Welcome to CDMF Bioconsulting

Discover how we can help pharmaceutical companies and contract research organisations with biomarker strategy and expertise.

Purpose

Many drugs have cured cancer in mice, yet failed to show efficacy in clinical trials. With the understanding that every cancer is different and every patient is different, the future of cancer treatment relies on precision medicine. CDMF Bioconsulting services are founded on the experience with advanced biomarker research, including planning, collection, testing, and interpretation.

 

CDMF Bioconsulting provides deep insights into predictive biomarkers helping your company understanding which patient population responds to the drug, and mechanistic biomarkers verifying how your drug is operating at the cellular and molecular levels.

Keytruda: how a good biomarker strategy results in a 20 billion dollars per year revenue

Pembrolizumab is one of the most sold drugs in the world. But do you know that this drug owes its success to a wise biomarker strategy?!

In many indications, Pembrolizumab alone did not show superiority compared to standard of care in the total patient population tested. As an example, the Keynote 48 Phase III trial (Burtness et al, Lancet 2019) evaluated the efficacy of Pembrolizumab versus Cetuximab+chemotherapy (Standard of care) as first line treatment for patients with recurrent/metastatic Head and Neck cancers. As indicated in the figure below, there was no survival benefit for the Pembrolizumab alone group in the total population.

However, retrospective biomarker analyses from previous Phase II trials suggested that patients with tumors positive for PDL1 demonstrated a better response to Pembrolizumab. Therefore, several sub-population analyses were prospectively included by Merck in their Keynote 48 trial, which proved to be a very wise choice: in patients with PDL1 CPS ≥ 1, Pembrolizumab alone increases the overall survival compared to Cetuximab + chemotherapy. This is one example of how a good biomarker strategy could lead to drug approval.

Full biomarker services during clinical development

During IND preparation

 ▪ Define biomarker tests to be performed during the clinical trial based on preclinical data and available literature.

 ▪ Align with clinical team for: a) implementation of biomarker testing in clinical trial protocol including schedule of assessments (SoA), and b) drafting of the informed consent form (ICF).

▪ Identify a central laboratory and design collection kits, operational specific document (OSD) and lab manual for biomarker collection.

▪ Identify technology platforms and CROs (for tests not performed in-house) that support biomarker assays and fall within a pre-specified budget (negotiated/competitive CRO price through CDMF Bioconsulting).

▪ Guide development of techniques with in-house researchers or CROs to specify material and methods of testing and review assay development results until validation of the tests.

During clinical trial

▪ Analyze and interpret biomarker assays: at the patient level:
    - by responder and non-responder criteria for ORR
    - by disease control (PR, CR, SD patients) an non-disease control (PD patients) criteria for ORR
    - by progression free survival
   - by overall survival (and any other outcome important for particular studies)

 ▪ Define predictive biomarkers for response to treatment using AI/machine learning strategies and multimodal analysis.

 ▪ Inform on the pharmacodynamic activity / validate mechanism of action of the drug in patients.

 ▪ Identify biomarkers linked to safety/ adverse events.

Mid-Trial, Interim Analysis, and End Trial

▪ Implement biomarker testing and prioritize assays to align with clinical outcome and budget.

▪ Quality Assessments: contribute subject matter expertise for quality events and protocol deviations related to biomarker studies in the clinical protocols.

▪ Engage with specialized clinical sites including staff PI and pathologists regarding the biomarker activities.

▪ Contribute to clinical protocol amendments as well as OSD and lab manual amendments/updates as needed.

▪ Coordinate with clinical operations team for operational aspects of biomarker activities including answering questions, providing guidance, and sample transfer from sites to central lab.

▪ Coordinate with clinical operations team and data management team for sample reconciliation (missing samples from sites and/or central lab).

Post Trial

▪ Contribute to sections of the CSR that require biomarker results.

▪ Define biomarker-based grouping and threshold to implement subgroup stratification or biomarker-based enrollment in future clinical trials.

▪ Biomarker-based enrollment of patients in future clinical trials: help with companion diagnostic design and development including identification of CROs that will develop the diagnostic kit, specification of the material and methods for testing, and review of assay development results until validation of the kit.

▪ For future all-comers clinical trials with stratification option: coordinate with the biostatistical team the implementation of subgroup analysis in the protocol with the aim to show efficacy of the drug in specific patients and potentially make the clinical trial successful in the circumstance where the trial would not demonstrate benefit to all comers.

Biomarker assay expertise

Whole exome sequencing

  • Knowing the precise mutational landscape for each patient can reveal that the drug is more efficacious in patients harboring specific mutations or sets of mutations.

  • Below $200 per sample*


    *indicative price, please consult for detailed pricing

RNA sequencing

  • RNA sequencing performed on whole tumor, on a subset of cells (cancer cells, CD8 T cells, NK cells…) can reveal that specific signalling pathways are involved in the response of patients to your drug. They can also inform/verify the effect your drugs is having on specific cell types.

  • Below $200 per sample*


    *indicative price, please consult for detailed pricing

TCR sequencing

  • Interindividual variability in the TCR repertoire (abundance and diversity of T cell clones) has been shown to influence the response to drugs. Exploring these parameters by TCR-sequencing could provide you with insights on specific responding populations as well as with the mechanism of action of your drug.

  • Below $300 per sample*


    *indicative price, please consult for detailed pricing

BCR sequencing

  • Interindividual variability in the BCR repertoire (abundance and diversity of B cell clones) has been shown to influence the response to drugs. Exploring these parameters by BCR-sequencing could provide you with insights on specific responding populations as well as with the mechanism of action of your drug.

  • Below $300 per sample*

    *indicative price, please consult for detailed pricing

Flow cytometry

  • A comprehensive characterization of the peripheral immune cells and their subsets can reveal specific immune populations involved in the response of patients to your drug. They can also inform/verify the immune response achieved by your drug .

  • Below $1500 per sample for a comprehensive characterization of the immune system (more than 150 cell types/subsets)*


    *indicative price, please consult for detailed pricing

Multiplex IHC

  • Multiplex IHC allows the spatial characterization of the tumor microenvironment (TME) by specifically assessing immune, stromal and tumor cell subsets. These have been linked to patient response to drugs and can also inform you on the effect of your drug on that TME.

  • TBD depending on the extent of the characterization you are seeking.

Multibiomarker analysis by AI/ML

  • Tumor biology is complex and a set of biomarkers usually predict with way more sensitivity and specificity which patients will respond to a drug.

    Once all the biomarker assays have been performed, Artificial intelligence/Machine learning (AI/ML) will identify the best set of biomarkers to use for patient response along with a specific scoring and cut-off for patient response. AI/ML can also identify specific patient population demographics responding to your drug.

About

Daniel De Magalhaes Filho is the founder of CDMF Bioconsulting. Daniel is a PhD immuno-oncologist researcher with 20 years of research experience including 6 years of industry experience.

As a consultant Daniel is helping pharmaceutical companies and CROs mainly with precision medicine and biomarker strategy but also with clinical and preclinical development.

Previously as a Principal Scientist at Rakuten Medical, his research focused on two areas. The first one related to biomarkers and understanding the mechanism of action of the drug in patients, including the discovery of predictive biomarkers. Working with several other members of the team as well as with external collaborators and CROs, Daniel uncovered two sets of biomarkers that might predict which patients would benefit from the drug. He also led the overall biomarker strategy, from clinical protocol implementation to analysis, in four additional clinical trials.

The second aspect of his research at Rakuten Medical involved preclinical models, where he characterized the immunological cell death induced by photoimmunotherapy, led the preclinical development of a new drug, and collaborated on various projects driven by other members of the translational sciences team.

Prior to his tenure at Rakuten Medical, Daniel worked in the JLABS San Diego incubator for Epicentrx, a startup company developing oncolytic virus. There he was also involved heavily with biomarkers and preclinical research, characterizing immunological response of patients treated with Epicentrx oncolytic virus, and engineering in vitro and in vivo oncolytic virus strains armed with immunomodulators.

Daniel obtained his PhD in physiology and physiopathology from Paris VI University (Paris, France) and completed his postdoctoral studies at the Salk Institute in San Diego, first in Andy Dillin lab, and then in Ron Evans lab. At the Salk Institute, he worked on several projects related to aging, cancer, immunology, metabolism and neurodegenerative diseases. His academic and industry work resulted in 15 peer reviewed publications including in Cell, Cell Reports, and Nature Communications. As he transitioned to the pharmaceutical industry, Daniel also obtained an MBA focused on how to start a scientific company.

Contact

Contact me to discuss your biomarker strategy and how CDMF Bioconsulting can provide expertise and solutions tailored to pharmaceutical companies and CROs. I will guide you to choose the best biomarker strategies and assays.