Staff Writer

Infinity Pharmaceutials Inc. has halted a Phase II study of its drug candidate for hormone-refractory prostate cancer because the product showed no biologic activity as a standalone treatment.

The product, IPI-504 showed no activity in HRPC patients previously treated with Taxotere (docetaxel). Nor did it show activity in those who had no prior treatment with Taxotere.

However, studies of IPI-504 in other cancers have shown evidence of biologic activity. Cambridge, Mass.-based Infinity and partner AstraZeneca plc said they remain committed to the program, which includes studies in gastrointestinal stromal tumors (GIST) and non-small-cell lung cancer (NSCLC).

That was Infinity's only trial in prostate cancer, said Julian Adams, president of research and development and chief scientific officer. However, he said, "We are not saying we gave up on prostate cancer by any means."

He pointed to the company's other candidates - an oral inhibitor of heat shock protein, IPI-493 and IPI-926, which inhibits the hedgehog pathway involved in cancer cell proliferation and survival. Both of those candidates, Adams said, might "offer a good deal of flexibility" in terms of how to treat prostate cancer.

Infinity and AstraZeneca also are jointly developing IPI-493. In preclinical models, IPI-493 has demonstrated high oral bioavailability in animals and selective and potent inhibition of Hsp90. A Phase I study of IPI-493 is imminent, Adams said.

The decision to end the study in hormone-refractory prostate cancer was a "mutually agreed upon," allowing the company to aggressively invest in other ongoing trials, Infinity spokeswoman Monique Allair said. She added that the partnership with AstraZeneca is "an outstanding alliance at this stage of the game, and I anticipate it will continue to be."

Under a deal reached in 2006, Infinity and Gaithersburg, Md.-based MedImmune agreed to split the development costs and any future profits from IPI-504. MedImmune is now the biologics unit of London-based AstraZeneca.

Christopher Raymond, an analyst with Robert W. Baird & Co., said in a research note, "We are unfazed by the discontinuation of a Phase II study of IPI-504 in HRPC, which we have long viewed as a bit of a flier. The lack of clinical activity in HRPC does not change our outlook on this molecule in GIST or NSCLC..."

Jeffries & Co. analyst Eun Yang agreed, writing in a research note that, "Discontinuation of early HRPC study has no impact on our projections. Phase III for IPI-504's (Hsp90 inhibitor) lead indication, refractory GIST, is on track to begin in 3Q. With solid financial standing (sufficient into 2010), we continue to view INFI as an attractive small-cap opportunity for long-term investors."

The product is in a Phase II study in patients with advanced NSCLC and a Phase Ib trial evaluating IPI-504 in combination with docetaxel.

In 2007, Infinity reported preliminary evidence of biological activity from the Phase I portion of the Phase I/II trial in patients with NSCLC who have received at least 12 weeks of treatment with a tyrosine kinase inhibitor. Infinity anticipates reporting preliminary results from the Phase II portion of the NSCLC trial by the end of the year.

Infinity also plans to commence an international Phase III registration study of IPI-504 in patients with refractory GIST in the third quarter of 2008, based on the activity and safety data reported at the 2008 annual meeting of the American Society of Clinical Oncology.

Infinity said it will conduct that trial under a special protocol assessment agreement with the FDA and pursuant to scientific advice from the European Medicines Evaluation Agency.

The company's lead target indication for IPI-504 is in GIST, Adams said, adding that the company is "very emboldened" by the activity seen in GIST and the early activity in NSCLC. Infinity also has preclinical studies of IPI-504 in other tumors and other combinations, according to the company website.

IPI-504 (retaspimycin hydrochloride) is Infinity's lead anti-chaperone therapy targeting heat shock protein 90. According to Infinity, inhibition of the Hsp90 chaperone knocks out a critical source of support for cancer cells, leading to tumor growth inhibition and cancer cell death. IPI-504 has shown potent and selective inhibition of Hsp90 in preclinical studies, the company said.

Shares in Infinity (NASDAQ:INFI) fell 30 cents Tuesday or 4 percent, closing at $7.25.