Berlin, 08 June 2010. The Berlin based biotechnology company MOLOGEN AG completed the evaluation of its clinical phase 1b study with the DNA immunomodulator MGN1703. The evaluation mainly confirmed the preliminary efficacy data of the DNA-based immunomodulator: The study showed that the efficacy of MGN1703 clearly exceeded expectations in the treatment of patients with advanced metastatic tumors: the cancer diseases of several patients could be stabilized during the course of treatment.

 

In the phase 1b open-label clinical study, performed at clinics at the universities of Essen and Cologne, patients were included who had various types of far-advanced metastatic and progressive solid tumor diseases for whom no further standard treatment options were available. As part of the study, patients were treated with MGN1703 in steadily increasing single and multiple dosage regimens. An accelerated dosage escalation procedure was selected that enabled dosage levels to increase from 0.25 mg to 60 mg per application in just five steps.

 

The investigational medicinal products were firstly examined as a single treatment within each dosage phase. When tolerability was good, the patients were then treated, following each single-dosage stage, with the same dosage twice a week over a period of 6 weeks, i.e. 12 injections. Following the 6-week period, and when patients responded to MGN1703 with a demonstrable stabilization of the cancer disease (disease control), they were then treated with MGN1703 twice a week for a further 6-week period, i.e. a further 12 injections.

 

 

The co-ordinating investigator, Prof Dr Max Scheulen, a specialist for internal medicine, hematology and oncology at the Clinic for Internal Medicine (tumor research) at the University Hospital of Essen, said: "Far advanced metastatic tumor diseases are especially difficult to treat when established therapies have been applied without showing any efficacy. In that respect one could say that any observed stabilization may be the result of the treatment with MGN1703. Nonetheless is it necessary to further examine those observations and to confirm them in a randomized comparison as it is not possible to predict the natural and individual course of tumor development. At the same time, MGN1703 is well tolerated and based on the results of the phase Ib study it is anticipated that MGN1703 has the potential to offer cancer patients a new treatment option.

 

Cancer stabilization

 

A total of 24 patients were included in the initial multiple-dosage part of the study. The disease stabilized in 9 of these following the first cycle of treatment. As part of the second 6-week multiple stage, 6 patients were treated. In 3 of them a continued stabilization of the disease was evident.

 

Those patients whose advanced tumor disease could be stabilized as part of the MGN1703 study then had the option to take part in a so-called compassionate use program and be treated externally to the study with MGN1703 twice a week for 6 weeks. Depending on the clinical response, this six-week treatment program was then repeated several times.

 

A total of 4 patients were included in the compassionate use program. For 3 of these patients, initially advanced cancers could be stabilized over extended periods. For example, a patient with colorectal cancer was able to be stabilized for a period lasting 14 months and showed a significant reduction of the metastases. In another patient with colorectal cancer, the disease could be stabilized over a 5 month period.

 

The disease in a patient with advanced lung cancer (non-small cell lung cancer) has now been stabilized for a total of 21 months. When the disease began to progress again after 14 months, the patient was re-treated with MGN1703 with a stabilization of the disease again being evident.

 

Excellent tolerability

 

As well as the impressive treatment outcomes for individual patients, the completed evaluation of data on the safety and tolerability of MGN1703 also confirmed the existing data to date. The side-effects that could be associated with MGN1703 were merely minor and common symptoms such as tiredness, headaches, rashes or an increased temperature. These also occurred only in individual cases. Side-effects did not cause the study to be terminated in any patient. None of the examined dosage levels showed any intolerability. For repeated dosages, no accumulation of MGN1703 in patients' bodies was observed. In the phase 2 clinical study with patients with metastatic colorectal cancer, the highest examined dosage levels of 60 mg per application will therefore be used as planned.

 

MOLOGEN also presented its clinical data for the completed phase 1b study with MGN1703 at this year's conference of the "American Society of Gene and Cell Therapy" (ASGCT) in Washington.

 

"We are excited about the outcomes of the phase 1b study. Even though relatively few patients were treated, the results impressively demonstrate the potential of MGN1703", said Dr. Matthias Schroff, CEO of MOLOGEN AG. "I am also very pleased that we were able to actually help some of these seriously ill patients. I would like to extend my deep gratitude to all the patients for participating in the study".

 

About MGN1703

 

MGN1703 is based on dSLIM® (“Double Stem Loop Immunomodulator”), an innovative DNA-based TLR9 agonist developed by MOLOGEN. dSLIM® activates the immune system against tumor-associated antigens by targeting various “danger” sensing receptors on certain immune cells, primarily TLR. Tumor-associated antigens (TAA) are released by cancer cells as a result of chemotherapy and radiation therapy. Once activated by dSLIM®, the immune system is able to overcome its fatal tolerance toward cancer cells as well as towards TAA, and attacks them selectively.

 

The results of the completed phase 1b study demonstrate an excellent safety profile of MGN1703. Treatment with the investigational medicinal product was well tolerated and no dose-limiting or serious side-effects were identified.

 

Very promising signs of efficacy were also found. MGN1703 was able to delay the progression of cancer diseases by at least 6 weeks in many cases, including patients with advanced metastatic tumor diseases with no further standard treatment options like the ones selected for the phase 1b study. In some cases it was even possible to delay the progression of the disease for up to 14 months.

 

In March 2010, MOLOGEN has received approval from the competent German and Austrian health authorities to conduct a continuative clinical study with MGN1703. The study is a phase 2, randomized, placebo-controlled, double-blind, multicenter clinical study to determine the efficacy and safety of subcutaneously administered MGN1703 for the treatment of metastatic colorectal cancer patients who responded to first-line therapy (IMPACT-study). The study is expected to start soon.