London, UK, 26 August 2009, Ark Therapeutics Group plc (“Ark” or “the Company”) announces today that its adenoviral short-form Vascular Endothelial Growth Factor D gene construct (Ad-VEGF D) is commencing Phase I/IIa clinical development for the treatment of refractory angina. Trial work will be conducted in collaboration with the AI Virtanen Institute in Kuopio, Finland. The programme (EG011) will use the angiogenic VEGF D ?N?C short-form gene, delivered via Ark’s already successfully developed adenovirus platform. Manufacturing to cGMP standards has already been completed at Ark’s Kuopio facility.
After a heart attack and successful recovery, an estimated 200,0001 patients per annum in the US and Europe, despite being given all existing treatments, are left with a relatively stable heart condition in which chest pain occurs after mild exertion or even when resting (refractory angina). This is because the heart muscle, usually around the area that has died during the heart attack, has insufficient blood supply to oxygenate the muscle properly (ischaemic myocardium). EG011 treatment is expected to increase the blood supply to these areas, thereby improving heart function and subsequent patient mobility.
The EG011 trial will be an ascending dose controlled study in up to 30 chronic angina patients who have already been treated unsuccessfully with available licensed approaches, usually stents and balloon angioplasty. Patients will receive a single dose of either 1x109, 1x1010 or 1x1011 viral particles of Ad-VEGF D, administered via the NOGA catheter system after NOGA mapping of the wall of the myocardium to locate the ischaemic areas. Controls will receive only NOGA mapping and patients will be blinded to the treatment groups. The study, recently approved by the National Agency for Medicines (NAM), will be conducted by Professor Ylä-Herttuala of the AI Virtanen Institute in Kuopio and Professor Juha Hartikainen and Doctor Marja Hedman of the Kuopio University Hospital. The study will assess the safety of EG011 as well as providing initial efficacy data.
Ark announced in June 2008 that, in its second pre-clinical therapeutic proof-of-principle study, EG011 had demonstrated an ability to grow new blood vessels and restore heart function following a heart attack (myocardial infarction). EG011 induced a four-fold increase in capillaries, which were haemodynamically functional at 21 days. 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, a highly significant (p=0.0002) result. A non active ‘marker’ gene (lacZ) in the same adenoviral vector was used as a control. EG011 appeared well tolerated with no differences in serious adverse events observed between active and control groups.
Professor Ylä-Herttuala, Consultant Director of Molecular Medicine at Ark commented; “We are pleased to be starting this important trial. Finland has one of the highest incidence of cardiovascular disease in the world and we have an exceptional understanding of the biology and treatment options. The shortform VEGF D gene has shown increasing promise as an angiogenic treatment agent and we have already identified patients who would be suitable for this new medical approach.”
Dr Nigel Parker Chief Executive Officer of Ark added; “The rapid progress we have made with this programme has been made possible by the use of our already established adenoviral platform and technology. The move into Phase I/IIa development is an important milestone. Ark’s combination of academic and industry expertise coupled with our unique manufacturing capability has now resulted in the first of our second generation gene-based medicines entering the clinic. EG011 is a very exiting product opportunity in a large market with significant unmet clinical need and we look forward to announcing progress on the trial as well as news on our other shortform VEGF D clinical candidates as the year progresses.”
Refs.
1 Company estimates and various sources
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.
Ark Therapeutics Group plc
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 six marketed devices, Kerraboot®, Kerraped®, KerraMax®, Kerraglove®, 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 both 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, where 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.
