Cytopia Commences Second Phase II Study in Brain Cancer

4 September 2008, Melbourne, Australia: Cytopia Limited (ASX:CYT) today announced that it is commencing enrolment for its Phase Ib/II study of CYT997, the companys novel vascular-disrupting anticancer agent, in patients with an aggressive form of brain cancer known as glioblastoma multiforme (GBM).

The GBM clinical trial is the first Phase II efficacy study in highly vascular, solid tumour indications for the company and the second in its suite of Phase II studies designed to investigate the anti-cancer activity of CYT997. Patient recruitment to the study will now commence, following regulatory approval in Australia and the United States.

The clinical study will investigate the activity of CYT997 in combination with two other marketed anticancer agents in approximately 30 patients at a number of clinical centres in Australia and overseas. Dr Jason Lickliter, Director of Oncology at the Frankston Hospital, will be Study Chairman for the program.

GBM is currently treated by surgical resection, and/or radiation and chemotherapy. Despite these treatments, the condition recurs in most patients, leading to a poor prognosis and median survival of less than 12 months. GBM tumours are highly vascular and heavily dependent on their own abnormal blood supply for growth, rendering them potentially susceptible to destruction by an anti-vascular agent such as CYT997.

The following table provides a summary of the key aspects of the Phase II GBM trial.

Name of trial	A Phase Ib/II Study of CYT997 in Combination with Carboplatin and Etoposide in Relapsed Glioblastoma Multiforme (CCL08001).
Primary endpoints	Assess safety and tolerability of escalating doses of CYT997 given in combination with standard carboplatin and etoposide therapy (Ph Ib), and estimation of progression-free survival at six months using the dose of CYT997 identified in the Phase Ib component (Ph II).
Secondary endpoints	Objective response rate, overall survival, safety and tolerability, effects on pharmacodynamic markers of vascular disruption and tumour apoptosis, and pharmacokinetic analyses.
Blinding status	Not blinded.
Product development status	Drug substance and drug product are manufactured to GMP standards.
Treatment method
Route	24 hour intravenous infusion dose (CYT997).
Frequency	Day 2 of a 21 day cycle.
Dose-levels	Maximum dose of 200 mg/m2 CYT997 dihydrochloride.
Number of trial subjects	Estimated 35 patients.
Subject selection criteria	Eligible patients must have glioblastoma multiforme that has progressed after surgery, radiation therapy and temozolomide chemotherapy.
Trial location	Initial site in Melbourne, Australia.
Expected completion	2Q 2010
Trial standard	ICH-GCP

This trial follows the successful conclusion last year of the companys Phase I safety study for intravenous CYT997, in which a prolonged delay in tumour growth was observed in seven of the studys 31 advanced cancer patients.

Significant perturbations in tumour blood flow were also demonstrated, suggesting that CYT997 potently disrupts tumour blood vessels. Findings from this study were recently presented at the American Society of Clinical Oncology Annual Meeting which attracts some 30,000 cancer specialists from around the globe.

Cytopia is also investigating the safety and anti-vascular activity of CYT997 when administered by mouth. Preliminary data from the companys Phase I oral study indicates that the compound is well absorbed after administration in capsule form. This key finding differentiates CYT997 from other vascular disrupting agents currently in development which can only be administered intravenously, limiting their clinical utility.

Enrolment into the companys Phase II study of CYT997 in relapsed multiple myeloma, a disorder of the bone marrow, is also ongoing.