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JMV 1843 : a Ghrelin Receptor Agonist Candidate for Clinical Development

JMV 1843 : a Ghrelin Receptor Agonist Candidate for Clinical Development. JMV 1843 pharmacological profile Binding affinity to GHS-R1a: IC 50 = 40 nM Binding affinity to h-Pituitary Glands: IC 50 = 23 nM Binding affinity to h-Hypothalamus: IC 50 = 15 nM

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JMV 1843 : a Ghrelin Receptor Agonist Candidate for Clinical Development

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  1. JMV 1843: a Ghrelin Receptor Agonist Candidate for Clinical Development • JMV 1843 pharmacological profile • Binding affinity to GHS-R1a: IC50 = 40 nM • Binding affinity to h-Pituitary Glands: IC50 = 23 nM • Binding affinity to h-Hypothalamus: IC50 = 15 nM • Activation of GHS-R1a in vitro (calcium release) ED50 = 0.8 nM • GH secretagogue effect by i.v., s.c. injection in rats • GH secretagogue effect by s.c. and oral route at 1 mg/kg in dogs • Requirements for the performance of a first trial in humans • Preparation of amount of substance necessary for the preclinical studies at a GMP (Good Manufacturing Procedure) quality • Acute toxicity studies in males and females of 2 animal species • No toxic dose of JMV 1843 by i.v. route: 30 mg/kg • Toxicity after repeated administration (2 to 4 weeks) in 2 animal species • Maximum tolerated dose of JMV 1843: 3 mg/kg/day by i.v. route • Safety pharmacology tests including central nervous system, cardio-vascular system, gastro-intestinal and metabolic assays • Evaluation of mutagenic potential • Preparation of a pharmaceutical formulation suitable for i.v. and oral administration in humans • Clinical trial authorization after approval by an Ethic Committee

  2. Phase 1 Clinical Study of JMV 1843 Administered by Oral Route (Healthy Males) OBJECTIVES To demonstrate the effect of JMV 1843 on GH secretion To investigate the effect on ACTH; Cortisol; Ghrelin; Prolactin; Insulin and Glucose To delineate the pharmacokinetic profile of JMV 1843 To assess safety/tolerability METHODS 36 healthy, male subjects were included in this study A dose escalation study investigating 5 different doses (0.005; 0.05; 0.125; 0.25 and 0.5 mg/kg) of JMV 1843 as a single oral administration of an aqueous solution in comparison to a placebo

  3. Phase 1 clinical study of JMV 1843 administered by oral route • JMV 1843 was well tolerated and no adverse events were reported • Maximal GH release was achieved following 0.5 mg/kg orally • Maximal GH release is achieved when plasma levels of JMV 1843 are between 5 – 6 ng/ml • Stimulation of GH appears to be selective as no other hormones measured were affected by administration of JMV 1843 (No effects on ACTH; cortisol; ghrelin; prolactin; insulin and glucose) • Next development phase is Phase 2 clinical study in cachectic cancer patients who can benefit from the anabolic effect of GH stimulated by JMV 1843

  4. Edinburgh, UK, 21 May 2007; Ardana today announces that the US Food and Drug Administration (FDA) has granted Orphan Drug status for ARD-07 (JMV1843), its oral Growth Hormone Secretagogue (GHS), which Ardana is developing as a diagnostic for growth hormone deficiency in adults. The diagnostic clinical development and toxicology programmes are ongoing and, subject to clinical outcome, the Company anticipates filing for registration at the end of the year with a possible launch in 2008. Ardana believes that GHS’ oral formulation will give clinicians a simpler and more effective test for growth hormone deficiency. Dr. Maureen Lindsay, Ardana’s CEO, said: “We are delighted and very encouraged that the FDA have granted Orphan Drug status for GHS. We believe that GHS could play a very important role in providing clinicians with a convenient, reliable and effective diagnostic test for growth hormone deficiency.” In addition to its possible use as a diagnostic, Ardana intends to undertake clinical trials to support registration of GHS in a number of adult therapeutic indications.

  5. ARDANA COMMENCES PHASE III REGISTRATION TRIAL FOR ITS ORAL GROWTH HORMONE SECRETAGOGUE DIAGNOSTIC Edinburgh, UK: 8 August 2007 : Ardana plc (LSE:ARA) today announces the commencement in the USA of a planned pivotal registration study of its oral growth hormone secretagogue (GHS) ARD-07 (JMV1843) which is in development for the diagnosis of growth hormone deficiency in adults. Results from the study are expected in the second half of 2007 and the Company anticipates filing for registration at the end of the year with a possible launch in 2008. This phase III study is a multi-centre, randomized, cross-over study investigating the safety and effectiveness of oral GHS as a Growth Hormone (GH) stimulation test. The study will be conducted under an Investigational New Drug (IND) application accepted by the U.S. Food & Drug Administration (FDA) in 10 centres in the USA with 80 subjects. Half of the subjects will be patients with proven GH deficiency and the other half will be matched controls (healthy subjects). As previously announced, the FDA granted Orphan Drug status for GHS in May 2007. Dr Maureen Lindsay, Ardana’s CEO said “This trial is an important step forward in the development of GHS, which we believe could play a pivotal role in the diagnosis of growth hormone deficiency by providing clinicians with a convenient, reliable and effective diagnostic test.”

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