First made-in-Singapore antibody-drug conjugate EBC-129 progresses to phase 1B dose expansion

The Experimental Drug Development Centre (EDDC), Singapore’s national platform for drug discovery and development, is pleased to announce that the Phase 1 trial for EBC-129 has progressed into dose expansion. 

EBC-129 is the first made-in-Singapore ADC to enter clinical development. The tumour antigen it targets is a specific N-glycosylated site conserved on both CEACAM 5 and 6 which is selectively expressed on cancer cells, over normal cells. This allows EBC-129 to address a broad range of solid cancers expressing either one or both tumour markers, including cancers prevalent in Asia like gastroesophageal and lung cancers, as well as cancers with very limited treatment options like pancreatic cancer and cholangiocarcinoma.

The Phase 1 trial began with a dose escalation study which evaluated the safety and tolerability of EBC-129 in patients with unresectable metastatic solid tumours. The first patient for the dose escalation was dosed at the National Cancer Centre Singapore (NCCS) in May 2023. EBC-129 is also being tested at the National University Cancer Institute, Singapore (NCIS), as well as the MD Anderson Cancer Center and the University of Colorado Cancer Center in the United States. The dose escalation study showed that EBC-129 is well-tolerated by cancer patients. Tumour shrinkage by ≥30% was observed in an oesophageal cancer patient as well as a pancreatic cancer patient.

The Phase 1 trial has now progressed into dose expansion, with the first patient for this part of the study dosed on 13^th May 2024. The dose expansion study comprises three groups of 15 patients each with gastroesophageal cancers, pancreatic ductal adenocarcinomas, and solid tumours expressing the tumour antigen at moderate or high levels.

The ADC and the immunohistochemistry (IHC)-based test used for patient selection were developed collaboratively by NCCS, A*STAR’s Bioprocessing Technology Institute (BTI) and the Institute for Molecular and Cell Biology (IMCB), as well as EDDC.

“Our team at NCCS has been very encouraged by the progress of this ongoing trial for EBC-129 which has shown good tolerability and early signs of efficacy in the dose escalation study,” said Clinical Assistant Professor Matthew Ng, Head, Department of Gastrointestinal and Neurological Medical Oncology, NCCS. “We have strong patient interest for participation in the dose expansion study and look forward to the development of EBC-129 as a potential treatment for cancer patients in the future.”

“I am excited to delve deeper into EBC-129’s promise as a therapeutic option for pancreatic and gastroesophageal cancers through the dose expansion study. The demand for safe and effective treatments in these cancer types remains substantial, and we are dedicated to addressing these unmet needs,” said Dr Yong Wei Peng, Senior Consultant, Department of Haematology-Oncology, NCIS.

 “We are thrilled by the positive developments we have seen in the dose escalation study, and grateful for all our collaborators as well as the team at EDDC, who have been instrumental for us to reach this milestone“, said Prof Damian O’Connell, EDDC’s Chief Executive Officer. “We will continue to work with our clinical partners to progress the dose expansion study and advance the potential of EBC-129 as an effective, targeted therapy for cancer patients.”

About EBC-129
 

EBC-129 targets a specific N-glycosylated site conserved on CEACAM5 and CEACAM6 and is highly tumour-specific. This epitope has functional importance in tumour formation, migration and metastasis. Thus, EBC-129 is able to address a wide range of solid tumours with high unmet medical needs, including lung, gastric, oesophageal, pancreatic, breast, ovarian and biliary tract cancers. 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, and has shown synergy with PD-1 inhibitors.

For more information on EBC-129 and its development, please refer to https://www.eddc.sg/first-made-in-singapore-antibody-drug-conjugate-adc-approved-to-enter-clinical-trials/.
 

For information about the trial, please visit Clinicaltrial.gov, trial identifier NCT05701527.

ABOUT THE EXPERIMENTAL DRUG DEVELOPMENT CENTRE

The Experimental Drug Development Centre (EDDC) is Singapore’s national platform for drug discovery and development, formed from the integration of the Experimental Therapeutics Centre (ETC), Drug Discovery and Development (D3), and Experimental Biotherapeutics Centre (EBC) in 2019. EDDC aims to develop therapeutics and diagnostics that save and improve the lives of patients in Singapore, Asia and around the world. Hosted by the Agency for Science, Technology and Research (A*STAR), EDDC works collaboratively with public sector and industry partners to translate the great science arising from Singapore’s biomedical and clinical sciences R&D into innovative healthcare solutions. For more information about EDDC, please visit www.eddc.sg.  

About the National Cancer Centre Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve its vision of being a global leading cancer centre, NCCS offers world-class care and shares its depth of experience and expertise by training local and overseas medical professionals.

To meet growing healthcare needs, the new NCCS building opened in 2023 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, advanced and innovative treatment such as proton therapy is offered at the new Goh Cheng Liang Proton Therapy Centre at NCCS.

In 2024, NCCS celebrates its silver anniversary, celebrating 25 years of advancing cancer care from breakthroughs to healing.

About National University Cancer Institute, Singapore

The National University Cancer Institute, Singapore (NCIS) is a national specialist centre under the National University Health System (NUHS), and is the only public cancer centre in Singapore that treats both paediatric and adult cancers in one facility. NCIS (n-sis) offers a broad spectrum of cancer care and management from screening, diagnosis and treatment, to rehabilitation, palliative and long-term care. NCIS’s strength lies in the multi-disciplinary approach taken by our clinician-scientists and clinician-investigators to develop a comprehensive and personalised plan for each cancer patient.

NCIS cancer services span across several acute hospitals: NCIS @ National University Hospital, NCIS @ Ng Teng Fong General Hospital, NCIS @ Alexandra Hospital, and the NCIS Radiation Therapy Centre @ Tan Tock Seng Hospital. We also deliver a range of cancer services for our patients’ convenience at satellite clinics in the community, as well as in the comfort of their homes. For more information, please visit www.ncis.com.sg.