BioWorld International Correspondent

LONDON - Astex Therapeutics Ltd. is hoping the initial public offering window will open in 2008, enabling it to capitalize on clinical data from its three lead products, which it reported last month.

"We're continuing to track the markets," CEO Harren Jhoti told BioWorld International. "Though there is no doubt the UK is in a dip." However, he pointed out 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 that, the company had to bolster its coffers with a £7.5 million (US$14.9 million) senior secured loan, taken out in November. It's rare for European biotechs to raise loans and that one 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 had a busy time at the end of 2007, publicizing the first clinical data from trials of its three targeted cell cycle inhibitor products, and making the final preparations to file a U.S. investigational new drug application on the fourth product to be generated by its fragment-based discovery platform, an Hsp90 inhibitor.

The highlight was the report that its aurora kinase inhibitor, AT9283, has shown 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 have shown a reduction in blast count.

The principal investigator Hagop Kantarjian of M.D. Anderson Cancer Center, said results to date 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 haematological malignancies, including AML and CML."

AT9283 is an inhibitor of the kinases Aurora A, Aurora B, JAK2, BCR-Abl and Fit-3. There is evidence that each of those have a role in the development and progression of a range of cancers.

The product is delivered by intravenous injection currently, but Jhoti noted that Astex is working on an oral formulation. In particular, it will allow the company to exploit its JAK2 activity in CML. AT9283 is also in a UK Phase I safety trial in solid tumors.

Jhoti said he is not perturbed by the recent decision of Merck and Co. 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. 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; Cyclacel Pharmaceuticals Inc., of Berkeley Heights, N.J., with CYC116; and South San Francisco-based Sunesis Pharmaceuticals Inc.'s SNS-314.

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, also.

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

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

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