Anti-Cancer Drug CYT997 Update

MELBOURNE, Australia, March 12 /PRNewswire-FirstCall/ -- Cytopia Limited
(ASX: CYT) has commenced dosing patients in the first of a suite of Phase II
clinical studies for its vascular disrupting agent (VDA), CYT997. These
studies will investigate the activity of this anti-cancer compound in specific
cancer types with high unmet medical need and poor prognoses.
VDAs are a new class of drugs to treat cancer and have potential for
"blockbuster" sales in the treatment of vascularized tumors. CYT997 has a dual
mechanism of action shutting down established blood vessels that supply the
tumor 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 US Food and Drug Administration in 2005 to
commence Phase I studies. During the 2008 financial year Cytopia has:
-- commenced dosing in its first Phase II study
-- finalized preparations for its second Phase II study
-- concluded its first Phase I safety and tolerability study with
intravenous administration
-- continued dose-escalation in its Phase I capsule dosing study (oral
administration)

Phase II clinical programs

1. Phase II trial in multiple myeloma
Cytopia commenced dosing in its first Phase II efficacy study in patients
with relapsed or refractory multiple myeloma in January 2008, some four months
after conclusion of its initial Phase I study. The Phase II study is a two-
stage design with an interim clinical activity analysis after 14 patients and
maximum enrolment of 24 patients. Enrolment into this efficacy study is
progressing on schedule and Cytopia anticipates undertaking interim data
analysis by September this year.
This clinical study follows an extensive body of preclinical studies,
including studies in cells from heavily pre-treated patients where CYT997
demonstrated significant antimyeloma activity. The potential activity of this
compound in multiple myeloma extends the utility of the drug beyond the core
focus of the Phase II studies in conventional solid tumors.
Cytopia also intends to file an Orphan Drug Designation application in the
United States for CYT997 in multiple myeloma within three months. Orphan drug
designation gives a range of development benefits including extended patent
protection and increased regulatory consultation.
2. Phase Ib/II trial in glioblastoma multiforme (GBM)
Cytopia is on schedule to commence a Phase II study for CYT997 in GBM
during the second quarter of 2008. CYT997 will be administered in combination
with two other approved anti-cancer agents.
GBM is an aggressive brain tumor commonly treated with radiotherapy,
surgical resection and chemotherapy. Unfortunately, many patients relapse and
subsequently have very poor prognoses. Experimental therapies which attack GBM
blood vessels have shown promise in treating this condition and Cytopia
intends to investigate the activity of its own vascular targeting agent CYT997
in this setting.
This clinical study will initially investigate the optimal safe dose for
CYT997 when administered with the standard chemotherapy (Phase Ib). Following
this initial safety assessment, the Phase II efficacy study will commence in a
two-stage design with scheduled interim analysis. It is anticipated that 25 to
30 patients will be enrolled into this study at sites in Australia, the United
States and the United Kingdom over an 18 month period. Overseas site selection
will be finalised within three months.
The study will also use advanced imaging techniques such as specialized
MRI to detect changes in tumor 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.
3. Further Phase II clinical trials
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 centers in Australia, the United States and Asia.
Activity in second-line mesothelioma could lead to expedited drug approval and
a fast-to-market strategy for the compound in this cancer indication.
It is anticipated that appropriate regulatory submissions to support this
study will be filed in the third quarter of 2008.
In consultation with its clinical advisory board, Cytopia is continuing to
refine its clinical development plan for further Phase II studies including
randomized studies in conditions such as melanoma and for Phase III studies as
new data arise from its preclinical and clinical activities.
Phase I clinical program
1. Phase I capsule clinical study
Cytopia has continued to accelerate dose-escalation in its Phase I oral
capsule safety and tolerability study during the past 6 months.
Data collected from this study to date suggests that the compound is
generally well tolerated following oral administration and that further
increasing doses of CYT997 are warranted. Patient enrolment into this study
will continue until the maximum tolerated dose for CYT997 after capsule
administration is determined.
Dosing in this study to date has been conducted at sites in Brisbane and
Townsville, although the Townsville site has been suspended due to the
departure of the local principal investigator. Given the expanded patient
enrolment, Cytopia is finalizing ethical approval for the study at leading
cancer centers in Adelaide and Melbourne and anticipates commencing dosing at
these new sites in the next four weeks.
The addition of the two new trial centers will further accelerate dosing
in this study. Initiation of these clinical centers also broadens the
company's clinical partners and lays a foundation for the company's Phase II
program. Given the generally favourable tolerability seen to date, it is not
anticipated that the trial will conclude before the third quarter of 2008.
2. Phase I intravenous infusion study
As previously reported, this study was successfully concluded in September
2007. Key findings from this study have guided the design and implementation
of the company's Phase II study program. Data from the Phase I study has been
accepted for an oral presentation in June 2008 at the 44th American Society of
Clinical Oncology General Meeting in Chicago.
Preclinical studies
Following the observation of synergy between CYT997 and 5-fluorouracil (a
standard chemotherapeutic agent) in preclinical studies, the company will soon
commence an expanded program of preclinical combination studies. These are
designed to determine which currently approved cancer therapies best synergize
with CYT997's vascular targeting properties. Data from these studies will
assist the company in the selection and design of later stage clinical
programs.
The company will also shortly commission synthesis of a third GMP-grade
batch of CYT997 to support its expanded clinical programs. Further preclinical
toxicology studies designed to broaden the available dosing regimes for
clinical studies will also commence in the next three months.
Together, these studies signal the company's ongoing confidence in, and
commitment to, the clinical development of CYT997.
The development timeline for CYT997 compares very favorably with the other
vascular disrupting agents currently in late stage clinical studies. By
December 2008, some five years after the discovery of this compound, the
company intends to be finalizing the first of its Phase II studies and will
have two further Phase II studies well established. Successful completion of
these programs in concert with additional preclinical data will add
significant value to Cytopia's leading drug asset.
About Cytopia
Cytopia Ltd is an Australian biotechnology company focused on the
discovery and development of new drugs to treat cancer. Cytopia conducts its
research and development via subsidiaries based in Melbourne, Australia and
New York and specializes in discovering new molecules that can inhibit enzymes
known as kinases, an exciting new class of drugs. Website: www.cytopia.com.au
SOURCE Cytopia Limited

Mr. Andrew Macdonald, Chief Executive Officer, +61 3 9208 4232,
andrew.macdonald@cytopia.com.au, or Dr. Gregg Smith, Director, Drug
Development and Ops, +61 3 9208 4234, gregg.smith@cytopia.com.au, both of
Cytopia Ltd