BioWorld Today Correspondent

Astex Therapeutics Ltd. is hoping the initial public offering window will open in the new year, enabling it to capitalize on the promising clinical data reported earlier this month for three lead products

"We're continuing to track the markets, though there is no doubt the UK is in a dip," CEO Harren Jhoti told BioWorld Today. He pointed out, however, that the company is "less exposed to the financial weather" than its counterparts. "We are in a strong position because our platform can generate lots of assets and we are comfortable doing licensing deals."

Despite those advantages, the company still had to bolster its coffers with a £7.5 million (US$14.9 million) senior secured loan in November.

It's rare for European biotechs to raise loans, and it is among the largest venture loans provided to a biotechnology company in Europe, according to the joint lenders Oxford Financial Services and GE Healthcare Financial Services.

Cambridge, UK-based Astex has been busy this month, publishing the first clinical data from trials of its three targeted cell cycle inhibitor products and making the final preparations to file an investigational new drug application on a fourth product generated by its fragment-based discovery platform, an Hsp90 inhibitor.

The highlight of its recent news was the report on its aurora kinase inhibitor, AT9283, which showed early signs of efficacy as a single agent in advanced acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) patients who were refractory to other treatments. Of 26 patients treated to date, one-third has demonstrated a reduction in blast count.

Principal investigator Hagop Kantarjian, of the M.D. Anderson Cancer Center in Atlanta, said those results are encouraging and support further clinical development.

"We see preliminary evidence of the anti-leukemic activity of AT9283 at well-tolerated doses in patients with relapsed and refractory hematological malignancies, including AML and CML," he said.

AT9283 is an inhibitor of the kinases Aurora A, Aurora B, JAK2, bcr-abl and Flt-3. There is evidence that each of those targets plays a role in the development and progression of a range of cancers. The product currently is delivered by intravenous injection, but Jhoti noted that Astex is working on an oral formulation. In particular, that will allow the company to exploit its JAK2 activity in CML.

AT9283 also is in a UK Phase I safety trial in solid tumors.

Jhoti said he is not perturbed by the recent decision of Merck and Co. Inc. and Vertex Pharmaceuticals Inc. to stop enrollment in the Phase II trial of MK-0457, the most advanced aurora kinase inhibitor in development, after safety data indicated a potential cardiovascular effect in one patient.

"AT9283 is different from other [aurora kinase inhibitor] compounds," he said. "It seems to have a unique profile. With [MK-0457] halted, we're in the leading pack."

Other aurora kinase inhibitors in Phase I development are R763, a joint product of Rigel Pharmaceuticals Inc., of South San Francisco, and Merck Serono SA, of Darmstadt, Germany; MLN8327 from Millennium Pharmaceuticals Inc., of Cambridge, Mass; CYC116 from Cyclacel Pharmaceuticals Inc., of Berkeley Heights, N.J.; and SNS-314 from South San Francisco-based Sunesis Pharmaceuticals Inc.

Following behind AT9283 in Astex's pipeline is AT7519, a selective inhibitor of certain cyclin-dependent kinases (CDK), which is in two multicenter Phase I trials, and AT9311, also a CDK inhibitor. Astex is developing AT9311 in collaboration with Novartis AG, of Basel, Switzerland, while Novartis has an option to license AT7519 later.

The flurry of activity around the clinical portfolio has been heightened for Jhoti, who stepped up to the position of CEO - for the third time - following the resignation of Leon Bushara after a mere 18 months in the role because, Jhoti said, "It just didn't work out."

Jhoti was founding CEO and stepped in again prior to Bushara 's appointment, when then-CEO Tim Haines left the company at the end of 2005. This time, Jhoti said, he will retain the role.