7:06 PM
May 10, 2018
 |  BC Innovations  |  Finance

Amplifying oligos

Five years of preclinical oligo deals show high demand for ASO, siRNA and mRNA

Editor's Note: This article was updated on Sep 14, 2018 at 6:29 PM PDT

The last five years have seen a steady stream of preclinical deals for antisense, siRNA and mRNA therapies that suggests pharmas are taking the modalities seriously as alternatives to traditional small molecules and antibodies. But interest in microRNAs and aptamers is lagging.

Biogen Inc.’s $1 billion deal with Ionis Pharmaceuticals Inc., announced April 20, marked the largest upfront payment for preclinical nucleic acid therapeutics, and signaled a commitment by Biogen to bring the modality into the core of its pipeline.

The 10-year extension of the partners’ 2012 partnership builds on the clinical and commercial success of Spinraza nusinersen, an antisense oligo approved to treat the Orphan disease spinal muscular atrophy (SMA). Spinraza originated from that partnership and was approved in 2016. In 2Q18, the drug was the largest growth driver in Biogen’s earnings.

Biogen said the expanded deal has the potential to validate about 50 targets across a wide range of neurological and neuropsychiatric diseases.

Spinraza became the second nucleic acid therapeutic to reach the market, following Ionis’ Kynamro mipomersen, an APOB-100-targeting antisense oligo partnered with Kastle Therapeutics LLC. Kynamro was approved in 2013 for hypercholesterolemia.

Enthusiasm for nucleic acid technologies has waxed and waned; while they promise new avenues for addressing a host of targets deemed undruggable by traditional modalities, they have yet to enter the mainstream, in part due to the difficulty of delivering them efficiently to tissues beyond the liver, kidney and circulation.

Since 2013, there has been a continued flow of preclinical partnerships formed involving the three main nucleic acid modalities: mRNA, siRNA and antisense oligos, with 26, 23 and 21 deals respectively recorded in BioCentury’s BCIQ database (see “Oligos on the Up”).

Figure: Oligos on the up

A look at the cumulative number of preclinical deals for different therapeutic oligonucleotide technologies from January 2013 to present shows mRNAs, siRNAs and ASOs pulling away from the pack. mRNAs, which topped the chart, had at least one deal during every six-month period over the last five years. Technologies with fewer than three preclinical deals, or with deals that did not specify oligo type, are not displayed. The deals in the oligo delivery category involved technologies for directing oligo therapies to specific tissues, while deals in the drug delivery category involved use of oligos, such as dendrimers, to deliver other types of drugs. Among the 21 deals covering oligo delivery technologies, 13 also involved another oligo category. Two of the deals announced since 2013 -- one covering mRNA and one covering siRNA and oligo delivery technologies -- have been terminated. Source: BCIQ: BioCentury Online Intelligence

A similar number of deals, 21, focus on delivery technologies.

Interest in microRNAs (miRNAs) has stalled, with four preclinical deals recorded since 2013, all before 1H16. But a trickle of deals for aptamers and small activating RNA (saRNA), with three and two respectively in the last two years, shows companies are still exploring the expanding list of nucleic acid options.

“It’s an interesting time in the RNA therapeutics space; this modality in general is getting validated by a number of companies. You no longer spend your time at investor board meetings trying to convince people that these are tractable,” said Wave Life Sciences Ltd. President and CEO Paul Bolno. Wave is developing stereopure versions of multiple oligonucleotide modalities, including antisense oligos and siRNAs.

The biggest players are pharmas, who see the deals as part of their external innovation strategy to bring in new capabilities to add to or complement their internal skill sets.

“We’re encouraged enough that we now have our own team internally, and we look forward to progressing molecules from that team, as well as partnering for this modality,” said Dash Dhanak, global head of discovery sciences at the Janssen R&D unit of Johnson & Johnson.

Of the top seven buyers, five are pharmas; several of the partnerships were expansive, covering multiple targets and indications. Dealmaking was...

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