Hanmi Pharmaceutical Partners with MSD to Test Novel Bispecific Antibody BH3120 in Combination with KEYTRUDA
核心洞察
Hanmi Pharmaceutical has entered a Clinical Trial Collaboration and Supply Agreement with MSD to evaluate its novel immunotherapy BH3120 in combination with KEYTRUDA for patients with progressive or metastatic solid tumors (搜索).
BH3120 utilizes Hanmi's proprietary Pentambody platform, targeting both PD-L1 (搜索) and 4-1BB (搜索) simultaneously to enhance anti-tumor immune responses specifically in tumor tissues while minimizing systemic immune activation.
The Phase 1 trial, led by Dr. Kim Dong-wan of Seoul National University Hospital, aims to overcome limitations of existing 4-1BB (搜索) targeting therapies by leveraging BH3120's demonstrated ability to decouple immune activity between tumor microenvironment and normal tissue.
Hanmi Pharmaceutical has entered into a Clinical Trial Collaboration and Supply Agreement (CTCSA) with MSD (known as Merck & Co. (搜索), Inc. in the United States) to evaluate the combination of its novel immunotherapy drug BH3120 with MSD's established anti-PD-1 (搜索) therapy KEYTRUDA (pembrolizumab) in patients with progressive or metastatic solid tumors (搜索).
Under the terms of the agreement announced on April 23, 2024, Hanmi will sponsor and conduct a Phase 1 clinical trial assessing the safety and efficacy of this combination therapy, while MSD will supply KEYTRUDA for the study. The trial will be conducted in both Korea and the United States.
Novel Dual-Targeting Mechanism
BH3120 represents a significant advancement in cancer immunotherapy, utilizing Hanmi's proprietary "Pentambody" bispecific antibody platform technology. This innovative approach enables a single antibody to simultaneously target two different molecules—in this case, PD-L1 (搜索) and 4-1BB (搜索) (CD137).
The drug's mechanism of action is particularly sophisticated, featuring an IgG-like bivalent bispecific antibody structure with biased binding affinities toward PD-L1 (搜索). This design enables BH3120 to induce potent anti-tumor activities specifically in tumor tissues where PD-L1 is overexpressed, while minimizing unwanted immune activation in normal tissues.
Dr. Kim Dong-wan, director of the Seoul National University Hospital Clinical Trials Center and principal investigator for the Phase 1 trial, explained the potential clinical significance: "Through the collaboration with MSD, we expect BH3120 in combination with KEYTRUDA could improve outcomes for patients with relapsed or refractory disease."
Addressing Safety Limitations of Current Therapies
A key advantage of BH3120 lies in its potential to overcome safety limitations that have hampered previous 4-1BB (搜索)-targeting antibody candidates. The 4-1BB pathway is a potent co-stimulatory signal for T cells that can enhance anti-tumor immune responses, but targeting it has proven challenging due to systemic immune activation and associated toxicities.
Non-clinical studies of BH3120 have demonstrated a clear decoupling of immune activity between the tumor microenvironment (TME) and normal tissue. This selective activation profile suggests BH3120 could deliver effective anti-cancer activity while maintaining a favorable safety profile—a critical balance that has eluded many previous immunotherapy approaches.
The drug has shown strong anti-tumor T cell activities in a tumor tissue-specific manner with clear dose dependency in preclinical models, both as monotherapy and in combination settings. Importantly, these effects were achieved while minimally modulating systemic immune responses.
Strategic Significance for Hanmi Pharmaceutical
For Hanmi Pharmaceutical, this collaboration represents a significant milestone in its immunotherapy development program. A company representative highlighted the strategic importance: "BH3120 is our first global clinical research project using the next-generation bispecific antibody platform technology 'Pentambody' in the field of immuno-oncology therapy, potentially changing the paradigm of anticancer treatment."
The company further emphasized its commitment to "surpassing the constraints of current therapies and innovatively boosting therapeutic efficacy through our next-generation immune-oncology therapy."
Broader Context in Cancer Immunotherapy
The collaboration comes at a time when bispecific antibodies are gaining significant attention in oncology. By simultaneously engaging two targets, these molecules can potentially deliver more precise and effective immune modulation than traditional monoclonal antibodies.
KEYTRUDA, MSD's blockbuster anti-PD-1 (搜索) therapy, has already demonstrated efficacy across multiple tumor types by blocking the PD-1/PD-L1 (搜索) immune checkpoint pathway. The addition of BH3120's 4-1BB (搜索) co-stimulatory activity could potentially enhance T cell activation specifically within the tumor microenvironment, potentially improving response rates and overcoming resistance mechanisms.
About the Companies
Hanmi Pharmaceutical, established in 1973, is a leading Korean biopharmaceutical company focused on oncology, obesity/metabolism, and rare diseases. The company has built a portfolio of more than 30 pipeline candidates and received FDA approval for Rolontis, a neutropenia treatment, in 2022.
The company's proprietary technologies include LAPSCOVERY, which prolongs the duration of action of biologics, and PENTAMBODY, the bispecific antibody platform being utilized for BH3120. Hanmi employs an "Open Innovation" strategy to enhance R&D synergies through collaborations with external partners.
MSD, operating as Merck & Co. (搜索), Inc. in the United States and Canada, is one of the world's leading pharmaceutical companies with a strong focus on oncology, including its flagship immunotherapy KEYTRUDA.
The Phase 1 trial will evaluate BH3120 in combination with KEYTRUDA across multiple types of solid tumors (搜索), potentially opening new treatment options for patients with limited therapeutic alternatives.