Rab Diagnostics presentation at LSX Nordic Congress in Bergen 2025
Rab Diagnostics at LSX Nordic Congress 2025 | Advancing Biomarker Innovation for ADCs
Rewatch Rab Diagnostics’ presentation from the LSX Nordic Congress 2025 in Bergen. In this session, we share how our team is pioneering the next generation of oncology-focused biomarker development to support Antibody-Drug Conjugate (ADC) innovation.
Through our proprietary RabCANCER platform and leading expertise in intracellular drug trafficking, we enable biopharma partners to make smarter, mechanism-driven decisions in drug development. By translating cutting-edge research into robust diagnostic tools and biomarker kits, we help bridge the translational gap, enabling precision medicine.
Headquartered in Oslo, Norway, and built on research from Oslo University Hospital, Rab Diagnostics is committed to scientific excellence and strategic collaboration. Watch this presentation to learn how we’re driving progress in ADC biomarker science and accelerating the delivery of effective, targeted cancer therapies.
Click the video to watch the presentation of Rab Diagnostics at the LSX Nordic Congress in Bergen, May 2025
Recent breakthroughs in ADC biomarkers: Key publications you should know – May, 2025
The following key publications outline our discoveries in the predictive power of RAB-GTPase trafficking biomarkers, with direct implications for ADC design, biomarker strategy, and clinical translation.
RAB5A as a Predictive Biomarker for T-DM1
Demonstrates that RAB5A expression levels predict patient response to T-DM1 across multiple clinical cohorts, introducing endocytosis regulators as clinically actionable biomarkers.
Differential Intracellular Mechanisms of T-DM1 vs. T-DXd
Compares two HER2-targeted ADCs, revealing that linker chemistry and RAB GTPase interactions dictate drug processing and cytotoxicity, independent of HER2 levels alone.
AACR 2025 Poster: Endocytosis as a Broad ADC Biomarker Axis
Extends biomarker validation to lung and breast cancer models, identifying additional Rab GTPases (Rabx) as modulators of T-DXd and SG efficacy, underscoring ADC-specific trafficking dependencies.
These studies form the scientific framework guiding Rab Diagnostics’ translational biomarker development and customized CRO solutions for pharma partners.
RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.
Summary:
This study identifies RAB5A, a marker of early endosomes, as a predictive biomarker for trastuzumab emtansine (T-DM1) efficacy in HER2-positive breast cancer. Both in vitro analyses and patient data from the I-SPY2 and KAMILLA clinical trials revealed that high RAB5A expression correlates with increased T-DM1 sensitivity. Notably, RAB5A combined with HER2 expression provided a more accurate prediction of T-DM1 response than either biomarker alone.
Why It Matters:
This research underscores the importance of intracellular trafficking components in ADC efficacy. For pharmaceutical development, especially ADCs like T-DM1, biomarkers such as RAB5A could refine patient selection, improve therapeutic outcomes, and guide assay development in clinical trials. CROs engaged in biomarker validation and patient stratification strategies should consider incorporating RAB5A assessment in their service offerings.
Citation:
Engebraaten, O., Yau, C., Berg, K., Borgen, E., Garred, Ø., Berstad, M. E. B., Fremstedal, A. S. V., DeMichele, A., van ’t Veer, L., Esserman, L., & Weyergang, A. (2021). RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer. Nature Communications, 12, 6427. https://doi.org/10.1038/s41467-021-26018-z
Link to original article: https://doi.org/10.1038/s41467-021-26018-z
The mechanisms of HER2-targeted ADCs are dependent on Rab GTPases.
Summary:
This study compares the intracellular processing of two HER2-targeted antibody-drug conjugates (ADCs): T-DM1 and T-DXd. While T-DM1 efficacy correlates strongly with HER2 and RAB5A expression, T-DXd efficacy is less dependent on HER2 and more loosely associated with RAB5A. Functional studies reveal distinct trafficking pathways, with T-DXd partly relying on RAB4A. The design of the ADC linker critically influences intracellular routing and cytotoxic efficacy.
Why it matters:
This research provides key insights into how intracellular trafficking components affect ADC performance, with implications for biomarker-guided patient selection and ADC design. For pharmaceutical development, especially in oncology, understanding RAB GTPase dependencies can optimize drug design and inform preclinical validation strategies. The findings are directly relevant to ADC biomarker discovery and companion diagnostic development.
Reference:
Medhus, A., Schink, K. O., Longva, A. S., Engebraaten, O., Berg, K., & Weyergang, A. (2025). The mechanisms of HER2-targeted ADCs are dependent on Rab GTPases. Therapeutic Advances in Medical Oncology, 17, 1–17. https://doi.org/10.1177/17588359251332473
Link to original article: https://doi.org/10.1177/17588359251332473
Posters:
Rab GTPases Drive HER2-Targeted ADC Efficacy: Insights from Comparative Cell Line Analysis
Summary
This study compares two HER2-targeting antibody-drug conjugates (ADCs)—T-DM1 and T-DXd—in HER2-positive breast cancer cell lines. While T-DM1 efficacy correlates with HER2 expression, T-DXd does not. Instead, both ADCs show stronger dependency on the early endosomal regulator RAB5A for cytotoxic efficacy. Knockdown and overexpression experiments confirm the differential trafficking and linker cleavage dependencies of the two ADCs.
Why it matters
The findings highlight the importance of intracellular trafficking, particularly Rab GTPase activity, in determining ADC effectiveness. For pharmaceutical developers, this underscores the need to consider not only antigen expression but also endosomal pathway components like RAB5A in biomarker discovery, ADC design, and patient stratification in clinical trials.
Reference
Medhus, A., Schink, K. O., Longva, A. S., Engebraaten, O., Berg, K., & Weyergang, A. (2025). The mechanisms of HER2-targeted ADCs are dependent on Rab GTPases [Conference presentation]. AACR Annual Meeting 2025.
Link to poster abstract:
View AACR Poster 3307 (search “Weyergang 3307” on the AACR portal)
Utilizing endocytosis as a predictive biomarker for ADCs
Summary
This study presents compelling preclinical and clinical data supporting Rab GTPases—specifically Rab5A and Rabx family members—as predictive biomarkers for the efficacy of antibody-drug conjugates (ADCs) such as T-DM1, T-DXd, and Sacituzumab Govitecan. Rab5A expression correlated with T-DM1 response across three clinical cohorts, while Rabx influenced the cytotoxic effectiveness of T-DXd and SG in breast and lung cancer cell lines. Knockdown experiments confirmed reduced ADC sensitivity when Rab GTPase levels were suppressed.
Why it matters
Identifying reliable biomarkers is critical to precision oncology. These findings emphasize that ADC response is not solely driven by target antigen expression but also by the intracellular trafficking capacity governed by Rab GTPases. For pharma and biotech developers, incorporating Rab GTPase profiling could enhance patient selection, optimize ADC design, and refine clinical trial stratification strategies.
Link to poster abstract
View AACR Poster 3104 (search “Medhus 3104” on the AACR portal)
The mechanisms of HER2 targeted ADCs are dependent on Rab GTPases
What if the key to ADC efficacy lies not in the target, but in the cell’s trafficking machinery?
In recent publication by Medhus co-authored by founders of Rab Diagnostics Anette Weyergang, Olav Engebraaten and Kristian Berg, the study shows that the mechanisms of HER2-targeted ADCs T-DM1 and T-DXd depend heavily on Rab GTPase-regulated trafficking, not just HER2 expression.
Key Findings:
T-DM1 efficacy strongly correlates with HER2 + RAB5A expression.
T-DXd efficacy depends primarily on RAB5A, independent of HER2 levels.
Linker design dictates whether payload release requires full lysosomal trafficking (T-DM1) or occurs earlier (T-DXd).
Bystander killing is crucial for T-DXd effectiveness in HER2-low settings.
Impact:
✅ Intracellular trafficking pathways should be studied during development of ADCs
✅ RAB5A emerges as a predictive biomarker for the efficacy of two different HER2-targeted ADCs.
✅ Tailoring ADC design to trafficking mechanism could enhance clinical outcomes.
Read the article here:
https://journals.sagepub.com/doi/epub/10.1177/17588359251332473
The quality behind Rab Diagnostics pharma services
Improved Precision for ADCs
Backed by world class peer-reviewed research, including recent findings published in Nature Communications, our team brings deep expertise in intracellular trafficking, biomarker development, and ADC mechanism-of-action studies.
We deliver:
• In vitro cell based models
• Gene/Protein expression analysis for Rab GTPases
• Endosomal trafficking and payload release studies
• Biomarker identification
As a trusted partner, we operate as an agile extension of your team, helping you de-risk development and accelerate progress.
At Rab Diagnostics, scientific rigor and quality is not just a principle, it’s the foundation of everything we do. Our R&D services are tailored for biopharmaceutical innovators seeking to understand the cellular processing of their antibody-drug conjugates (ADCs) and the impact on efficacy.
Science-Driven, Biomarker-Focused
Our research is anchored in peer-reviewed, published science from world leading cancer research at Oslo University Hospital, including our recent study in Nature Communications , which demonstrates how Rab GTPases regulate the intracellular trafficking and efficacy of HER2-targeted ADCs. This work reflects our unique expertise in cell biology, trafficking pathways, and predictive biomarkers.
Precision Meets Reliability
Whether you wish insights into Rab-GTPase effect on your lead ADC, biomarker discovery and validation, or custom assay development, our in-house team combines deep domain knowledge with robust experimental design and verified setup. We understand the high stakes of translational research and deliver data you can act on with confidence.
Trusted by Biotech Innovators
We operate as an extension of your R&D team, offering transparent collaborations that move your ADC forward faster and smarter. We design the studies and setup in close dialogue with our sponsors and ensure frequent updates and communication during studies. From early discovery, preclinical validation and retrospective expression studies on clinical samples, our services are tailored to meet the specific challenges of developing targeted ADCs for oncology.
Your Partner in Predictive ADC Science
Rab Diagnostics is more than a service provider, we are your strategic partner in precision oncology development. If your team is advancing ADCs, grounded in mechanistic insight, we’re here to help.
Explore our R&D services at www.rabdiagnostics.com or contact us directly to start a conversation.