Contributing Writer

Xanthus Pharmaceuticals Inc. bolstered its oncology pipeline by licensing exclusive rights from Schering AG for the development and commercialization of oral fludarabine in the U.S.

In exchange, Xanthus will pay an up-front licensing fee, milestone payments and royalties. Financial terms were not disclosed, but Xanthus CEO Richard Dean called the agreement "a fair deal for everybody."

The chemotherapy Fludarabine is a standard of care for chronic lymphocytic leukemia (CLL). The intravenous formulation is available generically and generates approximately $60 million in annual U.S. sales, Dean said. The oral formulation is marketed by Schering in the European Union for relapsed and first-line treatment of B-cell CLL, as well as in Canada for relapsed B-cell CLL.

Schering reported approximately $133 million in 2005 from global sales of oral and I.V. fludarabine, which it markets as Fludara.

"Fludarabine is a small market, so big pharma does not pay much attention to it, but it's an outstanding opportunity for us," Dean said, noting that he believes there will be a preference for the oral formulation, which Schering's patents cover through 2018.

Xanthus intends to schedule a meeting with the FDA to discuss the regulatory path for oral fludarabine, and Dean said the Cambridge, Mass.-based company is "planning for the possibility of an immediate filing or an additional clinical trial, if necessary."

The deal is Xanthus' second agreement with Schering; last month, Xanthus acquired worldwide rights to develop and commercialize several targeted cancer compounds from the Berlin-based company.

The lead compound in that program, P2045, is a small peptide that targets tumors overexpressing somatostatin receptors (SSTR). When combined with radioisotope Rhenium-188, P2045 is designed to deliver targeted radiation to tumors expressing SSTR.

Schering had completed several Phase I trials with radiolabeled P2045 in patients with small-cell and non-small-cell lung cancer prior to the license, and Xanthus now is continuing Phase I trials while evaluating a parallel path in Phase II studies in patients with metastatic non-small-cell lung cancer who have failed previous therapy.

"P2045 is earlier stage but potentially a very large market," said Dean, who is no stranger to Schering, having served as its head of strategic business development, diagnostics and radiopharmaceuticals prior to joining Xanthus in early 2004.

The acquisitions of oral fludarabine and P2045 from Schering serve to round out Xanthus' existing oncology pipeline. Oral fludarabine now is the company's most advanced clinical candidate, but following behind is Xanafide (amonafide malate), which is being evaluated in a Phase II trial for secondary acute myeloid leukemia (AML).

Xanafide, a small-molecule topo-2 inhibitor, produced encouraging results in an early single-site study, Dean said, who cited 40 percent to 50 percent complete remission rates. A planned interim analysis of the ongoing Phase II study was completed in June, and enrollment is ahead of schedule. Dean forecast completing enrollment by the end of this month and generating data in early 2007.

Xanthus also is conducting Phase II trials in metastatic breast and colorectal cancer with Symadex (imidazoacridinone), a small-molecule, dual-targeted FLT3 kinase and topo-isomerase inhibitor. Initial data from the trials might be available in the third quarter of 2007, and Xanthus is planning additional studies with the compound, including a trial in AML slated to begin in early 2007 and a trial in multiple sclerosis scheduled to start in late 2007. The company also plans to move Clomet (DMPEN, 4-demethylpenclomedine) into clinical trials for solid tumors next year.

Founded in 2001, Xanthus raised $10 million this spring from the syndicate of investors that supported its $32.8 million Series B round in December of 2003. The company is raising another round privately, and is keeping an eye on the public markets, as well. Dean said that "encouraging results of our Xanafide trial and these recent licensing deals could make us an ideal [IPO] candidate." (See BioWorld Today, Dec. 15, 2003.)