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Rhenovia Pharma - Predictive CNS Drug Discovery & Development by Biosimulation

Using its unique biosimulation platform Rhenovia Pharma offers services and partnerships for pharmacological profiling, target identification and validation, search for synergistic drug combinations, risk assessment for safety and toxicity of drug candidates in the nervous system.

Rhenovia is a world leading biotech-biopharmaceutical company in biosimulation applied to drug discovery and development (DD&D) for the nervous system (NS). Rhenovia was created in 2007 by seasoned professionals of the top-tier global pharmaceutical industry, world experts in neurobiology, especially cognition and neuropharmacology, and pioneers in computational neuroscience. Rhenovia is an independent, international company headquartered in France with branches in the US, Germany and Switzerland and a team of 12 employees and 13 external collaborators, scientific, legal and business advisors.

Multi-target synergistic drug combinations

Rhenovia's goals are to elaborate innovative technologies and identify better treatments for diseases of the nervous system, focusing first on Alzheimer's disease, depression, schizophrenia, bipolar disorder, epilepsy, stroke, Parkinson's disease, as well as rare/orphan diseases like Huntington's disease. Further developments target pain, addiction and muscular dystrophies. Rhenovia's basic conceptual approach is to exploit the two major hallmarks of NS diseases: the complexity of biological systems by building mathematical models and computer simulation platforms, and the multifactorial feature of NS by searching for multi-target synergistic drug combinations.

Drug discovery and development simulation

Rhenovia's objective is to revolutionise DD&D by using simulation to guide experimentation in order to:

  • Boost drug candidates in development
  • Improve success rates and efficacy
  • Reduce development cost and time to market
  • Prolong life cycles of patent-expiring drugs
  • Leverage past and present investments by identifying synergistic drugs

Validated and operational biosimulation platform

Rhenovia possesses the most elaborate biosimulation platform directly applicable to CNS Drug Discovery & Development (DD&D). RHENOMS™ models excitatory and inhibitory synaptic transmission integrating pre-, intra- and postsynaptic electrical, biophysical and biochemical processes. The first proprietary platform simulates cognitive deficit (long-term potentiation) and other pathologies associated with GLU/GABA homeostasis as well as Ca2+ and acetylcholine deregulation.

Rhenovia offers a high value added service for fees or milestone-driven partnership. Rhenovia performs customized studies using its tool box comprising:

  • Exhaustive numerical pharmacological profiling
  • Computerised target identification, testing and validation
  • High throughput search for synergistic drug combinations
  • Alternative numerical go-no go flowchart
  • Safety/toxicity risk assessment
  • Drug-drug interaction tool

Studies are carried out using dynamic elementary models (kinetic models of ionotropic or metabotropic receptors, ion channels, transporters or enzymes), integrated signaling and second messenger cascades and a global multi-synaptic model under physiological and pathological conditions.

Drugs are profiled in silico in numerous test systems equivalent to:

  • Intracellular electrophysiology
  • Patch clamp
  • Calcium imaging
  • Microdialysis/neurotransmitter release
  • Enzymatic activity (i.e. AChE)
  • Receptorion channel binding
  • cAMP/cGMP formation
  • IP3, 2AG synthesis
  • Neuronal/glial uptake

Outputs provide data for a large number of parameters, including:

  • Membrane potential
  • Selective ionic currents (Na+, K+, Ca2+)
  • LTP, LTD
  • Ligand & voltage gated ion channel function (transition between states, currents, open probability; AMPAR, NMDAR, nAChR, GABAAR)
  • Gq, Gi, Gs coupled receptor functions (second messengers, i.e., IP3, DAG, cAMP; GPCRs, i.e., mGluR1/5, mGluR2/3, H3, CB1, A1, mACh, 5-HT6, GABABR)
  • Pre and postsynaptic Ca2+ transients
  • Transport rate (glycine, glutamate, Na/Ca exchanger)
  • Enzymatic activity (AChE, BuChE, CamKII, PKA, PKC, PLC, Ca-ATPase)
  • Regulatory protein state (calmodulin, calcineurin)

Rhenovia proposes an opportunity assessment under confidentiality to evaluate with potential partners the phase of the drug discovery process with highest added value.

RHENOVIA PHARMA SAS
20C Rue de Chemnitz
F-68200 MULHOUSE, France

Tel: +33 389 3211 80
serge.bischoff@rhenovia.com
www.rhenovia.com