Potential Antibody Treatment for MS, by Immutep, Moving Toward Clinical Trials

With the development of a cell line that produces significant amounts of Immutep‘s treatment candidate, IMP761, the company is preparing to advance its antibody into clinical testing for autoimmune conditions, including multiple sclerosis (MS).

Immutep also reports that is adapting its manufacturing operations to comply with good manufacturing practices (GMP) to ensure that each batch of the medicine will meet high quality standards. This is a necessary step for regulatory agencies to allow a medicine to enter testing in people.

IMP761 is an antibody designed to prevent the proliferation and activation of inflammatory immune T-cells involved in autoimmune conditions like MS, inflammatory bowel disease, and rheumatoid arthritis.

It does so by binding and further activating an inhibitory receptor on the surface of these cells, called lymphocyte-activation gene 3, or LAG-3, a protein first discovered in 1990 by Frederic Triebel, Immutep’s chief scientist and medical officer.

This receptor is used to regulate immune responses, preventing T-cells from going haywire and attacking healthy tissues. Its activity appears to be abnormal in some people with autoimmune conditions.

By binding and activating LAG-3 on the surface of activated T-cells, IMP761 is believed to induce a stronger inhibitory signal, effectively stopping T-cells from proliferating and attacking healthy cells.

Immutep is manufacturing IMP761 in collaboration with Batavia Biosciences, which recently generated a cell line that produces even larger amounts of this treatment candidate than initially anticipated.

The pharmaceutical-grade cell line is essentially a hamster cell line — Chinese hamster ovary (CHO) — that produces the antibody using Batavia’s STEP-mAb technology.

“IMP761 is the first agonist antibody that targets the immune checkpoint LAG-3 for the treatment of autoimmune diseases, such as inflammatory bowel diseases, rheumatoid arthritis, and multiple sclerosis,” Marc Voigt, Immutep CEO, said in a press release.

“The cell line which was developed seems to be highly potent, and we are excited to be moving closer to clinical testing of this promising product candidate to treat the root cause of autoimmune diseases,” Voigt added.

Preclinical results published early this year showed that IMP761 selectively binds LAG-3 and decreases the normal T-cell proliferation and activation that happens in the presence of an antigen (a substance that is capable of stimulating an immune response).

Researchers saw similar effects in cultured cells and in a non-human primate model, in which IMP761 was also deemed safe and well-tolerated.

Another antibody candidate, called IMP731, in development by Immutep and Glaxo-Smith-Kline, also targets LAG-3. But unlike IMP761, it is designed to prevent autoimmunity by killing LAG-3-positive immune T-cells.