Market research figures compiled by Agilent Technologies reveal that in 2009, $407 million in direct financing was targeted to the development of oligonucleotide therapeutics in the U.S. This figure represents a combination of publically announced venture capital, private placement, IPO, secondary financing, and up-front collaboration payments.
The total deal value for therapeutic oligos in 2009—including up-front payments and potential milestone royalties—approached $2.8 billion, about the same as in 2006 and less than half the total for 2008. This total covers the full spectrum of oligo-based drugs: miRNAs, siRNAs, aptamers, decoys, antisense, immunostimulatory oligos, and other related drug classes.
Continuing an upward trend begun in 2003, the number of oligo therapeutic programs has increased each year, growing to 231 in 2009, representing a more than 8% increase from 2008.
As the number of oligo therapeutics in development continues to increase, so too does their complexity, the scale of oligo manufacturing to support late-stage development and commercialization programs, and the range of chemistries, modifications, delivery strategies, and purification and analytical methods. This diversity will be evident in the scope of presentations at IBC’s upcoming “TIDES” conference.
At the meeting, Agilent will unveil a novel technology for large-scale RNA deprotection. The technology combines chemical and engineering solutions that overcome the problems caused by the exothermic nature of conventional deprotections.
Heat-induced degradation of RNA during deprotection has, to date, hindered the ability to scale RNA production above 200 grams. Agilent has coupled on-column cleavage of RNA from the solid support with removal of the deprotecting groups in a semi-continuous, scalable process. The cleavage step involves pumping reagents through the synthesis bed and into a holding vessel. For deprotection, the contents of this vessel are continuously combined with deprotection reagents in a temperature-controlled mixed stream.
Paul Metz, director of operations at Agilent, describes this technology as another step in the company’s goal of transforming discrete steps in the manufacturing process into more continuous, closed process steps that facilitate automation and large-scale production.