Firm hopes selective depletion of activated T cells will lead to longer-lasting, safer therapy.

French immunotherapeutics firm Immutep could receive up to £64 million (about $100 million) from GlaxoSmithKline as part of a newly signed license agreement granting the latter exclusive worldwide rights to the preclinical-stage autoimmune disease candidate ImmuTune® IMP731 and other LAG-3 T-cell depleting antibodies.

Under terms of the deal GSK will take on all responsibilities and costs for developing IMP731. “For Immutep, the value created through this transaction will enable us to focus our resources on advancing our oncology assets, IMP321 and IMP701,” notes John Hawken, CEO. “IMP321 is ready for a Phase IIb/III trial in the chemo-immunotherapy of first-line metastatic cancer.”

The IMP731 antibody acquired by GSK is a cytotoxic antibody designed to deplete, rather than just block, the function of activated T cells implicated in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.The firm says such selective depletion of only activated, pathogenic LAG-3+ T cells could enable safer long-term immunosuppression because the pool of resting, LAG-3-negative T cells remains unaffected.

Immutep’s lead in house candidate, ImmuFact® IMP321, is an APC activator derived from a soluble form of LAG-3 that binds to MHC class II molecules expressed by dendritic cells. Designed to stimulate strong and sustained antitumor cytotoxic T-cell responses, IMP321 is being developed both as a low-dose adjuvant to cancer vaccines, and as a high-dose therapy in combination with first-line chemotherapy. Immutep claims initial studies have confirmed that administration of the candidate can double the clinical response rate when administered alongside chemotherapy. A Phase Ib study in metastatic renal cancer has previously shown IMP321 therapy led to a statistically significant increase in progression-free survival. A Phase I/II trial in metastatic breast cancer patients treated with first-line paclitaxel chemotherapy also showed that IMP321 therapy doubled the objective response rate.

In contrast to ImmuTune IMP731, which is a LAG3+ cell depleting antibody, IMP701 is a preclinical-stage ImmuTune antagonist monoclonal antibody targeting LAG-3.

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