HM97662 / Hanmi - LARVOL DELTA

A Novel and Potent EZH1/2 Dual Inhibitor, HM97662 Demonstrated a Wide Spectrum of Therapeutic Potential for Hematological Malignancies (ASH 2023) - "In conclusion, the present preclinical studies demonstrated that HM97662, an EZH1/2 dual inhibitor, had a promising and wide spectrum of therapeutic potential for hematological malignancies. It is urgent to assess the effectiveness of HM97662 in further clinical trials."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD38 • CDKN1C • CDKN2A • EZH2 • PRDM1 • SUZ12

HM97662, a novel EZH1/2 dual inhibitor, in patients with advanced or metastatic solid tumors: Initial results from a first-in-human phase I study (ESMO 2025) - P1 | "Enrollment in the 350 mg cohort is ongoing, with updated results to be presented at the meeting. Conclusions HM97662 demonstrated a manageable safety profile without significant toxicity leading to treatment discontinuation and showed preliminary anti-tumor activity, supporting continued clinical investigation."

Clinical • First-in-human • Metastases • P1 data • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • EZH2 • SMARCA4

Hanmi Pharmaceutical announced on the 22nd that it announced the results of a phase 1 clinical study of HM97662 in the form of a poster at the European Society of Oncology (ESMO Congress 2025) held in Berlin, Germany from the 17th to the 21st (local time). (Maeil Business Newpaper) - "In particular, partial remission of cancer lump size was observed in uterine sarcoma patients (300 mg administration), and in ovarian cancer patients (200 mg administration), the tumor size was reduced by up to 26% as the disease did not worsen for more than 15 months."

P1 data • Ovarian Cancer • Uterine Sarcoma

Hanmi's Next-Generation EZH1/2 Dual Inhibitor Demonstrates Potential to Overcome Resistance Mechanisms (MedigateNews) - "Hanmi participated in the 18th International Conference on Malignant Lymphoma (ICML 2025) held from June 17 to 21 in Lugano, Switzerland, where it presented preclinical data on HM97662 in a scientific poster session....At ICML 2025, Hanmi presented data showing that HM97662 more potently and dose-dependently inhibited H3K27 trimethylation in DLBCL (KARPAS-422) and multiple myeloma (MM1.S) cell lines, compared to the EZH2-selective inhibitor Tazemetostat (Tazverik). HM97662 monotherapy demonstrated significant tumor growth inhibition in DLBCL models. Moreover, in tazemetostat-resistant DLBCL cell lines generated through prolonged exposure to the EZH2-selective inhibitor tazemetostat, a compensatory upregulation of EZH1 protein expression was observed."

Preclinical • Diffuse Large B Cell Lymphoma • Multiple Myeloma

Hanmi Pharmaceuticals, ’EZH1/2 Dual Inhibitor’ Nonclinical Blood Cancer Study Results Presented at the International Lymphoma Society [Google translation] (BioTimes) - "According to the study presentation, HM97662 dose-dependently more potently inhibited histone protein H3 lysine 27 trimethylation (H3K27me3) in B-cell lymphoma (KARPAS-422) and multiple myeloma (MM1.S) cell lines compared to tazemetostat (Tazverik), an EZH2 selective inhibitor. In particular, in resistant cell lines established by long-term exposure to tazemetostat, an EZH2 selective inhibitor, a complementary increase in expression of the EZH1 protein was observed, and HM97662 maintained its antitumor activity in a tazemetostat-resistant animal model in which this resistant cell line was xenografted."

Preclinical • B Cell Lymphoma • Multiple Myeloma

AS A NOVEL EPIGENETIC MODULATOR, EZH1/2 DUAL INHIBITOR HM97662 EXHIBITS ANTITUMOR EFFICACY IN HEMATOLOGICAL MALIGNANCIES AND OVERCOMES EZH2-INHIBITOR MEDIATED RESISTANCE (ICML 2025) - "Finaly, the overcoming the EZH2 selective inhibitor mediated resistance by HM97662 was explored in KASPAS 422-tazemetostatR model. Epigenetic modulation of EZH1/2 is crucial in the tumorigenesis and progression of hematologic malignancies, making them attractive therapeutic targets. While EZH2 inhibition alone can lead to resistance due to compensatory role of EZH1 activity, EZH1/2 dual inhibition effectively overcomes its limitation and enhances anti-tumor efficacy. HM97662, a potent EZH1/2 dual inhibitor, leverages synthetic lethality by targeting key regulatory protein mutations, offering a promising strategy for treating hematologic malignancies."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • BTG2 • CDKN2A • EZH2

Dose Escalation and Expansion Study of HM97662 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=170 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial primary completion date: Feb 2025 ➔ Jan 2028

Trial primary completion date • Solid Tumor

Strong synergistic activity of an EZH1/2 dual inhibitor, HM97662, in combination with standard chemotherapy in preclinical models of advanced solid tumors (AACR 2025) - "Recent studies have shown that EZH2 plays a role in regulating cisplatin resistance in ovarian cancer...While irinotecan is commonly used as 2nd-line therapy due to its manageable toxicity and efficacy, its effectiveness as a monotherapy is limited by chemotherapy resistance...In conclusion, this preclinical study demonstrated that HM97662, an EZH1/2 dual inhibitor, has promising therapeutic potential against advanced solid tumors, either alone or in combination with standard-of-care cytotoxic agents. It is urgent to assess the effectiveness of HM97662 in further clinical trials."

Combination therapy • Metastases • Preclinical • Bladder Cancer • Gastric Cancer • Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • EZH2

NGS-based molecular profiling reveals remarkable anticancer synergy of EZH1/2 dual inhibitor HM97662 with standard-of-care therapy on small cell lung cancer (AACR 2025) - "Leveraging NGS, we identified molecular signatures predictive of enhanced response to the EZH1/2 dual inhibitor HM97662. These findings pave the way for personalized therapeutic strategies, offering renewed hope for patients with small cell lung cancer and other cancers with SCN feature as well."

Next-generation sequencing • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CDKN1A • EZH2 • SLFN11

Hanmi Pharmaceutical Presents the Most Research Outcomes at AACR, Innovating Beyond Obesity to Cancer Treatment (Korea IT Times) - "Hanmi Pharmaceutical has announced that it will present the highest number of research outcomes among domestic pharmaceutical and bio companies at the prestigious American Association for Cancer Research (AACR) for three consecutive years, demonstrating the future value of its cancer drug pipeline."

Preclinical • Oncology

A phase I, open-label, multicenter, dose escalation and expansion study of HM97662 (EZH1/2 dual inhibitor) as a single agent in patients with advanced or metastatic solid tumors (ESMO 2024) - P1 | "EZH1/2 repress the transcription of target genes by triggering tri-methylation of the lysine 27 residue of histone H3 (H3K27me3). Dose expansion part is designed to assess and confirm the efficacy, safety, pharmacokinetics, and pharmacodynamics of HM97662 with specific target disease determined by available preclinical study results and clinical outcomes. The final analysis will be performed once or separately for each part based on study progression."

Clinical • Metastases • Oncology • Solid Tumor • EZH2

"Hanmi Pharmaceuticals, management dispute settled for now, time to expect R&D results” [Google translation] (Insight Korea) - "Haitoo Investment & Securities reported on the 12th that Hanmi Pharmaceutical's second quarter performance would meet market expectations...'Beijing Hanmi is expected to record a +10% sales growth year-on-year due to balanced growth in products other than respiratory drugs even during the seasonal off-season, and Hanmi Fine Chemical is expected to turn a profit through expanded contract development and manufacturing organization (CDMO) sales and improved API mix.'...'In addition to top-line growth, R&D expenses, which had a high base compared to the same period last year due to the clinical entry of the BH3120 and HM97662 pipelines, are expected to decrease, contributing to improved profitability in the current quarter.'....'we expect annual sales in 2024 to increase 9.7% year-on-year to KRW 1.635 trillion, and operating profit to increase 21.5% to KRW 268.2 billion, achieving solid performance despite the limited expected technology royalties this year.'"

Sales projection • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Synergistic effects of EZH1/2 dual inhibition and cisplatin on lung cancer cell lines with loss of SMARCA4 and SMARCA2 (AACR 2024) - "The novel EZH1/2 dual inhibitor, HM97662, exhibits antitumor activity and a synergistic effect with cisplatin in lung cancer cell lines with concomitant loss of SMARCA4 and SMARCA2. These findings suggest the potential utility of EZH1/2 dual inhibition as a targeted therapeutic approach in lung cancers characterized by the dual loss of SMARCA4/2."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EZH2 • SMARCA2 • SMARCA4

Synthetic lethal strategy of an EZH1/2 dual inhibitor, HM97662, for the treatment of ARID1A-mutated solid cancers (AACR 2024) - "Enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of polycomb repressive complex 2 (PRC2), is known to catalyze tri-methylation of histone H3 at lysine 27 (H3K27me3), leading to repression of the transcription of its target genes involved in cell cycle regulation, cell proliferation, cell differentiation, and tumor suppression. In conclusion, these preclinical studies demonstrated that HM97662 as an EZH1/2 dual inhibitor, holds promising therapeutic potential for ARID1A-mutated solid cancers. It is crucial to evaluate the effectiveness of HM97662 in subsequent clinical trials."

Synthetic lethality • Bladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ARID1A • EZH2 • PBRM1 • SMARCA4

Hanmi Pharm to unveil new drug pipelines at AACR 2023 (Korea Biomedical Review) - "Hanmi Pharmaceutical said it would disclose new drug research projects at the upcoming annual meeting of the American Association for Cancer Research (AACR 2023) in the U.S....The new pipelines that Hanmi Pharmaceutical will unveil at the AACR include LAPSIL-2analog (HM16390), EZH1/2 dual inhibitor (HM97662), SOS1 inhibitor (HM99462), YAP/TAZ-TEAD inhibitor, mRNA anti-cancer vaccine, and PD-L1/4-1BB BsAb (BH3120)....On April 17, Hanmi is to disclose the results of its preclinical candidate BH3120....Beijing Hanmi Pharmaceutical and Hanmi plan to submit a phase 1 investigational new drug application to the U.S. FDA within this month."

Clinical data • IND • Preclinical • Oncology

A novel and potent EZH1/2 dual inhibitor, HM97662 demonstrates antitumor activity in T-cell lymphoma (AACR 2023) - "We further conducted chromatin accessibility assay and identified that the chromatin structures of them were loosened and highly transcribed after the treatment of HM97662.Based our in vitro pharmacology data, we evaluated an antitumor activity of HM97662 in EZH1/2 co-expressed HuT-102 T-cell lymphoma cell mouse xenograft model, and daily oral dosing of HM97662 showed potent tumor growth inhibition.In conclusion, the present studies demonstrated that HM97662 has promising prospective for the treatment of patients with T-cell lymphoma. Given that the necessity of new treatment options on T-cell lymphoma, it is urgent to assess the effectiveness of HM97662 in further clinical trials."

Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CASP3 • CDKN1A • CDKN1C • CDKN2A • EZH2 • SUZ12

Dose Escalation and Expansion Study of HM97662 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

Valemetostat: First approval as a dual inhibitor of EZH1/2 to treat adult T-cell leukemia/lymphoma. (PubMed, Drug Discov Ther) - "Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell lymphoma with a poor prognosis. Several other dual EZH1/2 inhibitors such as HH2853, HM97594, and HM97662 have also demonstrated potential in treating malignant tumors. Dual targeting EZH1/2 may have promising antitumor action in hematological malignancies and solid tumors."

Journal • Adult T-Cell Leukemia-Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • EZH2

Dose Escalation and Expansion Study of HM97662 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=140 | Not yet recruiting | Sponsor: Hanmi Pharmaceutical Company Limited

New P1 trial • Oncology • Solid Tumor