V158866

V158866 is the lead molecule in our FAAH programme with potential application in pain, multiple sclerosis associated spasticity, and other neurology indications.

V158866 is a selective, patent protected, fatty acid amide hydrolase (FAAH) inhibitor which arose from an internal research programme and is now in clinical development. It is being studied in a Phase II proof-of-concept study in neuropathic pain.

Our programme has also generated several back-up compounds including a peripherally-restricted FAAH inhibitor with similar pharmacokinetic profile to V158866.

V158866 successfully completed single and multiple ascending dose Phase I studies. These evaluated the safety, tolerability, pharmacokinetic and pharmacodynamic effects of V158866. Data from these studies were presented at the 14th World Congress of Pain in Milan in August 2012.

A Phase II POC study in up to 36 patients with central neuropathic pain due to spinal cord injury was initiated in 2013.  In August 2015, the Company announced results from this study in which the programme was being investigated in patients with neurophathic pain as a result of spinal cord injury.  Although the dosing of V158866 resulted in elevated endocannabanoid levels, on an intent-to-treat basis, the study failed to meet its pain reduction primary endpoint. Treatment did show a trend towards efficacy on a per protocol basis and was generally well tolerated.

We do not plan to make any further investment in this programme and seek to realise its potential value through partnering. 

Clinical applications of V158866 

The initial focus of our FAAH inhibitor programme has been in pain, since this is where there is currently most data with cannabinoids, but other indications including spasticity, sleep quality, and GI disturbances, also have significant potential.

FAAH is an integral membrane enzyme that hydrolyses the endocannabinoids (EC): AEA (anandamide), and to a lesser extent related signalling lipids such as OEA (ethanolamide) and PEA (palmitoyl ethanolamide). AEA and 2-AG (2-arachidonoyl-glycerol) are the endogenous ligands of CB1 and CB2 receptors. These receptors are also activated by THC (∆9-tetrahydrocannabinol), the principal active in cannabis. THC and other direct CB1 agonists have a range of clinical benefits including analgesia (particularly for neuropathic pain), anxiolysis, anti-depressant effects, anti-emmetic properties, appetite stimulation and muscle-relaxation/anti-spasticity. However, these are at the expense of multiple side effects resultant from direct CB1 agonists: including dizziness, impairment of cognition and motor control. Consequently, the clinical utility of CB1 agonists is compromised.

FAAH inhibition would be expected to augment the endogenous cannabinoid tone by decreasing the metabolic rate of AEA and other endogenous substrates. In contrast to the action of any exogenous CB1 agonists, FAAH inhibition should lead to specifically targeted activation of CB1 receptors only in areas where EC tone is enhanced. It is believed that pain is one of the triggering stimuli, which leads to enhance EC tone, and thus, FAAH inhibition may be able to augment EC-mediated anti-nociception without generating side-effect issues in the non-activated pathways. Finally, the action of FAAH inhibition is controlled by the rate of synthesis of AEA, and hence neural activity. Therefore, the resulting activation of CB1 receptors would be expected to mimic the physiological range, in contrast to those pharmacological responses achieved with CB1 agonists.

In support of this hypothesis, FAAH inhibitors and FAAH-knockout mice display analgesia and anti-inflammatory phenotypes without disruption to motility, cognition or body temperature, and thus, suggesting not only that the FAAH-mediated metabolic pathway regulates a discrete subset of the processes mediated by endocannabinoids, but also represents a promising target for treatment of pain, inflammation and other CNS disorders.

Licensing V158866

On the successful completion of the Phase II study in neuropathic pain, Vernalis will seek a licensing partner with expertise and proven capabilities in the development and commercialisation in one or more of the indications where V158866 has potential therapeutic applications.

To express an interest in discussing the potential licensing of this programme, please email corpcomm@vernalis.com

 

 

 

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Results Announcement for the year ended 30 June 2017

Vernalis plc (LSE: VER) today announces its audited financial results for the year ended 30 June 2017, following the year-end trading update published on 18 July 2017.

 

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