-
Phosphagenics’ patented anti-cancer agent, GTP-0805, when combined with leading breast cancer treatment tamoxifen, and delivered orally, resulted in a 78 per cent reduction in breast tumour growth compared to a 21 per cent reduction when tamoxifen alone was administered.
-
GTP-0805, combined with tamoxifen, resulted in earlier anti-tumour activity of tamoxifen.
Phosphagenics Limited (“Phosphagenics”) (ASX: POH) today announced the results of its pre-clinical trial with its patented anti-cancer agent GTP-0805.The results demonstrated that GTP-0805 given orally in combination with tamoxifen, inhibited the rate of tumour growth by more than three times the rate observed when compared to tamoxifen alone.
Conducted at Monash University, Melbourne, Australia, the trial was designed to examine the potential anti-tumour properties of various doses of oral GTP-0805, either given alone, or in combination with tamoxifen, in a recognised pre-clinical model for breast cancer.
The study showed that GTP-0805, delivered orally in combination with tamoxifen, resulted in a 78 per cent reduction in breast tumour growth compared to a 21 per cent reduction seen when tamoxifen alone was administered. In addition, GTP-0805 appeared to promote the earlier anti-tumour activity of tamoxifen.
Dr Esra Ogru , Executive Director of Research and Development at Phosphagenics, said the pre-clinical trial results suggest that GTP-0805 can improve the effectiveness of tamoxifen, a well established anti-cancer agent.
“The primary objectives of this trial were to determine whether there were any dose-dependent reduction in tumour growth, and whether GTP-0805 protected against the onset of tumour growth. This pre-clinical study clearly achieved both these objectives," Dr Ogru said.
“Breast cancer is one of the most common cancers in women and is a leading cause of cancer-related death amongst those aged between 35 and 54 years of age. To be developing a product that has the potential to enhance the activity of tamoxifen, one of the world’s leading breast cancer treatments, is certainly an exciting development,” she added.
Phosphagenics Managing Director, Harry Rosen said: “This result provides another significant opportunity for Phosphagenics to expand its pipeline and is another key milestone in Phosphagenics’ strategy to discover new and cost effective ways to enhance the bioavailability, activity, safety and delivery of proven pharmaceutical and nutraceutical products.
“The potential market for GTP-0805, both as an adjunct cancer therapy to tamoxifen and possibly to other cancer medications, could be significant. Phosphagenics will now investigate the combination of GTP-0805 with other cancer drugs and in other forms of cancer,” he said.
About GTP - 0805
GTP-0805 is a patented product that has been developed using Phosphagenics’ phosphorylation technology platform, a process where the addition of a phosphate group has been found to enhance the bioavailability, activity and safety of existing pharmaceuticals and nutraceuticals, as well as to assist in the production of drug delivery platforms. GTP-0805 may stimulate programmed cell death ("apoptosis), leading to the destruction of diseased cells and is thought to act as a signaling molecule and a modulator of various molecular pathways. Its mechanism of action is being further investigated by researchers at the University of California Medical Centre in Davis, California.
About Tamoxifen
Tamoxifen is a hormonal therapy that blocks the effect of oestrogen. It is used in the treatment of breast cancer and may also be used to prevent breast cancer in women who are at very high risk of developing the disease.
About the GTP-0805 Animal Trial
Objectives
Conducted at Monash University , Melbourne, , the primary objectives of this study was to establish if there was any dose-dependent tumor reduction properties associated with GTP-0805 treatment alone or in combination with tamoxifen. The protective effects of GTP-0805 were also examined in a pre-treatment study.
Study Outline and Key Results
Utilising female athymic nude mice, the study was conducted in three cohorts. In all three cohorts, animals were injected with 2 million MCF-7 human breast cancer cells and each cohort contained a control group that received no treatment.
Cohort one
The first cohort examined the effects of GTP-0805 pre-treatment on tumour growth during an 8 week period comparing no treatment versus GTP-0805 alone. Four doses of GTP-0805 were tested (n=5-10 animals per treatment group). Athymic nude mice were treated for 4 weeks with GTP-0805, and then injected with 2 million human breast cancer cells into their breast pad. The mice were maintained on the particular GTP-0805 dose for a further 8 weeks while tumour size was monitored 3 times a week by digital calliper readings.
Pre-treatment of GTP-0805 orally for 4 weeks resulted in up to a 24% average reduction in tumour size compared to the no treatment control group.
Cohort two
The second cohort examined the effects of four doses of GTP-0805 on tumour growth during an 8 week period, compared to 3 doses of tamoxifen and no treatment (n=8-10 animals per treatment group). In this study, there was no pre-treatment with GTP-0805 prior to injecting the mice with 2 million human breast cancer cells. The daily treatments only began once the cancer cells were injected into the mice.
Oral administration of GTP-0805 alone for 8 weeks resulted in up to a 13% average reduction in tumour size. Tamoxifen treatment however saw up to an average 53% reduction in tumour size following 8 weeks of treatment.
Cohort three
The third cohort examined the effects of GTP-0805 for 4 weeks in combination with the optimum tamoxifen dose (established during cohort 2), as well as for tamoxifen alone and against a no treatment control group. Three doses of GTP-0805 were tested (n=8-10 per treatment group).
Comparing the results to the no treatment control group, oral administration of GTP-0805 in combination with tamoxifen resulted in a 78% reduction in the average tumour size. Comparatively, tamoxifen alone only showed an average reduction in tumour size of 21% (refer Figure 1 below).
Figure 1
.jpg)
Discussion of results
Given these early results, this pre-clinical study has shown that GTP-0805 is orally bioavailable in a breast cancer animal model. GTP-0805 when given in combination with tamoxifen improved the effectiveness of tamoxifen in inhibiting tumour growth. Additionally GTP-0805 also improved the rate of onset of tamoxifen activity.
Treatment of athymic nude mice following the inoculation of human breast cancer cells with GTP-0805 showed a trend towards smaller tumour sizes (up to 13% reduction) compared to control after 8 weeks treatment. When the mice were pre-treated for 4 weeks with GTP-0805 and maintained on GTP-0805 for 8 weeks following cancer cell inoculation the average reduction in tumor size was higher (up to 24% reduction in size). Histological analysis of tumors also showed a trend towards less complex or severe tumors in mice treated with GTP-0805 compared to untreated (control) mice.
Whilst the results for GTP-0805 as a monotherapy are encouraging, the key finding was the substantial reduction in tumor size when GTP-0805 treatment was combined with tamoxifen. The results indicate a greater average reduction in tumor size with GTP-0805 treatment in half the time, when compared to treatment with tamoxifen alone. For example the mid-dose of GTP-0805 combined with tamoxifen resulted in 78% average reduction in tumour mass after four weeks of treatment (cohort three) whereas tamoxifen alone after eight weeks treatment resulted in 53% average reduction (cohort two) and only 21% average reduction after four weeks treatment (cohort three). This indicates that the combination may not only have enhanced effects on reducing the tumour size in these animals but also improving the rate of onset (activity) of tamoxifen.
In summary, this pre-clinical study has shown that:
About Phosphagenics Limited
Phosphagenics is a Melbourne-based, globally driven biotechnology company focused on the discovery of new and cost effective ways to enhance the bioavailability, activity, safety and delivery of proven pharmaceutical and nutraceutical products.
Phosphagenics’ core technology is built around the science and application of phosphorylation, a process where the addition of a phosphate group has been found to enhance the bioavailability, activity and safety of existing pharmaceuticals and nutraceuticals, as well as to assist in the production of drug delivery platforms.
Phosphagenics’ shares are listed on the Australian Stock Exchange (POH) and the London Stock Exchange's Alternative Investment Market (PSG). An ADR – Level 1 program has been established in the with the Bank of New York (PPGNY) for US investors to trade in Phosphagenics’ stock on the ‘over-the-counter’ market.
For more information, please visit Phosphagenics’ web site at www.phosphagenics.com
