Rakovina Therapeutics Showcases Potent AI-Developed ATR Inhibitors with CNS Penetrance at AACR-NCI-EORTC International Conference

Executive Summary

• Rakovina Therapeutics presented new preclinical data on AI‑discovered ATR inhibitors with demonstrated central nervous system (CNS) penetration at the AACR‑NCI‑EORTC International Conference.
• Multiple lead compounds showed >50 % ATR inhibition at <200 nM, superior potency to existing reference molecules, and measurable brain exposure in rodent PK studies.
• The results support continued optimization of the kt‑5000AI program and advance the prospect of developing ATR inhibitors for primary brain tumors and brain metastases.

Key Details

• Conference: AACR‑NCI‑EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, MA (Oct 23‑27, 2025).
• Program Highlighted: “Novel ATR inhibitors with CNS penetrance developed by artificial intelligence” (poster presentation).
• AI Platform Used: Enki™ generative AI platform from Variational AI to design small‑molecule candidates meeting a defined target product profile for CNS‑penetrant ATR inhibition.
• In vitro Findings:

• 50 % inhibition of ATR activity at concentrations below 200 nM.

• Potency exceeds reference compounds ceralasertib, tuvusertib, and elimusertib.
• Selectivity across the PIKK kinase family comparable to references.
• Metabolic stability confirmed in human liver microsome assays.
• In vivo Pharmacokinetic Findings:
• Lead compounds achieved measurable concentrations in both plasma and brain tissue after a single intraperitoneal dose of 5 mg/kg, confirming CNS penetration.
• Single‑dose administration was well tolerated, indicating acceptable safety for further preclinical work.
• Strategic Implication: First reported ATR inhibitors with meaningful CNS exposure, potentially expanding therapeutic options for patients with primary brain tumors and brain metastases where current treatments are limited.
• Quote (CEO/President): “Presenting at AACR‑NCI‑EORTC is an opportunity to highlight Rakovina’s progress in translating AI‑discovered compounds into preclinical validation to the scientific community… Developing ATR inhibitors capable of penetrating the blood–brain barrier could expand treatment options for patients with primary brain tumors and brain metastases.” – Prof. Mads Daugaard, President & CSO.

Notable Quotes

• “ATR is a central regulator of DNA damage repair and a validated target across multiple tumor types. Developing ATR inhibitors capable of penetrating the blood–brain‑barrier could expand treatment options for patients with primary brain tumors and brain metastases, areas where few effective therapies exist.” – Prof. Mads Daugaard, President & Chief Scientific Officer.