ANGIOGENESIS by hjkuiw354


									FACT SHEET | JULY 2008

                                                                                 Factsheet Contents

PROGEN                                                                           About Angiogenesis and Cancer
                                                                                 Progen’s Anti-Angiogenesis

                                                                                 Further Reading
                                                                                 Safe Harbour Statement

                                                           tain size (approx-   volved in the process of angiogene-
                                                         imately 1-2mm)         sis. These include fibroblast growth
                                                         it requires blood      factors (FGF-1 and FGF-2) and plate-
                                                         vessels to supply      let-derived growth factor (PDGF).
                                                         it with nutrients
                                                         and oxygen. An-        Progen’s angiogenesis products
                                                         giogenesis is the      have been developed to target a
                                                         process by which       number of proteins, including VEGF
                                                         new blood ves-         and FGF-2, which bind to a complex
                                                         sels grow. Target-     sugar called heparan sulfate. These
                                                         ing the process        growth factors require that binding
                                                         of angiogenesis        to trigger cell signaling. Progen’s
                                                         is a newly vali-       products are the first in develop-
                                                         dated approach         ment that can stop the cell signal-
                                                         to cancer treat-       ing involved in angiogenesis by
                                                         ment with 3 ap-        mimicking heparan sulfate and in-
                                                         proved products        hibiting more than one growth fac-
                                                         in this area, Avas-    tor at once. This makes them ideal
                                                         tin®,      Sutent®     products to combat angiogenesis
                                                         and Nexavar®.          effectively and have the potential to
                                                         The worldwide          combine effectively with other an-
                                                         an t i -angiogen -     giogenesis inhibitors such as Avas-
                                                         esis market is         tin, Sutent and Nexavar, that target
                                                         expected to be         different cancer mechanisms.
                                                         worth in excess
                                       of   USD$10     billion by 2010.         In addition to the growth factor ac-
Progen’s three cancer platforms                                                 tivity, Progen’s products inhibit the
target different aspects of the bi-    These three approved anti-angio-         enzyme heparanase, that breaks
ology of cancer, angiogenesis, cell    genesis products target angiogen-        down heparan sulfate. This is im-
proliferation and epigenetics. This    esis via a single, very well validated   portant as this process is critical to
factsheet is focused on the angio-     biological pathway which is medi-        the spread of the cancer throughout
genesis platform.                      ated by a protein called vascular        the body (metastasis).
                                       endothelial growth factor (VEGF),
Cancer cells have lost their ability   released by the tumor that triggers It is the dual mechanism of Progen’s
to divide in a controlled fashion. A   blood vessel growth.                   products that, we believe, differen-
tumor consists of a population of                                             tiates Progen’s angiogenesis plat-
rapidly dividing and growing cancer    In addition to VEGF, there are oth- form from others in development.
cells. Once a tumor reaches a cer-     er growth factors that are also in-


The PG500 series observed efficacy                  of heparan sulfate to prevent the                   PG500 Series
as an anti-tumour agent is based                    action of the enzyme heparanase,                    Progen has capitalized upon its
on inhibition of two biological                     thereby blocking heparan sulfate                    understanding of heparan sulfate to
processes critical to the growth                    cleavage, and to selectively bind to                create new potential candidates for
and progression of solid tumours,                   angiogenic growth factors (VEGF,                    the treatment of cancer. We have
angiogenesis and metastasis. A                      FGF2) thus blocking their roles in cell             named these the PG500 series,
feature common to both of these                     signaling. Through these actions,                   from which PG545 was chosen as
processes is the involvement                        both metastasis and angiogenesis                    the candidate for the additional
of heparan sulfate, a complex                       are inhibited. PG545, is the lead                   studies required to support an
polysaccharide (sugar), which is                    compound currently undergoing                       IND application with the US FDA.
an important structural component                   preclinical development in animal                   PG545 was selected over other
of the extracellular matrix (ECM)                   models of cancer. The diagram                       compounds in the series based on
of most tissues. The PG500 series                   below details the well documented                   a comprehensive target product
were developed as an antagonist                     mechanism of action of PG545.                       profile incorporating aspects such
                                                                                                        as efficacy, pharmacokinetics,
                                                                                                        safety, and ease of manufacture.
                                                                                                        Depending on the outcome of these
                                                                                                        further studies we expect to submit
                                                                                                        an IND application with the US FDA
                                                                                                        in early 2009.

                                                                                                        Drug Discovery - Heparanase
                                                                                                        Progen also has an active drug
                                                                                                        discovery     program      targeted
                                                                                                        towards the identification of
                                                                                                        molecules that selectively inhibit
                                                                                                        the enzyme heparanase and that
                                                                                                        can be formulated for oral delivery.
                                                                                                        These efforts are currently at
                                                                                                        the early stage of identifying the
                                                                                                        basic scaffolds around which our
                                                                                                        future drug candidates will be

FURTHER READING                                                                                        SAFE HARBOUR STATEMENT
                                                                                                       This factsheet contains forward-looking statements that are based
Parish, C.R. et al. “Identification of Sulfated Oligosaccharide-based Inhibitors of Tumor Growth and
Metastasis Using Novel in Vitro Assays for Angiogenesis and Heparanase Activity”, Cancer Research      on current management expectations. These statements may differ
1999, 59, 3433-3441.                                                                                   materially from actual future events or results due to certain risks and
                                                                                                       uncertainties, including without limitation, risks associated with drug
Joyce, J. A. et al. “A Functional Heparan Sulfate Mimetic in Tumor Angiogenesis and Invasion in a      development and manufacture, risks inherent in the extensive regulatory
Mouse Model of Multistage Cancer”, Oncogene, 2005, 24, 4037-4051. Erratum in: Oncogene, 2005, 24,      approval process mandated by the United States Food and Drug
                                                                                                       Administration and the Australian Therapeutic Goods Administration,

Cohen, L. et al. “Hepranase promotes growth, angiogenesis and survival of primary breast tumours”,     delays in obtaining the necessary approvals for clinical testing, patient
Int J. Cancer 2006, 118, 1609-1617                                                                     recruitment, delays in the conduct of clinical trials, market acceptance
                                                                                                       of PG545, PG11047 and other drugs, future capital needs, general
Ferro, V. et al. “PI-88 and Novel Heparan Sulfate Mimetics Inhibit Angiogenesis”, Seminars in          economic conditions, and other risks and uncertainties detailed from
Thrombosis & Hemostatis 2007, 33, 5, 557-562
                                                                                                       time to time in the Company’s filings with the Australian Securities

Sasisekharan, R. et al. “Roles of Heparan-Suphate Glycosaminologycans in Caner”, Nature Review         Exchange and the United States Securities and Exchange Commission.
Cancer 2002, 2, 521                                                                                    Moreover, there can be no assurance that others will not independently
                                                                                                       develop similar products or processes or design around patents owned
Folkman, J. “Angiogenesis: an organizing principle for drug discovery”, Nature Review Drug Discovery   or licensed by the Company, or that patents owned or licensed by the
2007, 6 273-286                                                                                        Company will provide meaningful protection or competitive advantages

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