We are developing dual selective inhibitors of PI3K-β/δ for the treatment of hematological and solid tumors.

Target: PI3K- p110β/δ

The phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinase enzymes which – through signal transduction pathway control, emerging functions in the tumor microenvironment, and mutational status – have become key targets for cancer therapy. Our clinical program focuses on isoforms PI3K-β and PI3K-δ.

PI3K-p110β

Wild-type PI3K-β is oncogenic when over-expressed, and, notably, can drive the growth of tumors that are defective in PTEN, the negative-regulator phosphatase of PI3K signaling. A role for PI3K-β in tumor metastasis has emerged, and rare mutations of the enzyme have been reported in cancer.

PI3K-p110δ

PI3K-δ is primarily expressed in the hematopoietic system and it plays a critical role in the signaling of hematological cancers. A role for PI3K-δ in regulatory T-cell (Treg) activity has also been discovered, with inhibition resulting in CTL activation and primary solid tumor growth inhibition.

Inhibitor: KA2237

Building on extensive expertise in the PI3K field, we have designed and developed a class of selective PI3K-β/δ inhibitors.

KA2237 is an ATP-competitive, reversible, orally-active, dual PI3K-β/δ-selective small molecule inhibitor. Given the functions of PI3K-β and PI3K-δ in cancer biology, KA2237 has the potential to leverage direct effects on tumor cell viability and tumor microenvironment modulation, by targeting the cancer cell-intrinsic and -extrinsic biologies of the two isoforms.

Phase I clinical trial

KA2237, our dual-selective PI3K-p110β/δ inhibitor, has been under investigation in a Phase I clinical trial for patients with B-cell lymphoma. The study is now closed to recruitment.

The Phase I clinical trial was conducted at The University of Texas MD Anderson Cancer Center, as part of our strategic collaboration.

For more information please visit ClinicalTrials.gov: NCT02679196.

We are now pursuing collaborative opportunities to assess the clinical efficacy of KA2237 in patients with solid tumors.