Mabwell has announced the first patient dosing in the United States for a clinical study of its novel nectin-4-targeting antibody-drug conjugate (ADC) Bulumtatug Fuvedotin (BFv) in triple-negative breast cancer (TNBC) patients previously treated with ADCs. The first subject was dosed at Memorial Sloan Kettering Cancer Center, marking a significant milestone in the company's global ADC development program.
Addressing Critical Unmet Medical Need
The multicenter clinical study (NCT06908928) aims to evaluate the efficacy and safety of BFv in TNBC patients previously treated with a taxane and an antibody-drug conjugate with a topoisomerase inhibitor payload. This patient population represents a significant unmet clinical need, as treatment options for TNBC remain limited despite recent therapeutic advances.
While topoisomerase inhibitor-based ADCs (TOPi-ADCs) are emerging as a mainstream post-standard therapy option, a high proportion of patients progress after TOPi-ADC treatment, indicating significant unmet clinical needs due to the lack of alternative therapies.
Novel ADC Technology Platform
BFv is a novel Nectin-4 targeting ADC leveraging next-generation site-specific conjugation technology. The drug is composed of a novel antibody, an optimized linker, and cytotoxic payload MMAE (Monomethyl auristatin E), providing a good profile of tumor binding and target specificity.
Studies demonstrate BFv's superior characteristics including more homogeneous components, significantly lower toxin release in plasma and enhanced cytotoxic payload delivery efficiency, which leads to substantially increased intratumoral drug concentration. The drug is protected by multiple patents in China and internationally through the PCT.
Broad Patient Coverage Potential
Considering the high expression of Nectin-4 in TNBC, BFv's clinical study on TNBC imposes no biomarker screening requirements, holding potential for broad patient coverage and offering a novel therapeutic option for TNBC patients.
Growing Disease Burden
TNBC accounts for approximately 15% to 20% of all breast cancer cases globally and is generally considered a subtype with the most malignancy due to the lack of specific therapeutic targets. The global number of incident cases of TNBC increased from 320.1 thousand in 2019 to 361.2 thousand in 2023, and is expected to further increase to 479.4 thousand in 2032. In China, the number of incident cases increased from 49.5 thousand in 2019 to 54.8 thousand in 2023, with projections reaching 65.4 thousand in 2032.
Established Clinical Development Program
Bulumtatug Fuvedotin stands out as the first clinical-stage drug candidate among Chinese companies for the Nectin-4 target and is the first Nectin-4 targeting ADC to disclose clinical efficacy data in cervical, esophageal, and breast cancers. For urothelial carcinoma, both monotherapy and combination therapy with a PD-1 inhibitor have advanced to Phase III clinical studies, making it the first among Chinese candidates and second globally in this field.
The drug has been granted Breakthrough Therapy Designation by CDE of NMPA in China for urothelial carcinoma and is the first Nectin-4-targeting ADC worldwide to enter Phase III studies for cervical cancer. BFv has received multiple Fast Track designations from the US FDA, including for locally advanced or metastatic Nectin-4-positive triple-negative breast cancer, as well as Orphan Drug designation.
Company Background
Mabwell is an innovation-driven biopharmaceutical company with the entire value chain of the pharmaceutical industry, focusing on oncology and aging-related disease indications. The company utilizes its proprietary next-generation IDDC™ platform for ADC development and aims to provide more effective and accessible therapy to fulfill global medical needs.
