PVG.L Regulatory News (PVG)

18 Jun 2008 07:00



EG011 (refractory angina) demonstrates ability to grow new blood vessels and restore heart function following heart attack

18 June 2008 - Ark Therapeutics Group plc ("Ark" or the "Company") announces today that EG011, its gene-based medicine being developed for refractory angina, has demonstrated an ability to grow new blood vessels and restore heart function following a heart attack (myocardial infarction). This was achieved during the final comparative gene selection work carried out by Ark's scientists in Finland in a second preclinical therapeutic proof-of-principle study.

After a heart attack and successful recovery, an estimated 200,000 patients per annum in the US and Europe are left with a stable heart condition but with chest pain occurring after mild exertion or even when resting, despite being given all existing treatments (refractory angina). This is because heart muscle, usually around the area that died during the heart attack, does not have sufficient blood supply to oxygenate the muscle properly (ischaemic myocardium). 

EG011, containing shortform Vascular Endothelial Growth Factor D (VEGF DΔNΔC), induced a four fold increase in capillaries, which were haemodynamically functional at 21 days with no regression. The amount of blood pumped from the ventricle where the heart attack occurred was restored from 60% to 90% of the level before the heart attack occurred, a highly significant result.

Study details

The study (n=50) compared four different types of gene in Ark's established adenoviral vector in an acute heart attack model. A non active 'marker' gene (lacZ) in the same adenoviral vector was used as a control. Following infarction of the left ventricle wall, the ventricle was first electrically 'mapped' from inside the heart to precisely identify the affected muscle area and the gene constructs were then injected directly into the area of heart muscle around the infarct which was deficient in blood and had impaired function (ischaemic myocardium). The various genes, which had all been shown previously to have some effect in either human or experimental trials, were compared specifically in terms of ability to grow new blood vessels (angiogenesis), the functionality viability (perfusion), stability and persistence of the new blood vessels and ability of the heart to pump blood (ejection fraction). 

VEGF DΔNΔC, which had been identified by Ark as promising in a healthy heart model (August 2007), showed superiority to the other VEGF forms producing a four fold increase (p=0.0001) in the mean capillary area adjacent to the infarct within six days of injection. This effect was maintained out to 21 days with no signs of regression nor evidence of arteriole formation. A transient small increase (50% lower than VEGF A) in accumulation of pericardial fluid was evident in the treated area at day 6 following new capillary formation and this level had returned to control levels by day 21. The left ventricle ejection fraction, which had dropped from nearly 70% before infarct to 46% after infarct, rose by over 16% (p=0.0002) with EG011 treatment, representing restoration of nearly 90% of the ventricular function. This compared favourably to a non significant rise of around 2% in marker gene controls. EG011 appeared well tolerated with no differences in serious adverse events observed between active and control groups. 

John Martin, Professor of Cardiovascular Medicine at University College London and Consultant Chief Scientific Officer at Ark, commented: "EG011's biology indicates it is the right gene to be effective in refractory angina where we need new functional blood vessels. Safe transient expression through Ark's proven adenoviral vector is also logical because we need short term angiogenesis. The improvement in the heart's ability to pump blood with EG011 is many times better than that published in the results for successful stem cell trials where on average around a three percent increase has been achieved. This early evidence suggests EG011 has the potential to be a major advance in the treatment of angina and in aiding recovery from the consequences of a heart attack." 

Nigel Parker, CEO of Ark, added: "Our first work was in healthy hearts and we have now taken that work further in a heart attack model representative of the disease and completed the gene comparisons. We could not have expected better results at this stage, which are consistent with the biology and will be published in a peer-reviewed article in due course. We are now moving to final clone selection and GMP production, so we can undertake the final toxicology work ahead of entering Phase I human studies."

Enquiries

Notes to Editors

Refractory angina and VEGF

Gene scientists, including those at Ark, have tried to grow new blood vessels for refractory angina by putting genes (VEGF A and VEGF121, VEGF C, VEGF D variants) into the coronary artery and heart muscle with some, but limited, success so far. A new catheter system which maps the function of the inside of the heart (NOGA system) to locate the ischaemia is now commercially available and also allows direct injection of a therapeutic locally into the problem area. This has allowed testing of the different VEGF gene variants by Ark scientists in models of myocardial ischaemia and to supplement previous knowledge in models of peripheral limb ischaemia. This work has shown that where previously tried VEGF variants can grow new blood vessels, these are not properly functional and leakage causing oedema occurs. 

More recently work by Ark has resulted in EG011 being developed, which shows significant prospects for the treatment of refractory angina in this system. This has been achieved by optimising the receptor binding properties of the gene to produce more angiogenesis and minimal oedema. Sharing the same adenoviral delivery platform as Trinam® and Cerepro®, the bulk of the key chemistry and manufacturing development work is already established and shown to be acceptable to regulators and development into man by Ark is expected to be relatively rapid compared to historical timeframes.

About Ark 

Ark Therapeutics Group plc is a specialist healthcare group (the "Group") addressing high value areas of unmet medical need within vascular disease, wound care and cancer. These are large and growing markets, where opportunities exist for effective new products to generate significant revenues. With four marketed devices, Kerraboot®, Kerraped®, Flaminal® and Neuropad®, and three further lead pharmaceutical products in late stage clinical development: Cerepro®, Vitor™, and Trinam®, the Group is transitioning from an R&D company to a commercial, revenue generating business.

Ark's own 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 statement.