Cell Therapeutics (CTI) is paying Chroma Therapeutics $5 million up front as part of a co-development and licensing deal for the latter’s late-stage anticancer candidate tosedostat. The agreement gives CTI exclusive marketing and co-development rights to the drug in North, Central, and South America. Under terms of the agreement CTI will shoulder 75% of tosedostat development costs, subject to a funding cap of $50 million over the first three years.
The partners expect to start a U.S.-European Phase III study evaluating tosedostat in elderly patients with relapsed or refractory acute myeloid leukemia (AML) during the latter part of 2011. Initiation of the trial will trigger another $5 million milestone payment to Chroma from CTI. Both FDA and the EU’s regulatory authority have granted tosedostat orphan drug status for the AML indication.
Tosedostat is an oral aminopeptidase inhibitor designed to block protein recycling and lead to tumor cell death. Phase I monotherapy and combination studies demonstrated the drug has significant antitumor activity without causing the typical side-effects of conventional cytotoxic therapies, the firms claim. Potential initial indications for the drug include AML, MDS and multiple myeloma.
“Tosedostat, similar to drugs like bortezomib and lenalidomide, represents a departure from conventional cytotoxic chemotherapy towards more tumor selective targeted therapy that interferes with cellular pathways necessary for tumor survival,” comments James A. Bianco, M.D., CTI’s CEO. “In initial clinical studies, tosedostat was well-tolerated, given orally once a day and produced encouraging response rates in difficult to treat patients with acute leukemia and a variety of blood-related cancers.”
U.K. firm Chroma is exploiting its expertise in chromatin biology and intracellular accumulation technologies to develop drugs against cancer and inflammatory disorders. Aside from tosedostat the firm has two other candidates in clinical development. CHR-3996 is an orally active optimised class I HDAC selective inhibitor that started in clinical development in 2008. Clinical development of a targeted HDAC inhibitor, CHR-2845, was also initiated during late 2008.
CHR-2845 has been developed using Chroma’s Esterase Sensitive Motif (ESM) drug enhancement technology. The platform involves the attachment of specific chemical motifs onto active drugs as a means of enhancing delivery to intracellular targets and accumulating the active molecule within target cells.
In 2009 Chroma signed a collaboration with GlaxoSmitKline (GSK) focused on developing macrophage-targeted compounds using the ESM technology for the treatment of inflammatory diseases. Under terms of the potentially $1 billion milestone and options-related deal, Chroma is undertaking four discovery and development programs to identify small molecule therapeutics. In August 2010 the firm received a milestone payment from GSK relating to progression of the macrophage-targeted HDAC inhibitor CHR-5154 into preclinical development.
Chroma licensed tosedostat from Vernalis in 2003. The latter will be entitled to royalties on future commercial sales of the drug.