Overview: Clinical drug failure prediction integrating safety and efficacy issues
Recent drug failures in the late clinical development stage clearly illustrate the difficulties of anticipating the benefit/risk ratio of a new class of drug during the discovery and preclinical stage, especially in the field of metabolic and cardiovascular diseases. New predictive solutions are needed that integrate efficacy and safety issues, long before clinical trial initiation.
Classical biomarkers and animal models are not sufficiently predictive of functional drug efficacy or unwanted effects.
The focus at Physiogenex is on the development of cutting-edge approaches in metabolic and cardiovascular diseases, covering both efficacy and safety concerns and thereby allowing key decisions to be made earlier in the drug discovery and preclinical development process. This will also cut the cost of developing innovative medicines.
Focus: Transversal predictive models and functional analyses
Given the notorious complexity of nutritional disorders, we are focusing on solutions to two major bottlenecks, by:
- developing a large panel of predictive animal nutritional models merging lipid, glucose and lipoprotein disorders and cardiac dysfunction, based on clinical observations;
- implementing platforms based on sensitive radiotracer kinetic methods designed to overcome the limits of classical surrogate plasma biomarkers in predicting clinical efficacy and safety.
Technologies & Expertise: Nutrition and biomarker-coupled radiotracers
Nutrition : Physiogenex has acquired unique expertise with animal nutritional models and diet composition. We are convinced that the nutritional approach remains the best way of obtaining an integrated and clinically relevant pathophysiological picture. We are continuously developing new models and approaches to better cover all the different components of metabolic and cardiovascular diseases, from visceral obesity to hyperglycemia, hepatic steatosis, inflammation, atherosclerosis, coronary artery disease, hypertension, and heart failure.
Biomarker-coupled radiotracers: This unique approach provides kinetic and mechanistic data which are more informative and more sensitive than those obtained with classical plasma biochemistry. Biomarker function-based techniques also overcome the classical limits of surrogate biomarkers in terms of predicting clinical efficacy and safety. Moreover, this approach offers an opportunity to implement individual-tissue techniques in vivo, which are also useful for stratifying heterogeneous patient populations and for characterizing disease mechanisms.
At Physiogenex, mechanistic studies are considered crucial not only for understanding complex innate biological processes but also for developing new tools to screen and to determine the efficacy and safety of medicines designed for metabolic and cardiovascular diseases. We believe that amalgamating the two objectives could provide huge mutual rewards.
Our R&D team is currently developing new in vivo kinetic methods as well as complementary animal models for selecting, optimizing and prioritizing candidate drugs.
Ultimate objective: to cover all aspects of metabolic and cardiovascular diseases, with a view to early strategic decision-making
Our ambitious strategy will eventually make it possible to evaluate FFA, lipoprotein and glucose fluxes in a large panel of animal nutritional models mimicking most features of human metabolic and cardiovascular diseases. In vivo single-tissue techniques will add further information critical for clinical trial design and for characterizing disease mechanisms.
R&D programs
- Program 1: In vivo HDL-c and LDL-c kinetics using radiotracers, and development of a dyslipidemic hamster model based on a nutritional approach
- Program 2: Development of predictive animal nutritional models of cardiovascular complications of type 2 diabetes.
Current R&D collaborations
- Joseph Fourier University, Grenoble (France): Validation of a new animal nutritional model displaying cardiac complications of the “insulin resistance syndrome” as observed in the clinical setting
- Hotel Dieu, INSERM, Nantes (France): Development and validation of in vivo kinetic studies for sensitive measurement of the production and catabolism of Apo A, Apo B and cholesterol transfer
- Hotel Dieu, INSERM, Nantes (France): Validation of a new animal nutritional model displaying hyperlipidemia leading to atherosclerosis
- European FP7 ADAPT, coordinated by Dr. Jürgen Eckel, German Diabetes Center : Adipokines as Drug Targets to Combat Adverse Effects of Excess Adipose Tissue.