AstraZeneca and Isis Pharmaceuticals to co-develop targeted oligonucleotide delivery methods

Initial project areas will be oncology and cardiovascular and metabolic diseases (CVMD)

UK-based drugmaker AstraZeneca and Isis Pharmaceuticals, based in Carlsbad, California, in the US are building on a collaboration formed in 2012 with a new alliance targeted at discovering and developing novel delivery methods for antisense oligonucleotides. The aim is for these drug delivery methods to be more effective at targeting the desired tissue.

The agreement builds on an existing collaboration between the two companies and supports AstraZeneca's research in the area of antisense oligonucleotide-based therapeutics and RNA biology. Initial project areas will be oncology and cardiovascular and metabolic diseases (CVMD).

Antisense oligonucleotides are short, single strands of DNA or RNA molecules. Rather than modulating the activity of already-formed proteins, they act before proteins are produced at the level of messenger RNA in the cell, thus opening up new opportunities for therapeutic intervention. The new delivery methods will aim to enhance the access of antisense oligonucleotides into specific organs and cells. They will build on Isis Pharmaceuticals' Ligand Conjugation Antisense (LICA) technology.

This could lead to a number of ground breaking drugs for both oncology and cardiovascular and metabolic diseases

The first example of this technology is Isis' GalNac-conjugated antisense oligonucleotides targeting liver hepatocytes, which lowers the therapeutic dose needed for liver targets by approximately 10-fold.

Under the terms of the agreement, each company will fund its own contribution and commit investigators to the project. They will work together on an agreed programme and share rights to the results.

AstraZeneca and Isis entered into their first collaboration, development and licensing agreement in 2012 in oncology, which was subsequently expanded in 2013 to include CVMD.

Under the 2012 agreement, one of the molecules being developed is AZD9150 (ISIS-STAT3Rx), a first-in-human, first-in-class, antisense oligonucleotide inhibitor of STAT3, which is being developed as an immunomodulatory agent in combination with MEDI4736, AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor.

A second product of that collaboration, an antisense oncology compound targeting the androgen receptor AZD5312 (ISIS-ARRx), is in Phase I trials.

The new delivery collaboration builds on this existing relationship and is expected to also bring benefits to these programmes, the companies say.

'This exciting collaboration very much supports AstraZeneca's research and development in the area of RNA-based therapeutics. If successful, we'll have a way to selectivity modulate therapeutic targets in specific cell types that are intractable to small molecules and antibodies. This could lead to a number of ground breaking drugs for both oncology and cardiovascular and metabolic diseases,' said Susan Galbraith, Head of the Oncology Innovative Medicines Unit at AstraZeneca.

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