AstraZeneca and Isis Pharmaceuticals said today they will expand their nearly three-year-old collaboration to include discovery and development of new therapies for cardiovascular, metabolic, and renal diseases using Isis’ antisense platform technology.

AstraZeneca agreed to pay Isis Pharma $65 million upfront, plus undisclosed payments tied to development and regulatory milestones, for each program that the pharma giant advances to clinical development. Isis Pharma is also eligible for tiered double-digit royalties on annual net sales for each program.

The expanded collaboration is intended to support AstraZeneca’s strategic approach of using RNA-targeted treatments in the additional therapeutic areas, while enabling Isis Pharma to extend its antisense technology to treating kidney diseases.

“By working together we aim to uncover targets and pathways that can be manipulated using antisense drug therapy,” Mene Pangalos, evp, innovative medicines and early development at AstraZeneca, said in a statement. “Antisense-based therapies are rapidly gaining momentum in the clinic and becoming an important component of our early stage pipeline.”

The latest deal between the companies is subject to clearances under the Hart-Scott Rodino Antitrust Improvements Act.

Antisense oligonucleotides target RNA to prevent the production of disease-causing proteins, increase the production of proteins deficient in disease, or target toxic RNAs unable to generate proteins.

AstraZeneca and Isis launched their collaboration in 2012, agreeing to discover and develop new antisense drugs therapeutics against five cancer targets. AstraZeneca agreed in return to pay Isis Pharma $31 million upfront. 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.

AstraZeneca added a second development candidate to the collaboration in 2013—ISIS-ARRx, an antisense drug designed to treat patients with prostate cancer by inhibiting the production of the androgen receptor (AR). Last year, the companies expanded their partnership again by launching a strategic alliance to discover and develop new delivery methods for antisense oligonucleotides.

At the 2015 American Association for Cancer Research Annual Meeting in Philadelphia in April, AstraZeneca reported clinical and preclinical data on ISIS-STAT3-2.5Rx (also called AZD9150) showing evidence of antitumor activity in patients with cancer including advanced/metastatic hepatocellular carcinoma and diffuse large B cell lymphoma. AstraZeneca also reported that, in preclinical studies, the combination of ISIS-STAT3-2.5Rx and AstraZeneca’s MEDI4736, an immune checkpoint inhibitor candidate, showed significantly greater antitumor activity than when either drug was administered alone.

AstraZeneca said it planned to initiate two clinical studies evaluating the ISIS-STAT3-2.5Rx/MEDI4736 combination this year. One such study—which will also compare the Isis Pharma compound with another AstraZeneca candidate, AZD5069—was not yet open for patient recruitment as of the latest update July 14 posted on

According to Isis Pharma’s Form 10-K annual report, submitted March 2 to the U.S. Securities and Exchange Commission, Isis Pharma received $23 million from AstraZeneca in 2014 and early 2015 related to the development of ISIS-AR-2.5Rx and ISIS-STAT3-2.5Rx.

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