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Silence's Cancer Rx Trial on Track as Firm Works out Milestones with Quark, Weighs Takeover Possibility


By Doug Macron

Silence Therapeutics this week provided a general corporate update, stating that its phase I cancer drug candidate Atu-027 remains on track in the clinic and that it is working on a new delivery system that is likely to be the foundation of its next clinical candidate.

It also said it has come to an agreement with Quark Pharmaceuticals over milestone payments it is owed in connection with a longstanding technology-licensing arrangement, and indicated that previously announced buyout negotiations it is holding with an undisclosed party remain ongoing, although no new details about potential transactions were available.

Atu-027 is a blunt-ended siRNA targeting the protein kinase PKN-3. Originally developed by Atugen, which was later acquired by Silence, the cancer drug entered a German phase I study in patients with solid tumors in mid-2009 (GSN 7/9/2009). The company expects it will be developed for gastrointestinal and lung cancers.

The open-label study is examining single and repeated intravenous infusions of Atu-027 in order to determine dose-limiting toxicities and the drug's maximum tolerated dose. Secondary outcome measures include the collection of pharmacokinetic data, safety and tolerability information, and clinical response.

Silence said the phase I trial is proceeding as expected with 18 patients thus far treated, and that it is expected to wrap up during the second half of 2011. The company had previously projected that the trial would be completed before the end of this year.

Publicly available data on Atu-027 has been limited, but last month researchers from Silence published data in Clinical Cancer Research showing that the drug could prevent pulmonary metastasis in multiple mouse models of breast cancer (GSN 11/11/2010).

Elsewhere in the company's pipeline is Atu-134, an siRNA-based treatment for acute lung injury that Silence CEO Philip Haworth told Gene Silencing News would most likely be the firm's next clinical candidate, largely because it incorporates a novel delivery technology.

While Atu-027 is based on Silence's so-called Atuplex technology, Atu-134 uses an approach called drug-assembling cholesterol complex, or DACC, the specific details of which Haworth declined to provide.

Although Silence has other drug candidates ready for IND-enabling studies, these all incorporate the Atuplex technology, and "we see no point in taking the same risk … with Atuplex until we know it's safe and works in man," he said. "It's not a good use of our limited resources to double-down without knowing" whether Atuplex is safe and effective.

"We really think it's best to develop multiple delivery systems that we can get into the clinic," Haworth added, and moving ahead with Atu-134 and the DACC approach is the clearest way to do that.

Still, Silence needs to raise additional funds before it is in a position to advance Atu-134 to the clinic, and Haworth said he doesn't envision an IND being filed on the drug until the end of 2011, at the earliest.

On the business side, Silence said that it has reached a deal with Quark under which it will receive up to $1.5 million in milestone payments in conjunction with an option agreement signed with Novartis over the p53-inhibiting agent QPI-1002.

The drug is being evaluated by Quark in separate phase II studies as a prophylactic against acute kidney injury in patients undergoing cardiac surgery, and to prevent delayed graft function associated with kidney transplantation.

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The drug, which incorporates technology owned by Silence and licensed to Quark, is designed to temporarily block the expression of p53, which is associated with apoptosis induction, to prevent ischemia-reperfusion-induced acute kidney injury in patients taken off a cardiopulmonary bypass pump, or in patients whose blood flow is re-established to a transplanted kidney.

In August, Quark said that Novartis had taken an option to exclusively license the worldwide rights to QPI-1002 (GSN 9/19/2010). In exchange, Quark received a $10 million upfront payment and a promise of up to $670 million in fees and milestones should the option be exercised.

Based on Silence's announcement this week, it appears that it and Quark were at odds over how much of Quark's payouts Silence is entitled to under their technology-licensing arrangement. The companies have been working together since at least 2005 (GSN 3/18/2005), but their relationship has been rocky at times as Quark took issue with how much credit Silence, which was previously known as SR Pharma, took for the success of its drug candidates (GSN 7/17/2008).

Nonetheless, Silence said that the companies have "reached agreement" on the Novartis issue, and that it is eligible to receive up to $1.5 million in milestones from Quark as a result of the option deal. It added that its share of future milestone payments could be as much as $80 million should Novartis exercise its option and successfully bring QPI-1002 to the market.

Meanwhile, Silence said that it remains a potential takeover target, but did not provide specifics on the possible timing or nature of any transaction.

In September, the company said that it was approached about potentially being purchased by the unnamed entity (GSN 9/9/2010).

Silence's CEO Philip Haworth told Gene Silencing News at the time that the company was required by the London Stock Exchange's AIM to make the announcement "because of the sharp rise in the [firm's] share price" over the preceding days.

Details about the "approach, which may or may not lead to an offer for the company," will be provided "in due course," Silence added at the time. This week, the company only said that it "remains in an offer period," and that it "continues to explore a variety of strategic opportunities."

Have topics you'd like to see covered in Gene Silencing News? Contact the editor
at dmacron [at] genomeweb [.] com.

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