Chris Ladel, PhD Merck Healthcare KGaA, Darmstadt Germany

1. Christoph Ladel
PhD
Merck Biopharma KGaA, Darmstadt, Germany
Disclosure Information
I have financial relationship(s) with:
Shareholder of Merck KGaA, Darmstadt, Germany
And employee of Merck Biopharma KGaA, Darmstadt, Germany
AND
My presentation does not include discussion of off-label or investigational use.

2. An industry point of view for
building a translational team
Chris Ladel, PhD
Merck Healthcare KGaA, Darmstadt Germany

3. Elements of Translational Medicine
Dolgos et al. Drug Disc Today 2016

4. Translational Assumptions and Risks
Available model
Non Available model
Translatable
Non Translatable
Unknown or not accessible
PK profile
PK in animals
If available incl. PD marker
Proximal Biomarkers
Distal Biomarkers
Disease Models
- Mouse DMM (histology)
- Rat ACLT or MMT (histology
and/or pain/gait disturbance)
- Human OA cartilage explants
- Chondrocyte cultures
Preclinical models Humans
Proximal Biomarkers
Distal biomarkers
Clinical Endpoint
- Imaging MRI/X-ray
- WOMAC; VAS; NRS etc
Translational
work
PK profile
Healthy
OA patients
Catwalk gait analyis

5. 5
Biomarker Status Quo: Where do we stand in OA
overall and what are we doing to fill the gaps?
Biomarker Type* OA community/OA compound data in
public domain
Collaborations with industry* as partner to address BM topics
Pharmacodynamic Biomarkers
(Target occupancy/ engagement,
Proximal and Distal BM)

• StepUpOA: proteomics in synovial fluid
Susceptibility/Risk Biomarkers
Prognostic Biomarkers
 Imaging, wet biomarker
• FNIH/OARSI PROGRESS: retrospective analysis of several RCT, imaging
and wet biomarkers
• IMI APPROACH: machine learning to define phenotypes, prospective
selected OA cohort, imaging and wet biomarkers, proteomics,
metabolonomics, epigentics
Diagnostic Biomarkers
Monitoring Biomarkers
 Imaging, no wet biomarker
• FNIH/OARSI PROGRESS
• IMI APPROACH
• OARSI initiative OA endotypes: definition of endotypes based on
literature and neuronal networks
Predictive Biomarkers Compound specific
Surrogate Endpoints • FNIH/OARSI PROGRESS: Major focus on imaging
Safety Biomarkers

• OARSI/OMERACT: definition of clinically relevant markers
* Terminology aligned with BeST ** industry involved: GSK, Pfizer, AbbVie, Servier, Samumed, Invossa, Astrazeneca, UCB

6. 6
OA deep dive – October 29th 2018
CONFIDENTIAL

7. Chris Ladel
PhD
Merck Biopharma KGaA, Darmstadt, Germany
Christoph.Ladel@Merckgroup.com
Contact Information