Lefitolimod (MGN1703)

By using the immunomodulator and TLR9 agonist dSLIM®, MOLOGEN AG is pursuing a highly promising pathway in the treatment of cancer-related diseases that is based on widespread activation of the immune system.

Mechanism of action lefitolimod (MGN1703)

In a healthy organism, diseased cells are recognized and destroyed by the immune system. With a cancer disease, this defense system stops working, i.e. the body develops a sort of "tolerance" toward the tumor cells. The immune system does not recognize the cancer cells anymore, preventing an immune response from being triggered. As a result, cancer cells are able to multiply unhindered.

One of the biggest hopes in cancer research rests on finding a way of overcoming this tolerance. Various antigens found on the cell surface of tumor cells play a key role in this. When healthy cells mutate into cancer cells, so-called tumor-associated antigens (TAAs) are formed at the same time and are then presented on the tumor cell membrane. Consequently, if it is possible to specifically influence the immune system so that it recognizes these antigens, there is a good chance of recovery from the disease or indeed a cure for it.

In the field of active immunotherapies, great hopes are riding on substances that bind to very specific receptors known as toll-like receptors (TLR). These receptors are part of the innate defense system. They are able, through activation of the immune system, to facilitate the recognition of tumor-associated antigens. Many years of research work have shown that toll-like receptor 9 (TLR9) plays a particularly important role in the fight against cancer. Substances that activate TLR9 are referred to as TLR9 agonists and form the main focus of global research and development activities.

The drug candidate lefitolimod (MGN1703) uses the dSLIM® technologies and acts as a TLR9 agonist. In the field of oncology lefitolimod (MGN1703) is is being developed for first-line maintenance treatment of colorectal cancer (phase III pivotal study). The phase II IMPULSE study shows positive results in two pre-defined and clinically relevant subgroups of patients. A more extensive evaluation of the IMPULSE data is currently ongoing. Furthermore, it is being tested in a phase I combination study with the checkpoint inhibitor Yervoy® (ipilimumab).

Moreover, the first trial (phase I/II) outside oncology indications began in 2015: in HiV positive patients. In June 2016, the first patient was recruited to an extended phase of this study.