Preclinical studies showed that treatment with IPI-145 suppressed PI3K signaling and cell growth in a subset of DLBCL cell lines. In several of these cells lines, treatment with IPI-145 and ibrutinib (a Bruton's tyrosine kinase, or BTK, inhibitor) led to a synergistic suppression of cell growth, providing a potential rationale for exploring IPI-145 in combination with ibrutinib in DLBCL.
Preclinical Data in T-ALL
In the presentation “The potent PI3K-delta,gamma inhibitor, IPI-145, exhibits preclinical activity in murine and human T-cell acute lymphoblastic leukemia” (Abstract #1438), data from preclinical studies of IPI-145 tested in both human and rodent cell lines of T-ALL showed that treatment with IPI-145 inhibited the growth of a subset of T-ALL cells deficient for PTEN (a phosphatase and tumor suppressor gene). Treatment with IPI-145 led to a greater inhibition of T-ALL cell growth compared to treatment with molecules selective for only PI3K-delta or PI3K-gamma, providing a potential rationale for combined PI3K-delta and -gamma inhibition for the treatment of T-ALL.
In a separate press release issued today, Infinity reported updated Phase 1 data in patients with indolent non-Hodgkin lymphoma (iNHL) which showed that IPI-145 was clinically active, with an overall response rate of 73 percent (11 of 15 evaluable patients) and a 20 percent complete response rate (3 of 15 patients). Eight patients (53 percent) remain progression-free for over one year. Additionally, translational data showed that IPI-145 affects key signaling molecules in the tumor microenvironment, providing a potential mechanistic rationale for the clinical activity of IPI-145 observed in patients with iNHL and chronic lymphocytic leukemia (CLL).The posters presented at the 55th Annual Meeting of ASH are available in the Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp. About the Development of IPI-145 for the Treatment of Blood Cancers Infinity is developing IPI-145, an oral inhibitor of Class I PI3K-delta,gamma. The PI3Ks are a family of enzymes involved in multiple cellular functions, including cell proliferation and survival, cell differentiation, cell migration and immunity. The PI3K-delta,gamma isoforms are preferentially expressed in leukocytes (white blood cells), where they have distinct and mostly non-overlapping roles in immune cell development and function. Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to develop differentiated therapies for the treatment of hematologic malignancies as well as inflammatory diseases.