SYDNEY, AUSTRALIA and NEW CANAAN, CT, Sep. 29, 2009 (Marketwire) --
SYDNEY, AUSTRALIA and NEW CANAAN, CT -- (Marketwire) -- 09/29/09 -- Marshall Edwards, Inc. (NASDAQ: MSHL), a pharmaceutical company specializing in clinical development of oncology drugs, today released data demonstrating that the efficacy of NV-128 in animal xenograft models is achieved without apparent toxicity.
NV-128 is a novel flavonoid small molecule mTOR inhibitor, capable of inhibiting both mTORC1 and mTORC2 pathways which are central to the aberrant proliferative capacity of both mature cancer cells and cancer stem cells.
The data demonstrated that NV-128 has much greater safety than some other mTOR inhibitors in mice bearing human ovarian cancer xenografts.
Most of the current compounds acting on this pathway are analogs of rapamycin, known as rapalogs. Rapamycin and its analogs are regarded as the archetypal inhibitors of mammalian target of rapamycin or mTOR. In addition to their reported toxicities, rapalogs have been shown to contribute to the development of drug resistant tumors and ultimately reduced effectiveness over time due to their inability to efficiently inhibit mTORC2, a complex of mTOR with "rictor" (rapamycin-insensitive companion of mTOR).
NV-128 administered daily resulted in a reduction in tumor volume of 51 per cent relative to untreated control animals after 15 days, compared to a 50 per cent reduction in mice given rapamycin every other day. However, whereas rapamycin treated mice lost 8 per cent of body weight over this period, NV-128 treated mice gained weight, finishing at 6 per cent above their starting weight after the 15 day period. This is a significant indicator of lack of toxicity for NV-128, whereas the weight loss in the rapamycin-treated mice was judged to be a reflection of the well documented toxicity of rapamycin in both animal and human studies. After 21 days the tumors were removed and weighed. In NV-128 treated mice, tumor mass was reduced by 41 per cent compared to vehicle controls, an effect equivalent to rapamycin treated animals in which tumor mass was reduced by 44 per cent.
In additional data released today by Marshall Edwards Inc., the Company reported that NV-128 was judged to be without cardiac toxicity, further indicating the likely safety of NV-128 in clinical use.
One limitation of many drugs in clinical application, including some mTOR inhibitors, is their interference with heart function causing the interval between heart beats to increase (known as the QTc interval).
