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

Executive Summary

• Rakovina Therapeutics presented pre‑clinical data on novel CNS‑penetrant ATR + mTOR dual inhibitors at the 2025 Society for Neuro‑Oncology Annual Meeting.
• The AI‑discovered compounds showed >50% ATR inhibition at 1 µM, potency comparable to or exceeding leading ATR inhibitors, and demonstrated measurable brain exposure in mouse PK studies.
• A virtual library of 138 predicted molecules yielded 43 synthesized candidates; multiple hits progressed to biochemical, cellular and pharmacokinetic evaluation, supporting further development toward brain‑tumor indications.

Key Details

• Program Focus: AI‑enabled discovery (Enki™ platform) of ATR/mTOR dual inhibitors designed to cross the blood–brain barrier for PTEN‑deficient tumors with high CNS metastasis risk.
• Compound Library & Synthesis: 138 virtual compounds generated; 43 priority molecules synthesized for testing.
• Biochemical Activity: Several compounds achieved >50% inhibition of recombinant ATR at 1 µM, matching or surpassing the potency of ceralasertib, tuvusertib, and elimusertib.
• Selectivity: Maintained comparable PIKK‑family selectivity to existing ATR inhibitors.
• Pharmacokinetics (Mouse): Single 5 mg/kg IP dose showed favorable tolerability, metabolic stability in human liver microsomes, and measurable CNS exposure.
• Disease Rationale: PTEN loss prevalent in lung (~35‑55%), breast (~30‑40%), prostate (~25‑50%), colorectal (~10‑40%), ovarian (~30‑50%) cancers; high rates of CNS metastasis especially in NSCLC (~55%). Dual ATR/mTOR inhibition aims to overcome resistance mechanisms in these settings.
• Presentation: Poster titled “Discovery and development of a novel CNS‑penetrating ATR inhibitor: Dual inhibition of ATR and mTOR in PTEN‑deficient tumors” presented at SNO 2025, Honolulu, Hawaii (Nov 19‑23).

Notable Quotes

“Sharing these data at SNO is an important milestone for our ATR/mTOR program… Seeing generative AI propose compounds with this level of precision gives us a fundamentally new way to address these difficult‑to‑treat cancers with a high risk of brain involvement.” – Prof. Mads Daugaard, President & CSO

“The reception to our data at SNO has been very encouraging… This program showcases how combining Variational AI’s Enki™ platform with the translational capabilities at the Vancouver Prostate Centre allows us to rapidly pursue differentiated DDR‑targeted therapeutics with potential clinical relevance in areas of significant unmet need.” – Jeffrey Bacha, Executive Chairman