LONDON – Cellact Pharma GmbH has sealed a $250 million plus royalties deal with Mundipharma International Ltd. for its phase II anticancer prodrug, Cap7.1.

Once it completes a reformulation to pave the way for manufacturing scale-up, Mundipharma will move forward to phase III in the treatment of biliary duct cancer, where Cap7.1 has EU orphan drug status.

Under the collaboration, Dortmund, Germany-based Cellact will receive a double digit up-front payment and milestones up to approval, followed by tiered royalties if Cap7.1 reaches the market.

The deal represents an exit for the investors Peppermint VC and NRW Bank, which have put €10 million (US$11.8 million) into Cellact since it was founded in 2007.

It is also a welcome 10th anniversary present for Nalan Utku, CEO, who in addition to leading her own research group as professor of immunology at the Charité University Hospital, Berlin, has single-handedly steered the product through preclinical and clinical development since it was outlicensed from Charité.

"I'm responsible for everything," Utku told BioWorld. "I'm definitely pleased with the deal," she said. "The alliance will also provide a valuable exit for our investors, Peppermint VC and NRW Bank, who have been supporting this program for many years."

Cap7.1 is a prodrug of the topoisomerase II inhibitor etoposide, which is converted to the active chemotherapy agent by carboxylesterase enzymes in the gastro-intestinal tract. The enzymes are particularly active in tumor cells.

Biliary tract cancer is the second-most common primary hepatobiliary cancer after hepatocellular cancer. There are surgical procedures and chemotherapies for treating early and locally advanced disease, but no approved second-line treatments.

In phase II studies as a second-line treatment, 56 percent of patients met the primary endpoint of disease control, including tumor shrinkage, compared to best supportive care. Cap7.1-treated patients had a one year survival rate of 41 percent, which Cellact said is around 20 percent higher than with standard of care.

Administering etoposide as a prodrug "makes it possible to increase the dose by two to three times," Utku said. "This is a more targeted approach. [The drug] still works as a topoisomerase inhibitor, but there are different chemical kinetics and a different release profile."

Although there has been no direct comparison, the side effect profile of Cap7.1 at the higher doses is similar to that seen with the recommended therapeutic dose of etoposide, of 50 mg to 120 mg/m²/day. Cap7.1 also has a similar toxicity profile to other topoisomerase inhibitors.

In an initial compassionate trial in three heavily pretreated pediatric patients with advanced neuroblastoma, Cap7.1 was very well tolerated at high dose levels of between 400/mg/m²/day and 800/mg/m²/day. Although doses exceeded the therapeutic dose of etoposide in adults, the only dose-limiting toxicity was reduced neutrophils.

In parallel with manufacturing scale-up, Utku said the shape of the pivotal phase III trial is now under discussion.

In addition to biliary tract cancer, Cap7.1 has been studied in small-cell and non-small-cell lung cancer, and would be relevant to other cancer types, including those that are multidrug-resistant. Cambridge, U.K.-based Mundipharma's license gives it the right to develop the product in different indications.