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Further Positive Phase II Results of Trinam Gene Therapy

24 Aug 2006

Clear evidence of effectiveness in breakthrough treatment for kidney failure patients

LONDON, UK | Aug 23, 2006 | Ark Therapeutics Group plc ('Ark') today announces further positive results from a Phase II trial of Trinam(R), its novel gene therapy to prevent

blood vessels blocking in kidney dialysis patients who have undergone vascular access graft surgery. Results of the low dose group were first reported in October 2005. The new data show that the access grafts of low dose patients remain functional for dialysis on average over five times longer (17.8 months) than control patients in the trial (3.3 months). In the high dose group, recruited after the low dose group, all patients with successful graft implants still have open grafts with patency averaging 8 months so far. For the primary end point of safety, no systemic distribution of Trinam(R) has been found in either of the high or low dose groups and the product is well tolerated.

Patients in renal failure depend on effective vascular access for haemodialysis, which removes blood from the body, cleans it and returns it, usually three times a week. Without dialysis these patients would die. A common method of gaining access to the circulatory system is via an artificial blood vessel (vascular access graft) surgically implanted between an artery and a vein in the forearm. However, in a majority of patients, the grafts become blocked due to overgrowth of muscle tissue inside the blood vessel (intimal hyperplasia) and this requires further complex surgery to allow dialysis to take place.

Trinam(R) is a combination of a vascular endothelial growth factor gene in an adenoviral vector (Ad-VEGF-D) and Ark's biodegradable local delivery collagen collar device (EG001). At the end of the access graft surgery procedure, the collar is fitted around the outside of the vein/graft join. The Ad-VEGF-D solution, which reduces the likelihood of blood clots and intimal hyperplasia, is then injected into the space between the wall of the collar and the blood vessel. This unique method of administration of the gene localises its delivery to the target tissue site, maximising efficacy, avoiding systemic distribution and thus minimising the potential for side effects.

The Phase II trial of Trinam(R) is an ongoing open-label, standard care controlled clinical trial that primarily assesses safety, with efficacy as a secondary measure. Of the 16 patients included in the study, six were assigned to a low dose group (one dose of VEGF 4 x109 viral particles) delivered at the time they underwent surgery either to implant a first vascular access graft or to insert a new graft in a different location after failure of a previous access procedure), six to a high dose group (4 x 1010 viral particles), and the remaining four to a control group receiving standard care only. One operational failure occurred in each of the low and high dose groups.

After up to two years of follow-up, none of the patients receiving Trinam(R) in either of the high or low dose groups exhibited serious side effects, other than those consistent with the nature of the operation and condition. In addition no systemic distribution of Trinam(R) was evident. The Ad-VEGF D was not detected outside the specific vein area treated by the surgeon, confirming the effectiveness of the EG001 delivery device.

In the low dose group, average patency has now increased to 17.8 months, with two of the five remaining open (one at 27 months and one at 22 months). One other patient recently blocked at 23 months. In the five patients in the high dose group, all grafts remain open and the average patency is 8 months so far. Three of these are now approaching patency of one year and the early indications are that the results in the high dose group will confirm those of the low dose group. Three of the four patients in the control group have blocked, with one remaining open at five months. The average patency period of the control group is currently 3.3 months.

In the US, patients in gene therapy studies are tracked for life and the graft patency data will therefore continue to improve in this ongoing study until all grafts are blocked. The study is being conducted at Duke University, The University of Miami and Vascular and Transplant Specialists in Norfolk, Virginia.

In the US and Europe, there are an estimated 150,000 cases each year where Trinam(R) might be used. In patients fitted with haemodialysis access grafts, up to 60% of the grafts block within a year of being inserted and repeat surgery shows more rapid failure rates(1). There are currently no approved drug therapies to reduce failure rates of haemodialysis access graft procedures. The clinical need for an effective treatment is such that the National Institutes of Health in the US has highlighted it as a priority requiring a solution in the Healthy People Directive 2010.

Commenting on the results, Dr Jeffrey Lawson, Associate Professor of Surgery and Pathology at Duke University, North Carolina and lead investigator in the trial, said:

'These initial data support the clinical effectiveness of Trinam(R) in dialysis patients. Instead of having the majority of vascular access grafts re-operated on within a year, if the early results of this trial continue, this treatment preserves the graft's functionality for a longer period, so patients can go about their lives normally and have fewer surgical interventions and complications. By delaying the rate of failure of dialysis access grafts, the treatment may also save healthcare systems some $15,000 to $20,000 for each intervention. This kind of technology is very exciting and early results suggest that it may have a valuable role to play in the treatment of kidney failure patients.'

Nigel Parker, Chief Executive of Ark, added:

'The results of this study so far have exceeded the Company's expectations in this very serious condition and confirm our original enthusiasm for the product's potential. Trinam(R) represents a breakthrough in targeted gene medicine and demonstrates Ark's expertise and leadership in this emerging field.'

(1)Reference: Rosas SE et al, Determinants of successful synthetic haemodialysis vascular access graft placement. J. Vasc. Surg. 2003;37:1036-42.

For further information:

Ark Therapeutics Group plc Tel: + 44 (0)20 7388 7722 Dr Nigel Parker, CEO Martyn Williams, CFO

Financial Dynamics Tel: +44 (0)20 7831 3113 David Yates Anna Keeble

Notes to Editors

Ark Therapeutics Group plc

Ark is a specialist healthcare group (the 'Group'), addressing high value areas of clear unmet medical need. With one marketed product, Kerraboot(R), and three further lead products in late stage clinical development: Vitor(TM), Cerepro(TM) and Trinam(TM), the Group is transitioning from an R&D focused company to a commercial, revenue generating business. Capitalising on over ten years of research in vascular biology and gene-based medicine, Ark has a broad product portfolio targeted at specific unmet clinical needs within vascular disease, wound care and cancer. These are large and growing markets, where opportunities exist for effective new products to generate significant revenues. Cerepro(TM) is on track to becoming one of the world's first commercially available gene-based medicines.

Ark's existing products are sourced from related but largely non-dependent technologies within the Group and have been selected to enable them to be taken through development within the Group's own means and to benefit from Orphan Drug Status and/or Fast Track Designation, as appropriate. This strategy has allowed the Group to retain greater value and greater control of clinical development timelines, and to mitigate the risks of dependency on any one particular programme or development partner. Ark has secured patents or has patent applications pending for all its lead products in principal pharmaceutical markets.

Ark has its origins in businesses established in the mid-1990s by Professor John Martin and Mr Stephen Barker of University College London and Professor Seppo Yla-Herttuala of the AI Virtanen Institute at the University of Kuopio, Finland, all of whom play leading roles in the Company's research and development programmes.

Ark's shares were first listed on the London Stock Exchange in March 2004 (AKT.L).

This announcement includes 'forward-looking statements' which include all statements other than statements of historical facts, including, without limitation, those regarding the Group's financial position, business strategy, plans and objectives of management for future operations (including development plans and objectives relating to the Group's products and services), and any statements preceded by, followed by or that include forward-looking terminology such as the words 'targets', 'believes', 'estimates', 'expects', 'aims', 'intends', 'will', 'can', 'may', 'anticipates', 'would', 'should', 'could' or similar expressions or the negative thereof. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors beyond the Group's control that could cause the actual results, performance or achievements of the Group to be materially different from future results, performance or achievements expressed or implied by such forward-looking statements. Such forward-looking statements are based on numerous assumptions regarding the Group's present and future business strategies and the environment in which the Group will operate in the future. Among the important factors that could cause the Group's actual results, performance or achievements to differ materially from those in forward-looking statements include those relating to Ark's funding requirements, regulatory approvals, clinical trials, reliance on third parties, intellectual property, key personnel and other factors. These forward-looking statements speak only as at the date of this announcement. The Group expressly disclaims any obligation or undertaking to disseminate any updates or revisions to any forward-looking statements contained in this announcement to reflect any change in the Group's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. As a result of these factors, readers are cautioned not to rely on any forward-looking state

SOURCE: Ark Therapeutics Group plc

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