Novacea Initiates Phase 1/2 Trial of AQ4N in Glioblastoma Multiforme

SOUTH SAN FRANCISCO, CA--Nov 1, 2006 -- Novacea, Inc. (NASDAQ:NOVC) today announced that it has initiated a multicenter, Phase1b/2a open-label clinical trial of AQ4N (banoxantrone), in combination with radiotherapy and temozolomide, for safety, tolerability and activity in patients with newly diagnosed glioblastoma multiforme (GBM).
The trial consists of two parts. The primary objective of the first part will be to evaluate safety and tolerability of three dose levels (200 mg/m2, 450 mg/m2and 750 mg/m2). The second part will further evaluate safety and tolerability as well as efficacy and the highest safe and tolerated dose of the AQ4N treatment determined in part one. Novacea expects to enroll approximately 60 patients in the trial.

“Initiating this trial is an important milestone for Novacea and the GBM patient community. For more than 20 years researchers have grappled with the issue of hypoxic (oxygen starved) tumors limiting the effectiveness of radiation and/or chemotherapy. In vitro data indicate that the level of response to radiation and/or chemotherapy in hypoxic tumor cells is one-third that of normally oxygenated cells. By selectively targeting the hypoxic tumor regions, we are hopeful that AQ4N will increase the anti-tumor activity of this regimen compared to the current standard of care,” said Brad Goodwin, chief executive officer of Novacea.

Novacea acquired North American rights toAQ4N from KuDOS Pharmaceuticals and is an investigational new drug designed to address the unmet medical needs of certain cancers such as GBM. While many tumors are refractory to radiation and/or chemotherapy, AQ4N is a prodrug that is designed to be activated in regions of tumor hypoxia. Upon activation, AQ4N binds to DNA and functions as a potent topoisomerase II poison thereby blocking the replication of rapidly dividing cancer cells leading to targeted tumor cell killing. Early clinical studies in patients with brain tumors have demonstrated that AQ4N is converted into its toxic form selectively in the hypoxic region of GBM tumors and not in the adjacent normal tissues.

WHATS THE DEAL?
Hypoxia is literally the lack of oxygen in cells. Glioblastoma multiforme is a type of brain cancer.
It is known that hypoxic fractions of tumours are less responsive to radiotherapy and chemotherapy. Tumor cells that are hypoxic are less responsive to radiation and chemotherapy which can be attributed to the fact that hypoxic cells are less active than oxic cells; they are not replicating and are thus less vulnerable to cell killing through DNA damage.

Banoxantrone is preferentially and irreversibly converted to AQ4 in the body, its cytotoxic form, in hypoxic tumour cells where it remains localized. When the surrounding oxygenated cells are killed by radiotherapy or chemotherapy bringing these AQ4-containing quiescent cells closer to the oxygen source, they become reoxygenated, attempt to resume replication and, in this state, are killed by AQ4 through potent DNA intercalation and topoisomerase II inhibition which are enzymes in the DNA replication process.


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