Adenosine Therapeutics Group
The acquisition of Adenosine Therapeutics in August 2008 expanded Clinical Data’s PGxHealth Division’s pipeline of therapeutics, to include drug candidates in cardiology, diabetes, inflammatory diseases and sickle cell anemia. The acquisition added Stedivaze™ (apadenoson), which is expected to enter Phase III testing in 2009 as a pharmacologic stress agent for myocardial perfusion imaging. Adenosine Therapeutics brings to PGxHealth an expansive molecular library of small molecules that act as highly selective agonists or antagonists for adenosine receptors. Adding the Adenosine Therapeutics Group to the PGxHealth division expands the therapeutics pipeline with both pre-clinical and clinical compounds, and acquired world-class expertise on the pharmacologic and physiologic roles of adenosine and its receptor subtypes.

The Adenosine Therapeutics Group strives to discover, develop and commercialize novel, therapeutic compounds acting on adenosine receptors through its exclusive, worldwide rights to an extensive pipeline of adenosine-related products and technology. The group has published over 100 scientific papers on the pharmacology and physiology of adenosine and has designed and synthesized hundreds of unique compounds. These efforts have led to compounds that have been identified for five separate programs. Forty years of research has lead to identifying multiple adenosine candidates for clinical development.

Adenosine is a naturally occurring, physiologically active molecule that is produced in many sites in the body in response to multiple stimuli for example, hypoxia, or metabolic activity). Adenosine binds locally to a number of different receptors to regulate cell functions and/or physiological responses such as vasodilation, heart rhythm, and glucose control. Adenosine mediates these effects by activating specific adenosine receptors found on cell membranes: A1, A2A, A2B and A3).

Each of the four adenosine receptor subtypes is coupled to a cell protein called the G-protein which is capable of stimulating (Gs protein) or inhibiting (Gi protein) the production of the intracellular signal transduction molecule, cyclic adenosine monophosphate (cAMP). Changes in the levels of cAMP affect the activity of intracellular protein kinases that in turn phosphorylate intracellular proteins or transmembrane ion channels (e.g., calcium (Ca++) or potassium (K+)). The phorphorylation of these proteins or ion channels results in specific physiological responses such as the vasodilation associated with activation of the A2A ). The illustration shows also that the A1 receptor is coupled to a (Go protein) that can act to directly modulate the transport of potassium (K+).

Depending on the location and expression of each receptor subtype, adenosine modulates a wide variety of physiological responses. However, the utility of adenosine as a therapeutic agent has been limited by lack of selectivity for the different receptor subtypes, thus triggering a broad range of undesirable effects or exaggerated responses.

Adenosine Therapeutics (AT) has developed technology that enables the development of small molecules that act as selective agonist (receptor activators) or antagonist (receptor blockers) at specific adenosine receptor subtypes. By designing molecules that can selectively activate or block the activation of these receptors by endogenous adenosine, AT’s molecules are able to evoke a receptor subtype specific pharmacodynamic effect, while minimizing or avoiding adverse or undesired effects from activity at other adenosine receptors.

To learn more about Adenosine Therapeutics Group drug development program, please view the pipeline. For investor questions, contact Dahlia Bailey at the EVC Group, 415-896-5862. For media inquires, contact Steve DiMattia at the EVC Group, 646-201-5445. For general business inquires about the Adenosine Therapeutics acquisition, email info@clda.com or (617) 527-9933 extension 3388.