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that based on the Phase 1 results, Isis and AstraZeneca have initiated a mid-stage study evaluating STAT3Rx in patients with recurring lymphomas. AstraZeneca also is evaluating other mid-stage studies for STAT3Rx, and has begun dosing in a mid-stage study of patients with liver cancer, Crooke said.
The second drug that AstraZeneca added to their collaboration is called ARRx, and is a compound that inhibits production of the androgen receptor in patients with prostate cancer. Isis said AstraZeneca plans to develop ARRx broadly for use in prostate cancer treatment as both a single agent and in combination with other cancer therapies.
There are already several drugs on the market that fight prostate cancer by reducing the androgens (male sex hormones) that are known to drive tumor growth in men with prostate cancer. Isis is betting that its technology will provide an advantage, Crooke said, because its antisense drugs are specific to a particular target. “We can (design) antisense drugs that selectively target a particular gene mutation, which could then be linked to worse disease outcomes, disease progressions, or treatment resistance,” Crooke said. “We can also discriminate between genes with disease-associated mutations and normal genes that may perform important cellular functions.”
Another advantage, Crooke said, is that antisense technology allows Isis to decrease the time and cost it usually takes to reach a clinical proof of concept once a molecular target has been identified. “This efficiency is achievable because our drugs all use the same basic chemistry, and we have a good understanding how our drugs will behave in preclinical and clinical studies,” Crooke said. “Our drugs are all manufactured, formulated, analyzed by the same processes. This of course is different from small molecules, which require that each of these processes be independently established for each new molecule.
“With the efficiency of antisense technology, we can rapidly evaluate both traditional targets for cancer as well as novel targets to determine which are better targets to reduce the growth and the lethality of cancer cells and we can do this with a relatively small highly efficient group of coyotes supported by the efficiency of our antisense technology platform.”