Drug Discovery Services
Clinical trials for Investigational New Drugs (IND) are perhaps the biggest cost associated with drug development. And yet, up to 90% of all INDs fail at some phase in clinical trials. This is mainly attributable to the fact that most IND research and development is done in animal models and cell culture. The translation of efficacy, clinical safety and toxicology data to humans is not assured.
The ReproCELL Group has ready access to live human tissues through our extensive clinical networks, in addition to human iPSC-derived 3D cell model systems to create custom assays that can provide predictive human data to de-risk your drug discovery programs. No other company has this unique combination of expertise and capabilities.
We help our clients manage risk and save money
Demonstrating human efficacy and safety at an early stage of development has an enormous commercial value to our clients’ research programs. For 10-20% of the drugs we have tested, the client decided to rethink their clinical strategy which seemed likely to fail based on the human tissue data. We estimate that this has resulted in net savings of more than $55 billion in total costs for our clients.
1. TARGET IDENTIFICATION
Determine the biological origin of the disease and potential targets for intervention using human tissue samples. Investigate receptor sites on particular cells that may be abberantly expressed in the disease state.
The BioServe Global Human BioRepository
BioServe’s Global BioRepository is one of the largest commercial human tissue banks in the world.
All samples are linked to approximately 200 data points about demographic, phenotypic, pathology and diagnostic information and drug history.
|We have it…||Our network has it…||Or, we can collect it|
Our BioRepository contains more than 600,000 human serum, frozen tissue, DNA, RNA, FFPE and other samples collected from over 120,000 consented and anonymized patients on four continents.
The BioServe Biospecimen Repository Network of partner organizations also provides broader access to rare samples and the ability to source material specific to your research needs through prospective collections.
BioServe continues to establish procurement partnerships with speciality clinics around the USA in a number of indications/ diseases, including autoimmune, inflammatory and rheumatology, urology and oncology.
2. TARGET VALIDATION
Investigate the target’s potential as a drug using fresh patient tissue or patient-specific iPSC-derived disease model cells.
Assess the Efficacy of Your Drug Candidate in Diseased and Healthy Tissue
- Compare activation of potential target and functional response.
- Explore differences in drug response between patients and relate responses to clinical histories.
|COPD lung||Healthy lung|
Patient-specific iPS Cell generation service
Custom iPSCs can be created by reprogramming patient samples (Fibroblast, Blood, Urine, etc.) with Stemgent’s exclusive StemRNA-NM footprint-free RNA technology. Patient-specific iPSCs are a self-renewing and expandable cell population with potential to differentiate into virtually any cell type.
We also have the ability to provide precision genome-edited cells by working with our leading industry partners. The ability to model human diseases using iPSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases.
ReproCELL iPSC-derived Differentiated Cells
ReproCELL offers iPSC-derived differentiated cardiac cells, hepatocytes, and neurons suitable for use in basic research as model systems for a variety of applications. Unlike primary cells which may come from random donors with variable genetic backgrounds, these iPSC-derived cells have strong lot-to-lot performance consistency.
ReproCELL also has the ability to prepare customized versions of iPSC-derived cell types as required.
3. LEAD IDENTIFICATION
Perform high throughput screening of drug candidates on complex cell systems grown in 3D for physiologically meaningful data to identify potential leads.
Alvetex 3D Cell Culture Models
3D cell cultures using ReproCELL’s Alvetex technology deliver more in vivo-like results than traditional 2D monolayer cultures.
- Highly porous inert scaffold made from cross-linked polystyrene (200 μm thick).
- Suitable for a wide range of cell types including primary or iPSC-derived cells from most organs, various stem cells, cancer, and complex co-culture models.
- Automation – 96 well and 384 well plate formats compatible with high throughput screening and a variety of assays and techniques.
- Build more predictive biological models by maintaining in vivo physiological properties, enhancing cell viability and longevity.
- Simple histology, imaging and RNA/protein isolation analysis endpoints.
- Add perfusion in 3D for another step closer to in vivo.
SEM of Alvetex Scaffold
96 well and 384 well plate formats available
Co-culture of primary keratinocytes and primary dermal fibroblasts forming a full-thickness human skin construct
Triple fluorescent staining of HepG2 cells grown in 3D on Alvetex Scaffold
4. LEAD OPTIMIZATION
Accurately predict in vivo bioavailability and drug metabolism using human tissue, eliminating well known differences between human and alternative model systems.
Determine the Potency of Your Drug
- Compare the potency of your candidate drug versus other drugs on the market.
|Small intestine ileum||Effect of Inhibitors of Chloride Secretion in Human Ileum|
Increase the Confidence of Your First-in-Man Dose Estimate
- Measure compound permeability, transporter, or metabolic enzyme activity in human intestinal tissue in order to accurately predict in vivo bioavailability and drug metabolism.
- Eliminate well-known differences between human and animal or cell models in bioavailability and metabolism by using human tissue.
|In vitro human gut permeability correlates well to expected clinical absorption
5. PRE-CLINICAL SAFETY
Are your test compounds safe in humans? Evaluate the pre-clinical safety of compounds using human tissue.
Find Out if Your Drug is Safe in Human Tissue Prior to Clinical Trials
- Measure adverse effects on heart or lung muscle contractility or blood vessel contraction/dilation.
- Conduct comparative studies across species.
|Human heart||Force of contraction measured in organ baths|
6. CLINICAL TRIALS
Troubleshoot clinical problems by investigating the mechanisms of clinically-observed adverse effects using human fresh tissues.
Investigate Unexpected Side Effects Observed in Clinical Trials
- Obtain independent verification of your clinical results.
- Examine adverse effects e.g. unforeseen effects on blood vessel dilation/constriction effecting blood pressure.
|Human small artery|