Isis Pharmaceuticals said today it earned a $10 million milestone payment from AstraZeneca after the pharma giant added a second development candidate to their six-month-old collaboration on new cancer drugs. The payment raises to $35 million the up-front and milestone funds Isis has received from AstraZeneca since the collaboration was launched in December 2012.
The candidate, ISIS-ARRx, is an antisense drug designed to treat patients with prostate cancer by inhibiting the production of the androgen receptor (AR). Isis said AstraZeneca plans to develop ISIS-ARRx (also called AZD5312 and previously called ISIS-AZ1Rx) for prostate cancer patients both as a single agent and in combination therapy.
"AR is a well-validated target in prostate cancer, and our antisense approach may allow us to avoid the limitations of other therapeutic approaches that others have tried to inhibit this target," Isis COO B. Lynne Parshall said in a statement.
Because ISIS-ARRx can inhibit the production of all known forms of AR, including variants of the AR gene, Isis and AstraZeneca reason that the drug could be an effective treatment for all stages of prostate cancer, including in patients resistant to current therapies that largely involve countering androgens by blocking ARs or removing circulating androgens. Those therapies are only initially effective in delaying disease progression in patients with metastatic prostate cancer, as resistance to treatment develops.
ISIS-ARRx is the first drug to emerge from research into development under AstraZeneca’s partnership with Isis, which granted AZ an exclusive license to develop and commercialize the drug. Isis agreed to develop ISIS-ARRx through completion of IND-enabling toxicology, with AZ agreeing to make payments tied to development milestones, as well as double-digit royalties on sales of the drug candidate.
Isis and AstraZeneca initially focused their cancer collaboration on development of Isis’ ISIS-STAT3Rx for advanced lymphomas. The companies have since expanded their work to include an additional cancer indication: On May 6, Isis said AstraZeneca had launched a Phase Ib/IIa clinical study assessing the safety and efficacy of ISIS-STAT3Rx in patients with advanced metastatic hepatocellular carcinoma (HCC) who have failed first-line therapy.
ISIS-STAT3Rx is designed to inhibit the production of signal transducer and activator of transcription 3 (STAT3), which is overexpressed in numerous types of cancers. ISIS-STAT3Rx is among drug candidates that Isis and AstraZeneca agreed to develop under a collaboration designed to commercialize antisense therapeutics against five cancer targets.