AstraZeneca and Isis Pharmaceuticals said today they will expand their nearly two-year-old research collaboration by launching a strategic alliance to discover and develop new delivery methods for antisense oligonucleotides. The value of the expanded collaboration was not disclosed.
The new delivery methods build on Isis Pharmaceuticals’ Ligand Conjugation Antisense (LICA) technology. The new collaboration aims to improve the targeting of the oligonucleotides—especially in people with oncology and cardiovascular and metabolic disease—into specific organs and cells.
“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,” Susan Galbraith, head of AstraZeneca’s Oncology Innovative Medicines Unit, said in a statement.
The first example of a treatment that incorporates LICA is Isis Pharma’s GalNac-conjugated antisense oligonucleotides targeting liver hepatocytes. The technology helps lowers the therapeutic dose needed for liver targets by approximately 10-fold, AstraZeneca and Isis Pharma said.
AstraZeneca and Isis Pharma said they will work together on an agreed program and share rights to the results. Both companies agreed to fund part of the work and commit investigators to the collaboration.
Isis plans to apply what it learns from the new collaboration broadly across its antisense technology platform, while AstraZeneca can do likewise across its broader RNA-based, small molecule and antibody R&D activities, the companies reason.
The companies launched their first collaboration in 2012, agreeing to discover and develop new antisense drugs therapeutics against five cancer targets, using AstraZeneca’s personalized-medicine experience. AstraZeneca agreed in return to pay Isis Pharma $31 million upfront—$25 million upon signing, the other $6 million in the second quarter of 2013 tied to the research program continuing.
As part of that original deal, Isis Pharma granted AstraZeneca an exclusive license to develop and commercialize ISIS-STAT3Rx (also called AZD9150), a first-in-human, first-in-class, antisense oligonucleotide inhibitor of STAT3.
Back in 2012, AstraZeneca agreed to oversee all development of ISIS-STAT3Rx, other than an ongoing clinical trial which Isis agreed to complete. At the time, ISIS-STAT3Rx was under evaluation as a monotherapy in an early clinical trial in patients with advanced lymphomas. The companies’ collaboration also covered a preclinical program and an option to license products developed under a separate research program.
Isis Pharma was made eligible for payments tied to achieving clinical milestones for the ISIS-STAT3Rx program and preclinical milestones for the other programs. Isis was also eligible for downstream development and approval milestone payments, license fees for research program targets, and royalties on sales from successfully commercialized products.
Last week, Isis Pharma said it earned a $7.5 milestone payment for the advancement of ISIS-STST3Rx in patients with advanced cancers. AstraZeneca is evaluating ISIS-STAT3Rx in a Phase I/II clinical study in patients with advanced metastatic liver cancer, and plans to begin additional clinical studies assessing the drug candidate.
Upon launch of a Phase II study, Isis added, it will be eligible for another $7.5 million milestone payment, plus an additional $10 million milestone payment.
In total, Isis is eligible to receive up to $70 million in milestone payments as ISIS-STAT3Rx advances through clinical development. Isis is also eligible to earn up to $170 million in regulatory milestone payments plus royalties on the commercial sales of the drug.
Since the original 2012 deal, AstraZeneca and Isis Pharma expanded their partnership to include development of a prostate cancer drug, triggering a $10 million milestone payment to Isis Pharma, as well as development of antisense drugs therapeutics against five CVMD targets.
The companies have also agreed to develop ISIS-STAT3Rx in combination with AstraZeneca’s MEDI4736, an investigational anti-PD-L1 immune checkpoint inhibitor. The companies also launched Phase I trials for a second product developed through their collaboration, an antisense oncology compound targeting the androgen receptor AZD5312 (ISIS-ARRx).
The expanded collaboration comes just three days after Isis Pharma said it will offer $425 million in convertible senior notes due 2021 in a private placement. In addition to repurchasing older notes, the company said it would use the remainder of the net proceeds in part to develop unspecified drugs in its pipeline to later stages of development prior to partnering.