Delving into the Latest Updates on EBC-129 with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

EBC 129, EBC129

Target

CEACAM5 x CEACAM6 x Tubulin

Mechanism

CEACAM5 antagonists(Carcinoembryonic antigen related cell adhesion molecule 5 antagonists), CEACAM6 inhibitors(Carcinoembryonic antigen related cell adhesion molecule 6 inhibitors), Tubulin inhibitors

Therapeutic Areas

Neoplasms

Active Indication

Advanced Malignant Solid Neoplasm

Inactive Indication-

Originator Organization

EXPERIMENTAL DRUG DEVELOPMENT CENTRE

Active Organization

EXPERIMENTAL DRUG DEVELOPMENT CENTRE

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC39H67N5O7

InChIKeyDASWEROEPLKSEI-UIJRFTGLSA-N

CAS Registry474645-27-7

Prostate stem cell antigen (PSCA) is expressed in all stages of prostate cancer, including in advanced androgen-independent tumors and bone metastasis. PSCA may associate with prostate carcinogenesis and lineage plasticity in prostate cancer. PSCA is also a promising theranostic marker for a variety of other solid tumors, including pancreatic adenocarcinoma and renal cell carcinoma. Here, we identified a novel fully human PSCA antibody using phage display methodology. The structure-based affinity maturation yielded a high-affinity binder, F12, which is highly specific and does not bind to 6,000 human membrane proteins based on a membrane proteome array assay. F12 targets PSCA amino acids 63-69 as tested by the peptide scanning microarray, and it cross-reacts with the murine PSCA. IgG1 F12 efficiently internalizes into PSCA-expressing tumor cells. The antimitotic reagent monomethyl auristatin E (MMAE)-conjugated IgG1 F12 (ADC, F12-MMAE) exhibits dose-dependent efficacy and specificity in a human prostate cancer PC-3-PSCA xenograft NSG mouse model. This is a first reported ADC based on a fully human PSCA antibody and MMAE that is characterized in a xenograft murine model, which warrants further optimizations and investigations in additional preclinical tumor models, including prostate and other solid tumors.

31 Dec 2024·OncoImmunology

CD20 expression regulates CD37 levels in B-cell lymphoma – implications for immunotherapies

Article

Author: Domagala, Joanna ; Gehlert, Carina Lynn ; Firczuk, Malgorzata ; Majchrzak, Martyna ; Graczyk-Jarzynka, Agnieszka ; Inderberg, Else Marit ; Winiarska, Magdalena ; Prochorec-Sobieszek, Monika ; Barankiewicz, Joanna ; Bobrowicz, Malgorzata ; Wälchli, Sébastien ; Dostalova, Lenka ; Marhelava, Katsiaryna ; Kusowska, Aleksandra ; Zhylko, Andriy ; Forcados, Christopher ; Poreba, Marcin ; Szumera-Cieckiewicz, Anna ; Kubacz, Matylda ; Pepek, Monika ; Krawczyk, Marta ; Fidyt, Klaudyna ; Peipp, Matthias ; Šmída, Michal ; Baranowska, Iwona ; Granica, Monika ; Slusarczyk, Aleksander

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.

01 Dec 2024·CANCER SCIENCE

Anti‐tissue factor antibody conjugated with monomethyl auristatin E or deruxtecan in pancreatic cancer models

Article

Author: Tsumura, Ryo ; Matsumura, Yasuhiro ; Takashima, Hiroki ; Anzai, Takahiro ; Yasunaga, Masahiro ; Koga, Yoshikatsu

Abstract:

Antibody–drug conjugates (ADCs) have been recognized as a promising class of cancer therapeutics. Tissue factor (TF), an initiator of the blood coagulation pathway, has been investigated regarding its relationship with cancer, and several preclinical and clinical studies have presented data on anti‐TF ADCs, including tisotumab vedotin, which was approved in 2021. However, the feasibility of other payloads in the design of anti‐TF ADCs is still unclear because no reports have compared payloads with different cytotoxic mechanisms. For ADCs targeting other antigens, such as Her2, optimizing the payload is also an important issue in order to improve in vivo efficacy. In this study, we prepared humanized anti‐TF Ab (clone.1084) conjugated with monomethyl auristatin E (MMAE) or deruxtecan (DXd), and evaluated the efficacy in several cell line‐ and patient‐derived xenograft models of pancreatic cancer. As a result, optimizing the drug / Ab ratio was necessary for each payload in order to prevent pharmacokinetic deterioration and maximize delivery efficiency. In addition, MMAE‐conjugated anti‐TF ADC showed higher antitumor effects in tumors with strong and homogeneous TF expression, while DXd‐conjugated anti‐TF ADC was more effective in tumors with weak and heterogeneous TF expression. Analysis of a pancreatic cancer tissue array showed weak and heterogeneous TF expression in most TF‐positive specimens, indicating that the response rate to pancreatic cancer might be higher for DXd‐ than MMAE‐conjugated anti‐TF ADC. Nevertheless, our findings indicated that optimizing the ADC payloads individually in each patient could maximize the potential of ADC therapeutics.

1

News (Medical) associated with EBC-129

09 Mar 2023

·www.prnewswire.com

WuXi XDC Congratulates EDDC on FDA Clearance of IND Application for First Made-in-Singapore Antibody-Drug Conjugate

SHANGHAI, March 8, 2023 /PRNewswire/ -- WuXi XDC ("XDC"), a leading global CRDMO company dedicated to end-to-end bioconjugate services, congratulates its partner, the Experimental Drug Development Centre (EDDC), Singapore's national drug discovery and development platform hosted by the Agency for Science, Technology and Research (A*STAR), and its collaborators on clearance by the U.S. FDA for EBC-129 to begin its first-in-human trial in patients with solid tumors. EBC-129 is the first made-in-Singapore antibody-drug conjugate (ADC). With the employment of WuXi XDC's proprietary integrated technology platforms, all of the CMC studies for EBC-129's Investigational New Drug (IND) application were completed effectively and at the highest level of quality. The partnership between EDDC and WuXi XDC demonstrates how collaborative science can translate research into promising therapeutic candidates when enabled by CRDMOs. Dr. Jimmy Li, CEO of WuXi XDC, commented, "Congratulations to EDDC and its collaborators on reaching this exciting milestone. We are honored to enable innovative partners such as EDDC in advancing ADCs from research to clinical trials through WuXi XDC's integrated and open-access bioconjugate technology platform. We wish the program great success for the future benefit of patients worldwide." About WuXi XDC WuXi XDC, a joint venture between WuXi Biologics and WuXi STA, provides end-to-end contract research, development and manufacturing services for bioconjugates, including antibody drug conjugates (ADCs). The company's services cover antibodies and other biologics, chemical payloads and linkers, as well as bioconjugated drug substance and drug product. WuXi XDC has been successful in bringing multiple ADC projects to the Investigational New Drug (IND) filing stage in 15 months or less, nearly cutting in half the traditional development timeline. For more information about WuXi XDC, please visit: . Contacts Media [email protected] Investor [email protected] SOURCE WuXi Biologics

INDADC

100 Deals associated with EBC-129

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	US	EXPERIMENTAL DRUG DEVELOPMENT CENTRE	28 Apr 2023
Advanced Malignant Solid Neoplasm	Phase 1	SG	EXPERIMENTAL DRUG DEVELOPMENT CENTRE	28 Apr 2023

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05701527 (ESMO2024) Manual	Phase 1	Solid tumor	16	EBC-129 0.3 mg/kg	xorcyqbzgr(bwkdhmfbvv) = not reached kwlhjefjfc (nxruopubky ) View more	Positive	14 Sep 2024