BioCity Announces FDA Clearance Of The Investigational New Drug Application For Its First-In-Class Antibody Drug Conjugate Targeting Glypican 3

Shanghai /PRNewswire/ - BioCity Biopharma today announced that the U.S. Food and Drug Administration (FDA) has cleared the company's Investigational New Drug (IND) application for a Phase 1 study of BC2027. BC2027, which is BioCity's second first-in-class antibody drug conjugate (ADC) approved for clinical development, targets Glypican 3 (GPC3), a proteoglycan found in the outer membrane of cancer cells. BioCity's first ADC, BC3195, which is directed against another novel target called placental-cadherin (CDH3), a cell adhesion molecule that confers invasiveness and metastatic properties to cancer cells, is also in clinical trials.

GPC3 is specifically up-regulated in the most common type of liver cancer, hepatocellular carcinoma (HCC), several types of lung and esophageal cancer, and other malignancies, although rarely or not expressed in normal liver tissues, making GPC3 a rational treatment target for cancers that express it. Recently, clinical activity has been noted with chimeric antigen receptor (CAR) T cells and other therapies targeting GPC3, demonstrating the potential of GPC3 as a therapeutic target.

BC2027 binds with very high affinity to GPC3 and efficiently internalizes into cancer cells where it releases its cancer killing payload. In addition to directly killing cancers cells in which it enters, BC2027's cancer activity is enhanced as it kills other cancer cells indirectly via a "bystander effect". In preclinical studies, BC2027 was also quite safe and tolerable while demonstrating robust anticancer activity with greater than 90% inhibition of tumor growth in some well-established cancers. These findings indicate the potential for BC2027 to be a novel, safe, and effective cancer treatment.

The uniqueness of GPC3 as a target also suggests that BC2027 may in part overcome the challenges of cancer drug resistance. Dr. Yong Jiang Hei, CEO of BioCity, noted that "Drug resistance has increasingly become a challenge in cancer treatment. BioCity aims to develop next generation therapies with the potential to delay and overcome drug-resistance. Among different strategies, developing novel ADCs is an important approach to address the inherent drug resistance of HCC and many other cancers, as well as secondary drug resistance resulting from available anticancer therapies." He added, "Now BioCity has two first-in-class, novel ADCs in global clinical development, thereby resulting in a competitive edge as BioCity's ADCs are clearly differentiated. The company will strive to advance the clinical development of these exciting ADC therapeutics to meet the unmet clinical needs and benefit patients worldwide as early as possible." Dr. Hei says.

HCC and GPC3
Liver cancers are highly prevalent worldwide with approximately 860,000 newly diagnosed cases and 750,000 ^①deaths annually. Among liver cancers, 90% are HCC. In addition, the poor prognosis of the disease represents a significant unmet medical need.

In recent years, with the rapid development of systemic therapies for HCC, the standard of care for advanced HCC has evolved from traditional chemotherapy to multi-kinase inhibitors and immune checkpoint inhibitors, or the combination of the two. However, the efficacy of these therapies is limited and further advances in treatment are urgently needed.

GPC3 is highly expressed in more than 70% HCC and the expression level correlates with the extent of disease progression. Therefore, GPC3 is a specific tumor marker and closely related to disease prognosis, making it a promising target for the treatment of HCC^②.

About BioCity
Founded in December 2017, BioCity is a clinical-stage biopharmaceutical company committed to developing novel and highly differentiated, modality-independent therapeutics for cancer and autoimmune disorders including chronic kidney diseases (CKD). The company has established a pipeline of more than 10 innovative drug candidates including small molecules, monoclonal and bispecific antibodies as well as ADCs.

Currently, BioCity Biopharma has six oncology assets in Phase 1 clinical development, including the first-in-class CDH3-targeting ADC and GPC3-targeting ADC, WEE1 and ATR inhibitors targeting the DNA damage response (DDR) pathway, and agents targeting the immune system, a T cell engager (CD3/EGFR BsAb) and an immune checkpoint inhibitor (TIM-3 mAb). In addition, an endothelin A (ETA)-receptor selective antagonist for CKD is in phase 2 clinical development.

For more information, please visit www.biocitypharma.com

^①Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024. doi:10.3322/caac.21834

^②Yang X, Yang C, Zhang S, Geng H, Zhu AX, Bernards R, Qin W, Fan J, Wang C, Gao Q. Precision treatment in advanced hepatocellular carcinoma. Cancer Cell. 2024 Feb 12;42(2):180-197. doi: 10.1016/j.ccell.2024.01.007. PMID: 38350421.