BioWorld International Correspondent
LONDON - Xenova Group plc reported positive results in a third Phase IIa trial of XR9576 for the prevention of multidrug resistance in cancer, and said it is at an advanced stage of negotiations to license the drug and take it forward to Phase III.
CEO David Oxlade told BioWorld International, "We have been in discussions with a number of partners to fund Phase III and have identified a preferred party. Discussions are at a relatively advanced stage, and our aim of signing a deal by mid-2001 seems reasonable."
At the same time, Xenova, based in Slough, said it is dropping XR5000, its first-generation topoisomerase inhibitor, after three Phase II trials in ovarian, glioblastoma and non-small-cell lung cancers failed to show significant responses. This follows failure in Phase IIa in colorectal cancer, announced in June 2000.
"The markets have anticipated we would drop XR5000 since the colorectal results," said Oxlade. "There were a number of small, minor responses, but nothing major. We're interested in drugs with a clear, commercially competitive profile. There's no point in taking a thing forward if it will not attract significant interest from partners."
There are two second-generation compounds, XR11576 and XR5944, in preclinical development. Oxlade said that whereas investigators started to see efficacy with XR5000 at doses that were not well tolerated, "The follow-on compounds are much more potent, and one is available orally."
Xenova's share price fell by 25 percent last week, to 66.5 pence, following the announcement that it is to take over Cantab Pharmaceuticals plc in an all-share deal. Cantab's stock price also fell sharply, ending the week 19 percent down at 98.5 pence. The merger offer of 11 new Xenova shares for every seven Cantab shares valued each Cantab share at £1.40, based on a closing price of 89 pence per Xenova share on Feb. 16.
Cantab put itself up for sale last year, and Oxlade said a lot of speculative money had gone into Cantab in the hope of a cash bid or a partial cash bid. "The share price fell when it was announced the bid was all paper, and valuing the shares at £1.40, not the £1.60 that was talked about. And because it was a ratio offer, that moved Xenova's share price down, too."
In addition, he said there was a lot of "questionable comment," about the strategic fit between the two companies. In part this is due to a perception that Cantab, based in Cambridge, is an infectious diseases specialist, whereas its portfolio of genetically engineered vaccines includes several cancer products.
"It is now beginning to sink in that what we are trying to do is capitalize on the evolving trend in cancer toward combination therapy," said Oxlade.
This is exemplified by XR9576, a P-glycoprotein modulator, which prevents tumors from developing resistance to chemotherapeutics by blocking the P-glycoprotein pump that ejects the drugs from cancer cells.
In the third of three successful Phase IIa studies, in which XR9576 was administered in combination with the cytotoxic drug vinorelbine, there was no interaction between the two. In common with the two earlier trials with the cytotoxics paclitaxel and doxorubicin, there was anecdotal evidence of efficacy.
Tito Fojo of the U.S. National Cancer Institute, who conducted the vinorelbine trial, said, "Assays have indicated that a single dose of XR9576 is sufficient to block the action of the P-glycoprotein pump for in excess of 24 hours, and imaging studies have also indicated that XR9576 can effectively block the P-glycoprotein-mediated efflux from tumors."