Hanmi Pharm continues to unveil new anticancer drug pipelines globally

Hanmi Pharmaceutical presented research results on its anticancer drug pipeline at the international cancer conference “AACR-NCI-EORTC 2025” held in Boston, Mass., from Wednesday to Sunday (local time).

Hanmi Pharmaceutical announced on Wednesday that it presented five non-clinical research results in poster presentations: EP300 selective degraders; SOS1-KRAS interaction inhibitors (code name: HM101207); STING mRNA anticancer drugs; p53-mRNA anticancer drugs; and YAP/TAZ-TEAD inhibitors.

The EP300 selective degrader, which drew significant attention at this presentation, is an anticancer drug that utilizes Hanmi's novel modality, “Targeted Protein Degradation (TPD)” platform technology. It acts on the principle of “synthetic lethality,” selectively killing cancer cells that depend on the EP300 protein or harbor mutations in the CBP gene.

EP300 and CBP proteins are transcription co-activators with histone acetyltransferase activity. While they function complementarily in normal cells, EP300 dependency has been reported in CBP-mutated cancers. Furthermore, the high structural similarity between the two proteins poses challenges for the development of drugs that selectively target EP300.

Hanmi Pharmaceutical R&D Center Senior Researcher Jung Seung-hyun explains the research behind “SOS1-KRAS Interaction Inhibitor (HM101207),” a promising candidate for global anticancer combination therapy, to attendees using a poster. (Courtesy of Hanmi Pharmaceutical)

At the conference, Hanmi Pharmaceutical presented results showing that an EP300-selective degrader exhibits antitumor activity in EP300-dependent and CBP-mutated cell lines. Furthermore, in a prostate cancer xenograft model, it demonstrated superior tumor-suppressing effects compared to existing first-line therapies and dual EP300/CBP inhibitors.

The research findings drew significant attention for suggesting a new treatment option for EP300-dependent and CBP-mutated cancers, based on the EP300-selective degrader's excellent metabolic stability and potential for oral administration.

Another presentation revealed results confirming the superior antitumor efficacy of the “SOS1-KRAS interaction inhibitor (HM101207)”—noted as a promising candidate for global anticancer combination strategies at the International Conference on RAS Targeted Drug Development last September—compared to competitive drugs.

HM101207 is a novel inhibitor (SOS1-panKRAS Modulator) that blocks the binding between the “SOS1” protein, which plays a key role in the signaling cascade, and KRAS. This prevents the activation of the lethal “KRAS mutation” among cancer-causing gene mutations.

By inhibiting the binding of the SOS1 protein to various KRAS mutations and thereby reducing signaling activity, HM101207 can suppress cancer growth. It is expected to overcome the resistance that arises with the administration of already approved KRAS G12C inhibitors, RTK inhibitors, or MAPK signaling pathway inhibitors.

Notably, HM101207 demonstrated potent synergistic anticancer effects in combination with various RAS-off inhibitors. With superior target specificity and minimal drug-drug interactions (DDIs) compared to other SOS1 competitive drugs currently in development, HM101207 holds promise for use in global anticancer combination strategies.

Hanmi Pharmaceutical also presented research results on novel immunotherapy drugs based on the “mRNA platform,” a next-generation modality, demonstrating its potential to lead a paradigm shift in drug development.

The STING mRNA anti-cancer drug is a therapeutic that directly induces the expression of the STING (Stimulator of IFN Genes) protein to trigger a potent anti-cancer immune response. It fundamentally reconfigures the starting point of the immune response, presenting a new direction with a “reboot” strategy against tumors.

Traditionally, immuno-oncology drugs have primarily focused on restoring T-cell function through immune checkpoint inhibitors. Existing STING agonists face limitations in therapeutic efficacy due to metabolic instability, reduced cytoplasmic delivery efficiency, and decreased STING expression in actual cancer tissues.

At this conference, Hanmi Pharmaceutical presented results confirming significant tumor growth inhibition and a favorable safety profile in colorectal and lung cancer animal models using STING mRNA monotherapy alone. Hanmi's STING mRNA-based anticancer drug is expected to demonstrate strong synergistic effects when combined with various anticancer agents.

Another mRNA platform-based drug candidate, the p53 mRNA anticancer drug, is a therapeutic that induces apoptosis (programmed cell death) in cancer cells by restoring normal intracellular expression of the p53 protein, a key tumor suppressor gene. At this conference, results were presented showing effective inhibition of cancer cell growth in orthotopic animal models of lung and ovarian cancer.

Notably, it demonstrated excellent synergistic effects when combined with taxane-based chemotherapy and proved antitumor activity in lung and ovarian cancer animal models when combined with Abraxane. Furthermore, the p53 mRNA-targeting anticancer drug showed effective activity even in paclitaxel-resistant cell lines, suggesting potential to overcome resistance.

Hanmi's YAP/TAZ-TEAD inhibitor regulates the excessively activated YAP/TAZ-TEAD signaling in Hippo pathway-mutated cancers by targeting the palmitate-binding pocket (PBP), which plays a key role in stabilizing TEAD.

At this conference, research was presented showing that Hanmi's YAP/TAZ–TEAD inhibitor demonstrated excellent growth inhibitory activity in Hippo pathway-mutated mesothelioma cell lines and significantly reduced YAP/TAZ–TEAD target gene expression in a dose-dependent manner.

Furthermore, in a mesothelioma xenograft mouse model, the anti-tumor efficacy and target gene suppression capability of Hanmi's inhibitor were confirmed. It also demonstrated superior safety compared to competitive drugs, as evidenced by nephrotoxicity indicators such as proteinuria.

“Hanmi’s core anticancer pipeline is expanding into innovations across targeted protein degradation (TPD), mRNA, cell and gene therapies (CGT), ADC, and sdAb, aiming to drive global leadership in next-generation modalities,” Chief R&D Officer Choi In-young said.