FDA Grants Orphan Drug Designation to YB-200 for Hepatocellular Carcinoma

FDA

The FDA has granted an orphan drug designation to the CEACAM1/5 antibody YB-200 for the treatment of patients with hepatocellular carcinoma (HCC).¹

“This designation is an important milestone in our development of CEACAM antibodies as anti-cancer treatments,” Katrin Rupalla, PhD, founder and chief executive officer of Ymmunobio, said in a press release. “We’re very pleased to continue our investigation into CEACAM antibodies for the treatment of hepatocellular carcinoma.”

CEACAM1 and CEACAM5 are part of the carcinoembryonic antigen (CEA) family.² CEACAM1 is found on a variety of immune cells and acts as a cell-to-cell communication molecule. The signal transduction process is associated with immune cell activation, apoptosis, proliferation, and differentiation.

In the pathophysiological stage, CEACAM1 and 5 are dysregulated in various malignancies including breast, lung, and gastrointestinal cancer, resulting in a novel checkpoint blockade mechanism mediated by homophilic CEACAM1-to-1 and heterophilic CEACAM1-to-5 interaction between immune and tumor cells, respectively.

CEACAM1/5 expression is typically associated with poor prognosis. YB-200 is part of a novel class of CEACAM1 antibodies that provides checkpoint inhibition as well as direct immune agonistic effects on immune cells.1 Specifically, YB-200 is a novel IgG1 antibody targeting CEACAM 1/5, which has been shown to retain the immune agonistic function of CEACAM1 on leukocytes in addition to potentially inhibiting both the homophilic and heterophilic checkpoint blockade of CEACAM1 and 5 on tumor cells.²

Previously, preclinical data studying the in vivo anti-tumor activity of YB-200 and its effect on immune cells were presented at the 37th Annual SITC Annual Meeting in an HCC model.²

The antitumor activity of YB-200 was evaluated with the validated ReactionBiology’s SubQperior^® experimental syngeneic liver Hepa-1-6 tumor model. The tumor cells were injected into the mammary fat pad of C57BL/6 mice. On the fifth day after tumor cell injection, the animals were randomized to two groups. The median tumor size was approximately 50 mm³.

Mice were treated through intraperitoneal injection biweekly for 3 cycles with either isotype control or YB-200 at a dose of 10 mg/kg. Animals were euthanized on day 20, and tumors were then collected for flow cytometry analysis. Flow cytometry for immune-cell profiling was performed using the ReactionBiology All-in-one^® staining panel.

Results showed that treatment with YB-200 was well tolerated and led to approximately 80% reduction in tumor growth compared with the isotype control, meeting the prespecified threshold for statistical significance. Moreover, YB-200 produced a 10-fold increase in B cells in the tumor microenvironment compared with the control and resulted in a statistically significant increase in CD3+ and CD4+ T cells and reduction in granulocytes.

References

1. FDA Grants Orphan Drug Designation to Ymmunobio's CEACAM Antibody for the Treatment of Liver Cancer. News release. Ymmunobio. February 28, 2023. Accessed March 1, 2023. https://www.ymmunobio.com/post/fda-grants-orphan-drug-designation-to-ymmunobio-s-ceacam-antibody-for-the-treatment-of-liver-cancer 
2. Janicot M, Rupalla K, Schmidt A, et al. Novel, immune agonistic CEACAM1/5 antibody (YB-200) demonstrates anti-tumor efficacy and significantly increases B-cell response in syngeneic liver Hepa1-6 tumor microenvironment. J Immunother Cancer. 2022;10(suppl 2):A1438. doi:10.1136/jitc-2022-SITC2022.1384