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AACR: New Drugs

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At AACR, pharmaceutical and biotech companies are taking the opportunity to publicize some new and promising compounds they are testing to treat various kinds of cancer. AstraZeneca's Nigel Brooks presented AZD4547, a selective inhibitor of FGF receptors 1, 2, and 3. FGF and FGFR signaling occurs in many human tumors and controls tumor angiogenesis. According to Brooks, AZD4547 potently and selectively inhibits FGFR downstream signaling in cell lines. It has also been shown to cause dose-dependent tumor-growth inhibition in a Snu16 gastric xenograft model, he added.

Array Biopharma's Kevin Koch presented ARRY-380, an oral selective HER2 inhibitor for the chronic treatment of patients with HER2-positive cancers. This compound has improved selectivity and potency and diminished interaction in EGFR, Koch said. It has also been shown to inhibit trastuzumab-resistant p95 truncated HER2 — truncation at high levels has been shown to be prognostic of poor prognosis and survival. ARRY-380 also combines well with standard-of-care therapies, especially trastuzumab, Koch added, and a Phase I expansion study of the compound is ongoing.

Chugai Pharmaceutical's Hiroshi Sakamoto presented CH5424802, a potent and selective ALK inhibitor. It has been shown to be efficacious in xenograft models of cancers with ALK gene alterations like non-small-cell lung cancer and neuroblastoma, among others. The compound has better efficacy than crizotinib and is also effective against crizotinib-resistant mutations, Sakamoto said.

Finally, Bristol-Myers Squibb's Matthew Lorenzi presented BMS-911543, a highly selective JAK2 inhibitor. JAK2 pathway activation is a hallmark of chronic myeloproliferative diseases, Lorenzi said. The compound, a potent JAK2 inhibitor, is associated with less potential for immunosupression in vivo. There is data implicating JAK2 in other malignancies as well, Lorenzi said, and the compound is currently in testing for myelofibrosis, though to realize the full potential of JAK2 inhibition in solid tumors will require combination therapies.

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