Isis Pharmaceuticals, Inc. has earned a $7.5 million milestone payment, the first of two milestone payments totaling $15 million, from AstraZeneca for the advancement of ISIS-STAT3Rx, also referred to as AZD9150, in patients with advanced cancers.  

Isis will earn the second $7.5 million milestone payment from AstraZeneca upon initiation of a phase 2 study.  Isis has completed a clinical study of ISIS-STAT3Rx in patients with advanced cancers and plans to present results from this study at an upcoming medical meeting.  AstraZeneca is currently evaluating ISIS-STAT3Rx in a phase 1/2 clinical study in patients with advanced metastatic liver cancer.  AstraZeneca plans to initiate additional clinical studies to further evaluate ISIS-STAT3Rx.

"AstraZeneca's expertise and resources in the area of oncology drug development are a significant benefit for the clinical development of ISIS-STAT3Rx," said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals.  "We are pleased, not only with the substantial resources and expertise that AstraZeneca has brought to this program, but also with their commitment to advancing ISIS-STAT3Rx into clinical development."

Under the amended terms of agreement, Isis has earned a $7.5 million milestone payment.  Upon initiation of the phase 2 study, Isis will earn a second $7.5 million milestone payment and 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.  In addition, Isis is eligible to earn up to $170 million in regulatory milestone payments plus royalties on the commercial sales of the drug.

ISIS-STAT3Rx is the first drug in Isis' pipeline that incorporates Isis' Generation 2.5 chemistry, which Isis developed to increase potency of antisense drugs, thereby creating opportunities for drugs like ISIS-STAT3Rx to be effective in more difficult-to-treat cancers.  ISIS-STAT3Rx is designed to inhibit the production of signal transducer and activator of transcription 3 (STAT3), a protein critical for tumor cell growth and survival.  In addition, STAT3 is an important mediator of signaling in the JAK2/STAT3 pathway, which has been previously shown to be an important target for drug development.  Because STAT3 is activated in numerous types of cancer, ISIS-STAT3Rx has the potential to be broadly useful for both solid and hematologic tumors.  ISIS-STAT3Rx has been shown to reduce STAT3 levels in preclinical tumor models and produce anti-tumor activity.  Inhibition of STAT3 has also been shown to block the induction of tumor-associated cytokines involved in the progression of cancer, such as IL-6, IL-1, TGF, and IL-10, which could serve as important biomarkers in clinical studies.