Reconstructed Organ Platform
Greater than ninety percent of new drugs do not reach the market because they fail during clinical development. Reconstructed organ technology is a preclinical platform designed to evaluate investigational therapeutics, drug candidates, and drug combinations within the native microenvironment of human tissues under the conditions of environment-mediated drug resistance (EM-DR) responsible for failure of multiple treatment regimens in patients. Therapeutic agents that retain potency under EM-DR established by the elements of tumor microenvironment recapitulated within each reconstructed organ, demonstrate high correlation with clinical response. Our pharmaceutical partners are using the reconstructed organ technology to eliminate ineffective compounds and identify drugs and drug combinations that will actually work in patients.
A successful drug candidate has to overcome drug-resistance induced by the multiple factors in tumor microenvironment.
What can I learn from reconstructed organ technology?
Reconstructed Organ platform is fully customizable to the tumor and tissue of interest providing physiological microenvironment for target discovery and assessment of potency, selectivity, specificity, drug resistance, and potential toxicity of therapeutic agents and drug combinations. Utilizing the reconstructed organ platform drug developers can interrogate lead compounds and drug candidates against enriched populations of primary (bulk) tumor cells, as well as against invasive, metastatic, and cancer stem cell populations providing a comprehensive overview of the targeting capabilities of investigational compounds and drug combinations and identifying compounds most likely to succeed in the clinic.
Reconstructed Organ platform provides organ- and disease-specific solution to the problem of preclinical testing. Reconstructed Organ platform offers significant cost and time savings by eliminating ineffective compounds early in the process of drug development, streamlining those agents that can overcome EM-DR for clinical trials.
- Drug candidate screening
- Off-target toxicity
- Rescue of failed drug candidates
- Target/biomarker discovery
Reconstructed organs exhibit high correlation with clinical response making it an ideal system to identify drug candidates having highest chances of reaching the patients.
The physiological microenvironment of reconstructed organs and their ability to mimic clinical response provides an ideal platform to evaluate drug efficacy early during development and to identify sources of potential drug resistance. Utilizing PD-3D™ for preclinical testing eliminates ineffective compounds early in development allowing our partners to prioritize their drug development pipelines to focus on those drugs most likely to succeed in the clinic.
Reconstructed organ platform provides the means to identify specific patient populations responsive to the drug candidates allowing our partners to focus clinical trials on the specific group of patients with the highest likelihood of clinical response.
rBone™ recapitulates bone marrow microenvironment and allows for long-term culture of hematopoietic compartments providing an ideal platform to evaluate hematopoietic toxicity of investigational drugs.
Epithelial & stromal toxicity
Epithelial and epithelial-stromal organoids reconstructed by the reconstructed organ platform mimic human tissue architecture for assessment of drug toxicity on non-malignant epithelial populations.
Reconstructed organs provide physiological microenvironment for organotypic culture of non-malignant hepatocytes where hepatic toxicity of investigational compounds can be evaluated under native conditions of human liver.
Many drug candidates are ‘killed’ in preclinical development when they do not demonstrate sufficient efficacy in animal models. Reconstructed organ technology has the capacity to differentiate between true failures and agents that are ineffective in animal models that may not accurately represent the conditions of human tissue environment (human-rodent incompatibility) captured by the reconstructed organ platform. Furthermore, reconstructed organs can be utilized to identify drug combinations to rescue drugs that have failed as single agents.
As a discovery platform, reconstructed organs can identify new and unique molecular targets that retain fidelity during cancer progression from localized to metastatic disease. Reconstructed organ technology can also be used to screen for disease-specific biomarkers and follow their fluctuations as a function of treatment and disease stage.