Avila's PI3Kα inhibitor preclinical study data presented at AACR meeting

Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, today presented results of preclinical studies on its novel Phosphoinositide 3-kinase alpha (PI3Kα) inhibitor at the American Association for Cancer Research 102^nd Annual Meeting in Orlando, Florida.

In a poster titled "Discovery of an Irreversible PI3Kα-Specific Inhibitor," Avila researchers describe the use of structure-based drug design to discover a series of covalent drug compounds, including the lead compound CNX-1351, that selectively inhibit PI3Kα through an irreversible covalent bond. Potent inhibition of PI3Kα activity was achieved with these covalent drug compounds, even after compound removal, confirming the prolonged duration of activity. Importantly, only cell lines driven by PI3Kα were inhibited by these PI3Kα-selective inhibitors. In addition, CNX-1351 demonstrated in vivo inhibition of PI3Kα and tumor growth inhibition in a mouse xenograft model.

The PI3K pathway regulates cell growth, proliferation and survival and is active in many types of human tumors. While several PI3K inhibitors are currently in clinical development, most are pan-PI3K inhibitors and are not selective relative to the multiple isoforms of this enzyme. Tumor biology data suggest that targeting PI3Kα specifically, as opposed to disrupting other members of the complex PI3K signaling cascade, could be advantageous in terms of improving both clinical potency and safety.

"Avila's work on the PI3Kα target is a prime example of how covalent drugs have many advantages including improvements in potency, selectivity, prolonged duration of action, and translational biomarker opportunities," commented Juswinder Singh, PhD, Co-founder and Chief Scientific Officer of Avila Therapeutics. "Our covalent drug platform has generated targeted small molecule inhibitors of PI3Kα, with specific and potent irreversible inhibition and prolonged duration of action, and activity in vivo. We look forward to further development of our PI3Kα program."

Source: Avila Therapeutics™, Inc.