Leapfrog Bio’s Precision PGx Platform™ discovered a clinically significant link between the EP300 gene and bromodomain and extra-terminal domain (BET) protein inhibitors
Presentation describes the discovery, characterization, and clinical development plan for Leapfrog Bio’s LFB-190 to treat solid tumors related to loss of function of the EP300 gene.
SAN MATEO, Calif., Dec. 10, 2024 (GLOBE NEWSWIRE) -- Leapfrog Bio, a clinical-stage precision oncology company identifying novel therapies for undruggable cancer-driving mutations, today announced that Tomas Babak, PhD, the Company’s Chief Scientific Officer, will present evidence that Leapfrog Bio’s Precision PGx Platform™ discovered a clinically significant link between the EP300 gene and bromodomain and extra-terminal domain (BET) protein inhibitors. The presentation titled, “EP300 loss of function is a pan-cancer sensitizer to BET inhibition,” will take place at the AACR Special Conference in Cancer Research in Toronto, Canada and will focus on the discovery, characterization and clinical development plan for Leapfrog Bio’s BET inhibitor LFB-190 to treat solid tumors with EP300 loss of function.
Loss of transcriptional control is a hallmark of cancer and can be an essential driver of cancer initiation and progression. BET proteins regulate the expression of multiple cancer-related genes and pathways; several molecules targeting this family of proteins have been tested in early phase clinical trials, although these molecules had shown limited clinical success as monotherapies. After conducting hundreds of pharmacogenetic screens using its Precision PGx Platform™, Leapfrog Bio discovered an interaction between BET protein inhibition and the EP300 gene loss of function (LOF) similar to PARP-BRCA1/HRD in significance. The Company believes it has also discovered the mechanism of action for this synthetically lethal relationship between BET protein inhibition and EP300 LOF.
“It was gratifying to identify this essential interaction, as there has been so much research and activity related to BETs inhibitors,” said Tomas Babak, PhD, CSO of Leapfrog Bio. “Discovering a strong interaction between BET proteins and the mutated EP300 gene resulting in LOF—as well as the mechanism that drives it—using the Precision PGx Platform™ is a meaningful validation of the platform’s ability to identify therapies for previously undruggable cancers caused by LOF mutations. Two-thirds of all cancers are caused by mutations in tumor suppressor genes, such as what we see here with EP300, yet less than one percent of LOF tumor suppressor genes have been drugged to date. With Leapfrog Bio’s platform, we can repeatedly uncover candidates that address the unmet needs of patients with cancers caused by LOF mutations.”
Leapfrog’s Lead Candidate, LFB-190, exploits the relationship between BET inhibition and EP300 LOF mutations. The Company’s Phase 2-ready compound was clinically studied prior to Leapfrog’s research and a recommended Phase 2 dose has been established.
Greg Vontz, CEO of Leapfrog Bio added, “This discovery demonstrates the ability of the Precision PGx Platform™ to uncover potential therapeutic solutions for the 10M patients with cancers driven by LOF mutations. We have filed IP around this discovery and are currently preparing for LFB-190’s entry into Phase 2 in lung, colon and bladder cancers in 2025.”
About Leapfrog Bio
Leapfrog Bio is a clinical-stage precision oncology company accelerating cancer drug development by identifying clinical stage molecules that can be retargeted as directed therapies for cancers with undruggable driver mutations. The company’s lead program is a Phase 2 proof-of-concept trial evaluating a small molecule in three solid cancers with an unaddressed, but frequent, loss-of-function genetic mutation. The company’s Precision PGx Platform provides a repeatable and scalable in vitro system to identify existing small-molecule drugs that can be developed to treat cancers driven by loss-of-function mutations with a high probability of clinical success. The clinically validated platform has been described in the peer-reviewed article “Pharmacogenomic Discovery of Genetically Targeted Cancer Therapies Optimized Against Clinical Outcomes” appearing in Nature PJ Precision Oncology. For more information, visit www.leapfrog.bio.
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Janine McCargo
6 Degrees
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