Arno Therapeutics, Inc. announced the dosing of the first patient in a Phase II clinical study of its third-generation camptothecin compound, AR-67, in patients with Glioblastoma Multiforme (GBM), an aggressive form of brain cancer. The Phase II, open-label study in up to 56 patients is designed to evaluate the efficacy of AR-67 dosed intravenously for five days on a 21-day cycle until the onset of toxicity requiring discontinuation or tumor progression, and will include two-cohorts. One cohort will enroll patients who have progressed rapidly after treatment with Avastin(R) (Genentech), a drug recently approved to treat GBM, and the other cohort will enroll patients who have not recently received treatment with Avastin(R). The study is being conducted as a multi-centered study led by Duke University, a leading center in the treatment of brain cancer. The primary objective of the Phase II study is to evaluate the progression free survival of patients with GBM treated with AR-67. Secondary endpoints include response rate, and overall survival rate. AR-67 is a novel, third-generation camptothecin analogue that inhibits Topoisomerase I activity, and has demonstrated clinical activity and an excellent safety profile in clinical studies, as well as improved pharmacokinetic properties, compared with approved first and second-generation products Hycamtin(R) (Topotecan) and Camptosar(R) (Irinotecan), respectively, as demonstrated by the increased stability of the active lactone form of AR-67 in blood. Arno has completed a Phase I single agent, clinical study of AR-67 in patients with advanced solid tumors. A separate Phase II study for the treatment of myelodysplastic syndrome (MDS) is currently enrolling patients who have progressed following regimens containing hypomethylating agents.

Arno Therapeutics, Inc. announced the presentation of a poster at the annual American Society of Hematology meeting that describes the preclinical activity of Arno's drug candidate AR-42 against leukemia stem cells. AR-42 is a broad spectrum inhibitor of both histone and non-histone deacetylation proteins that demonstrated potent activity against Acute Myeloid Leukemia stem cells. LSCs are believed to be able to initiate and perpetuate AML while displaying resistance to standard chemotherapies. The ability to target these cells with therapeutic compounds may help improve patient outcomes. The poster's findings show that AR-42 preferentially targets LSCs compared to normal healthy cells. The research also suggests that AR-42 is active through a mechanism that differentiates it from other compounds with preclinical anti-LSC activity. AR-42 (formerly known as HDAC-42) is an orally available, broad spectrum inhibitor of both histone and non-histone deacetylation proteins, which may both be important in cancer progression. Histone deacetylase inhibitors are a growing class of compounds that target histone deactylase, a molecule involved in determining which genes are expressed in a particular cell. In preclinical studies, AR-42 has shown activity against a broad spectrum of deacetylation targets and increased potency compared to vorinostat, the first HDAC inhibitor to obtain FDA approval. Arno currently plans to commence an investigator-initiated Phase I/IIa study with AR-42 in collaboration with an academic institution in the first half of 2010.

Arno Therapeutics Inc. announced the dosing of the first patient in a Phase II clinical study of AR-67 in adult patients with Myelodysplastic Syndrome (MDS) who have failed prior therapies. MDS is a group of pre-malignant blood disorders marked by abnormal production of blood cells by the bone marrow. The Phase II, open-label, single-arm study is designed to evaluate the efficacy of AR-67, dosed intravenously for five days over four cycles or approximately 16 weeks. Up to 25 patients are expected to be enrolled in this clinical trial, which is being conducted at the University of Texas M.D. Anderson Cancer Center (MDACC), in Houston, Texas. The primary objective of the Phase II study is to determine the response rate of AR-67 in patients with MDS. Secondary objectives include evaluation of the safety, response duration and disease-free survival of patients with MDS treated with AR-67.