Isis Pharmaceuticals, Inc. and AstraZeneca have formed a strategic alliance to discover and develop novel delivery methods for antisense oligonucleotides. The new delivery approaches seek to target the desired tissue more effectively. The agreement builds on an existing collaboration between AstraZeneca and Isis Pharmaceuticals and supports AstraZeneca’s research and development capabilities 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, antisense oligonucleotides 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. The methods build on Isis Pharmaceuticals’ Ligand Conjugation Antisense (LICA) technology. The first application of this technology is Isis’ GalNac-conjugated antisense oligonucleotides targeting liver hepatocytes, which lowered the therapeutic dose needed for liver targets by approximately 10-fold, according to the company.

Under the agreement, each party will fund its own contribution and commit investigators to the collaboration. In line with AstraZeneca’s open innovation approach, the companies will work together on an agreed program and share rights to the results. Isis can apply learnings from this collaboration broadly across its antisense technology platform ,and AstraZeneca can similarly apply learnings across its broader RNA-based, small-molecule and antibody research and development activities. 

Isis Pharmaceuticals and AstraZeneca entered into a collaboration, development, and license agreement in 2012 in oncology and subsequently expanded it in 2013 to include CVMD. Under the 2012 agreement, one of the molecules being developed is AZD9150 (ISIS-STAT3_Rx), 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-AR_Rx), is in Phase I trials.

Source: Isis Pharmaceuticals