BioWorld Today Correspondent

LONDON – Immutep SA landed an exclusive $100 million worldwide license with GlaxoSmithKline plc for its preclinical Immutune program IMP731, in treating autoimmune diseases, as it edges toward the larger prize of a deal for its lead product IMP321, which it hopes will crystallize this week in negotiations at the J.P. Morgan Healthcare conference in San Francisco.

"IMP731 is a preclinical program which has proof of concept in animal models of T-cell mediated inflammation. GSK will now choose [in] which diseases they develop the product," John Hawken, Immutep CEO, told BioWorld Today.

IMP731 is an IgG1 antibody, which works by depleting the chronically activated T cells that are a hallmark of autoimmune diseases. It does this by targeting lymphocyte activation gene-3 (LAG-3), which is involved in the activation of long-lived effector memory T cells.

Deleting such chronically activated T cells rather than blocking one of their functions, for example, the production of TNF alpha or inflammatory interleukins, represents a new therapeutic approach, Hawken noted. While a subset of activated T cells are suppressed, the pool of inactive LAG-3 negative T cells is left untouched.

"There are two competitive advantages to knocking out only the activated pathogenic T cells," Hawken said. "First, the immune system can still defend against viral attack, and second, the effect seems to last [for] several months, after one injection." IMP731 is effective in animal models of T-cell mediated inflammation and graft rejection.

Under the terms of the agreement, GSK now takes on all responsibility for developing the antibody, with Paris-based Immutep receiving an up-front payment and milestones up to the $100 headline figure, and will also be eligible to royalties on any marketed products.

"It's very important we managed to get a good partner for IMP731, because it puts us in a strong position to negotiate terms for IMP321," Hawken noted. Discussions on doing this are "quite far advanced," with due diligence in progress, and Hawken hopes these negotiations to be further advanced at meetings this week at the J.P. Morgan conference.

In September 2010, Immutep published data on a Phase II trial in which IMP321, a recombinant soluble LAG-3 fusion protein, administered with first-line paclitaxel, showed clinical benefit in 90 percent of patients with metastatic breast cancer. Correlations were observed between levels of monocytes – the primary target cell for IMP321 – before treatment, and the degree of activation of monocytes during treatment.

The 30-patient study was an open-label fixed-dose-escalation trial carried out in three cancer centers in the Paris region. IMP321 induced both a sustained increase in the number and activation of monocytes and dendritic cells, and an increase in the percentage of natural killer and long-lived cytotoxic effector-memory CD8 T cells.

At six months, 27 patients had stable disease. Immutep said that provided the data needed to progress to a Phase IIb/III trial.