The dSLIM® immunomodulator (Lefitolimod)

dSLIM® (double Stem Loop Immunomodulator) is a novel TLR9 agonist developed by MOLOGEN AG.
The dSLIM® molecule works by binding to the toll-like receptor 9 (TLR9). This receptor occurs in and on certain immune cells in humans and animals. Toll-like receptors are structures from the innate defense system. They recognize the DNA patterns of invading pathogens that do not exist in the cells' own DNA. In fact, they are able to recognize not only intracellular pathogens, such as viruses, but also extracellular ones such as fungi. The particular structure of the dSLIM® molecules allows them to simulate the invasion of pathogens and thus trigger a broad activation of the immune system without actually causing any illness. 

Universal principle of action

Thanks to dSLIM®'s universal mode of action, it can theoretically be used against a variety of different cancerous diseases, but also against other diseases that have so far been difficult to treat effectively. The use of dSLIM® in cancer therapy has already been investigated in numerous experiments and indicates particularly marked anti-tumor effects. The extensive pre-clinical tests have provided highly promising results regarding the efficacy and tolerability of this modern immunotherapy.

Molecule structure as key to exceptional tolerability

dSLIM® molecules from MOLOGEN are made up exclusively of non-coding DNA. The DNA is not chemically modified. The structure of the dSLIM molecule has been designed in the shape of a barbell and comprises two single-stranded loops that are linked together by a double-stranded stem. It is a closed molecule without open ends. Many competitor companies, in contrast, use single-stranded DNA molecules, which need to be protected from rapid breakdown within the body through chemical modifications at their ends. The closed dSLIM® molecule from MOLOGEN does not need any such chemical modifications. It is consequently tolerated much better and causes only mild side effects that have the characteristics of a typical (desired) immune reaction (reddening of the injection sites, mild fever, etc.).


Design of the dSLIM® molecule


 

Use in the fight against cancer

MOLOGEN AG is deploying the ability of the dSLIM® molecule to activate the immune system on a widespread and powerful scale to fight cancer.
In cancer patients, the immune system ceases to recognize cancer cells and is therefore also unable to fight them. By administering dSLIM®, the immune system is activated on a large scale and thereby enabled once again to break through the tolerance toward the cancer cells and recognize them again. This empowers the immune system to fight the cancer cells itself. The mode of action behind dSLIM® is also known as active immunotherapy. 

Use in the fight against HIV

In addition to the studies in the area of oncology, investigations with lefitolimod for the treatment of HIV (Human Immunodeficiency Virus) started in 2015. The aim of the extended phase I study is to investigate whether lefitolimod can activate the immune system in HIV patients to enhance destruction of the HIV infected cells. This could expand the potential range of applications for the product.

Lefitolimod (MGN1703) - active immunotherapy 

MOLOGEN AG is developing the dSLIM® technology under the project name lefitolimod (MGN1703) to fight cancer in a variety of indications and HIV. Efficacy, safety and tolerability are being investigated within clinical studies. One phase Ib clinical study has already demonstrated very good tolerability with few side effects and has delivered initially highly promising efficacy data.

To confirm this efficacy, lefitolimod (MGN1703) is currently being tested in four clinical studies: In a pivotal study in metastasized colorectal cancer, a randomized study in small cell lung cancer as well as an extended phase I study in HIV. 

Furthermore, in 2016 a combination study has started with lefitolimod and the checkpoint inhibitor ipilimumab (Yervoy®) in patients with advanced tumors.

 

 

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