Proacta and Yakult Honsha are expanding their collaborative research, development, and commercialization agreement to include Proacta's PR610, a hypoxia-activated prodrug for the treatment of cancer. The initial agreement, signed in February, for Proacta's hypoxia-activated prodrug, PR509, granted Yakult research, development, and commercialization rights to that compound in Japan.
"Based on recent preclinical study results, we believe that PR610 could perform very well in the clinic," says John C. Gutheil, M.D., Proacta's CEO. "We have developed a strong relationship with Yakult in the short time that we have been working together. We are delighted that Yakult is interested in PR610 and that they share our optimism regarding the potential of this molecule."
PR509 and PR610 are irreversible multikinase inhibitors discovered at the Auckland Cancer Society Research Centre, University of Auckland. Reversible multikinase inhibitors (MKI) are already being used to treat cancer. Resistance, however, can develop to reversible MKIs. In addition, reversible MKIs have side effects that limit their use at higher doses, according to Proacta.
Both PR509 and PR610 utilize an irreversible MKI that is activated only in areas of severe hypoxia. Localized release of the irreversible MKI leads to higher concentrations in the tumor relative to normal tissues. In addition, irreversible MKI inhibitors are not affected by some of the resistance mechanisms that limit use of reversible MKI inhibitors, states Proacta.
PR509 and PR610 are currently targeted for development in non-small-cell lung cancer (NSCLC) resistant to reversible tyrosine kinase inhibitors such as erlotinib and/or gefitinib, where an effective treatment has yet to be established. In addition to NSCLC, Proacta expects to evaluate the molecules in other cancers such as gastric, breast, and pancreatic cancers that are currently treated with first-generation reversible tyrosine kinase inhibitors.