San Diego, USA
Shanghai, China
March 15, 2024

 

ABM Therapeutics, Inc, a clinical-stage biopharmaceutical company with a focus on treating brain cancers and cancer metastases today announced preclinical data about its self-developed pMEK inhibitor ABM-4095 in the treatment of RAS mutant cancers and pancreatic cancer will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting, taking place in San Diego, California, April 5-10.

 

Poster: 1947 / 25

Poster Session：Drug Resistance 2: Ras GTPase
Location：Section 24
Time：April 8, 2024, 9:00 AM - 12:30 PM
Title：Studies on pMEK inhibitors for the treatment of RAS-mutant cancers as a single agent or combinations

 

Abstract
RAS mutations are the most common oncogene in human cancers and KRAS has the highest frequency in non-small cell lung cancer (NSCLC) and pancreatic cancer (PDAC). KRAS G12C inhibitors have been approved to treat NSCLC patients. However, drug-resistance is eventually developed for these treatments. Preclinical studies suggested MAPK pathway reactivation is one possible mechanism. Among many MEK inhibitors in clinical development, CH5126766 binds to MEK1 inactive conformation and blocks its phosphorylation and activation. We believe this compound should prevent MAPK “paradoxical activation” commonly observed in most RAF and MEK inhibitors such as vemurafenib and cobimetinib. We studied this compound in various in vitro assays and found its potential in combating the paradoxical activation, which might be the cause of drug-resistance for MAPK signal pathway inhibitors, including RAS-, RAF- MEK- and ERK-inhibitors, as a single agent or in combination with above-mentioned inhibitors. In addition, we are developing a series of compounds based on CH5126766, by improving the inhibition of MEK1/2 kinase activity in addition to its activation. In summary, studies on the pMEK inhibitor demonstrated that this class of compounds might mitigate the MAPK pathway reactivation and prolong drug efficacies in clinical. Detailed research results will be discussed.

 

Click on the link to learn more information:
https://www.abstractsonline.com/pp8/#!/20272/presentation/3313

 

Poster: 592 / 2

Poster Session: Kinase and Phosphatase inhibitors 1
Location：Section 25
Time：April 7, 2024, 1:30 PM - 5:00 PM
Title： A novel pMEK inhibitor ABM-4095 for the treatment of pancreatic cancer

 

Abstract
The MEK-ERK pathway is often activated in tumors by mutations of upstream BRAF- or RAS-proteins. The RAS is frequently mutated in several cancers, especially in pancreatic cancer with an about 95% rate. Pancreatic cancer has the highest mortality rate with a 5-year survival rate of 8% and a median survival of 6 months. Targeted therapies have been extensively evaluated in pancreatic cancer, however, survival improvement of this aggressive disease using a targeted strategy has been minimal. The only currently approved targeted therapy is erlotinib in combination with the chemotherapy drug gemcitabine. To date, four MEK inhibitors that block RAF-activation have been approved by the FDA, but their ability to inhibit ERK signal activated by RAS-mutations is limited due to the induction of MEK phosphorylation by relief of ERK-dependent feedback inhibition of RAF. Here, we report a novel small molecule, ATP-uncompetitive, pMEK inhibitor ABM-4095 that potently prevents phosphorylation of MEK by RAF with moderate inhibition of MEK kinase activity. Most of MEK inhibitors approved by FDA or in clinical trials increase pMEK levels instead. ABM-4095 has a good cell permeability. Its anti-cancer efficacy has been demonstrated both in the in vitro cancer cell line proliferation assay and in vivo xenograft models. In a Miapaca-2 xenograft model, ABM-4095 showed good dose-dependent tumor inhibition as a single agent or combining with the KRAS G12C inhibitor AMG-510, and tumor regressions were observed. In summary, ABM-4095 is a potent pMEK inhibitor with a high activity against the RAS-mutant pancreatic cancer in vitro and in vivo. Detailed preclinical results will be presented.

 

Click on the link to learn more information:
https://www.abstractsonline.com/pp8/#!/20272/presentation/4122

 

About ABM Therapeutics
ABM Therapeutics, a clinical-stage biopharmaceutical company with a mission to focus on the small molecule research and development of novel drugs for the treatment of cancer, and on brain cancer and cancer metastases. ABM has been building its broad and robust proprietary pipeline to construct a brain medicine R&D platform. ABM’s pipeline includes several programs in various stages of discovery and development, most of which have improved brain permeability to address the unmet needs of treating cancers and metastases in the brain.