NexGenix Pharmaceuticals' NXD30001, one of several novel, radicicol-based Hsp90 inhibitors in its compound series, demonstrated efficacy in breast cancer tumour xenograft models without evidence for liver and kidney toxicity.

The potency, tolerability, pharmacokinetic and pharmacodynamic properties of NXD30001 and its derivatives indicate that it, or an analog, may be useful in the treatment of breast and other forms of cancer with an improved dosing and therapeutic window compared to 17AAG, the first-in-class Hsp90 inhibitor currently in phase II clinical trials for cancer.

The compound series appears to bind Hsp90 in a different mode than 17AAG or radicicol and exhibit higher affinity to Hsp90 than radicicol. NXD30001 and its analogs efficiently inhibit cell proliferation and deplete multiple Hsp90 client proteins such as Her2, Akt, c-Raf, Cdk4, and Cyclin D1 in Her2-overexpressing breast and other cancer cell lines at low nanomolar concentrations. Pharmacokinetic studies demonstrate that NXD30001 can achieve potential therapeutic levels via intraperitoneal (i.p.) dosing and that the compound accumulates in tumours at above micromolar concentrations.

Tumour pharmacodynamic analysis demonstrated depletion of multiple Hsp90 client proteins, including Her2, after a single dose; these client proteins remained undetectable for more than two days, consistent with the pharmacokinetic tumour data.

"A number of analogs with activity similar to or better than NXD30001 have been synthesized and are being evaluated for oral bioavailability, tolerability, and efficacy" stated Allan Rubenstein, MD, CEO, NexGenix. "Our intent is to progress an i.v. formulation of NXD30001 into IND-enabling studies for breast cancer, and to develop an oral formulation from the series for neural tumours, such as those found in Neurofibromatosis Type 2, and for neurodegenerative disorders."

NexGenix Pharmaceuticals, a US-based biotechnology company developing a novel Hsp90 inhibitor series for cancer, neural tumours and neurodegenerative disorders, presented data on the Hsp90 inhibitor programme at the GTCBio 5th Annual Cancer Drugs Research and Development Conference in Phoenix, Arizona.