Immutep Reports Exposure-Dependent Inhibition of T-Cell-Driven Responses in IMP761 Phase I Study

Clinical-stage biotechnology company Immutep (ASX: IMM) has released positive data from a Phase I study of first-in-class lymphocyte activation gene-3 (LAG-3) agonist antibody IMP761 aimed at treating autoimmune diseases by targeting their root cause.

The randomised placebo-controlled, double-blind, first-in-human study conducted by the Centre for Human Drug Research in the Netherlands showed the drug was well-tolerated across a cohort of healthy volunteers at all seven dose levels (0.03 milligrams per kilogram to 14mg/kg), with no serious or severe adverse events reported.

Volunteers were immunised three times with keyhole limpet haemocyanin before receiving small injections of the glycoprotein into the dermis to produce a measurable T-cell-driven local intra-dermal reaction.

The model is seen as the standard way of testing whether a drug can dampen a strong tissue T-cell-driven immune response to a foreign antigen, potentially enabling it to silence T-cell responses to self-peptides in patients with autoimmunity.

Statistically Significant Results

Chief scientific officer Dr Frédéric Triebel said the new data built on positive first-in-human results presented at this year’s European Alliance of Associations for Rheumatology congress in London by demonstrating statistically significant, exposure-dependent suppression of immune responses after a single IMP761 infusion.

“These results derived from a large double-blinded trial clearly show the immuno-suppressive effect of IMP761 on a strong antigen-driven T-cell response in tissues, without safety concerns,” he said.

“After this challenging proof-of-concept in healthy participants, we are confident that direct T-cell receptor inhibition through LAG-3 agonism opens a new frontier in the treatment of autoimmune patients where the root cause of the disease is driven by the overreaction of a few weak-affinity self-peptidereactive pathogenic T-cells that should be controlled by IMP761.”

Results from the multiple ascending dose portion of the Phase I study are scheduled for release in the new year to inform dose selection for a future Phase II program.