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”).
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