Hanmi Unveils its Next-Generation ‘MAT2A Inhibitor’ Targeting Metabolic Vulnerabilities of Cancer Cells

<Novel Oncology Pipeline, HM100760>
 

Hanmi Presents Three Posters Highlighting Research Results on New Anti-Tumor Therapies at ENA held in Spain

MAT2A Inhibitor Leverages 'Synthetic Lethality'―A New Breakthrough for Intractable Cancer
HER2 Exon 20 Insertion Broadens Targets to Include KRAS, EGFR, and Other Mutant Cancers

Eun Joo Kwak, Wongi Park, and Hyung-Seok Yoo, from Hanmi Pharmaceutical R&D Center presented research findings on three next-generation anticancer drugs at the EORTC-NCI-AACR 2024 International Cancer Conference.

Hanmi Pharmaceutical has strenghtened its position as an innovation leader in oncology by unveiling a novel oncology pipeline, the ‘MAT2A inhibitor,’ at a prestigious global cancer conference. The MAT2A inhibitor is attracting attention as a potential breakthrough for intractable cancers, by targeting the metabolic vulnerabilities of cancer cells.

From October 23 to 25 (local time), Hanmi presented three key research findings at the prestigious ‘EORTC-NCI-AACR 2024’ international cancer conference in Barcelona, Spain (October 23-25). The presentations highlighted advances in their pipeline, including the MAT2A inhibitor (HM100760), a selective HER2 exon 20 insertion mutant inhibitor, and the SOS1 inhibitor (HM99462).

The MAT2A inhibitor has garnered significant attention for its novel approach, leveraging the principle of synthetic lethality. This innovative anticancer drug specifically targets cancer cells lacking the MTAP (methylthioadenosine phosphorylase) gene, which plays a crucial role in certain metabolic pathways. 

Currently, no therapies that directly target MTAP deletions are available, and prior clinical trials for similar treatments have been discontinued due to safety concerns. Unlike previous attempts, Hanmi’s MAT2A inhibitor showed strong potential as a next-generation therapy, offering both enhanced efficacy and reduced toxicity.

In preclinical studies, Hanmi demonstrated potent antitumor activity in various MTAP-deficient cancer cell lines, including pancreatic and lung cancers, using HM100760. The drug also exhibited strong anticancer effects in MTAP-deleted animal models. Based on these promising results, Hanmi plans to initiate nonclinical toxicity testing in the first half of the following year.

At the conference, Hanmi also introduced research on selective HER2 exon 20 insertion mutant inhibitors, originally presented at AACR 2024. This therapy shows promise as a treatment for non-small cell lung cancer (NSCLC). 

The selective HER2 inhibitors demonstrated reduced side effects by enhancing specificity for EGFR (epidermal growth factor receptor) wild-type and showed robust anticancer activity in animal models of HER2 exon 20 mutations and HER2 wild-type tumors through oral administration. Additionally, Hanmi observed a reduction in brain metastasis levels compared to the control group when administering selective HER2 inhibitors in a brain metastasis animal model, confirming the drug’s efficacy in inhibiting brain metastasis.

The third presentation highlighted HM99462, a novel SOS1 inhibitor designed to prevent activation of KRAS mutations by blocking the binding of the SOS1 protein to KRAS. While inhibitors for KRAS G12C mutation have been approved for lung cancer and colon cancer, they face limitations such as resistance mechanisms and reduced efficacy.

Hanmi's HM99462 showed strong anticancer activity against various KRAS mutant solid tumors, including KRAS G12C, G12D/V/S, and G13D mutations. It also demonstrated a synergistic effect when combined with EGFR mutation inhibitors, showing potential for the treatment of EGFR mutant lung cancer. Hanmi aims to submit an Investigational New Drug (IND) application for phase 1 clinical trials in the first half of next year.

Dr. In Young Choi, Head of Hanmi R&D Center, commented, “As the field of MAT2A inhibitor development is still emerging, Hanmi’s MAT2A inhibitor has shown outstanding anticancer efficacy and holds significant potential as a next-generation therapy. We remain committed to discovering novel approaches that will reshape cancer treatment and address the challenges of intractable cancers.”

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