Inhibition of angiogenesis as a new treatment modality

E Sussex, UK --- 26th July, 2002 --- In recent years angiogenesis has been recognized by the pharmaceutical industry as a scientific area offering potential treatment options for numerous diseases. It is particularly relevant to companies focusing on cardiovascular diseases such as myocardial infarction and stroke, as well as such indications as cancer and inflammation. ThromboGenics Ltd is an exciting biotechnology company that is exploiting this potential.

Inhibitors of angiogenesis are anticipated to represent a major focus of anti-cancer therapy.  It is estimated that by 2006, the market for all products that play a role in angiogenesis is likely to reach $1.75 billion. An important sub-segment of this market will be the treatment of diabetic retinopathy. This complication of diabetes has become the leading cause of blindness in the United States in middle-aged adults, with enormous human and economic costs.  Inhibitors of angiogenesis may also offer treatment options for various inflammatory diseases.

Strategies aimed at blocking the effects of vascular endothelial growth factor (VEGF), one of the key angiogenic growth factors, have lead this therapeutic class. Scientists within the Center for Transgene Technology and Gene Therapy, a group closely affiliated with ThromboGenics, have exploited targeted mutagenesis in animals to advance potential targets into early pre-clinical studies in animals.

ThromboGenics and its extensive consortium of collaborators have elucidated the mechanisms by which antibodies to a second growth factor, placental growth factor (PlGF), may have therapeutic potential in a number of diseases - including abdominal adhesion, diabetic retinopathy and cancer. Inhibitors of PlGF binding (studies supported by creation of mice with a specific gene deletion of PlGF) are able to limit the growth of tumors and development of retinopathies in experimental animals. The further development of these approaches is thus likely to advance therapeutic antibodies within the context of angiogenesis and acute inflammatory states, and could represent a major therapeutic advance.

A recent review by LeadDiscovery of the potential of PlGF as an inhibitor of angiogenesis concluded that PlGF may have particular advantages over strategies aimed at VEGF. Targeting of antibodies to VEGF within tumors may be difficult since VEGF is so widely expressed – limiting their potential efficacy. In contrast, the expression of PlGF, which acts in concert with VEGF to mediate adaptive response to angiogenesis, is limited principally to diseased or inflamed tissue, and thus may circumvent this problem. “We believe that the use of molecular strategies aimed at targeting PlGF may offer significant advantages over other approaches " says Dr. Randall Moreadith, President and Chief Operating Officer of ThromboGenics Ltd.

According to Dr Jon Goldhill, CEO of LeadDiscovery,   “ThromboGenics' PlGF technology once again demonstrates this company's capacity to combine novelty with first class drug development.  We have already reported on SY161-P5, a cost-effective treatment of acute myocardial infarction, and more recently ThromboGenics reports that a similar molecule, SY162, has completed Phase II development for central venous catheter (CVC) thrombosis.  By way of a further example, our recently updated report on ThromboGenics' microplasmin program in ischemic stroke suggests that this molecule may have indications in other thrombotic diseases like peripheral arterial occlusive disease (PAOD)". Statistics indicate a total of about 15 million people, in the US alone, suffer from CVC thrombosis or PAOD. A significant proportion of these patients would benefit from thrombolytic therapy as primary treatment or as an adjunct to surgical intervention, representing a potential pharmaceutical market of at least US $ 250 million. Following the withdrawal of the thrombolytic of choice for these indications, the regulatory authorities have identified this as an unmet need. Dr Goldhill indicates that “although Alteplase has recently emerged as the first-line therapy for occluded CVCs, there is no approved agent offering a clinically preferable option to surgery in acute limb ischemia." ThromboGenics is developing staphylokinase and its variants (SY161-P5 & SY162) and microplasmin which, like the first generation thrombolytic, streptokinase, are not only anticipated to be very cost effective - but in preliminary clinical trials they are very effective thrombolytics. Unlike streptokinase however, they have low antigenicity and are extremely selective for thrombus bound plasmin(ogen).

Dr Goldhill concludes, "New fields or old, inhibitors of angiogenesis or thrombolytics, ThromboGenics’ scientists have redefined existing approaches, emerging with a pipeline of novel opportunities for a range of unmet needs and serious conditions. We firmly believe that this company will play a key role in rolling forward medicine this decade". ThromboGenics is in discussions with a number of major pharmaceutical companies regarding licensing and co-development opportunities. “Moreover”, says Dr. Randall Moreadith, "We have a rich and rapidly developing pipeline and we expect this to be the tip of the iceberg. Our scientists in Belgium are some of the most prominent in the world, and our longstanding history in the fields of thrombosis and hemostasis provides us with unique insight and opportunities".

In short, ThromboGenics’ portfolio offers many new approaches to the field of cardiovascular disease. This portfolio, including an overview of the company's angiogenesis and staphylokinase programs is described in Pipelines, which can be found at http://www.leaddiscovery.co.uk/pipelines/ThromboGenics.html.

LeadDiscovery is a UK based pharmaceutical consultancy company supported by a web platform (www.leaddiscovery.co.uk) offering three key services. TherapeuticAdvances is a bulletin of cutting edge research with commercial potential circulated to over 4,500 industrial personnel. DiscoveryDossiers represent in depth analyses of drug discovery options selected by LeadDiscovery specialists or produced for institutions wishing to stimulate strategic partnerships. PharmaceuticalSolutions is a client-lead service through which LeadDiscovery is able to offer advice and project management relating to pre-clinical target selection and drug development.

 

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