M9466 + tuvusertib

M9466 + tuvusertib is an experimental oral combination therapy under investigation for advanced solid tumors and neoplasms, such as castration-resistant prostate cancer and ovarian cancer. - **M9466** is a highly potent and selective PARP1 inhibitor. It blocks poly(ADP-ribose) polymerase 1 (PARP1), an enzyme critical in DNA repair, mainly targeting tumors with impaired homologous recombination repair mechanisms. - **Tuvusertib** is a small molecule inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase, an enzyme central to the DNA damage response; ATR inhibition disrupts cancer cells’ ability to repair damaged DNA, especially in combination with other DNA repair pathway inhibitors. Combining a PARP1 inhibitor (M9466) with an ATR inhibitor (tuvusertib) is designed to produce synthetic lethality in tumor cells with defective DNA repair by blocking parallel DNA repair pathways, leading to enhanced tumor cell death. The combination is being studied for safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in early-phase, open-label clinical trials in solid tumors. Both agents are given orally. The developer is EMD Serono Research & Development Institute (part of Merck KGaA)[1][4][5][7].