BH3120 / Hanmi - LARVOL DELTA

A Phase I, Open-Label, Multinational, Multicenter, Dose Escalation and Expansion Study of BH3120, as a Single agent and in Combination with pembrolizumab, in Patients with Advanced or Metastatic Solid Tumors (ESMO-IO 2025) - P1 | "The Dose-Expansion Part is designed to additionally evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of single agent BH3120 and pembrolizumab combination, for specific indications. As of August 11, 2025, dose escalation cohorts for Arm A and Arm B, as well as Backfill Cohorts are actively recruiting, and Dose-Expansion Part is expected to begin in 2026.Clinical trial identification NCT06234397.Legal entity responsible for the study Hanmi Pharmaceutical Co., Ltd."

Clinical • Combination therapy • Metastases • Oncology • Solid Tumor • TNFRSF9

BH3120, a PD-L1x4-1BB bispecific antibody, exhibits favorable safety profiles in distinct in vivo and ex vivo liver toxicity evaluations (AACR 2025) - P1 | "To understand potential risks of liver toxicity with BH3120, sensitive in vivo and ex vivo models for liver toxicity evaluations were established: a mice model with mild liver inflammation induced by Concanavalin A, and human liver organoids co-cultured with immune cells to mimic the histological and physiological changes in patient's liver tissues.In both models, BH3120 was not associated with significant elevation of liver inflammation markers, indicating minimal risk of liver toxicity that is in line with the safety results we previously reported. The property of BH3120 to minimize systemic immune modulation enables de-coupling of anti-tumor efficacy from systemic toxicities, and would provide flexibility in combination with different anti-tumor treatments."

IO biomarker • Preclinical • Oncology

Transcriptional modulations of tumor microenvironment by BH3120, a PD-L1x4-1BB bispecific antibody, in patient-derived organotypic tumor spheroids (PDOTS) model (AACR 2025) - "In particular, RNAs representing CD4+ T cell, CD8+ T cell, NK cell, and B cell signals, and certain co-stimulators, proinflammatory cytokines, and chemokines were notably increased. Combination of BH3120 and PD-1 inhibitor resulted in the relevant genetic modulations with high magnitudes implicating potential synergism in RNA level."

Biomarker • Clinical • Tumor microenvironment • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • TNFRSF9

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

Hanmi Pharmaceutical and Beijing Hanmi Progress Clinical Trials of Co-developed BH3120 as a Next-Generation Cancer Immunotherapy (PRNewswire) - "On November 25, Hanmi announced that it presented the research and clinical progress of BH3120 in a poster session at the Society for Immunotherapy of Cancer (SITC) conference....During the SITC presentation, Hanmi outlined the background, design, and clinical progress of BH3120. Currently, a global Phase 1 clinical trial is underway in South Korea and the United States, assessing the safety and tolerability of BH3120 as a monotherapy in patients with advanced or metastatic solid tumors. The Phase 1 clinical trial has progressed smoothly through cohort 3 (1 mg/kg) of the dose escalation phase, with no dose-limiting toxicities (DLT) or grade 3 or higher adverse drug reactions observed to date....In September, Hanmi obtained approval from both the Korean Ministry of Food and Drug Safety and the U.S. Food and Drug Administration (FDA) to modify the Phase 1 trial plan to evaluate BH3120 in combination with KEYTRUDA."

Trial status • Solid Tumor

A phase I, open-label, multinational, multicenter, dose escalation and expansion study of BH3120 (4–1BB x PD-L1 BsAb) in patients with advanced or metastatic solid tumors (SITC 2024) - P1 | "The Dose-Expansion Part is designed to evaluate and confirm the safety, efficacy, pharmacokinetics, and pharmacodynamics of BH3120 when administered at the RD, with specific indications. The final analysis will be performed once or separately for each part based on study progression."

Clinical • Metastases • Oncology • Solid Tumor • CD8 • PD-L1 • TNFRSF9

Dose Escalation and Expansion Study of BH3120 Alone or With Pembrolizuamb in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=245 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Jul 2027 ➔ Jan 2028 | Trial primary completion date: Feb 2027 ➔ Aug 2027

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

"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

Hanmi Pharm partners with MSD for clinical trial of cancer therapy BH3120 (Korea Biomedical Review) - "Hanmi Pharmaceutical said it has entered into a clinical trial collaboration and supply agreement (CTCSA) with Merck....The partnership is set to advance the clinical research of Hanmi's dual-antibody therapy, BH3120, combined with MSD's immunotherapy drug, Keytruda. Under the terms of the agreement, Hanmi will lead as the sponsor of the phase 1 clinical trial, which will evaluate the safety and efficacy of the combination therapy using Keytruda and BH3120 in patients with advanced or metastatic solid tumors. MSD will supply Keytruda for use in these clinical trials."

Licensing / partnership • New P1 trial • Solid Tumor

BH3120, PD-L1 X 4-1BB bispecific antibody, plus PD-1 antagonist results in synergistic anti-tumor efficacy with excellent safety profile (AACR 2024) - "In the meantime, increased PD-1 induced by BH3120 can be blocked by PD-1 antagonist.This bi-directional mechanism results in rapid eradication of tumor tissues shortening the time to regression, indicating potentially fast control of tumor burden and associated symptoms. With the characteristics decoupling co-stimulatory activity in TME from that in normal tissues, BH3120 either as a monotherapy or in combination with PD-1 antagonist was not associated with liver toxicity and other concerns in relation to excessive modulation of immune cells systemically.Safety profile and clinical signs with BH3120 are being investigated in early-stage clinical trials as a monotherapy and in combination with a PD-1 antagonist."

Clinical • IO biomarker • Oncology • PD-L1

Hanmi Pharmaceutical "Starts dosing phase 1 patients with next-generation immunotherapy using 'Pentambody'" [Google translation] (HIT News) - "On the 13th, Hanmi Pharmaceutical registered the first patient participating in the phase 1 clinical trial evaluating 'BH3120 (PD-L1/4-1BB BsAb)' for patients with advanced or metastatic solid cancer at a domestic university hospital and completed the first dose. It was announced on the 19th that it was done."

Trial status • Solid Tumor

Dose Escalation and Expansion Study of BH3120 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=191 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited

New P1 trial • Oncology • Solid Tumor

Hanmi begins clinical trial of dual antibody immunotherapy BH3120 (Korea Biomedical Review) - "Hanmi Pharm has taken the first step toward clinical trials of BH3120, a double-antibody anticancer drug candidate it is developing as its next-generation pipeline. According to the Ministry of Food and Drug Safety (MFDS), Hanmi received approval for a phase 1 clinical trial of BH3120 on Friday. Hanmi plans to confirm the safety and efficacy of BH3120 in patients with advanced or metastatic solid tumors. Only Seoul National University Hospital has registered for it so far....The phase 1 trial will be conducted as a global clinical trial."

New P1 trial • Oncology • Solid Tumor

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

BH3120, a bispecific antibody targeting 4-1BB and PD-L1 simultaneously, stimulates T cells in tumor tissue preferred manner (AACR 2023) - "To verify this hypothesis, BH3120 was compared with reference bispecific antibodies. Combination of BH3120 with a PD-1 antogonist does not result in elevation of transaminase enzymes, while the reference bispecific antibodies, when combined with the same PD-1 antagonist, show significant increase of the enzymes and macrophage in liver.In the toxicology studies conducted so far with cynomolgus monkeys, NOAEL of BH3120 was determined to be 200 mg/kg (QW X 5)."

Oncology

BH3120: A novel bispecific antibody targeting 4-1BB and PD-L1 with well balanced efficacy and safety profiles (AACR 2022) - "Moreover, combination of BH3120 with an immune checkpoint inhibitor shows synergistically enhanced anti-tumor efficacy. Supported by these results, IND enabling studies of BH3120 are on-going and clinical evaluations are planned from later in 2022."

Clinical • Oncology • TNFRSF9