IMP761 dampens T-cell activity in healthy adults: Clinical study
Drug candidate targets immune cells that become overactive in MS
In healthy adults, a single low dose of Immutep’s immunosuppressive candidate IMP761 continues to be safe and appears to reduce the activity of T-cells — immune cells that become overactive in multiple sclerosis (MS) and other autoimmune diseases.
This is according to data from an ongoing Phase 1 clinical study (NCT06637865). It is recruiting up to 49 healthy volunteers at a single center in the Netherlands to test how safe IMP761 is when given as an intravenous, or into-the-vein, injection at single or multiple increasing doses.
Because no side effects have been reported with the highest dose of IMP761 tested so far (0.9 mg/kg), the company plans to continue testing the drug at higher doses — 2.5 mg/kg, 7 mg/kg, and 14 mg/kg. Additional data are expected in the second half of this year.
“We look forward to evaluating higher dosing levels of IMP761 and hope to further enhance its ability to safely silence the dysregulated [T-cells] responsible for many autoimmune diseases,” Frédéric Triebel, MD, PhD, Immutep’s chief scientific officer, said in a company press release.
IMP761 activates protein to prevent attacks by T-cells
In MS, the immune system mistakenly launches inflammatory attacks on myelin — a protective sheath around nerve fibers — leading to progressive damage in the brain and spinal cord and the accumulation of disability. These attacks are partly driven by overactive immune cells such T-cells.
IMP761 is an antibody designed to target and activate the LAG-3 receptor on the surface of activated T-cells. LAG-3 is a checkpoint protein that prevents the immune system from mounting too strong a response. By activating it, IMP761 is expected to send a stronger stop signal to T-cells, preventing them from attacking a patient’s own tissues.
“LAG-3 expression on activated T cells is known to be highly specific to disease sites, and particularly in areas of chronic inflammation. This unique specificity enables the potential for IMP761 to have a more targeted approach with fewer side effects than other therapies,” Triebel said.
As part of the Phase 1 clinical study, healthy adults are randomly assigned to receive either increasing doses of IMP761 or a placebo. Some participants will receive an injection of a protein called keyhole limpet hemocyanin (KLH) to trigger a controlled immune response in the skin. The goal of this is to measure how well IMP761 dampens this immune response.
The early pharmacological data showing substantial [T-cell] suppression at the highest dose level of IMP761 are very promising, especially in conjunction with its continued favourable safety profile, and highlight the potential efficacy of this LAG-3 agonist in treating autoimmune diseases.
Results from participants given the 0.9 mg/kg dose have shown that 10 days after the second injection of KLH, the amount of T-cells in the skin was reduced by 80%, suggesting it may dampen an unwanted immune response.
“The early pharmacological data showing substantial [T-cell] suppression at the highest dose level of IMP761 are very promising, especially in conjunction with its continued favourable safety profile, and highlight the potential efficacy of this LAG-3 agonist in treating autoimmune diseases,” Triebel said.
About the Author
