Controlling Tumour Growth and Spread:
Anti-Angiogenesis and Anti-Metastatic Compounds
PI-88 and PG545 are anti-cancer agents with a dual mechanism of action critical to the growth of solid tumours and progression, namely angiogenesis and metastasis. A common feature of these two processes is the involvement of heparan sulfate, an important structural component of the extracellular matrix. Anti-angiogenic therapy is based on the hypothesis that blocking new blood vessel formation in tumours will stop or slow their growth. Progen's technology works to disrupt tumour growth by preventing the process by which angiogenic growth factor proteins trigger blood vessel growth. Progen's compounds do this by mimicking the action of an essential sugar heparan sulfate, ultimately preventing the cell signalling required for the formation of new blood vessels. The compounds also block signalling of multiple growth factors such as FGF-1, FGF-2 and VEFG.
Anti-metastatic therapy aims to limit tumour spread to distant sites in the body but the approach has yet to yield an approved agent based on a specific mechanism of action. Progen's compounds also inhibit the enzyme heparanase. Heparanase has been identified as a particularly important player in metastasis and its expression directly correlates with the metastatic spread of various tumours. This is the only enzyme capable of cleaving heparan sulfate, an essential step in the cell signalling process. By inhibiting this enzyme, Progen's compounds can help stop the spread of cancer (metastasis) throughout the body.
It is this dual mechanism exploited by Progen's anti-angiogenesis and anti-metastatic technologies that differentiates its compounds from others in the market and in development.
PI-88 - Oncology Indications Partnered
PI-88 is a first-in-class heparanase inhibitor with an extensive patent family in all the key markets covering its composition of matter and use in oncology. In June 2010, Progen signed a license and collaboration agreement with Medigen Biotechnology Corporation to complete product development and global commercialisation of PI-88 for use in oncology. Medigen have commenced a Phase 3 clinical trial (named PATRON) in post-resection liver cancer with sites open in Taiwan, China and South Korea. This randomised, placebo-controlled, multinational trial will enrol approximately 500 subjects. Disease free survival will be employed as the primary endpoint for efficacy assessment. Other endpoints such as time to recurrence, tumour recurrence rate and overall survival will be measured as secondary endpoints. Medigen is expecting to complete its enrolment of 500 patients by the end of 2013.
PG545 - Non-Onclogy and HCC Indications Partnered
PG545 is a fully synthetic single chemical entity small molecule heparan sulfate mimetic which displays potent anti-tumour and anti-metastatic activity in pre-clinical models. It is the result of a development program by Progen with the aim of improved chemistry, manufacturing and controls (CMC), efficacy, pharmacokinetics and reduced toxicity.
PG545 was originally developed for subcutaneous injection for patient self-administration. Progen now proposes intravenous administration following local site reactions observed in patients in a Phase 1a clinical trial in patients with advanced cancer. PG545 will commence a Phase 1 clinical trial for PG545 in late 2013 by intravenous administration with the primary objective of the study to determine the maximum tolerated dose as defined by significant dose limiting toxicity.
- Initiate PG545 Phase 1 clinical trial in advanced cancer patients using the IV route of administration
- Identify preclinical proof-of -concept in specific cancer types in preparation for Phase 2 clinical studies
- Prepare PG545 Investigational New Drug (IND) filing for the US FDA
- Initiate PG545 Phase 2 trial in selected cancer indication
- Seek licensing and partnering opportunities for oncology indications of PG545 as it continues pre-clinical and clinical development
- Continue to support our partner Medigen Biotechnology Corporation in the development and commercialisation for the licensed indications of PI-88 and PG545