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Silence Puts Preclinical Cancer Drug on Back Burner to Advance Candidates with Newer Delivery Tech

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By Doug Macron

Silence Therapeutics this week announced that it has put on hold the development of its preclinical cancer drug Atu137 after determining that the drug's potential clinical profile is “too similar” to the company's phase I solid tumor therapy Atu027.

As a result, the firm said it will shift its attention onto an as-yet undisclosed preclinical candidate that makes use of another one of its proprietary delivery technologies.

Silence also said this week that data from the ongoing trial of Atu027 confirms that roughly 37 percent of patients receiving the drug achieved stable disease following the treatment phase of the study. Dosing has now been initiated in the next-to-last cohort of the trial, which is expected to be completed by mid-2012, the company added.

Atu027 is a blunt-ended siRNA that silences the protein kinase PKN-3. It is delivered intravenously using Silence's AtuPlex lipid-based, endothelium-targeting delivery technology. Atu134 similarly uses the AtuPlex technology, but is designed to silence CD31.

This summer, Silence released phase I data showing that Atu027 was well tolerated in all dosing cohorts up to 0.18 mg/kg, and that nine patients achieved stable disease after repeated treatment, with six of the cases confirmed after three months. This week, the company said that the number of patients with stable disease has increased to 10 of the 27 treated to date.

In light of the AtuPlex technology's apparently positive safety and efficacy, Silence said in September that it was aiming to move Atu134 into phase I testing during the first half of 2012, with production of drug materials for preclinical toxicology experiments already underway (GSN 9/22/2011).

In animal models, Atu134 “appears to have a profound impact in slowing the progression of solid tumors,” the company said at the time.

Since then, however, Silence has decided that the profiles of the two drugs were “looking closer than we had initially anticipated at the time we decided to take [Atu134] into full-scale preclinical development,” Silence CFO Max Herrmann told Gene Silencing News this week.

More specifically, the drugs were seen as having a biological effect in very similar tumor types. “As we looked at the indications we might take forward for the two programs, they we're looking closer and closer” to the same thing, he said.

As a small company with limited resources, Herrmann said, Silence decided that it made better sense to put its resources behind a drug candidate that uses its liver-specific DBTC delivery technology rather than Atu134.

According to Silence, the DBTC technology uses the same cationic lipid used in AtuPlex molecules, but is designed to specifically target hepatocytes and other liver cells.

He said that it was too early to comment on the specific nature of the program that will replace Atu134 as Silence's next drug to enter the clinic, and declined to offer a timeline on when an announcement might be made.

Herrmann did say that Silence hasn't completely written off Atu134. “We've not made any decisions on what the future is” for the drug, he said, adding there is always the possibility that it could be partnered or that Silence would restart its development down the road.


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