By Doug Macron
Having taken the helm of Silence Therapeutics after the departure of its second chief executive in less than a year, the company's newly appointed CEO Tony Sedgwick sees continued advancement of the phase I cancer drug Atu027 as one of his key goals.
Meantime, Silence remains focused on demonstrating the potential of two new delivery technologies and expects to have a second clinical candidate incorporating one of them ready for human testing by early next year, Sedgwick said this week.
Silence had been under the leadership of Philip Haworth since 2010 when it merged with California-based Intradigm, which had been headed by Haworth (GSN 12/17/2009). However, the cost of maintaining facilities in both the US and Europe — Silence is headquartered in the UK but maintains research and development operations in Germany stemming from its 2005 merger with Berlin-based Atugen (GSN 7/29/2005) — proved too great and last year the company shuttered its US facility (GSN 4/28/2011).
As part of that reorganization, Haworth, who lives in California, agreed to resign from the firm.
In September, Silence tapped then-COO and former Atugen CEO Thomas Christely to replace Haworth. Around that same time, it also hired Sedgwick — previously CEO of Novacta, Cambridge Biotechnology, and Daniolabs — as its chief business officer.
Last week, however, the company announced that Christely had left for “personal reasons,” prompting the promotion of Sedgwick to the CEO role.
Now directing the company he just joined, Sedgwick said that one of his top priorities is to wrap up the ongoing phase I trial of Atu027 while hammering out a phase II development strategy.
Atu027 is Silence's most advanced drug, having been inherited from Atugen. It comprises blunt-ended siRNAs targeting the protein kinase PKN-3 that have been formulated with the company's AtuPlex liposomal delivery technology.
In June, Silence presented preliminary phase I data at the American Society of Clinical Oncology meeting showing that the drug was well tolerated at doses up to 0.18 mg/kg in patients with solid tumors and suggesting that it may offer therapeutic benefit (GSN 6/9/2011).
According to Sedgwick, that study remains on track for completion by mid-2012. And while a phase II trial is the plan, just how it will be structured is not yet decided as Silence decides which indication it should pursue in the planned study.
Additionally, he told Gene Silencing News that the company is not in a position to initiate phase II development of Atu027 on its own given the complexity and cost of running a cancer trial.
“We would really be looking for a partner ... who is a strong navigator of the therapeutic space because we're a small biotech with 25 people or so,” he said. “We need somebody who is more attuned with the oncology space” and who could “help with the heavy lifting of taking a molecule into a bigger phase II.”
Sedgwick said that negotiations with possible partners are ongoing, but declined to provide a timeline on when a deal might be struck.
As that effort continues, Silence also remains focused on advancing its other delivery technologies, including DBTC, which uses the same cationic lipid as the AtuPlex technology but specifically targets hepatocytes and other liver cells, and DACC, which selectively targets the lung endothelium.
As reported by Gene Silencing News, Silence shelved another AtuPlex-delivered cancer drug called Atu134 in late 2011 in order to focus on these newer delivery approaches (GSN 11/10/2011).
Although Silence has a handful of other oncology-oriented molecules in its pipeline other than Atu134, Sedgwick indicated that the company's preclinical lung injury treatment Atu111, which uses the DACC technology, would likely be next in line to enter the clinic.
“One of the things I'm going to be doing is pushing [Atu]111,” he said, adding that part of Silence's near-term game plan is to have a new drug entity ready for the clinic by 2013, whether through a partnership or on its own.
In doing so, the company will not only be broadening its lineup of in-house clinical candidates, but also taking steps to demonstrate the breadth of its delivery capabilities to companies that might be interested in licensing its technology for their own RNAi drugs.
At the same time, Sedgwick expects that Silence's molecule-related intellectual property will become increasingly attractive to companies looking to play in the RNAi market, especially in light of recent decisions by patent officials in the US and Europe.
A cornerstone of Silence's IP estate is a set of patents covering the so-called Zamore design rules. Named for University of Massachusetts research Phillip Zamore, they broadly relate to methods of enhancing the ability of an antisense strand to act as a guide strand; RNAi agents with enhancing silencing activity; and compositions for siRNAs, as well as pre-microRNAs, shRNAs, and vectors that perform gene silencing.
Late last year, the US Patent and Trademark Office upheld the validity of four Zamore patents after a re-examination request was made by an undisclosed party (GSN 12/15/2011). Opposition proceedings against the IP are ongoing in Europe at the request of Alnylam Pharmaceuticals, Novartis, and Alcon.
“We are one of the premier companies that owns patents in this space,” Sedgwick said. “As [RNAi] technology takes off, we're thinking we'll be in a good position” in terms of licensing opportunities.
“And it will take off; it's just [a matter of] when,” he added.
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