More warnings signs for ATR inhibition

Synthetic lethality is a hot topic in oncology, but the shine might be coming off one of the approaches here, ATR inhibition. Yesterday Bayer discontinued its contender elimusertib, swiftly followed by AstraZeneca today scrapping a trial of its ATR blocker ceralasertib. Importantly, development of ceralasertib continues; indeed, this is the most advanced ATR project. But smaller groups like Aprea and Artios might be watching Astra’s next moves nervously. Other big companies taking a punt on ATR inhibition include Merck KGaA, which has switched focus from berzosertib to tuvusertib, and Roche, which licensed camonsertib from Repare for $125m up front last year. Camonsertib monotherapy has failed to impress, but at the time of the deal some analysts suggested that combination with PARP inhibitors could provide a way forward – notably, Impact Therapeutics is also looking at its ATR blocker, IMP9064, with a PARP. Other combinations are in play, and Repare reported data at the recent Triple meeting on a pairing of camonsertib and its PKMYT1 inhibitor lunresertib – which proved difficult to interpret. ATR inhibitors in clinical developmentProjectCompanyNotePhase 3CeralasertibAstraZenecaPh3 Latify + Imfinzi in post-IO NSCLC continues; ph2 Monette + Imfinzi post-IO melanoma discontinued for futility Nov 2023Phase 1/2ATRN-119Aprea Therapeutics (via Atrin)First data from ph1/2 in solid tumours at AACR-NCI-EORTC Oct 2023ART0380Artios PharmaFirst data from ph1/2 +/- gemcitabine/irinotecan in solid tumours at ESMO 2023IMP9064Impact TherapeuticsFirst data from ph1/2 +/- senaparib in solid tumours at ESMO 2023CamonsertibRoche (licensed from Repare)Ph1/2 in solid tumours completes Jan 2024TCC1727F-star TherapeuticsPh1/2 in solid tumours completes Mar 2025SC0245BioCity BiopharmaPh1/2 + irinotecan in SCLC completes Sep 2025TuvusertibMerck KGaAPh1/2 DDRiver NSCLC 322 + Libtayo post-IO completes Aug 2026Phase 1ATG-018Antengene CorporationPh1 Atrium in solid tumours & haematological cancers completes Mar 2024HRS2398Jiangsu HengRuiPh1 recruitingDiscontinuedElimusertibBayerDiscontinued Nov 2023BerzosertibMerck KGaAPh2 DDRiver SCLC 250 discontinued Jun 2022Source: OncologyPipeline.