BIO Asia–Taiwan 2023 亞洲生技大會

BIO Asia–Taiwan 2023 亞洲生技大會

講師

Hsing-Mao Chu

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Session 8 – Strategic Insights into CMC Program Design:
Pioneering Biologics Development Excellence

Date:25 July (Thursday)
Time12:30– 12:50 (GMT+8)

Hsing-Mao Chu

CEO
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T-E Meds, Inc.

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Art Hsing-Mao Chu received his Ph.D. degree from National Taiwan University in 2010, studying protein-protein and protein-ligand interactions at atomic resolution. He joined Dr. Tse-Wen Chang’s laboratory in the Genomics Research Center, Academia Sinica in 2011 to study CemX on human mIgE and develop anti-CemX antibodies.

In 2015, he was hired as Director of R&D, Immunwork and was promoted to V.P. of R&D in 2019. He leads a dynamic team focused on developing ADCs, ARCs, and fatty acid (FA) bundle-modified peptide drugs. As a result of the collaborative efforts within the team, two remarkable ultra-long-acting peptide drugs initiated their first-in-human trials in 2024H1. These include a once-biweekly FA bundle-modified GLP-1 receptor agonist and a once-monthly FA bundle-modified octreotide analogue. 

Expanding his scope in 2023, he assumed the CEO position at T-E Meds, Inc., a sister company of Immunwork, dedicated to developing ADCs/ARCs platform and products. Dr. Chu is a co-inventor in more than 70 granted patents.

Speech title & Synopsis

Drug Bundle-Based ADC Platform: Achieving Site-Specific Conjugation, DAR of 8 or 12, and Dual Payloads

T-E Meds, Inc. specializes in developing antibody drug conjugates (ADCs) and antibody radionuclide conjugates (ARCs) using its innovative “multi-arm linker” and proprietary “drug bundle” technology. These drug bundles are meticulously constructed on multi-arm linkers, effectively packing small drugs. Each drug bundle has a conjugating arm with a terminal functional group for click reactions, such as dibenzocyclooctyne (DBCO), trans-cyclooctene (TCO), or a maleimide group, enabling site-specific conjugation with antibody molecules. 

Various drug bundles have been developed, containing different drugs such as immunomodulators (e.g., lenalidomide), topoisomerase I inhibitors (e.g., Dxd, exatecan, and SN38), and microtubulin inhibitors (e.g., MMAF and MMAE) bundles for constructing high-DAR (drug-to-antibody ratio) ADCs. These bundles can carry two or more drug molecules, either identical or diverse, attached via cleavable or non-cleavable linkers. Additionally, a DOTA chelator bundle is available for producing high-CAR (chelator-to-antibody ratio) ARCs, which can be labeled with radionuclides like 111In or 177Lu for diagnostic or therapeutic use. 

T-E Meds’ drug bundles can be applied to various antibodies through different conjugation chemistries. For instance, in the combined “CHO-TEM ADC” technology, which utilizes CHO Pharma’s glycan modification technology, a specific enzyme trims carbohydrate side chains of an antibody, attaching four azido groups. Subsequently, four of T-E Meds’ DBCO-containing drug bundles conjugate site-specifically to the modified antibody molecule via strain-promoted azide-alkyne cycloaddition (SPAAC), resulting in the generation the CHO-TEM ADC product. This highly efficient manufacturing process yields high-DAR (8 or 12) and dual-drug ADCs, demonstrating high stability, solubility, and strong efficacy. 

So far, the drug bundle platforms have been examined and proven feasible through several cases. With these novel technologies, several drug bundle-based ADC and ARC drug candidates have been identified and developed, showing potential for achieving a better benefit/risk balance for patients in need in the future.

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