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Infinity initiates Phase I myeloma drug trial

13-Jul-2005

Infinity Pharmaceuticals announced the initiation of a phase I clinical trial of the company's lead investigational anticancer agent for the development of a potential treatment for patients with multiple myeloma. The compound will subsequently be developed for additional hematologic (blood) cancers and solid tumour indications.

IPI-504 is a small molecule compound specifically designed to attack a cancer cell's machinery for maintaining protein homeostasis, the process by which cells continue the orderly formation and destruction of proteins.

Infinity 's IPI-504, the company's Heat Shock Protein 90 (Hsp90) inhibitor, has shown that inhibition of Hsp90 forces cancer cells to "commit suicide" through a process of programmed cell death or apoptosis.

Heat-shock protein 90 (HSP90) is a cellular chaperone protein required for the activation of several eukaryotic protein kinases, including the cyclin-dependent kinase CDK4. Geldanamycin, an inhibitor of the protein-refolding activity of Hsp90, has been shown to have antiproliferative and antitumour activities.

Additional in vitro research by Infinity has demonstrated that IPI-504 binds to Hsp90 more tightly than 17-AAG. In addition, IPI-504 acting as a sole agent shows potent cytotoxic activity against multiple myeloma cells which are resistant to current therapies including bortezomib-resistant cells.

When examined in vivo, IPI-504 demonstrated a 71 per cent reduction in multiple myeloma tumour growth relative to controls in a preclinical xenograft model. It was also found to decrease serum Immunoglobulin lambda chain concentrations (similar to M protein in the human disease), enabling monitoring of disease burden with a surrogate marker.

Furthermore, in vivo reduction in tumour growth was also observed in several other human xenograft models, including models of breast, prostate and ovarian cancer.

The phase I trial of IPI-504 will evaluate the potential anti-tumour activity and the tolerability of various doses in subjects with relapsed or relapsed, refractory multiple myeloma.

"We are encouraged to begin our first clinical trial of IPI- 504 and look forward to further exploring its use as a single agent and in combination with other chemotherapeutic agents to attack cancer cell survival," said Julian Adams, chief scientific officer at Infinity.

"A key advantage of the compound relative to other Hsp90 inhibitors is its intravenous administration to patients using a simple water-based formulation," he added.

Multiple myeloma is a progressive, incurable hematologic (blood) cancer characterised by the growth of specific cells in the blood called plasma cells. These cells are normally part of the immune system and make proteins called antibodies.

In myeloma, plasma cells proliferate in the bone marrow, which often results in extensive skeletal destruction and/or pathologic fractures, and low blood counts. In addition, they produce abnormally large quantities of proteins, which lead to other clinical findings including kidney failure and may lead to increased susceptibility to infection.

The Multiple Myeloma Research Foundation estimates the frequency of multiple myeloma as 4-5 new cases per 100,000 persons per year. In the United States approximately 50,000 people are living with multiple myeloma and roughly 15,000 new cases are diagnosed each year.

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