continuing operations fell to $1.1 million, or $0.01 per share, from $1.5 million, or $0.02 per share, one year ago.

Total operating costs in the quarter rose to $1.8 million from $1.4 million, in part because of an increase in foreign patent filings and attorney fees associated with Calando’s intellectual property portfolio.

Arrowhead generated no revenues during the period.

At the end of March, Arrowhead had $4.8 million in cash and cash equivalents and said it expects that it will be able to fund its operations through at least the next 12 months.


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