Rakovina Therapeutics Showcases Compelling Preclinical Data on AI-Discovered CNS-Penetrant ATR/mTOR Inhibitors at the 2025 Society for Neuro-Oncology Annual Meeting

Core Insights - Rakovina Therapeutics has announced significant advancements in its AI-enabled ATR program, showcasing novel ATR/mTOR dual inhibitors designed for brain penetration and efficacy in PTEN-deficient tumor models [1][2][10] Group 1: Discovery and Development - The company presented a poster at the 2025 Society for Neuro-Oncology Annual Meeting detailing the discovery of CNS-penetrating ATR inhibitors that combine ATR and mTOR inhibition, targeting PTEN-deficient tumors [2][4] - The lead molecules were specifically engineered to cross the blood-brain barrier, making them potentially effective against primary brain cancers and those with a high risk of brain metastasis [2][4] Group 2: Efficacy and Mechanism - The AI-discovered ATR/mTOR inhibitors demonstrated over 50% ATR inhibition at 1 µM, showing comparable or superior potency to existing ATR inhibitors like ceralasertib, tuvusertib, and elimusertib [3][7] - These compounds are designed to co-target ATR and mTOR pathways, which are critical for the survival of PTEN-deficient tumors, potentially overcoming resistance mechanisms associated with ATR-only therapies [4][6] Group 3: Clinical Relevance and Future Directions - The pharmacokinetic profiling indicated favorable tolerability and measurable CNS exposure in mice, supporting further evaluation in brain tumor models [8][9] - The company aims to advance its pipeline of DNA-damage response inhibitors into human clinical trials, leveraging AI technologies for rapid drug candidate optimization [11][12]