AstraZeneca intends to build a $1.5 billion manufacturing facility in Singapore for antibody drug conjugates (ADCs), enhancing global supply of its ADC portfolio. ADCs are next-generation treatments that deliver highly potent cancer-killing agents directly to cancer cells through a targeted antibody.

The planned greenfield facility, supported by the Singapore Economic Development Board (EDB), will be AstraZeneca’s first end-to-end ADC production site, fully incorporating all steps of the manufacturing process at a commercial scale. Manufacturing of ADCs is a multi-step process that comprises antibody production, synthesis of chemotherapy drug and linker, conjugation of drug-linker to the antibody, and filling of the completed ADC substance.

“We welcome AstraZeneca’s decision to establish a manufacturing presence in Singapore for the first time. It will also be a first for AstraZeneca – an end-to-end manufacturing facility for novel antibody drug conjugates that enables precision therapy for cancer,”noted Png Cheong Boon, Chairman, Singapore Economic Development Board.

“This greenfield investment is a strong show of confidence in Singapore’s biopharmaceutical manufacturing capabilities and talent, strengthens our ecosystem in supporting the development and manufacturing of precision medicines, and creates meaningful jobs and economic opportunities for Singapore. We look forward to a successful partnership with AstraZeneca,” Boon added.

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Industry leading portfolio
“AstraZeneca has built an industry-leading portfolio of cancer medicines including antibody drug conjugates which have shown enormous potential to replace traditional chemotherapy for patients across many settings,” said Pascal Soriot, Chief Executive Officer, AstraZeneca.

“Singapore is one of the world’s most attractive countries for investment given its reputation for excellence in complex manufacturing, and I am excited for AstraZeneca to locate our $1.5 billion ADC manufacturing facility in the country,” Soriot concluded.

AstraZeneca has a broad portfolio of in-house ADCs including six wholly owned ADCs in the clinic and many more in preclinical development.

In February 2034, the Biologics License Application (BLA) for datopotamab deruxtecan, a specifically engineered TROP2-directed DXd antibody-drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo, was accepted by the US Food and drug Administration.  The investigational drug is being developed for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. The Prescription Drug User Fee Act date, the Food and Drug Administration (FDA) action date for its regulatory decision, is during the fourth quarter of 2024.[1][2][3][4]

The BLA is based on results from the pivotal TROPION-Lung01 Phase 3 trial in which datopotamab deruxtecan demonstrated a statistically significant improvement for the dual primary endpoint of progression-free survival (PFS) compared to docetaxel, the current standard of care, in patients with locally advanced or metastatic NSCLC treated with at least one prior line of therapy. For the dual primary endpoint of overall survival (OS), interim results numerically favoured datopotamab deruxtecan over docetaxel in the overall population; however, results did not reach statistical significance at the time of data cut-off. In patients with nonsquamous NSCLC, datopotamab deruxtecan showed a clinically meaningful PFS benefit and a numerically favourable OS trend. The trial is ongoing and OS will be assessed at final analysis.

Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Sustainability in healthcare
As part of AstraZeneca’s commitment to driving sustainability in healthcare, the Company will work with Singapore’s government and other partners on green solutions for the ADC facility. This facility will be designed to emit zero carbon from its first day of operations.

AstraZeneca aims to begin design and construction of the manufacturing facility by the end of 2024, with targeted operational readiness from 2029.

Clinical trial
Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer With or Without Actionable Genomic Alterations (TROPION-LUNG01) – ClinicalTrials.gov ID NCT04656652

Reference
[1] Chen R, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58.
[2] Majeed U, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14(1):108.
[3] Pircher, A, et al. Docetaxel in the Treatment of Non-small Cell Lung Cancer (NSCLC) – An Observational Study Focusing on Symptom Improvement. Anticancer Research. 2013;33(9):3831-3836.
[4] Mito R, et al. Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol Int. 2020;70(5):287-294.

Featured image by Zhu Hongzhi on Unsplash

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