Dublin, Ireland, 29th March 2006
AGI Therapeutics plc reports results of clinical studies for two product candidates.
AGI Therapeutics plc ("AGI" or the "Company"), a speciality pharmaceutical company focused on gastrointestinal drug products, today reported the outcome of a clinical study on its AGI-022 product candidate and preliminary data from a clinical study on its AGI-010 product candidate. Both product candidates are modified release oral formulations of existing drugs used to treat gastrointestinal diseases.
Details of the Clinical Studies
AGI-022
AGI-022 is a delayed/controlled release oral formulation of 4-aminosalicylate sodium ("4-ASA-Na"), which AGI believes will be effective in the treatment of ulcerative colitis. AGI-022 is designed to release 4-ASA-Na in the lower gastrointestinal tract and so optimise the delivery of the drug to the affected sites in ulcerative colitis.
Ulcerative colitis is a chronic, recurrent, relapsing and remitting inflammatory disease of the colon and/or rectum, and its prevalence is estimated at almost 1 million patients across the seven major pharmaceutical markets (US, Japan, Germany, UK, France, Italy and Spain) and the incidence of new cases in these countries is estimated at 50,000 per annum. The aminosalicylate class of anti-inflammatory drugs is used to treat ulcerative colitis and many of those currently marketed are presented as modified release oral formulations. 4-ASA is an aminosalicylate drug which is not currently available in an oral modified release form for the treatment of ulcerative colitis. Global annual sales of aminosalicylate drug products used to treat inflammatory bowel diseases such as ulcerative colitis are currently estimated to be at least US$700 million.
AGI has completed and is now fully reporting on a human pharmacokinetics study in 16 healthy human subjects designed to characterise the in-vivo drug release profiles of three delayed release/ controlled release formulations of AGI-022 compared with a reference solution of 4-ASA-Na. Each study formulation was given as a single 250mg dose. The study demonstrated delayed in-vivo release profiles that correlated with the different in-vitro release patterns of the three formulations of AGI-022. In addition, the AGI-022 formulations achieved markedly reduced peak plasma levels (Cmax), and a reduced ratio of parent ASA to n-Acetyl metabolite levels, confirming the controlled release profile of the formulations.
Based on the plasma level and urinary excretion profiles observed in this study, one of the current formulations has been selected as optimal and will be the basis of future clinical development. AGI believes that AGI-022 may offer certain advantages compared with currently marketed 5-aminosalicylate ("5-ASA") therapies, including; a superior tolerability profile, a more reliable and targeted delivery to the affected sites in ulcerative colitis and a more efficient therapy with potential dose-sparing versus currently marketed 5-ASA therapies. Based on its controlled release profile, it is anticipated that AGI-022 would be dosed twice daily.
AGI is now seeking to enter into licensing agreements for AGI-022 with pharmaceutical marketing partners in order to complete development and registration of the product.
AGI-010
AGI-010 is a delayed/controlled release formulation of the proton pump inhibitor drug ("PPI"), omeprazole, which AGI believes will be effective in treating nocturnal acid breakthrough ("NAB"), a prevalent aspect of gastro-esophageal reflux disease ("GERD").
GERD is the most common of the major gastrointestinal disorders and its prevalence in the general population is estimated to range from 20 to 40 per cent. Proton pump inhibitors are commonly used drugs in the treatment of GERD and are one of the largest selling drug classes with global annual sales in excess of US$20 billion. NAB is estimated to occur in more than 70 per cent of h.pylori-negative and in up to 50 per cent of h.pylori-positive patients on PPI therapy and modification of the dosage regime of existing PPIs has only had limited success in controlling the symptoms of NAB despite improving acid suppression.
AGI has developed CHRONAB, an approach to the formulation of PPIs, to specifically address NAB. AGI's lead CHRONAB product candidate is AGI-010, which is a delayed/controlled release formulation of omeprazole, one of the most commonly prescribed PPI drugs. AGI-010 is designed to be taken once-daily at night-time and align PPI drug exposure with the period of NAB (typically midnight to 6am).
AGI has completed a combined human pharmacokinetics and pharmacodynamics study in 16 healthy human subjects to characterise the in-vivo drug release and the intra-gastric pH profiles of three delayed release/ controlled release CHRONAB formulations of AGI-010 given as 40mg once-daily at bedtime (fasted) compared to marketed omeprazole (PrLosec®) given as 20mg twice-daily morning and evening before meals. Each study formulation was dosed for five consecutive days. Preliminary data from the study demonstrates that each of the three AGI-010 formulations achieved a delayed/controlled release profile with a marked delay in the time-course of in-vivo release resulting in peak drug exposure (Tmax) at 7.8 hrs, 7.6 hrs and 8.6 hrs respectively post-dosing. Based on these results, AGI believes that the time course of drug release from the current formulations is over-extended and the release profile of AGI-010 will now be optimised to achieve a better alignment of drug release and absorption with the target NAB period (12 midnight to 6 am).
Commenting on the outcomes of these clinical studies, Dr. John Devane, Chief Executive Officer of AGI, said:
"We are very pleased with the final outcome of the clinical study on AGI-022. We are also encouraged by the preliminary data from the clinical study on AGI-010 and will now proceed to optimise a lead formulation from this study for further clinical testing. We believe that each of these products offers potential improvements to current therapy in ulcerative colitis and nocturnal acid breakthrough in GERD patients respectively and will target significant opportunities in these markets. We will now seek to out-license the commercial rights to AGI-022 so that the further stages of the development and regulatory process for this product can be completed in co-operation with marketing partners. In the case of AGI-010, we plan to complete the optimisation of a lead formulation and a confirmatory human pharmacokinetics and pharmacodynamics study by year end".
Contact Information
AGI Therapeutics
David Kelly, Chief Financial Officer
Tel: +353 1 449 3254
Financial Dynamics - UK
Sarah MacLeod
Tel: +44 (0) 20 7831 3113
Financial Dynamics - Ireland
Aisling Garvey
Tel: +353 1 663 3607