Activartis Develops Cancer Vaccine in Phase II, Seeks Partner

Activartis GmbH (formerly Trimed Biotech GmbH) recently announced it is developing a cancer immunotherapy concept that is currently in Phase II clinical trials. Initially directed against aggressive brain cancer, it will in principle be applicable to all types of cancerous diseases and therefore has blockbuster potential. The therapeutic platform combines a completely novel proprietary and IP-protected approach (the utilization of a bacterial danger signal in combination with the patient’s tumor antigens) with a proven successful concept (dendritic cells) to mobilize the patient’s immune system to combat the disease.

The Activartis proprietary technology platform focuses on dendritic cells (DCs), the key regulatory elements of the immune system. To trigger an immune response against tumor cells, the immune system’s tolerance of cancer cells must be overridden. By presenting a bacterial danger signal (LPS, lipopolysaccharide) in combination with the patient’s tumor antigens to the patient’s dendritic cells, Activartis’ therapeutic agent tricks the cells into recognizing the tumor as dangerous, which triggers an immune reaction to the tumor antigens. The DCs then activate tumor-specific T cells (including the killer T cells that attack tumor cells) to destroy tumor tissue. The Activartis therapeutic concept is the first active immune therapy that activates release of the immune modulatory cytokine interleukin 12 (IL-12), a signaling molecule that is of central importance in polarizing an immune response based on killer T cell activity.

The proprietary technology involved is part of a trend-setting approach to individualized medicine. Utilizing the patient’s own tumor tissue, Activartis aims to mobilize the patient’s immune system to develop a tailored immune response to their specific tumor in order to recognize and destroy the disease. The therapy is therefore, in principle, applicable to all cancerous diseases.

Autologous dendritic cell therapies represent a major milestone in the development of cancer immune therapy and a paradigm shift in cancer treatment. In April 2010, the FDA approved the first autologous dendritic cell therapy for the treatment of advanced prostate cancer. However, the use of an antigen specific to a particular tumor means that it cannot be used against other cancers. The technology is also highly dependent on antigen selection and is exposed to the potential variability of cancers in different patients.

The Activartis cancer vaccine technology eliminates these drawbacks by employing a more advanced technology, which uses the complete spectrum of tumor antigens unique to an individual patient’s cancer.

The handling and logistics requirements for Activartis therapeutic agents are more simple and less complicated to manage. The agents may be frozen, conserved, and shipped, meaning that a patient’s whole course of treatment can be produced at one time. Outpatient treatment of the patients is completed in minutes.

Currently, Activartis is testing its therapy in a randomized, open-label, two-arm, multi-center, Phase II clinical study of glioblastoma multiforme (GBM) at eight clinical institutions in Austria, including three university hospitals. GBM is the most aggressive and lethal form of brain cancer. The disease often progresses rapidly, and prognosis is nearly always poor (median survival is approximately 14 months). The primary objective of the study is progression-free survival, with overall survival as the secondary goal. The interim results of the study are expected to be available in the second half of 2012.

The safety and efficacy of Activartis’ therapeutic agent has been demonstrated in four Phase I pilot studies, including more than 100 patients with different indications (brain, bone, kidney, prostate cancer, and a heterogenous selection of pediatric cancers). Clinical development is backed by AOP Orphan Pharmaceuticals, an Austrian pharmaceuticals company that acquired Activartis in 2006. The partners plan to apply for orphan drug designation. Following successful completion of Phase II, Activartis and AOP Orphan are planning to collaborate with an industrial partner who will co-sponsor Phase III clinical development, manufacturing, registration, and market launch as well as the clinical development of Activartis DC cancer vaccine technology for further indications.

Activartis (originally Trimed) was founded by Vienna cancer researcher Thomas Felzmann, MD, in 2003 as a spin-off from the renowned St. Anna Children’s Cancer Research Institute. Patents filed in 2002 have been granted in most relevant markets. A US patent for IL-12 secreting DCs was granted early in 2011. In 2006, Activartis was acquired by AOP Orphan Pharmaceuticals, which was founded in 1997 and is headquartered in Vienna. AOP Orphan is a leader in the clinical development and distribution of drugs for rare diseases.