NEW YORK – Leapfrog Bio on Wednesday said it will move on to a Phase II trial of its bromodomain and extra-terminal domain (BET) protein inhibitor LFB-190 in lung, colon, and bladder cancer after establishing evidence of a synthetically lethal mechanism targeting the EP300 loss-of-function cancer driver mutation.
Previous clinical studies of LFB-190 have established a recommended Phase II dose.
Leapfrog CEO Greg Vontz said in a statement that the company will start the Phase II clinical trial in 2025 and test that recommended dose in cancers with EP300 loss-of-function mutations.
The firm uses a drug screening platform, dubbed the Precision PGx Platform, to identify therapies targeting loss-of-function mutations, which are common cancer drivers. At an American Association for Cancer Research conference in Toronto this week, the company described how it conducted hundreds of pharmacogenetic screens using the PGx Platform and discovered an interaction between BET protein inhibition and the EP300 gene loss of function similar to the association between homologous recombination repair deficiency or BRCA1/2 mutations and PARP inhibitor response. "The company believes it has also discovered the mechanism of action for this synthetically lethal relationship between BET protein inhibition and EP300 [loss of function]," Leapfrog said in a statement.
The San Mateo, California-based company uses CRISPR screening and next-generation sequencing to identify genes that drive cancer through a loss of function when mutated. Most cancer therapies target driver genes associated with a gain of function and seek to suppress the activation of the mutated gene. However, those mutations account for only about 30 percent of cancers, according to Leapfrog. The company believes its technology focusing on loss-of-function mutations could unlock therapies for an additional two-thirds of cancer patients.