Shares in Mologen AG rose 13 percent Monday on interim survival data indicating that a small subgroup of patients with metastatic colorectal cancer experienced lengthy – and ongoing – progression-free survival (PFS) with cancer immunotherapy MGN1703.

By last April, three of four patients who continued to receive the drug through a compassionate use program, after completing a phase II trial, attained PFS for 32 months, 36 months and 40 months, respectively. Overall survival data for the study, called Impact, are not yet available, as the necessary number of events has yet to occur. After an average follow-up of more than 17 months, 28 of the 43 patients in the drug treatment group were still alive. About 70 percent of the overall study population needs to reach death before the company can perform the analysis. "We expect this to happen by the beginning of the coming year," CEO Matthias Schroff told BioWorld Today.

In the meantime, Berlin-based Mologen will move MGN1703, a Toll-like receptor 9 (TLR9) agonist, into a pivotal phase III trial, called Impala. That study, which will get under way in the third quarter, will recruit about 540 patients across eight European countries and, potentially, the U.S., where the company has an open investigational new drug application. Once it completes the present study, it aims to add selected clinical centers in the U.S. The study's primary endpoint will be overall survival.

"Overall survival seems to be a much better endpoint for immunotherapy than progression-free survival," Schroff said.

MGN1703 is being positioned as maintenance therapy for patients who respond to first-line chemotherapy. Mologen previously reported that the drug, which is designed to break immune tolerance toward cancer, achieved the primary endpoint of the Impact study, a prolongation of PFS, although the statistical significance and the duration were both marginal. Analysis of a predefined subgroup of 46 of the 59 patients recruited, defined by their biomarker and treatment profiles, firmed up the result considerably. In that group, median PFS was doubled, with a high level of statistical significance. (See BioWorld Today, May 15, 2012.)

Schroff was anxious to manage expectations around the mature Impact data. "Don't expect convincing overall survival data from 59 patients with colorectal cancer," he said. "We hope to see an interesting trend." A small number of complete responses to the induction therapy in the control arm could easily mask a drug treatment effect, in an indication that has two-year median survival at present.

That profile will now form part of the set of inclusion criteria for Impala. It includes having a reduced tumor burden after first-line therapy, as defined by normal Recist criteria; normal levels of carcinoembroynic antigen (CEA); a widely used marker for colorectal cancer; and a defined level of activated natural killer T cells. The trial will be powered to demonstrate a 30 percent difference in overall survival between the treatment and control arms in those patients who initially respond to the induction therapy.

MGN1703 is what Mologen terms a dSlim, or double stem loop immunomodulator) molecule. It is a closed structure, comprising two single-stranded DNA loops joined by a double-stranded stem. It appears to engage both the innate and adaptive arms of the immune response, Schroff said. It first activates plasmacytoid dendritic cells, which leads to the activation of natural killer cells and natural killer T cells, the subsequent release of interferons and cytokines, and the eventual activation of myeloid dendritic cells.

Schroff linked the lack of a deal for the product to the phase III failure of another TLR9 agonist, PF3512676, which New York-based Pfizer Inc. in-licensed from Coley Pharmaceutical Group Inc., in non-small-cell lung cancer. That failure had a major dampening effect on the wider field of TLR-based drug development. (See BioWorld Today, June 21, 2007.)

Even though the two products have differing profiles – MGN1703 engages dendritic cells whereas the Coley drug acted on B cells – prospective partners are waiting on overall survival data before making any moves. "It's our job to convince them our molecule behaves differently," Schroff said.

Shares in Mologen (FRANKFURT:MGN) closed Tuesday at €9.75 (US$13.34), a further gain of 3 percent on Monday's close of €9.51.