EPO Newsletter

Expanding Antibody-Drug Conjugate (ADC) Offerings at EPO
EPO has played a key role in several recent developments in ADC research, including validating the efficacy of mesothelin-targeting ADCs in our Patient-Derived Xenograft (PDX) models for ovarian cancer and mesothelioma.

Our PDX models have also shown enhanced efficacy when ADCs were combined with Standard-of-Care (SoC) chemotherapy, revealing key insights into ADC targeting and internalization, and offering promising new strategies to address tumor resistance mechanisms.

Lung Cancer Breakthroughs and Collaborations
EPO has identified PDX models demonstrating potent antitumor efficacy by achieving selective tumor shrinkage in CAIX-overexpressing tumors, particularly within squamous cell carcinoma (SCC) subtypes.

We also evaluated treatment with multiple toxic agents, including auristatin-based ADCs targeting C4.4A in Non-Small Cell Lung Cancer (NSCLC), which showed robust efficacy comparable to SoC treatments.

“Methodology” Spotlight on IncuCyte for in vitro ADCs
We are leveraging IncuCyte technology to generate in vitro ADC data for validation of ADC effectiveness in tumor-targeting and for providing insights into drug efficacy and resistance mechanisms.

Overcoming Drug Resistance in Triple-Negative Breast Cancer (TNBC)
In our EGFR-resistant PDX models, treatment with EGFR-targeting ADCs improved tumor reduction and extended survival, offering new hope in overcoming the treatment challenges of TNBC.

Similarly, our HER2-overexpressing breast cancer PDX models treated with combination ADC and SoC chemotherapy showed enhanced preclinical outcomes, highlighting ADC´s potential as a promising treatment for patients with HER2-positive cancers.

Highlighting Recent Publications:

• Molecular Cancer Therapeutics, 2014: Detailed characterization of mesothelin-targeting ADC for treating mesothelin-expressing tumors (mesothelioma, ovarian, and pancreatic).
• Molecular Cancer Therapeutics, 2011: Study on CAIX-targeting ADC, showing significant tumor reduction in CAIX-overexpressing cancers.
• Molecular Cancer Therapeutics, 2017: Research on C4.4A-targeting ADC, highlighting its efficacy in squamous cell carcinoma subtypes.
• Oncotarget, 2018: Mesothelin-targeting ADC shows potent antitumor activity in mesothelin-expressing ovarian cancer models, both as monotherapy and in combination with standard treatments.
• Journal of Experimental Cancer Research, 2023 (Paper 5): Study on the efficacy of HER2-targeting ADCs in HER2-positive breast cancer, revealing enhanced outcomes in combination therapies.
• Nature Cancer, 2023 (Paper 6): Research on EGFR-targeting ADCs in triple-negative breast cancer, providing new hope for overcoming drug resistance.

Our colleague Turn on Javascript! is attending this year’s ADC Conference and will be in San Diego (Nov 4–7) and San Francisco (Nov 7–8); reach out to arrange an in-person meeting or video call.

For more information, contact Turn on Javascript! to discuss how we can accelerate development of your therapeutic ADC.

Best regards,
Jens Hoffmann & Wolfgang Walther
CEO & CSO at EPO Berlin-Buch

With detailed data on chemosensitivity, we can provide models that are either sensitive or resistant to standard-of-care (SoC) drugs, allowing for innovative testing of resistance strategies.

Genomic Insights
We offer integration of chemosensitivity data with RNA sequencing and mutation datasets, available on request. This allows for deeper understanding of drug response and resistance mechanisms to improve research precision.

Induced Resistance Models
EPO has developed select PDX models with induced resistance to drugs like doxorubicin, vincristine, and cetuximab. These models are fully characterized to help identify resistance pathways and new therapeutic approaches.

Highlighting Recent Publications
One notable recent study in the Journal of Controlled Release was co-authored by our team members Dr. Diana Behrens and Prof. Wolfgang Walther. This research demonstrates the efficacy of paclitaxel-loaded polymeric micelles in treating triple-negative breast cancer (TNBC) using our paclitaxel-resistant PDX models.

We also share below recent publications that highlight the value of our PDX models in advancing drug resistance research:

Cancers, 2023: Development of pancreatic cancer PDX models for molecular analyses and chemosensitivity testing.

Frontiers in Oncology, 2023: Insights into glioblastoma PDX models and temozolomide resistance.

Molecular Cancer, 2021: Predictive molecular signatures in colorectal cancer PDX models for personalized treatments.

For more information, contact Turn on Javascript! or Turn on Javascript! to discuss how we can accelerate your therapeutic oncology development.

Best regards,
Jens Hoffmann & Wolfgang Walther
CEO & CSO at EPO Berlin-Buch

Our expertise extends to the development of orthotopic models that accurately replicate the metastatic process in vivo. These models not only metastasize in a manner consistent with human disease but can also be rigorously analyzed using PCR to track human cells, complemented by detailed histological examinations (POSTER). These capabilities have already been successfully applied to helping our partners with compound development.

In addition to our extensive PDX platform, we are pioneering the development of Invasive Lobular Carcinoma (ILC) models in collaboration with an academic partner. These rare models will become available to our clients in the long run.

Our commitment to innovation and precision in breast cancer research positions us as a key partner for advancing your therapeutic projects. Whether you are focused on TNBC, metastasis, or rare subtypes like ILC, our models and expertise are designed to support your goals and accelerate the development of new cancer treatments.

If you woud like to discuss your project and plans, please contact our subject matter expert, Turn on Javascript!, directly.

Best wishes,

Jens Hoffmann & Wolfgang Walther

CEO & CSO at EPO Berlin-Buch

Key topics include implementing state-of-the-art, reproducible and predictive oncology models to enhance target selection, facilitate biomarker discovery and facilitate clinical translatability.

Come by our booth and meet our CEO Jens Hoffmann and our colleague Joseph Herbert for an expert chat. We would also like to take this opportunity to welcome Joseph Herbert as our new Business Development colleague for the US. Joe brings a wealth of experience to the role, and we are thrilled to have him supporting our US clients. Please feel free to schedule a meeting with Joe and Jens in advance via this Turn on Javascript!.

We look forward to seeing you soon in Boston!

Best wishes,

Jens Hoffmann & Wolfgang Walther
CEO & CSO at EPO

12th Tumor Model Summit Boston

July 23-24, 2024

The Westin Boston Seaport District
425 Summer Street
Boston, MA 02210

ITCC-P4, a non-profit initiative, is passionately committed to a future free from childhood cancer. It provides the world’s most extensive collection of freshly patient-derived pediatric tumor models, enriched with comprehensive molecular and pharmacological data. This empowers advanced preclinical cancer research, crucial for meeting FDA guidelines in the approval of novel pediatric oncology drugs. https://itccp4.com/

By blending EPO’s scientific expertise with the knowledge of ITCC-P4’s globally recognized academic disease-experts, we strive to deliver excellent services to elevate your drug programs.

We are also delighted to announce steady progress in our pediatric research initiatives, with two new publications offering insights into pediatric cancer mechanisms and drug responses.

In a collaborative approach we have demonstrated that elimusertib shows potent preclinical antitumor activity in pediatric solid tumor models, potentially leading to significant clinical responses in patients. https://pubmed.ncbi.nlm.nih.gov/36753540/

Another publication highlights the RAS pathway as a promising therapeutic target for alveolar rhabdomyosarcoma (aRMS), a group of pediatric cancers with skeletal muscle characteristics. https://pubmed.ncbi.nlm.nih.gov/38159110/

We’re excited to harness our scientific expertise alongside leading pediatricians to elevate your drug programs. Please reach out directly to our subject matter expert Turn on Javascript! for any queries or to discuss your project.

Best regards,

Jens Hoffmann & Wolfgang Walther

CEO & CSO at EPO Berlin-Buch

Brain Tumor Meeting 2024

At the meeting, EPO will report on its thoroughly characterized glioblastoma (GBM) PDX models and the establishment of a new panel of matching GBM PDX-derived glioma cell lines. These PDX-derived cell lines show individual cell morphologies and growth pattern, as well as expression of established cancer stem cell markers.

By establishing and continously expanding our in vitro/in vivo GBM pipeline, EPO is able to perform rapid in vitro sensitivity screenings in association with selection of suited models for subsequent in vivo studies as valuable tool for accelerated drug development. We are excited to continue leveraging our capabilites and scientific expertise in the GBM space to our clients, providing the best possible service to enhance your drug programs.

Please connect directly with our subject matter expert Turn on Javascript! to discuss your project. Additionally, we invite you to explore our comprehensive overview poster providing a detailed glimpse into our GBM expertise. (POSTER LINK)

Best wishes,

Jens Hoffmann & Wolfgang Walther

CEO & CSO at EPO Berlin-Buch

Afterwards, we invite you to enjoy delicious burgers, wine and crafted beer and to connect with us and colleagues.

As space is limited, please sign up with Turn on Javascript!

We also proudly present our brand new scientific developments during the poster sessions. Stop by and chat with our experts about your drug development plans and how our preclinical tumor models and expertise can help advance your program.

Poster #2048

Title: Integrated tumor models for immune oncology using live cell imaging for prediction of treatment efficacy in vitro and in vivo

Poster Section on 28, Poster Board 5 presented on Monday Apr 8, 9:00 AM - 12:30 PM

Poster #2836

Title: Assessment of therapeutic antibody efficacy without the interference of murine Fc receptors allows for investigation of human antibody-dependent cellular cytotoxicity mediated by NK cells in the FcResolv™ hIL-15 NOG mouse model

Poster Section 10, Poster Board 23 presented on Monday Apr 8, 1:30 PM - 5:00 PM

Poster #5334

Title: Humanization of NOG mice and next-generation NOG strains to induce lineage-specific differentiation of immune cells for assessment of novel immune cell therapies, check point inhibitors, and immune cell engagers for translational immuno-oncology research

Poster Section 4, Poster Board 14 presented on Tuesday Apr 9, 1:30 PM - 5:00 PM

We look forward to seeing you during the reception and our poster session!

Best wishes,

Jens Hoffmann & Wolfgang Walther

CEO & CSO at EPO

The project's focus is on the development of T cell receptor (TCR)-T therapies for solid tumors, specifically targeting Pancreatic Ductal Adenocarcinoma, Colorectal Carcinoma, and Breast Cancer. The collaborative effort aims to identify therapeutic TCR’s from patients, ultimately leading to the establishment of both personalized and off-the-shelf TCR-T cell therapies.

EPO Berlin-Buch contributes with its extensive expertise in preclinical evaluation of novel cell and immune therapies for cancer patients. This multi-faceted collaboration holds promise for advancing research and contributing to the development of innovative and effective treatment options for individuals with these challenging types of cancers.

... with clinical partners from Germany and Italy. By this, 45 PC‑PDX models were generated, which in the majority represent ductal adenocarcinomas (PDAC). The mutational profile of the PDXs, the sensitivity of the models toward standard of care (SoC) drugs gemcitabine, 5-fluorouracil, oxaliplatin, and abraxane, and combinations thereof were analyzed and correlated to the their molecular profile. This was done to reveal potential signatures for response or resistance of the PDAC PDX models to the drug treatments. In conclusion, this published study strongly supports the importance and value of PDX models for improvement of therapies of PC and offers new options for pre-clinical testing of more effective therapies to treat PC. (Weblink)

on computational and functional analyses, which have used the CRC PDX of the oncotrack initiative, to which EPO has contributed a significant panel of CRC PDX models. The study identifies IGF2BP2 as most abundant in CRC, being associated with chemoresistance and which in conclusion represents a potential therapeutic target. The study supports the great value of CRC PDX pre-clinical models to reveal novel mechanisms of chemoresistance and to design new therapeutic resistance overcoming strategies for CRC. (Weblink)

EPO has just recently published a new study on molecular characterization and chemosensitivity testing of its established glioblastoma (GBM) PDX model panel in the journal Frontiers Oncology. Highlights of this study include:

• A panel of 26 patient-derived subcutaneous xenograft (PDX) GBM models was established and screened in immunodeficient mice, providing a valuable platform for studying GBM biology.
  
• Sensitivity to a drug panel with different modes of action was determined, revealing the best treatment responses for temozolomide (standard of care), irinotecan, and bevacizumab.
  
• Intracranial models, which mimic the tumor microenvironment in the brain, showed reduced drug sensitivity due to the blood-brain barrier limiting drug penetration to the tumor.

These findings provide significant insights into the heterogenous and complex biology of GBMs and offer a promising avenue for developing targeted therapies. Further research on molecular markers and drug optimization using this platform can pave the way for improved treatment options for GBM patients.

Read study

analyses of these models and their response toward drug treatment as well as correlation analyses on drug responsiveness and molecular profiles are presented. This publication demonstrates the value of such PDX models for pre-clinical testing to identify new therapeutic targets, molecular signatures and to evaluate novel therapeutic approaches.

Consulting and published in Communications Biology (Gürgen D et al., Comm Biol 5:59; 2022). Detailed molecular analyses of the NSCLC PDX signaling networks enabled identification of intervention points to more effectively prevent the development of drug resistance of these tumors. Based on this, treatment of EPO’s NSCLC PDXs with a combination of cabozantinib, afatinib, plerixafor and etoricoxib resulted in efficient overcoming of resistance for these tumors and an improved therapeutic outcome. This study is an excellent example that molecular data sets of PDX models can be used effectively for design and testing of novel therapy concepts.

Dear Colleagues,

Unfortunately, the pandemic situation has just once again prevented us from attending the AACR meeting in person and has forced us to cancel our on-site poster presentations.

After a break of more than 3 years due to the pandemic, we were very much looking forward to meeting you again in person at this year's AACR and to share the latest developments on preclinical tumor models at the posters.

If you are attending the AACR, we look forward to a lively online poster discussion with you via the "AACR Annual Meeting 2022: E-Poster" webpage.

For those not attending the meeting, we are sending the link to our posters here:

Poster#1: Humanized mouse models for ...

Poster#2: Breaking the crosstalk of ...

Please contact us with any question: Turn on Javascript!

Best Regards

Jens Hoffmann

CEO