First-In-Class Approach to Targeting Immune Suppressive Macrophages by Selectively Inhibiting PI3K-Gamma

Eganelisib is a first-in-class, oral, once-daily, immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma). Selective PI3K-gamma inhibition represents a unique and potentially transformative approach within immuno-oncology (I/O), and IPI-549 has the potential to be a first-in-class therapy. Preclinical research conducted by Infinity and academic collaborators demonstrates that IPI-549 works by reprogramming key immune suppressive cells (called M2 macrophages or myeloid derived suppressor cells (MDSCs)) within the tumor microenvironment from a pro-tumor function to an anti-tumor function, decreasing immune suppression and increasing immune activation, ultimately leading to the activation and proliferation of T cells that can attack cancer cells1,2.

Eganelisib is being evaluated in multiple mid-stage clinical studies including:

  • MARIO-275: MARIO-275 (MAcrophage Reprogramming in Immuno-Oncology) is a global, randomized, controlled combination study of eganelisib combined with Opdivo® in I/O naïve urothelial cancer;
  • MARIO-3: MARIO-3 is the first eganelisib combination study in front-line advanced cancer patients, evaluating eganelisib in combination with Tecentriq® and Abraxane® in front-line TNBC and in combination with Tecentriq and Avastin® in front-line RCC;
  • Arcus Biosciences Collaboration: In collaboration with Arcus Biosciences, Infinity is evaluating a checkpoint inhibitor-free, novel combination regimen of eganelisib plus AB928 (dual adenosine receptor antagonist) plus Doxil® in advanced TNBC patients; and
  • MARIO-1: In 2019, Infinity completed enrollment in MARIO-1, a Phase 1/1b study evaluating eganelisib as a monotherapy and in combination with Opdivo (nivolumab) in patients with advanced solid tumors including patients refractory to checkpoint inhibitor therapy. With these studies Infinity is evaluating eganelisib in the anti-PD-1 refractory, I/O-naïve, and front-line settings.

[1] Kaneda, M., Messer, K., Ralainirina, N., Li, H., et al. PI3Kγ is a molecular switch that controls immune suppression. Nature, 2016 Nov;539:437–442.

[2] De Henau, O., Rausch, M., Winkler, D., Campesato, L., et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature, 2016 Nov;539:443-447.