Infinity, Bristol-Myers Squibb Expand Collaboration Evaluating IPI-549 and Opdivo

Infinity Pharmaceuticals has expanded its existing clinical collaboration with Bristol-Myers Squibb evaluating IPI-549 in combination with Opdivo to include patients with triple negative breast cancer (TNBC) who have not been previously exposed to anti-PD-1 or anti-PD-L1 therapy. IPI-549 is an oral, selective phosphoinositide-3-kinase gamma (PI3K-gamma) inhibitor which targets immune-suppressive tumor macrophages, and Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immune suppression. IPI-549 is currently being evaluated in a Phase 1/1b clinical study in patients with advanced solid tumors and is believed to be the only selective PI3K-gamma inhibitor in clinical development.

Preclinical data have demonstrated that M2, or pro-tumor, macrophages are associated with resistance to checkpoint inhibitor monotherapy, and treatment with IPI-549 in combination with checkpoint inhibitors can overcome this resistance by reprogramming macrophages from the M2 phenotype to the M1, or anti-tumor, phenotype. A component of this ongoing Phase 1/1b study is designed to explore the potential of combining these two agents to overcome resistance in patients previously treated with checkpoint inhibition. The addition of a cohort of patients with TNBC who have not previously received anti-PD-1 or anti- PD-L1 therapy provides an important opportunity to explore the potential of the combination of IPI-549 and Opdivo to improve efficacy for patients with a type of cancer where there is limited benefit from monotherapy treatment with checkpoint inhibitors.

"The expansion of our ongoing clinical study of IPI-549 and our clinical collaboration with Bristol-Myers Squibb represents an important component of our strategy to bring better treatment options to patients," stated Adelene Perkins, chief executive officer at Infinity. "Particularly, expanding our study to include patients with triple negative breast cancer who have not been previously treated with a PD-1 or PD-L1 immune checkpoint inhibitor allows us to evaluate whether IPI-549 in combination with Opdivo can increase the number of patients who respond to checkpoint inhibition. To date, very few patients with triple negative breast cancer respond to checkpoint inhibitors alone, leaving these patients with very limited therapeutic options."

The ongoing Phase 1/1b study being conducted by Infinity is designed to evaluate the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in approximately 200 patients with advanced solid tumors. The four-part study includes monotherapy and combination dose-escalation components, in addition to monotherapy expansion and combination expansion components. Patient enrollment is complete in monotherapy dose-escalation, and monotherapy expansion is ongoing. Combination dose-escalation is also ongoing, and combination expansion is expected to begin in the second half of 2017.

The combination expansion component includes multiple cohorts designed to evaluate IPI-549 in patients with specific types of cancer, including patients with non-small cell lung cancer (NSCLC), melanoma, and head and neck squamous cell carcinoma (HNSCC) whose tumors show initial resistance or subsequently develop resistance to immune checkpoint blockade therapy. This combination expansion component will now also add a cohort of patients with TNBC who have not been previously exposed to immune checkpoint blockade therapy. Although there has been great progress in the treatment of cancer, there remains a need for additional treatment options. NSCLC, melanoma, HNSCC and TNBC account for more than 22 percent of all new cancer cases in the U.S.

IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 reprograms macrophages from a pro-tumor, M2, to an anti-tumor, M1, phenotype and is able to overcome resistance to checkpoint inhibition as well as to enhance the activity of checkpoint inhibitors. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors. IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

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