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The challenges of moving oncology assets between regions

Author: Eva Lymberopoulos, BSc MSc MRes
Theme: Expansion of pharmaceutical assets outside of China
Key Words: Cancer, Clinical Trials, Oncology, ADC, Drug Development, China

Moving pharmaceutical assets between regions e.g. from China to global markets, is exciting but presents unique challenges. At the forefront of precision oncology and immunotherapy are antibody-drug conjugates (ADCs) and bispecific antibodies, offering highly targeted approaches to treat complex diseases. These innovative modalities are transforming the treatment landscape by addressing unmet clinical needs and delivering enhanced efficacy with reduced off-target effects. However, differences in the intra-tumour bacterial composition, genetic predispositions, and environmental factors often result in inconsistent drug efficacy and safety profiles across regions.

At BioCorteX, we are uniquely placed to determine variations in intra tumour bacteria and de-risk clinical trials when deciding to move assets between regions. Our immense knowledge graph, coupled with our innovative Carbon Mirror approach, allows us to test compounds in-silico across different geographical regions. Together with our clinical and scientific expertise, this enables us to understand why differences between regions emerge and devise effective strategies to mitigate these, ensuring treatments achieve their full global potential. 

The problem

Upon a successful (pre)clinical studies, early trial or commercialisation, in or out-licensing to different geographical regions may be an important next step. However, when running a clinical trial with the asset in the new population, results often do not translate. This has been found, for example, for Immune checkpoint Inhibitors (ICIs), a kind of immunotherapy for cancers such as lung, skin, or breast cancer. A 2021 meta-analysis showed that the magnitude of the benefits experienced by ICI therapies differs between Asia, North America, and Europe; with Western patients consistently experiencing improved outcomes (Li et al. 2021).

What we know

Recently, the intra tumour bacteria (both in the tumour microenvironment, as well as intracellularly) has been increasingly recognised for its role in cancer progression and treatment success (Chen et al. 2022). The role of problematic bacteria in the onset and progression of cancers, as well as the response to treatment has been formally recognised as one of the Hallmarks of Cancer (Hanahan 2022). For example, in a recent whitepaper, we have shown significant drug-bacteria interactions in the tumour microenvironment impacting ADC binding.

Importantly, the composition of intra tumour bacteria varies systematically between geographical regions (Lymberopoulos et al. 2021; Gupta, Paul, and Dutta 2017; internal proprietary data) and can therefore significantly alter clinical trial translatability. 

Why do people from different countries have different intra tumour bacteria signatures?

This phenomenon has a variety of reasons. For the gut bacteria, an obvious contributor is regionally-varying diet, as well as hygiene habits, prescription patterns of antibiotics, pesticide use, and wastewater management, among other factors (Govender and Ghai 2025). Bacteria within the tumour is less obvious to explain, however, the mutational profile of the tumour influences the intra tumour bacteria composition (Burns and Blekhman 2018), and it is known that the prevalence of different mutations varies between regions (e.g. in head and neck cancer: Novoplansky et al. 2022).

Why does it matter?

As mentioned above, cancer treatments are known to interact with intra tumour bacteria which affects the response to the treatment. Such effects differ from country to country, making replication of clinical trial success more difficult. For example, our own award-winning research has found that across four oncology trials, there was a significant difference in the drug-bacteria(gut) interactions seen between Japan and the US. Importantly, these differences were directly related to one-year survival, which was reduced in US patients. For pharma companies, such interactions introduce uncertainty, which is exacerbated when moving geographical regions. Ultimately, this uncertainty can lead to potentially huge financial losses and termination of pharmaceutical development of compounds which could work if only given the right target population. If the bacteria-drug interactions can be predicted and accounted for before running a clinical trial in a new population, such risks can be mitigated and seemingly unsuccessful assets potentially saved.

Our value proposition

This is where BioCorteX can help. Not only are we aware of the influence of the intra tumour bacteria, but we can transform this knowledge into executable insights. Our proprietary Carbon Mirror platform models these region-specific variations in the bacteria composition of patients in-silico, optimising clinical trial design for your target populations. We have data across 49 different countries and 28 cancer types, enabling us to serve a variety of global markets and company profiles. We have specific expertise in moving assets from China into global markets.

Contact us for more information on how we can help de-risk your asset!

Bibliography

Burns, Michael B., and Ran Blekhman. 2018. ‘Integrating Tumor Genomics into Studies of the Microbiome in Colorectal Cancer’. Gut Microbes 10 (4): 547–52. https://doi.org/10.1080/19490976.2018.1549421.

Chen, Yan, Fa-Hong Wu, Peng-Qiang Wu, Hong-Yun Xing, and Tao Ma. 2022. ‘The Role of The Tumor Microbiome in Tumor Development and Its Treatment’. Frontiers in Immunology 13. https://www.frontiersin.org/articles/10.3389/fimmu.2022.935846.

Govender, Priyanka, and Meenu Ghai. 2025. ‘Population-Specific Differences in the Human Microbiome: Factors Defining the Diversity’. Gene 933 (January):148923. https://doi.org/10.1016/j.gene.2024.148923.

Gupta, Vinod K., Sandip Paul, and Chitra Dutta. 2017. ‘Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity’. Frontiers in Microbiology 8. https://www.frontiersin.org/articles/10.3389/fmicb.2017.01162.

Hanahan, Douglas. 2022. ‘Hallmarks of Cancer: New Dimensions’. Cancer Discovery 12 (1): 31–46. https://doi.org/10.1158/2159-8290.CD-21-1059.

Helmink, Beth A., M. A. Wadud Khan, Amanda Hermann, Vancheswaran Gopalakrishnan, and Jennifer A. Wargo. 2019. ‘The Microbiome, Cancer, and Cancer Therapy’. Nature Medicine 25 (3): 377–88. https://doi.org/10.1038/s41591-019-0377-7.

Li, Manyu, Jiannan Yao, Huiyun Zhang, Yang Ge, and Guangyu An. 2021. ‘Geographic Heterogeneity in the Outcomes of Patients Receiving Immune Checkpoint Inhibitors for Advanced Solid Tumors: A Meta-Analysis’. Translational Cancer Research 10 (1): 310–26. https://doi.org/10.21037/tcr-20-1800.

Lymberopoulos, Eva, Giorgia Isabella Gentili, Muhannad Alomari, and Nikhil Sharma. 2021. ‘Topological Data Analysis Highlights Novel Geographical Signatures of the Human Gut Microbiome’. Frontiers in Artificial Intelligence 4. https://www.frontiersin.org/articles/10.3389/frai.2021.680564.

Novoplansky, Ofra, Sankar Jagadeeshan, Ohad Regev, Idan Menashe, and Moshe Elkabets. 2022. ‘Worldwide Prevalence and Clinical Characteristics of RAS Mutations in Head and Neck Cancer: A Systematic Review and Meta-Analysis’. Frontiers in Oncology 12 (May):838911. https://doi.org/10.3389/fonc.2022.838911.

Zhao, Lin-Yong, Jia-Xin Mei, Gang Yu, Lei Lei, Wei-Han Zhang, Kai Liu, Xiao-Long Chen, Damian Kołat, Kun Yang, and Jian-Kun Hu. 2023. ‘Role of the Gut Microbiota in Anticancer Therapy: From Molecular Mechanisms to Clinical Applications’. Signal Transduction and Targeted Therapy 8 (1): 1–27. https://doi.org/10.1038/s41392-023-01406-7.

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