GSK and Duality Biologics have entered into an exclusive option agreement for developing and commercializing DB-1324, a potentially best-in-class antibody-drug conjugate (ADC) candidate.
Under the agreement, DualityBio will grant GSK an exclusive option to obtain a license to develop and commercialize DB-1324 worldwide (excluding mainland China, Hong Kong, and Macau).
DB-1324 is an ADC candidate built with DualityBio’s proprietary and clinically validated Duality Immune Toxin Antibody Conjugate (DITAC) platform. Currently, in preclinical development, the molecule leverages DualityBio’s DITAC platform against a gastrointestinal (GI) cancer target. There is a high unmet medical need for patients with GI cancer as it represents 35% of all cancer-related deaths and approximately 26% of the global cancer incidence.[1]
This ADC molecule has the potential to unlock multiple combination therapy opportunities to complement GSK’s oncology portfolio strategically.
GSK will pay $30 million upfront and additional pre-option milestone payments to obtain an exclusive option for exclusive worldwide rights for DualityBio’s ADC. Upon GSK exercising this option, DualityBio will receive an option exercise fee as well as potential development, regulatory, and commercial milestone payments totaling up to US $ 975 million.
Following commercialization, GSK will pay tiered royalties on DB-1324’s global net sales. In turn, DualityBio wil pay GSK royalties on net sales in mainland China, Hong Kong, and Macau.
Collaboration
“DualityBio is dedicated to becoming a leading global next-generation ADC company. We are very glad to have entered into this agreement with GSK,” noted John Zhu, Chief Executive Officer of Duality Biologics.
“Through this collaboration, we will work together to advance our innovative ADC program in gastrointestinal cancer to address unmet medical needs. DualityBio’s unique and validated ADC technology platform can continue to empower more partners around the world and provide innovative treatment options for global patients,” Zhu concluded.
GSK portfolio
“GSK has built a portfolio of novel antibody-drug conjugates underpinned by our deep expertise in tumor cell-targeting mechanisms,” said Hesham Abdullah, SVP, Global Head Oncology, R&D, GSK.
The company’s existing ADC development includes the BCMA-targeting belantamab mafodotin (Blenrep®), and B7-H3- and B7-H4-targeting projects the company licensed from Hansoh Pharma.
B7-H3
The B7-H3-targeting ADC (HS-20093, also known as GSK5764227 or GSK’227; see: Drugmap; Overview B7-H3 ADCs) is being investigated in patients with extensive-stage small-cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. [2]
Data from a dose escalation and expansion trial presented at the World Conference on Lung Cancer (WCLC) 2024, held September 7-10, 2024 in San Diego, California, USA, demonstrated a 61.3% (n=31) and 50.0% (n=22) overall response rate (ORR) and median PFS 5.9 months (n=31）and 7.3 months (n=22) in patients receiving 8.0 mg/kg and 10.0 mg/kg of HS-20093 respectively (as of data cutoff of June 30, 2024). The safety and tolerability profile of the investigational drug in patients with ES-SCLC mainly included hematologic and gastrointestinal events. Grade ≥3 treatment-related adverse events (with incidence ≥10%) were neutrophil count decreased (39.3%), white blood cell count decreased (33.9%), lymphocyte count decreased (25.0%), platelet count decreased (17.9%), and anemia (16.1%).[2]
B7-H4
HS-20089 (see: Drugmap) is a novel B7-H4 targeted ADC that conjugates a humanized anti B7-H4 lgG1 monoclonal antibody with a small molecule toxin topoisomerase I inhibitor via a protease-cleavable linker.
The agent was evaluated in the dose-escalation portion of an open-label phase 1 study (NCT05263479), which enrolled patients with locally advanced or metastatic tumors that were unselected for B7-H4 expression
“Given the unique ability of ADCs to address certain targets on tumor cells while sparing healthy ones, we are confident in our strategic […] advances in new treatments for the most challenging tumor types,” Abdullah added.
Clinical trials
A Study of HS-20089 in Patients With Advanced Solid Tumors – ClinicalTrials.gov ID NCT05263479
References
[1] Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA, et al.Global burden of 5 major types of gastrointestinal cancer. Gastroenterology, 159(1):335–349.e15.
[2] Wang J, Duan J, Wu L, et al. Efficacy and safety of HS-20093 in extensive stage small cell lung cancer in a multicenter, phase 1 study (ARTEMIS-001). Presented at: 2024 IASLC World Conference on Lung Cancer; September 6-10, 2024; San Diego, CA. Abstract OA04.06.
Feature image: GSK-Scientists-Conducting-Research. © GSK. Used with permission
