Data on 2 Drugs, Identified Via AI, Shared at Conference
Research Report

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Rakovina Therapeutics Inc. (RKV:TSX.V) presented new proof-of-concept data on Compound A and Compound C, two small-molecule, ATR inhibitors identified through its partner's artificial intelligence (AI) platform, reported Dr. Douglas Loe, managing director and analyst at Leede Financial Inc., in a Nov. 28 Week In Review note.

The biopharma shared the data via a poster session on Nov. 23 and 24 at the Society for Neuro-Oncology's annual meeting in Hawaii.

In his report, Loe shared what stood out to him in the presented data. 

Identified Via AI Platform

Rakovina presented data pertaining to Compound A and Compound C, two distinct ataxia-telangiectasia & Rad3-related (ATR)-inhibiting drugs identified through partner Variational AI's Enki AI platform.

Loe explained that these ATR inhibitors, or serine/threonine kinase proteins, are members of the PIKK (phosphatidylinositol 3-kinase-related kinase) family of enzymes, known to be biomarkers of DNA damage responses that are triggered in cancer cells.

Two Active Clinical Programs

In addition to Rakovina's preclinical ATR-inhibiting drug program, a few other active clinical programs exist that are testing the same. One of the two leading candidates is private company, EMD Serono's, tuvusertib, a fluorinated nitrogen heterocycle-based drug. At least seven active Phase 1/2 studies are on track to generate survival data with tuvusertib, between 2026 and 2029. Tuvusertib's synergy with other DNA-active drugs was documented in two different places: a July 2024 paper published by National Institutes of Health researchers in Molecular Cancer Therapeutics and a May 2024 paper published by Texas-based MD Anderson researchers in Clinical Cancer Research.

The other leading candidate is AstraZeneca Plc's (AZN:NYSE; AZN:LSE) chemically distinct but functionally related ATR inhibitor ceralasertib. Phase 2 testing of ceralasertib in solid tumors is ongoing. Preclinical and cellular assays published last year in Nature Communications documented that ceralasertib showed some synergistic activity with a single anti-PD-L1 monoclonal antibody drug, AstraZeneca's Imfinzi (durvalumab).

Similarities Among Drugs

When compared to tuvusertib and ceralasertib, Rakovina's Compound A and Compound C showed comparable ability to inhibit ATR's kinase in biochemical assays, reported Loe.

In a different batch of enzyme inhibition assays, like ceralasertib, Compound A, and Compound C were shown to have selectivity for inhibiting other PIKK enzymes. Along with ATR, they were shown to inhibit an immune-relevant protein called mTOR (mammalian target of rapamycin). MTOR is Pfizer Inc.'s (PFE:NYSE) immunosuppressive agent, Rapamune (sirolimus).

Also like ceralasertib and tuvusertib, Compound A and Compound C showed little to no inhibition of other protein kinases.

Short Half-Lives

Lastly, when comparing Compound A to Compound C, despite equivalent dosing of both, Compound A achieved higher peak plasma and brain concentrations.

Half-lives were similar, though, around 30 minutes, Loe pointed out. He added that Rakovina might want to address the short half-lives with some sort of extended-release drug formulation technology for a longer duration of anti-tumor effects.