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After Losing Another CEO, Silence Management Aims to Fill in Corporate Gaps


After the departure of its CEO last summer — the company’s third top executive to step down in two years — Silence Therapeutics is aiming to rebuild itself as a company with an improved business model that can help it advance drug candidates beyond phase I and realize more value from its RNAi technologies, according to one official.

“You take our core RNAi trigger, our three delivery platforms, and the very strong safety profile of [the phase I cancer drug Atu027] … and we’ve got the core of a really good company,” Silence’s recently appointed director of corporate strategy Ali Mortazavi said this week.

However, Silence has long lacked expertise in bringing a drug through late-stage clinical development toward commercialization, he said.

To correct this, Silence aims to find “patient investors” willing to support a measured approach to the selection of the kind of drug candidates and indications that are most likely to yield robust data that would attract partners.

Even early-stage clinical data can be sufficient to drive deals with bigger industry players — a key goal for any small biotech — if they are generated in well-designed studies, he said, pointing to Alnylam Pharmaceuticals’ agreement with Sanofi subsidiary Genzyme for the Asian rights to its phase I TTR-mediated amyloidosis program (GSN 10/25/2012).

Prior to striking that arrangement, Alnylam released phase I data showing that the drug, called ALN-TTR02, could trigger up to 94 percent reductions in levels of its target protein after a single dose. Even though that study was conducted in healthy volunteers, the close link between the disease and levels of the protein made the results particularly compelling.

In contrast, many companies in the RNAi space follow a path of “just trying to get some data in the clinic and pray,” Mortazavi said. “What happens is you start choosing … indications where you can get the fastest results,” which, for instance, ends up leaving holes in biomarker data.

“It’s about good design of drugs and indications and endpoints,” he said.

Silence has been “very well equipped … on the preclinical research [and development] side,” he said. “The core science and core capabilities have been there for a long time,” given that the company really began in 1998 as a spinout of Ribozyme Pharmaceuticals, which later became Sirna Therapeutics.

“The capabilities we really need are in the clinic — scientific advisory boards, MDs, a chief operating officer … the people who basically make drugs, in the end,” Mortazavi said. With such a team in place, Silence would be in a position to better guide Atu027 and other agents out of phase I and into later-stage studies.

He conceded that adding personnel to its roughly 33-member team will require money, and that Silence is currently evaluating all of its options to boost its cash position from the roughly £8 million ($12.1 million) it currently has on hand.

But attitudes toward RNAi as a therapeutic modality have become more optimistic lately after falling in the wake of Pfizer and Roche’s move to end all of their in-house RNA drug programs in late 2010 and early 2011, especially with Alnylam and other companies achieving success in the clinic, Mortazavi noted.

“Things have improved … and from an investor’s perspective, [success is] not five years away — it’s happening now,” he said. And with Silence poised to begin a phase Ib/IIa trial of Atu027, with data available as soon as late 2014, Mortazavi is optimistic that the company can follow up the £5.2 million it raised last August with another round of fundraising that will give it the resources to fill in any gaps in its corporate structure.

Despite its long history, “it was only last year that we [released] credible safety data on Atu027” and its delivery vehicle, he said. “My job … is to raise the capital to make this a real company.”