Big week for Australian biotechs part II

Melbourne biotech Cytopia has commenced dosing patients in the first of a suite of Phase II clinical studies for its vascular disrupting agent CYT997.

Cytopia said the studies will investigate the activity of CYT997 in specific cancer types with high unmet medical need and poor prognoses, such as multiple myeloma and glioblastoma multiforme.

CYT997 has a dual mechanism of action shutting down established blood vessels that supply the tumour with nutrients and oxygen and also direct cytotoxic properties.

Capable of being delivered orally as well as intravenously, the compound was discovered by Cytopia scientists in 2003 and an Investigational New Drug application was accepted by the FDA in 2005 to commence Phase I studies.

Dosing in the company's first Phase II efficacy study in patients with relapsed or refractory multiple myeloma began in January 2008. The Phase II study is a two-stage design with an interim clinical activity analysis after 14 patients and maximum enrolment of 24 patients.

Cytopia also intends to file an Orphan Drug Designation application in the US for CYT997 in multiple myeloma within three months.

The company said it was on schedule to commence a Phase II study for CYT997 in glioblastoma multiforme (GBM) during the second quarter of 2008. CYT997 will be administered in combination with two other approved anti-cancer agents.

The study will also use advanced imaging techniques such as specialised MRI to detect changes in tumour blood vessels as a marker for CYT997 activity. Interim data should be available by June 2009 with final data for this program in late 2009.

In addition, following favourable findings in mesothelioma patients in Cytopia's Phase I trial, the company is undertaking feasibility analysis for a Phase II study in mesothelioma patients who have failed the currently approved drug, Alimta (pemetrexed).

This single-arm study of 20-30 patients would potentially be conducted at multiple centres in Australia, the US and Asia, the company said.

It is also studying different delivery methods, including an oral capsule and intravenous infusion.

Melbourne biotech Benitec has announced that its licensee, the US company Tacere Therapeutics, has signed a license agreement with Japanese biotech Oncolys BioPharma to develop and commercialise Tacere's RNAi-based hepatitis C virus compound TT-033 throughout Asia.

Benitec said in a statement that the deal was a validation of the Benitec ddRNAi "expressed" approach for treating chronic infectious diseases including hepatitis C.

Benitec has an equity holding in Tacere Therapeutics and also receives milestone and royalty payments.

Under the terms of the agreement, Oncolys and Tacere will form a joint steering committee to work with Tacere and Pfizer to oversee preclinical research and development of TT-033, to be called OBP-701 by Oncolys.

TT-033 is a novel therapeutic product containing three separate RNAi elements targeted against the hepatitis C virus itself and entrapped in an AAV protein coat.

AAV delivery methods have demonstrated clinical safety, and preclinical studies with TT-033 have shown the ability to penetrate hepatocytes, the site of HCV replication, at high levels following a single intravenous administration.

In preclinical animal studies, this "cocktail in one drug" monotherapy targeted and cleaved the hepatitis C virus itself at three different sites simultaneously without toxicity.