Peplin has demonstrated in pre-clinical studies that its lead molecule PEP005 (ingenol mebutate) has the potential to treat many forms of cancer. To date Peplin has successfully completed pre-clinical studies, filed an IND and commenced clinical studies for its proprietary PEP005 (ingenol mebutate) Gel. Two other drug candidates, PEP005 (ingenol mebutate) for injection and PEP005 (ingenol mebutate) for intra-cavitary delivery), are nearing completion of pre-clinical studies in preparation for the filing of INDs for leukemia and bladder cancer, respectively.

Peplin's strategy of contracting out pre-clinical studies to world class specialists enables the best available expertise to be devoted to the development of Peplin's products. 

PEP005 (ingenol mebutate) Gel
In research conducted by Peplin at QIMR and published in the international peer reviewed journal Cancer Research, Peplin has demonstrated that three daily topical applications of PEP005 (ingenol mebutate) Gel onto the skin above the tumor was effective for completely curing a panel of aggressive mouse and human tumours growing subcutaneously in mice. These tumors comprised melanoma and squamous cell carcinoma (both skin cancers) and lung, cervical and prostate cancers. Importantly, after a few weeks the skin over the previously existing tumor is almost normal, without significant scarring or loss of flexibility.

PEP005 (ingenol mebutate) for injection
We have completed a pre-IND meeting with FDA and have a clear view on the pre-clinical package required to file an IND and the plan for the drug's early clinical development.

In April 2005 we were pleased to announce that research Peplin had undertaken into the anti-leukemic properties of PEP005 (ingenol mebutate) for injection was accepted for publication in Blood, the journal of the American Society of Hematology. The key findings of this research comprised:

• Activity:
  • PEP005 (ingenol membutate) is a highly potent killer of established leukemia cell lines; and
  • it encourages primary human acute myelongenous leukemia cells to commit suicide at very low concentrations of drug.
• Selectivity:  At these low drug concentrations healthy cells are not affected.
• Safety:  Preliminary in vivo toxicology data indicates the potential for a viable therapeutic window. 
• Mode of action:  PEP005 (ingenol mebutate) achieves this cancer killing by a process of restoring the natural cell suicide mechanism (apoptosis) in leukemia cells. The restoration of the apoptotic pathway appears to be by way of a protein kinase C delta mediated process.

Activation of protein kinase C delta is a novel approach to the management of acute myelogenous leukemia and, while knowing how a drug works is helpful, it is potentially doubly important in this case because this target may represent a predictor of activity for PEP005 (ingenol mebutate). Over-expression of protein kinase C delta in leukemia cells appears to be a biomarker of whether leukemia cells will respond to PEP005 (ingenol mebutate) or not. This may provide a valuable tool to stratify and select patient populations and accelerate clinical development.

The powerful and comprehensive findings in this research program give us significant confidence to push forward with a formal leukemia development program. Advances in the treatment of this blood-borne cancer are sorely needed and we are excited by the opportunity to bring a new therapeutic alternative to sufferers of this disease.

Click here for more information.

PEP005 (ingenol mebutate) for intra-cavitary delivery
Again our focus on the clinical development of PEP005 (ingenol mebutate) Gel has limited our ability to push PEP005 (ingenol mebutate) for intra-cavitary delivery for bladder cancer forward.

During the course of the 2005 financial year we completed a pre-IND meeting with FDA.

We have completed a pre-clinical package necessary to initiate clinical trials. This program is presently on hold; we expect to review our plans to file an IND and initiate clinical trials when capital and management resources can be secured.

Click here for more information.

Pre-clinical activities are conducted internationally by many research institutions under contract for Peplin. These include:

Manufacturing

• The cultivation, extraction and purification activities are undertaken by various Peplin contractors based in and around south-east Queensland and formulation is undertaken by Penn Pharmaceuticals in the UK.
• In addition, the State Department of Primary Industries and Fisheries, Redland Research Station at Cleveland, Queensland and two groups in the UK have evaluated the optimal growing conditions for the plant to enhance the production of PEP005 (ingenol mebutate).

• Research
  • Queensland Institute of Medical Research in Brisbane, Australia
  • Birmingham University in Birmingham, UK
  • Oncotest in Freiburg, Germany
  • Cardiff Institute of Tissue Engineering & Repair, UK
    
• Pre-clinical development
  • Covance in Harrogate, UK
  • MedPharm in London, UK
  • Charles River Laboratories in Edinburgh, UK
  • Battelle in Columbus, Ohio, US
  • Penn Pharmaceutical Services in Gwent, UK
  • Evotec in Abingdon, UK
  • Wolfe Laboratories in Watertown, Massachusetts, US