Hanmi Pharmaceutical releases new anticancer pipeline HM100760

Hanmi Pharmaceutical said Wednesday that it presented three posters on the results of its research on MAT2A inhibitor (HM100760), a selective HER2 exon 20 insertion mutation inhibitor, and SOS1 inhibitor (HM99462) at the EORTC-NCI-AACR 2024, an international cancer conference held in Barcelona, Spain, from Wednesday to Friday last week (local time).

The MAT2A inhibitor unveiled in this presentation is an anticancer drug that works on the principle of synthetic lethality. It targets cancer tumors by deleting the MTAP (methylthioadenosine phosphorylase) gene, which plays an important role in certain metabolic pathways in the cell.

No commercially available therapies target MTAP, and the leading drug studied previously discontinued its clinical trial due to safety concerns.

Therefore, the company said, developing next-generation therapeutics with high efficacy and low toxicity targeting MAT2A has been in the spotlight.

In this study, Hanmi Pharmaceutical confirmed the antitumor activity of HM100760 in various MTAP-deficient cell lines, including pancreatic and lung cancer. It also demonstrated excellent anticancer effects in animal models with MTAP gene deletion. Based on these findings, Hanmi Pharmaceutical plans to begin nonclinical toxicity testing in the first half of next year.

In another presentation, the results of a study confirming the potential to develop a selective HER2 exon 20 insertion mutation inhibitor—unveiled first as a treatment for non-small cell lung cancer (NSCLC) at the American Association for Cancer Research (AACR) 2024 in April—were introduced.

Hanmi's selective HER2 inhibitor minimizes side effects by increasing selectivity for wild-type EGFR (epidermal growth factor receptor). Through oral administration, it has shown anticancer activity in animal models of HER2 exon 20 insertion mutant and HER2 wild-type tumors. Hanmi also demonstrated brain metastasis inhibition in an animal brain metastasis model, confirming a decrease in brain metastasis levels compared to the control group.

Hanmi Pharmaceutical's HM99462 is a novel SOS1 inhibitor that inhibits the binding between the SOS1 protein and KRAS. This acts as a signal transduction cascade to prevent the activation of lethal KRAS mutations among cancer-causing gene mutations.

HM99462 exhibited anticancer activity in various KRAS-mutated solid cancer cell lines, including KRAS G12C, G12D/V/S, and G13D, by inhibiting KRAS-SOS1 protein binding regardless of KRAS mutation type. In addition, it showed synergistic effects through vertical inhibition with EGFR mutation inhibitors, confirming its therapeutic potential for EGFR-mutated lung cancer. Based on these findings, Hanmi Pharmaceutical plans to file an investigative new drug application to enter phase I clinical trials in the first half of next year, according to the company.

“As the emerging MAT2A inhibitor development market is still in its early stages, Hanmi's MAT2A inhibitor has demonstrated excellent anticancer efficacy and has shown innovative potential as a next-generation treatment,” said Choi In-young, head of Hanmi Pharmaceutical R&D Center. “We will continue to explore new and original approaches to change the cancer treatment paradigm and overcome intractable cancers.”