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Roche re-enters gene silencing space with $250m LNA acquisition

By Dan Stanton+

05-Aug-2014
Last updated on 11-Aug-2014 at 10:04 GMT

Roche re-enters RNAi space with $250m Santaris acquisition

Roche has renewed its interest in gene silencing drugs, paying $250m (€187m) for Santaris Pharma including its ‘antisense’ Locked Nucleic Acid (LNA) platform.

In 2011, the Swiss Pharma Giant sold its RNA interference (RNAi) pipeline, delivery technologies and research facility to Arrowhead Research Corporation exiting.

Yesterday, Roche paid $250m – plus a potential $200m more in milestone payments – to buy Copenhagen, Denmark-based biotech Santaris (owned in part by private equity firms Forbion Capital Partners and Seventure Partners) in a deal that adds three RNA-targeted therapies to its pipeline as well as the proprietary microRNA Locked Nucleic Acid (LNA) Drug technology.

Such therapies offer a number of benefits over traditional small molecule and monoclonal antibody approaches, according to Santaris, including reducing candidate failure due to pharmacokinetic/toxicology predictability, and increased Chemistry, Manufacturing and Control (CMC) efficiency.

“The acquisition of Santaris provides Roche the unique opportunity to merge their deep expertise in disease biology, target selection, toxicology, formulation, and drug delivery with the most extensive experience in designing and producing LNA oligonucleotides, a technology that Roche believes will redefine RNA-targeting medicine in the future,” a Santaris spokesperson told in-Pharmatechnologist.com.

“With this acquisition, Roche plans to create a base for RNA-targeting medicine research near Copenhagen, keeping all approximately 50 employees.”

Single vs double stranded approach

Roche’s former interest saw an investment of “over a billion dollars” in 2006 which included acquiring the license to Alnylam’s small interfering RNA (SiRNA) technology, a double-stranded approach to developing therapies.

However, according to Santaris, such compounds are limited by the relative size of the molecule which leads to poor cellular uptake and the need for complex delivery vehicles, whilst a single-stranded approach - known as microRNA or ‘antisense’ – is based on smaller molecule size which aids drug delivery, as well as reduces the complexity and cost of manufacturing. However, traditionally antisense drugs have had a low-affinity for their RNA targets, leading to insufficient potency.

The LNA platform is an antisense approach but overcomes such limitations, the firm says, due to an increase in affinity caused by modifying RNA that contains an oxy-methylene bridge between the 2' and 4' carbons in the ribose ring.

The news will come as a boost to RNA-therapeutic developers who have seen Big Pharma turning its back on gene silencing drugs. In 2012 , Alnylam was forced to axe jobs after Novartis ended an RNAi alliance, whilst in January this year, Merck & Co. followed Roche’s example and divested its SiRNA business for $700m .

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