AbbVie has taken up its option to license an immune checkpoint inhibitor from Argenx. The deal gives AbbVie the global rights to an anti-GARP antibody designed to block the immunosuppressive activity of regulatory T cells (Tregs).
Studies suggest membrane protein GARP is involved in the activation of TGF-β1, a protein secreted by Tregs. When activated, TGF-β1 inhibits the activation and proliferation of other T cells, limiting the extent of the immune attack on a tumor. Argenx thinks targeting GARP can block the production of TGF-β1 and thereby free the immune system from immunosuppressive shackles imposed by Tregs.
AbbVie placed a tentative bet on the idea in 2016 when it paid $40 million upfront and committed to $20 million in near-term preclinical milestones to secure the option to license Argenx’s anti-GARP antibody, ARGX-115. The agreement tasked Argenx with taking ARGX-115 through IND-enabling studies, at which point AbbVie would decide whether to fully commit to the program.
The preclinical data package put together by Argenx has persuaded AbbVie to take up the worldwide license to the asset. In return, AbbVie has agreed to pay up to $625 million in milestones—a figure set in the 2016 deal—and take charge of further development.
Argenx and AbbVie are far from the first drug developers to pay attention to anti-TGF-β and its siblings, but they have reason to think ARGX-1115 may fare better than earlier attempts to disrupt the activity of the protein.
Genzyme put a TGF-β ligand inhibitor through early-phase trials more than a decade ago. Others, including Eli Lilly, have gone after the pathway by targeting TGF-β receptors. Lilly is still enrolling patients in trials of its TGF-β drug galunisertib—including in an Opdivo combination study—but the field is yet to catch light.
The researchers that helped give rise to ARGX-115 think anti-TGF-β antibodies suffer from problems that are avoided by targeting GARP. Notably, studies suggest GARP activates latent TGF-β in Tregs but not in other cells where it's present. This may give ARGX-115 a better safety profile than anti-TGF-β antibodies, which neutralize the protein wherever it is found in the body.
AbbVie is now set to find out if the idea holds up in the clinic. Neither it nor Argenx have discussed specific indications. The mechanism of action of ARGX-115 lends itself to multiple tumors types, both as a monotherapy and in combination with other immuno-oncology drugs.