SF1126

SF2626

Pipeline

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is vital to several essential biological processes, such as cell growth, survival, motility, and metabolism. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. However, the role of PI3K in a wide range of normal biologic processes raises potential concerns about its inhibition in non-cancerous tissues.

SF1126 is the first small molecule dual PI3K-mTOR inhibitor in clinical development that is designed to overcome these concerns by incorporating a peptide inhibitor of αvβ3- and αvβ5-integrins, which are transmembrane cell adhesion proteins expressed in new tumor vasculature and within the tumor compartment. By targeting integrins, SF1126 is designed to deliver more active drug in the vicinity of the tumor with lower inhibition of PI3K in normal cells and tissue. SF1126 inhibits all four class I PI3K isoforms along with other cancer targets such as mTOR, DNA-PK, PIM1, and PLK1. In preclinical studies, SF1126 has shown attractive pharmacokinetic and pharmacodynamic properties and compelling efficacy in xenograft models, both as a single agent and in combination with other therapies.

To date, nearly 50 patients with solid tumors or hematological malignancies have been treated with SF1126 in Phase I trials. Administration of SF1126 at doses ranging from 90 to 1,110 mg/m2 has been generally well tolerated. One event of Grade 3 study drug-related dose-limiting toxicity (DLT) was reported in 1 of 3 patients at 180 mg/m2. That cohort was expanded and no further DLTs were observed. The most common treatment-related adverse events have been nausea, vomiting, diarrhea, fever, fatigue and chills.