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Preclinical data for ADRX-0706, a fully proprietary investigational antibody=drug conjugate or ADC being developed by Adcentrx, will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10, 2024, in San Diego, CA.

In three separate presentations preclinical data for Adcentrx’s lead ADC program, ADRX-0706 will be presented.

ADRX-0706 includes a novel, fully human, IgG1 antibody targeting human the Nectin cell adhesion protein 4 (Nectin-4) linked to a novel tubulin inhibitor payload, AP052, via Adcentrx’s proprietary i-Conjugation™ technology using a cleavable linker and stable conjugation chemistry.

Nectin-4 is a validated tumor target and highly expressed in various solid cancers including urothelial cancer, head-and-neck caner, breast cancer, lung cancer, pancreatic cancer, ovarian cancer, and cervical cancer, while the expression in normal or healthy tissues is limited. [1]

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In 2019 the first-generation ADC targeting Nectin-4, enfortumab vedotin-ejfv (Padcev®; Astellas Pharma and Seagen/Pfizer) received accelerated US Food and Drug Administration (FDA) approval for the treatment of urothelial cancers, and is currently approved for frontline therapy in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, providing groundbreaking improvement in patient survival. However, in treating patients with enfortumab vedotin researchers also observed safety-driven limitations, which required a reduced and/or interrupted drug exposures, which, in turn impacting treatment efficacy.

To overcome these limitations Adcentrx has developed ADRX-0706, a Nectin-4-targeting next-generation ADC based on a new platform technology.

This novel platform technology generates highly stable ADCs with a drug-antibody-ratio (DAR) of eight (8), substantially expanding the therapeutic window of auristatin-based ADCs beyond existing vedotin-technology. Preclinical data presentations show improved therapeutic window of ADRX-0706, enhanced bystander effect and improved payload delivery to Nectin-4 expressing tumors while minimizing exposure to normal tissues.

Details of the three AACR poster presentations are below:

Presentation Title:Preclinical characterization of ADRX-0706: A next-generation anti-Nectin-4 antibody-drug conjugate with improved therapeutic window
Abstract Number:1891
Session Date & Time:Monday, April 89:00 a.m. – 12:30 p.m. PT
Session Title:Antibody-Drug Conjugates and Bispecific Antibodies
Presentation Title:ADRX-0706 Nectin-4 antibody-drug conjugate PK/PD characterization elucidates its widened therapeutic window
Abstract Number: 1902
Session Date & Time:Monday, April 89:00 a.m. – 12:30 p.m. PT
Session Title:Antibody-Drug Conjugates and Bispecific Antibodies
Presentation Title:Advancing a novel tubulin-inhibitor ADC technology: The Adcentrx auristatin platform offers enhanced efficacy and safety profiles compared to vedotin technology
Abstract Number:1909
Session Date & Time:Monday, April 89:00 a.m. – 12:30 p.m. PT
Session Title:Antibody-Drug Conjugates and Bispecific Antibodies

 

Clinical trials
A Study of ADRX-0706 in Select Advanced Solid Tumors –  ClinicalTrials.gov. – NCT06036121

Highlights of prescribing information
Enfortumab vedotin-ejfv (Padcev®; Astellas Pharma and Seagen/Pfizer) [Prescribing Information]

Reference
[1] Bouleftour W, Guillot A, Magne N. The Anti-Nectin 4: A Promising Tumor Cells Target. A Systematic Review. Mol Cancer Ther. 2022 Apr 1;21(4):493-501. doi: 10.1158/1535-7163.MCT-21-0846. PMID: 35131876.

Featured image: The AACR 2014 Annual Meeting (San Diego) – Poster Hall Photos Advocacy Pavilion. Photo courtesy: 2014 © AACR/Todd Buchanan. Used with permission.

 

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