Cytopia Nominates JAK2 Clinical Candidate for Myeloproliferative Disorders

Clinical study to commence late this year

MELBOURNE, Australia, March 17 /PRNewswire/ -- Cytopia Limited (ASX: CYT)
has selected CYT387, a selective and potent JAK2 inhibitor, for formal
preclinical development to treat myeloproliferative disorders (MPDs). This
follows extensive laboratory experimentation and includes the recent
demonstration of activity in an in-vivo model of myeloproliferative disease.
Myeloproliferative disorders are a group of diseases including
myelofibrosis, polycythemia vera (PV) and essential thrombocythemia (ET) that
affect over 150,000 patients in the USA and more than twice that worldwide.
Over 95% of PV cases and over 50% of ET and primary and secondary
myelofibrosis cases are believed to be caused by a mutation in the JAK2 kinase
enzyme. This renders the kinase permanently active and leads to the
overproduction of particular blood cells.
No specific treatments exist for these diseases and untreated progressive
disease can lead to leukemia or myelofibrosis. CYT387 possesses an excellent
selectivity profile against a large panel of kinases and other pharmacological
targets. It also has excellent pharmacokinetics including oral bioavailability
and in preclinical models has a promising safety profile.
CYT387 has also recently shown efficacy in a well-validated in-vivo model
of myeloproliferative disorders in studies in the laboratory of physician-
scientist Michael Deininger MD PhD at Oregon Health & Science University
Cancer Institute, USA. Results showed a profound effects on abnormal blood
counts and clinical symptoms of MPDs in mice that were dosed orally.
Dr Deininger said, "We are highly encouraged by Cytopia's compound in this
model of myeloproliferative disease which clearly indicates significant
improvement of symptoms and disease remission. The favorable data from this
animal model augers well for activity of the compound in the clinic."
The compound will now be progressed into formal preclinical studies
including IND-enabling toxicology studies. This program will lead to the
submission of an Investigational New Drug (IND) application with the US Food
and Drug Administration(FDA) in the fourth quarter of 2008. The preclinical
development program has already been considered by the FDA in pre-IND reviews,
including a face-to-face meeting with FDA reviewers last month.
"The accumulated data for CYT387 clearly indicates that this compound has
an excellent potency and safety profile for the treatment of patients with
MPDs. We are aggressively progressing this compound through formal preclinical
studies with the aim of beginning clinical trials by the end of this year,"
said Mr. Andrew Macdonald, CEO of Cytopia.
About JAK2
The discovery of a specific single activating mutation in the JAK2 enzyme
in MPDs in 2005 has focused attention on developing a therapy for these
diseases through selective inhibition of JAK2. To successfully address these
chronic diseases with a JAK2 inhibitor, the specificity and resultant
tolerability profile is a key element of the product profile required for a
"best in class" inhibitor.
CYT387 is a specific JAK2 inhibitor with excellent potential for safe and
efficacious chronic human dosing. It has been derived from Cytopia's knowledge
of basic biology of JAK kinases, a strong structural biology program that has
delivered multiple co-crystal structures of JAK2 complexed with inhibitors,
and the subsequent development of an extensive chemical library of JAK2
inhibitors through an integrated computational and medicinal chemistry
platform.
Cytopia is developing a suite of JAK2 inhibitors for multiple indications
including the treatment of certain cancers, particularly lymphomas and solid
tumors where JAK2 has been shown to be up-regulated, and for cardiovascular
diseases such as pulmonary hypertension.
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 Chris Burns Ph.D., Director, Research,
+61-3-9208-4235, chris.burns@cytopia.com.au, both of Cytopia Limited