On November 24, 2025 Rakovina Therapeutics Inc. ("Rakovina" or the "Company") (TSX-V: RKV)(FSE: 7JO0) a biopharmaceutical company advancing cancer therapies through AI-enabled drug discovery, reported impressive results from its AI-enabled ATR program at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting which took place November 19-23 in Honolulu, Hawaii.
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The poster, titled "Discovery and development of a novel CNS-penetrating ATR inhibitor: Dual inhibition of ATR and mTOR in PTEN-deficient tumors," highlights the discovery and early characterization of novel ATR/mTOR dual inhibitors designed using the Enki generative AI platform. The compounds are engineered to modulate two well-established cancer-driving pathways that, despite their importance, have never before been combined in a single therapeutic agent. Notably, Rakovina’s lead molecules were designed specifically to cross the blood–brain barrier and reach tumor cells within the central nervous system, supporting their potential relevance in primary brain cancers and cancers with a high risk of brain metastasis.
Rakovina’s senior management team presented the findings showing that the AI-discovered ATR+mTOR inhibitors achieve meaningful CNS penetration, addressing a key limitation of current clinical ATR inhibitors, which have poor CNS distribution. In direct comparisons, multiple Rakovina compounds showed >50% ATR inhibition at 1 µM and exhibited equal or greater enzymatic potency than leading ATR inhibitors ceralasertib, tuvusertib, and elimusertib, while maintaining similar PIKK-family selectivity.
Importantly, these compounds were engineered with a mechanistic rationale to co-target ATR and mTOR, two pathways on which PTEN-deficient tumors (including those prone to brain metastasis) are highly dependent. By simultaneously blocking ATR-mediated DNA damage response and mTOR-driven survival signaling, these CNS-penetrant inhibitors have the potential to overcome key resistance mechanisms in PTEN-deficient cancers and deliver therapeutic effects not achievable with ATR-only agents.
PTEN deficiency in cancer
PTEN is one of the most frequently lost tumor-suppressor genes in human cancer and serves as a key brake on the PI3K/AKT/mTOR signaling pathway that governs cell growth, metabolism, and survival. Its loss promotes unchecked proliferation, genomic instability, therapy resistance, and aggressive tumor progression.
PTEN deficiency is particularly prevalent in cancers with a high propensity for CNS spread, including ovarian, lung, breast, and melanoma – where tumor cells rely heavily on mTOR-driven growth and survival. In these settings, mTOR becomes an adaptive escape pathway, especially under ATR inhibition, allowing PTEN-deficient tumors to accelerate growth and diminish the effectiveness of ATR-only therapeutic strategies.
Prevalence of PTEN deficiency and CNS metastases in major cancers
Cancer type Approximate frequency of PTEN loss Est. CNS Metastases Prevalence
Lung cancer ~ 35-55 % ~55% in NSCLC
Breast cancer ~ 30-40 % ~40%
Prostate cancer ~ 25-50 % ~8%
Colorectal cancer ~ 10-40 % ~6%
Ovarian cancer ~ 30-50 % ~5%
Endometrial carcinoma ~ 50 % 1-2%
Glioblastoma (brain) ~ 80-85 % n/a (primary brain tumor
Using the ENKI generative AI platform, the Company designed a virtual library of 138 predicted compounds, from which, 43 priority molecules were synthesized for evaluation in biochemical and cellular assays. Multiple compounds demonstrated >50% inhibition of recombinant ATR at 1 µM and exhibited potency comparable to or exceeding ATR inhibitors currently in development including ceralasertib, tuvusertib, and elimusertib.
Pharmacokinetic profiling in mice following a single 5 mg/kg intraperitoneal dose revealed favorable tolerability, metabolic stability in human liver microsomes, and measurable CNS exposure, supporting further evaluation in brain tumor models.
"Sharing these data at SNO is an important milestone for our ATR/mTOR program," said Prof. Mads Daugaard, President and Chief Scientific Officer of Rakovina Therapeutics. "To our knowledge, no company has previously generated a single small-molecule therapeutic designed to combine ATR and mTOR inhibition with CNS penetration. 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."
"The reception to our data at SNO has been very encouraging," added Jeffrey Bacha, executive chairman of Rakovina Therapeutics. "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."
(Press release, Rakovina Therapeutics, NOV 24, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-showcases-compelling-preclinical-data-on-ai-discovered-cns-penetrant-atr-mtor-inhibitors-at-the-2025-society-for-neuro-oncology-annual-meeting [SID1234660906])