Silence assessing R&D after successful fund-raising

Silence Therapeutics' raising of almost £40 million from investors last week means it now has some decisions to make regarding its R&D priorities.

The success of the fundraising means that Silence is now sitting on some £59 million and has the resources it needs to accelerate its R&D programmes, according to chief executive Ali Mortazavi, who will now decide, with the rest of the board, how to make the best use of the cash.

Silence's pipeline is currently headed by pancreatic cancer candidate Atu027, which is generating excitement following release of phase IIa results last month that backed the safety of the compound – and also showed preliminary evidence of efficacy, with an increase in progression-free survival.

The conventional approach for a biopharma company would be to invest heavily in that programme to bring it to market quickly, but Silence's broad platform in RNA means it has to consider its next moves carefully.

"In RNA therapeutics, because of the specificity of the molecules, much of the work and cost base is in the pre-clinic," in other words ensuring that molecules are being delivered to the right target and exerting the desired effect, he told pharmaphorum.

"We are switching gene targets very fast and looking at a number of indications in order to identify the very best candidates to take forward," he added. "We have a lot of different payloads, and a lot of different delivery systems to consider."

Silence's current burn rate is around £10 million a year and this is expected to go up significantly as it accelerates its R&D investment both in its established area of RNA interference (RNAi) – which involves switching off genes – as well as the emerging field of messenger RNA (mRNA) replacement that offers the possibility of switching genes on.

Atu027 clearly remains a critically important programme for the company, but it is remaining a little coy on its plans for the programme as it examines the data and determines the best pathway forward, said Mortazavi.

The results have also reinforced the possibility of extending the use of Atu027 into other solid tumours. Studies in head and neck cancer are already under consideration, for example, although the company may also consider a second pancreatic cancer trial. Meanwhile, the data raise the prospect of possible licensing deals for the technology.

That said, "the majority of our R&D spend – at least in the coming year or two – should be in the preclinical R&D engine and technology," he said.

The success of the fundraising reflects an increasingly bullish investment environment in the UK – albeit still lagging behind the US – and shows that the appetite is there for companies with a robust platform.

Silence has also been aided by recognition that, after years of research, the technologies behind RNA therapeutics have improved dramatically, particularly with regard to improved delivery systems and cellular uptake of the RNA payload.

"The ability to target as yet 'undruggable' targets with a whole new class of therapeutics is fast becoming a reality," said Mortazavi.

With so much attention being paid to initiatives such as whole genome sequencing, it is easy to overlook that a genetic toolkit will be needed to take advantage of the findings that come out of those projects.

A key inflection point for the entire RNA interference sector could come later this year when Alnylam reports pivotal, phase III data on its lead candidate patisiran, a treatment for transthyretin-mediated amyloidosis in patients with familial amyloidotic polyneuropathy.

Assuming those studies are positive, the RNA therapeutics sector could see its first approval and launch of a RNAi-based drug and delivery system within the next year or two.