Two of Pathway Therapeutics’ existing investors, GBS Ventures and CM Capital Investments, have topped off the firm's coffers with another $7.5 million to fund Phase I development of its lead dual PI3K apha/mTOR inhibitor PWT33597, in patients with advanced solid tumors. The additional investment has been made on the back of FDA acceptance of the IND filing for PWT33597, and progression of additional PI3K delta-selective inhibitors into lead optimization.
Pathway is focused on the discovery and development of isoform-selective PI3K inhibitors for the treatment of cancer and inflammatory diseases in targeted patient populations. The firm says PWT33597 demonstrates excellent in vitro selectivity for its targets, with negligible activity against other lipid kinases, protein kinases, or other pharmacologically relevant targets, at biologically active concentrations.
The dose-escalating, single-agent Phase I trial will evaluate the safety, tolerability, and pharmacokinetics of PWY33597 in patients with advanced solid tumors, and also investigate pharmacodynamic correlation between PWT33597 exposure and markers of the PI3K pathway in tumors and surrogate tissues. After the maximum tolerated dose has been reached, the Phase I program will be expanded to measure activity in specific tumor types with PI3K pathway dysregulation.
In contrast with PI3K alpha, the PI3K delta isoform is overexpressed in B-cell leukemias and lymphomas and plays a key role in cancer cell proliferation and survival, Pathway notes. Inhibition of PI3K delta in hematological malignancies has also been clinically validated. The kinase is exclusively expressed in leukocytes, and has also been implicated in various autoimmune and inflammatory diseases, including rheumatoid arthritis, allergy, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus.