Frontier Medicines Corp. has granted LG Chem Ltd. an exclusive worldwide license to develop and commercialize FMC-220, a covalent p53 Y220C activator, outside of Greater China. Frontier retains ownership and full control in Greater China.
Astex Pharmaceuticals Inc. is getting $35 million up front and up to $500 million per program as it extends its drug discovery collaboration with Merck & Co. Inc. to include small-molecule activators of the p53 tumor suppressor protein. The number of programs was not disclosed, but they will target forms of p53 that have lost their function as a result of cancer-induced mutations in the TP53 gene. The aim will be to override the mutation and restore the ability of the wild-type protein to bind DNA and perform its functions as a transcription factor.
Results from a French study of a cohort of individuals with the inherited rare disease Fanconi anemia shed light on how some people with this condition go on to develop secondary leukemia. Writing in the Feb. 2, 2023, issue of Cell Stem Cell, the authors also described some initial tests on cell lines in a mouse model of a drug that has potential to treat individuals with Fanconi anemia who progress to leukemia.
The development of cancer after p53 inactivation is determined by a series of genomic changes that occur in four steps. The loss of heterozygosity of TP53 (the gene encoding p53 in humans, named Trp53 in mice) is followed by an accumulation of deletions, genome doubling, and the emergence of gains and amplifications. In a study published in the August 17, 2022, issue of Nature, researchers have further observed that these four phases of genomic evolution are associated with specific histological stages before and after the malignant condition developed.
While Aprea Therapeutics Inc.’s data disclosed July 21 from the phase II trial with eprenetapopt – also known as APR-246, a reactivator of mutant tumor suppressor protein p53 – plus azacitidine (AZA) whetted interest in taking aim at the “guardian of the genome,” the company’s fortune took an unexpected turn when the FDA smacked a partial clinical hold on work with the duo.
A team led by researchers at Johns Hopkins University School of Medicine has developed bispecific antibodies that were able to target tumors driven by mutations in the tumor suppressor TP53 and the oncogene RAS, as well as subsets of T cells in T-cell malignancies.
