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Major New Review Supports the Broader Potential of CeNeS COMT,Inhibitor Discovery Programme

CAMBRIDGE, U.K. 2nd July 2007 - CeNeS Pharmaceuticals (AIM:CEN) ("CeNeS" or "the Company") the Cambridge-based biopharmaceutical company today announced that a paper published this week in CNS Drugs(1) further supports the hypothesis that a catechol-O-methyltransferase (COMT) inhibitor that acts in the brain would be a useful agent to address profound cognitive deficits in schizophrenia and bipolar disorder. CeNeS has an ongoing discovery programme to develop novel COMT inhibitors.

The paper reviews the preclinical and clinical data surrounding COMT and includes studies carried out by the world leading group based at the National Institute of Mental Health, Bethesda, Maryland, USA. The paper's authors collate recent developments in the analysis of the role of COMT genotypes and their involvement in cognitive deficits in schizophrenia and bipolar disorder. The paper supports the view that there is potential to use COMT inhibitors in ameliorating their cognitive deficits via an effect on prefrontal cortex brain function. As part of their conclusions the authors note, "The development of newer COMT inhibitors that can permeate the BBB (blood brain barrier) effectively and are devoid of serious adverse effects will allow expansion of the search for more specific, selective therapies for the treatment of cognitive disorders".

CeNeS has a leading position in the discovery of a novel series of COMT inhibitors with a programme currently focused on drugs for treatment of Parkinson's disease. In addition to this, the continuing progression of the scientific rationale for the potential use of COMT inhibitors in the treatment of schizophrenia and bipolar disorder places the CeNeS discovery programme in a good position in an exciting area of neuroscience.

Neil Clark, Chief Executive of CeNeS said: "CeNeS is excited about its discovery programme's potential to deliver improved drugs for the treatment of Parkinson's disease. Academic data continues to suggest that COMT inhibitors may also have therapeutic utility in addressing the poorly treated negative symptoms of schizophrenia. This is in addition to the established market for COMT inhibitors in the treatment of Parkinson's disease. If this extra indication is established the market size for a novel, centrally acting COMT inhibitor would increase substantially". ENDS

1 Apud and Weinberger, CNS Drugs 2007, 21, 535-557.

For more information please contact: CeNeS Pharmaceuticals plc Neil Clark, CEO Tel: +44 (0)1223 266 466

JM Finn Geoff Nash Tel: +44(0) 207 628 9688

Financial Dynamics Ben Brewerton/Emma Thompson Tel: + 44 (0) 207 831 3113 About CeNeS Pharmaceuticals CeNeS is a biopharmaceutical company specialising in the development and commercialisation of drugs for pain control, sedation and other CNS disorders such as Parkinson's disease. The company is based in Cambridge, England. For further information visit the CeNeS web site:

About COMT inhibitors Two COMT inhibitors have been introduced to the market, tolcapone and entacapone. However, tolcapone was withdrawn from the EU market in late 1998 due to liver toxicity, which is unrelated to COMT inhibition. Tolcapone has recently been re-introduced to the market in Europe but, as in the US, its use is severely restricted. As such, entacapone (co-marketed by Orion and Novartis) is the only unrestricted COMT inhibitor available in the major markets. However, entacapone has a number of drawbacks, namely a short half-life, relatively low oral bioavailability and minimal brain penetration. Tolcapone and entacapone, in common with the majority of known potent COMT inhibitors, contain the undesirable 3-nitrocatechol unit that is associated with poor oral absorption, short plasma half-life and extensive metabolism issues. The goal of breaking away from this nitrocatecho l series has been achieved by CeNeS scientists, and a number of discrete chemical series without the nitrocatechol group have been identified. The COMT inhibitor programme was carefully chosen by CeNeS in line with our strategy to have a low-risk profile and to address a clear commercial opportunity. A number of potent compounds are now being evaluated in the lead optimisation process, prior to selection of a development candidate.

About Parkinson's disease Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. It affects approximately 2 per cent of the population over the age of 65, representing approximately 4 million patients worldwide. Parkinson's disease results from a loss of the neurotransmitter dopamine in the brain. Replacement therapy using L-DOPA, the precursor of dopamine, is the main treatment for Parkinson's disease. However, L-DOPA is quickly metabolised in the gut and liver allowing only a small proportion (approximately one per cent) to reach the brain. Therefore, L-DOPA is formulated with agents that inhibit the breakdown of L-DOPA by DOPA-decarboxylase, such as carbidopa and benserazide. The enzyme catechol-O-methyltransferase (COMT) also causes significant depletion of L-DOPA in the brain and periphery, limiting the efficacy of L-DOPA replacement therapy. The global market for drugs targeting Parkinson's disease was $1.7 billion in 2003 and is forecast to grow substantially over the next decade with an increased prevalence of the disease as a consequence of the ageing population. COMT inhibitors currently have more than a 10% share of the Parkinson's disease market by value and their usage is growing.

About Schizophrenia Schizophrenia is a debilitating mental illness characterized by disturbances such as hallucinations and delusions as well as a range of negative symptoms, including cognitive disturbances. Cognitive disturbances often prevent schizophrenia patients from readjusting to soci ety and require patients to be under medical care for their entire lives. Despite the availability of a variety of current antipsychotic drugs with worldwide sales exceeding USD $12 billion, cognitive disturbances are poorly addressed by existing therapies and represent a large unmet medical need in schizophrenia therapy.


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