www.pharmidex.com

Blood-brain barrier solutions: powered by NeuroPK^®

Pharmidex is an innovative research company focussed on disorders of the central nervous system (CNS). Our unique integrated package of blood-brain barrier solutions covers the discovery spectrum: from predicting and assessing the ability of compounds to cross the blood-brain barrier (BBB) to delivering compounds across it. In this way we help expedite the transition of NCEs from hit to optimised lead.

PREDICTING BRAIN PERMEATION: Clarity™ is our proprietary in-silico technology to predict the ability of compounds to cross the blood-brain barrier. Unlike some models currently available, it will be informed on the basis of a single set of consistent brain penetration data. This screen will allow libraries of virtual or actual compounds to be segmented on the basis of brain penetration, which serves to both reduce development time and increase the probability of success.

ASSESSING BRAIN PERMEATION: We are highly experienced in conducting studies to assess the ability of compounds to permeate the BBB.

• Pharmidex is world leader in In-vivo assessment of brain penetrability and free concentration of compounds in extracellular fluid (ECF) – NeuroPharmacoKinetics or NeuroPK^® for short. NeuroPK^® delivers a comprehensive assessment of the concentration and duration of a test compound in the ECF of a distinct brain region, in ventricular CSF as well as blood. These studies can be conducted at the discovery and preclinical phases and can be accompanied by neuropharmacodynamic studies, thus permitting the relationships to be established between neuropharmacokinetic and neuropharmacodynamic data (NeuroPK/NeuroPD).

DELIVERING COMPOUNDS ACROSS THE BBB: Cerense™ is a unique product development platform, offered in collaboration with Genzyme Pharmaceuticals, to substantially improve the development success of CNS medicines that normally exhibit poor permeation of the BBB. Proprietary formulation technology opens the BBB and delivers unmodified drug compounds into the brain. It can thus unlock the potential of compounds constrained by poor BBB penetration (such as –peptides, proteins, antibodies and siRNA), as well as open new avenues for CNS medicines research.

COMPLEMENTARY OFFERINGS: We also offer the following services.

• In-vivo screening models cover general DMPK profiling – JV and JV/HPV cannulation, bile duct cannulation, gut segmental absorption and a number of in-situ approaches – to the highest possible standards. (In addition to these traditional approach to clinical DMPK studies, Pharmidex is breaking new ground by offering innovative approaches to the assessment of the concentration of a compound in human tissue (e.g. skin) or blood over time. This delivers more precise assessment of maximal concentration and half life which will help optimise the dosing regimen).
• At the in-vitro level we have a number of primary and immortalised cell lines that allow for the reliable rank ordering of permeability across the blood-brain barrier of NCEs. Penetrability™ uses Madine-Darby Canine Kidney (MDCK) II cells engineered to over-express P-glycoprotein (P-gp). This allows us to assess BBB permeation and Pgp mediated efflux in the same system. We also provide a comprehensive set of DMPK screens, including drug metabolism, stability, inhibition and induction.
• Comprehensive bio-analytical capabilities including LC-MS/MS and neuro-chemical assessment.

In conclusion… The ability of Pharmidex to integrate neuroscience, DMPK and CNS drug discovery expertise means that our services add tangible value to CNS drug discovery projects by accelerating time to market, improving the probability of success and increasing safety by identifying optimal dosage levels. It can also deliver value to non-CNS projects that need to establish that their test compounds do not cross the BBB and thus have a liability to cause CNS side-effects.

For more information contact:
Business Development Manager, Pharmidex
Tel: +44 (0)870 2405978 | Mobile: 07943 846 878 |
Email: business@pharmidex.com
www.pharmidex.com