San Diego, USA
Shanghai, China
April 21, 2023

 

ABM Therapeutics, a clinical-stage biopharmaceutical company with a focus on treating brain cancers and cancer metastases today announced 4 cancer research posters have been presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place in Orlando, Florida, April 14-19. The posters attracted a lot of cancer researchers.

 

Poser #4177

It is in the session of Novel Antitumor Agents 1 (Abstract #476)
Title: ABM-1310 has significant improved BBB-penetration and intracranial tumor growth inhibition compared to FDA approved BRAF inhibitors
Compared with FDA-approved BRAFV600 inhibitors Vemurafenib, Dabrafenib and Encorafenib, ABM-1310 has the smallest molecular weight and 6-45 times increased ratio of drug concentration in plasma and brain tissue, and 33~500 times increased ration of free drug concentration in plasma and brain tissue. In a melanoma brain metastasis model, ABM's innovative BRAF/MEK inhibitors combination, ABM-1310 and ABM-168, significantly inhibited intracranial tumor growth, and prolonged the median survival of mice to over 69 days, while the median survival of vehicle control group, and of the three marketed BRAF/MEK combos of Vemurafenib/Cobimetinib, Dabrafenib/Trametinib and Encorafenib/Bimetinib were 27, 55, 33 and 49 days, respectively. In primary brain tumor (glioma) DBTRG-05MG model, the combination of ABM-1310 and ABM-168 also showed similar results. These preclinical results show that, compared with the approved BRAFV600 inhibitors, ABM-1310 has significantly improved blood-brain barrier permeability, can effectively inhibit the growth of intracranial tumors, and prolong the survival of intracranial tumor-bearing animals. The clinical research of ABM-1310 is ongoing in multiple clinic centers in China and the United States. We hope ABM-1310 will bring new treatment options to patients with brain metastases or primary brain tumors.

 

Poster #4038

It is in the session of Novel Antitumor Agents 1 (Abstract #475)
Title：Preclinical development of ABM-168, a novel MEK Inhibitor to treat cancer with brain tumors
This poster shows the results of multiple preclinical experiments on small-molecule allosteric MEK inhibitor, ABM-168, developed by ABM Therapeutics. MEK is a downstream molecule of RAS and RAF in the MAPK signaling pathway. MEK inhibitor ABM-168 specifically and potently inhibited the growth of multiple tumor cell lines with abnormally high levels of MAPK caused by RAS or RAF or NF-1 mutation. ABM-168 shown good efficacy in multiple animal models including the Colo-205 subcutaneous tumor model, the orthotopic model of human glioma LN-229, the systemic metastasis model of melanoma, and brain metastasis model of melanoma. In addition, compared to FDA-approved small molecules MEK inhibitors, ABM-168 has a smaller molecular weight and significantly improved blood-brain barrier permeability. The IND of ABM-168 was approved by the FDA in October 2022. Phase I clinical trial is ongoing in multiple clinic centers in the United States.

 

Poster #6238
It is in the session of DNA-reactive Agents, HDAC and Methyltransferase Inhibitors, and Tubulin Agents (Abstract #6238)
Title：ABM-2752, a potent and selective HPK1 inhibitor with excellent efficacies as a single agent or in combination with a PD-1 antibody
This poster shows the results of multiple preclinical experiments on a novel small molecule HPK1 inhibitor, ABM-2752, developed by ABM Therapeutics. HPK 1 is a negative regulator of T cell and B cell activation. Inhibiting HPK1 or co-inhibiting HPK1 and PD-1 may be a promising tumor immunotherapy. ABM-2752 potently inhibited HPK1 kinase activity (IC50 =6.4nM), and had limited effect on the other MAP4K family member except MAP4K-5. In the in vitro T cell activation assay, ABM-2752 induced T cells to release IL-2 and inhibited the phosphorylation of SLP-76, a downstream molecule of HPK1. ABM-2752 shown good efficacy in multiple in vivo models. For example, in the MC38 model of syngeneic mouse intestinal cancer, high dose of ABM-2752 alone or in combination with PD-1 antibodies at medium dose or high doses of ABM-2752, were all effective on tumor growth inhibition, and extending animals survival time. In ADME and PK studies, ABM2752 also showed good drug-like properties. The project is currently in process of the IND-enabling studies.

 

Poster #5982
It is in the session of Cyclin-dependent Kinases and Cyclin-dependent Kinase Inhibitors (Abstract #1080)
Title：A potent and selective CDK8 inhibitor ABM-3249 with excellent efficacies in multiple in vivo cancer models.
This poster shows the results of multiple preclinical experiments of small molecule CDK8 inhibitor ABM-3249，which was developed by ABM Therapeutics. CDK8 is a member of the CDK kinase family. It can bind to Cyclin C and regulates gene transcription and plays a role in tumor cell invasion, metastasis and drug resistance. Inhibiting CDK8 may become a potential targeted therapy. ABM-3249 potently inhibited the enzymatic activity of CDK8 (IC50=1.3nM), but had limited inhibition on other CDK kinases (IC50s were about 49-100 folds higher than that of CDK8). ABM-3249 also significantly inhibited the phosphorylation of downstream molecule STAT1. In the subcutaneous tumor model of MV4-11, 15-days treatment of ABM-3249 almost eliminated the tumors, and the tumor remained unchanged for 5 more weeks after stopping dose. In the MC38 syngeneic model , ABM-3249 single drug effectively inhibited tumor growth, and shown an synergic tumor inhibitory effect when combined with PD-1 antibody. In preliminary tolerance studies, ABM-3249 also showed a good safety window.

 

About ABM Therapeutics
ABM Therapeutics, a clinical-stage biopharmaceutical company with a mission to focus on small molecule research and development of novel drugs for the treatment of cancer, and on brain cancer and cancer metastases. ABM has been building a broad and robust proprietary pipeline to construct a brain therapeutics 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.