Evaluation of candidate-biomarkers predictive of therapy response or resistance using digital PCR on plasma-derived cell-free DNA

Servier is a French pharmaceutical group and key-player in oncology. For their LONSURF pipeline, they have initiated a phase I dose escalation study with the exploratory objective to evaluate biomarkers that may predict response and resistance to LONSURF in combination therapy. To this end, Biogazelle used digital PCR to quantify cancer gene mutations in patient plasma samples.

The analyses were preceeded by custom assay and method validation for the mutations of interest, introducing extensive quality control of the experimental procedures. The successful relationship between Biogazelle and Servier will be continued through mutation testing in the frame of an ongoing phase IIa clinical trial, also with the aim to evaluate biomarkers predictive of response and resistance to LONSURF in combination therapy.

"We are very satisfied with how this project is managed at Biogazelle. The project managers at Biogazelle again show off their high level of expertise and open communication. As this project is running well, we are keen on working with Biogazelle on future clinical projects"

- dr. Brian Lockhart, Director of Biotechnology, Servier, France

Development of a non-invasive diagnostic microRNA test for endometriosis

Endometriosis is an estrogen-dependent disease that results in pelvic pain and infertility. It is histologically characterized by the displacement of endometrial tissue to extrauterine locations. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7-11 years from onset of symptoms to definitive diagnosis. Unfortunately, this delay in diagnosis may have significant consequences in terms of disease progression.

The team of prof. D’Hooghe at KU Leuven prioritized the discovery of a sensitive and specific microRNA biomarker for the nonsurgical detection of endometriosis. To this end, they called upon Biogazelle's biomarker development program. The performance of the resulting miRNA signatures was successfully confirmed in an independent patient cohort. These promising results warrant the further development of this non-invasive diagnostic test for clinical implementation, leading to earlier diagnosis and preventing disease progression to advanced stages.

"We decided to collaborate with Biogazelle because of their comprehensive expertise in miRNA expression analysis. Based on suggestions and recommendations from Biogazelle's experts we fine-tuned our project on miRNA biomarker discovery. The entire project proceeded as expected, in a pleasant cooperation and we could easily ask for advice and support with troubleshooting."

- dr. Arne Vanhie, Department of Obstetrics and Gynaecology, KULeuven, Belgium

RNA-based biomarker to determine biological response

The Belgian biotech company argenx is currently running a clinical trial of ARGX-110, a first-in-class SIMPLE antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, solid tumors and severe autoimmune diseases.

To determine the biological response to ARGX-110, Biogazelle has developed and validated an RT-qPCR-based test for accurate and sensitive CD70 mRNA measurement on whole blood. Measurement of this RNA biomarker on samples coming from their clinical study (currently in phase 2a) is also performed at Biogazelle.

"argenx is a clinical stage human monoclonal antibody therapeutics company. Our business model relies on outsourcing and Biogazelle is our outsourcing partner to set-up and perform mRNA analyses in both the pre-clinical and clinical phases of our running projects.
We selected Biogazelle because they have a decade of experience in real-time PCR experiment design, assay development and data-analysis. The scientific support by Biogazelle's project manager has been outstanding. I would recommend Biogazelle as a solid service provider with a highly professional and personal approach."

- dr. Karen Silence, Project Manager ARGX-110, argenx, Belgium

RNA-based diagnostic test for MS patient stratification

GeNeuro has developed the antibody GNbAC1 as therapeutic in Multiple Sclerosis (MS), and a Phase IIb study is currently running. geNeuro wanted Biogazelle to develop an RNA-based test to stratify MS patients that will likely benefit from a treatment with GNbAC1.

To this end, Biogazelle is currently validating an RT-qPCR based method for accurate measurement of MSRV-Env (Multiple Sclerosis associated retrovirus envelope protein) in peripheral blood mononuclear cells (PBMCs). Pending successful development of the method, Biogazelle will perform the MSRV-Env RNA quantification of the phase 2 and phase 3 clinical trial samples.

Development of PrimePCR qPCR assay portfolio

Biogazelle developed the most comprehensive portfolio of validated Research Use Only (RUO) qPCR assays for human, mouse, rat. The assays are commercialized by Bio-Rad under the PrimePCR brand. Assay development was performed using our primerXL pipeline incorporating state-of-the-art in silico assay validation. All qPCR assays were wet lab validated (including deep amplicon sequencing to confirm specificity) and come with a validation report.

The PrimePCR catalog currently contains more than 312 000 assays, including in silico validated assays for 10 additional model organisms. As the collaboration with Bio-Rad continues, the PrimePCR catalog will be further expanded with RT-qPCR assays for 60,000 human lncRNAs.

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