- Approval has been obtained from the U.S. Food and Drug Administration (FDA) to conduct the first-in-human trial for EBC-129 in patients with solid tumours.
- EBC-129 is the first made-in-Singapore antibody-drug conjugate (ADC) that is entering clinical development. It is able to selectively target cancer cells across a range of solid tumours.
- The ADC and the test to be used for patient selection were discovered and developed through the collaborative efforts of A*STAR’s Bioprocessing Technology Institute and Institute for Molecular and Cell Biology, the Experimental Drug Development Centre, and the National Cancer Centre Singapore.
The epitope that EBC-129 binds to is a specific glycosylation site that is conserved on both carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 5 and 6, which are cell surface receptors over-expressed in cancer cells. While drugs targeting only CEACAM5 are in advanced clinical testing, it has been challenging to develop drugs targeting CEACAM6 as it is also expressed on the surface of normal cells. However, by targeting only the glycosylated form of CEACAM5/6, EBC-129 is able to target cancer cells exclusively, and also acts on a wider range of cancers as it can target cells that express CEACAM5 or CEACAM6 alone, as well as those that express both CEACAM5 and 6. The payload used in EBC-129 is monomethyl auristatin E (MMAE), which has been extensively tested and approved for clinical use in other marketed ADCs. As such, development can be fast-tracked as the side effects, which are mostly mediated by the payload, can be predicted in advance and the effective dose is known. Furthermore, MMAE was shown to mediate a superior immunogenic cell death in combination with checkpoint inhibitors (immunotherapy), raising the possibility of combination therapy.
How EBC-129 was developed
The parties also collaborated with A*STAR’s Institute of Molecular and Cell Biology (IMCB) to develop an immunohistochemistry (IHC) assay required for patient selection.
“The antibody development team at BTI has built strong capabilities to generate and characterise monoclonal antibodies (mAbs) against novel glycosylated targets on cancer cells. This differentiated property enhances the mAbs selectively, giving us better tools to kill cancer cells. The US FDA’s approval for the initiation of trials for EBC-129 is a validation of our platform and the maturity of the drug development ecosystem in Singapore to collaboratively enhance the impact of research and drug discovery for potential patient outcomes,” said Dr Koh Boon Tong, Executive Director, BTI.
“The approval of an IND (Investigational New Drug) application for EBC-129 by the FDA is a testament to strong inter-institution collaborations in Singapore that can drive a bench-to-bedside pipeline of therapeutic development,” said Associate Professor Daniel Tan, Director of the Experimental Cancer Therapeutics Unit (Phase I), NCCS. “Most importantly, EBC-129 addresses an unmet need for patients who have exhausted standard therapies, by providing a novel ADC agent that directly targets cancer cells while sparing normal, healthy cells.”
About the Clinical Trial
The clinical trial will determine the safety and tolerability of EBC-129 in cancer patients, and subsequently evaluate its anti-cancer activity in different tumour types. The study will also evaluate the safety of combining EBC-129 with a checkpoint inhibitor. Additional information will be gathered including determining the drug levels in the blood and the levels of CEACAM5 and CEACAM6 in the serum. The study will be open to patients with metastatic solid tumours that cannot be cured surgically, including cancers of the lung, stomach, biliary tract, ovary, breast, prostate, colorectum and oesophagus amongst others.
Moving forward, approvals will be sought from the Health Sciences Authority (HSA) and relevant ethics boards for the trial to open to patients in Singapore through the NCCS and National University Cancer Institute, Singapore (NCIS). Ethics board approvals will be obtained for trial sites in the US, which will include major cancer centres.