Press Releases

Dublin, Ireland, April 20th 2006 - AGI Therapeutics plc ("AGI" or the "Company"), a speciality pharmaceutical company focused on gastrointestinal drug products, today reported the audited financial results for AGI Therapeutics Research Limited, formerly AGI Therapeutics Ltd, for the year ended 31 December 2005. AGI Therapeutics Research Limited is the operating subsidiary of AGI Therapeutics plc which was created as a holding entity prior to the Company's recent flotation.

The admission document for AGI Therapeutics plc, issued on 21 February 2006, included audited results for the years ended 31 December 2004 and 2003 and unaudited results for the nine months ended 30 September 2005 for AGI Therapeutics Research Limited.

AGI's listing on the AIM market of the London Stock Exchange and the IEX market of the Irish Stock Exchange on 27 February 2006 raised gross proceeds for the Company of €42.5 million (£29.2 million) through the placing of 33,730,159 ordinary shares at €1.26 (86.5p) per ordinary share.

2005 Operating Highlights

• Established the formulation, manufacturing methods and sources of supply, and manufactured clinical trial supplies for all six clinical product candidates
• Completed enrolment of Phase II trial in 132 patients for AGI-001 (espindolol) in functional dyspepsia
• Completed enrolment of Phase II trial in 128 patients for AGI-003 (arverapamil) in non-constipation dominant irritable bowel syndrome
• Completed enrolment of Phase II trial in 67 patients for AGI-001 (espindolol) in irritable bowel syndrome
• Initiated two further Phase II trials for AGI-004 (mecamylamine) in functional diarrhoea and AGI-006 (arbaclofen) in functional dyspepsia
• Grant of US Patent No. 6,849,661 for AGI-003

Post Period End Highlights

• Dr Ronan Lambe appointed non-executive Chairman (January 2006)
• Successful admission to trading on the AIM market of the London Stock Exchange and the IEX market of the Irish Stock Exchange raising net proceeds of €39.6 million (February 2006)
• Completed enrolment of Phase II trial in 82 patients for AGI-004 (mecamylamine) in functional diarrhoea (March 2006)
• Positive results in human pharmacokinetics trial of AGI-022 (4-aminosalicylate sodium), confirming the target controlled release and delivery (March 2006)
• Preliminary results from human pharmacokinetics and pharmacodynamics trial of AGI-010 (omeprazole) confirming controlled release profile. Profile will now be further optimized to target nocturnal acid breakthrough in gastro-esophageal reflux disease (March 2006)
• Mr. David G. Kelly appointed as Chief Financial Officer, effective as of 2 May 2006 (see separate announcement today)

Commenting on the 2005 results and on the outlook for 2006, Dr. John Devane, Chief Executive Officer of AGI, said:

"This has been a very pleasing period of progress for the Company, highlighted by our successful flotation earlier this year. During the last 12 months, we have initiated five Phase II clinical trials and a further two human pharmacokinetics and pharmacodynamics studies on our six clinical stage products. During 2006 we expect to complete and report on our five Phase II clinical trials and we can look forward to a significant stream of clinical news through the remainder of the year."

Chief Executive's Statement

Since we established AGI in 2003 to specifically focus on the development of a broad and balanced portfolio of products targeting the gastroenterology market, we have made significant progress both in advancing our current products from concept stage into human clinical trials and in strengthening the financial and operational capabilities of the company.

In 2004, we raised €9.5 million in an initial private funding. We sought this funding to allow us to undertake clinical trials for our six product candidates and establish their clinical profiles in a range of gastrointestinal clinical indications. During 2005, we successfully initiated five Phase II clinical trials and two human pharmacokinetic and pharmacodynamic studies on our six product candidates, along with undertaking all of the important formulation, manufacturing and regulatory work which was required to carry out these trials. Our clinical trials have progressed well and we expect they will be completed on schedule and within budget.

AGI's business model involves the use of third party providers to augment our internal capabilities, and we have established relationships and agreements with a number of high quality clinical research organisations (CROs) and other suppliers in support of our programmes.

During 2005, we deemed it was desirable that AGI would itself have the capability to continue to advance at least one of its lead products beyond the current stage of development in order to realise for the Company the significant added value which can accrue through late-stage clinical development, and we determined, with the support of our Board and shareholders, that the Company should seek to raise further capital to pursue this objective. In the second half of 2005, we began the process of planning for an AIM and IEX admission together with an institutional fundraising, which we successfully completed in February 2006, raising net proceeds of €39.6 million.

We are continuing to look to expand our intellectual property portfolio and to add new product candidates to our pipeline. During 2005, we also filed two new patent applications relating to the use of the KME drugs to treat constipation. We will continue to try to identify new KMEs with potential utility in gastrointestinal diseases and disorders which may themselves become clinical candidates in the future.

We are also continuing to seek to strengthen both our management team and our Board. We were fortunate in having Dr. Ronan Lambe join our Board last year, initially as an independent non-executive Director in December 2005 and subsequently as non-executive Chairman in January 2006. Dr. Lambe has provided excellent stewardship during our AIM and IEX admission process and we look forward to his continuing leadership and guidance as we seek to grow and further establish our business. We also appointed Paul Donnelly as interim Chief Financial Officer of the company in preparation for our admission. Paul's financial knowledge and experience was invaluable to us during this process. We have subsequently been able to announce the appointment of David Kelly as our permanent Chief Financial Officer, and we expect to announce further additions to our management team and Board during 2006 and into 2007.

We currently have six product candidates in clinical development, each of which we believe could address unmet medical needs in gastrointestinal disease categories where there are either few or no existing approved drug therapies or where the effectiveness of existing approved drug therapies can be improved. Our primary objective is to now complete all our ongoing clinical trials during the course of 2006 and, dependent on the results of these trials, to identify and select a lead product candidate which we will further develop by undertaking a Phase III clinical programme. We will also seek to enter into commercial partnering agreements for our product candidates and anticipate that we will be able to enter into some such partnerships by the end of 2006.

AGI's product candidates in clinical development are:

AGI-001 (espindolol) - Functional Dyspepsia

AGI-001 is an oral dosage form of the S-isomer of pindolol (espindolol) which is being developed for the treatment of functional dyspepsia, a functional disorder of the upper GI tract, in both men and women.

Functional dyspepsia, also referred to as non-ulcer dyspepsia or NUD, is a cluster of chronic or recurrent upper GI symptoms, including early satiety, abdominal distension and fullness and discomfort and pain, not associated with any known structural abnormality.

Estimates as to the prevalence of functional dyspepsia vary, with some studies suggesting that it affects up to 25 per cent of the US population annually and accounts for up to 5% of all visits to primary care physicians, while other studies report a prevalence of between 10 and 20 per cent of the population in the US and Europe. The incidence of functional dyspepsia in men and women is similar. No prescription therapeutic drug products have been found to have a high success rate in the treatment of functional dyspepsia and there are as yet no therapeutic drug products approved for its treatment in the US.

The Company has developed a solid oral dosage form of AGI-001 and a Phase II clinical trial evaluating the efficacy of AGI-001 in the treatment of functional dyspepsia is currently ongoing. This trial is a randomised, double-blind, placebo-controlled, parallel group, dose escalation trial conducted at multiple sites in Europe in a total of 132 functional dyspepsia patients. The trial is fully enrolled and the treatment phase is now complete. It is expected that preliminary results of this trial will be available in Q2, 2006.

AGI-003 (arverapamil) - diarrhoea-predominant Irritable Bowel Syndrome ("d-IBS")

AGI-003 is an oral dosage form of the R-isomer of verapamil (arverapamil) which is being developed by AGI for the treatment of diarrhoea-predominant irritable bowel syndrome ("d-IBS") in both men and women.

IBS is a functional disorder (i.e. an abnormality or disturbance of normal function which cannot be directly attributed to anatomical or biochemical defects) that comprises a cluster of gastrointestinal symptoms which are likely to be life long and can include diarrhoea, constipation, abdominal pain and distension, which vary in intensity. Altered intestinal motility is a major component of IBS and patients are diagnosed and sub-typed according to their predominant symptom of bowel disturbance as either "d-IBS", constipation-predominant ("c-IBS") or mixed/alternating symptoms of diarrhoea and constipation ("m-IBS").

The prevalence of IBS has been estimated in US population-based studies at between 10 and 20 per cent and surveys conducted in Europe estimate a similar range of IBS prevalence there. It is estimated that there is an approximate equal prevalence of each of the d-IBS, c-IBS and m-IBS sub-types. IBS is reported to be about twice as prevalent in women as in men. While an estimated 75 per cent or more of current sufferers remain undiagnosed and untreated, IBS remains the most common diagnosis made by gastroenterologists and leads to a substantial reduction in quality of life, accompanied by considerable socio-economic and psychological consequences.

AGI-003 is being targeted to compete in the diarrhoea-predominant segment of the IBS market, which is estimated to account for approximately one third of all IBS patients. The annual market for prescription therapeutic drug products for IBS in the US was estimated at more than US$350 million in 2003 and is predicted to grow rapidly to more than US$1 billion by 2010. These sales are currently largely for products treating the c-IBS component, and whose use is currently restricted to women only.

A solid oral dosage form of AGI-003 has been developed by the Company and a Phase II clinical trial evaluating the efficacy of AGI-003 in the treatment of non-constipation predominant irritable bowel syndrome is currently ongoing. This trial is a randomised, double-blind, placebo-controlled, parallel group, dose escalation trial conducted at multiple sites in Europe in a total of 128 non-constipation predominant IBS patients. This study is fully enrolled and the treatment phase is now complete. It is expected that preliminary results of this trial will be available in Q2, 2006.

AGI-001 (espindolol) - Irritable Bowel Syndrome

AGI-001 is also being developed by the Company for the treatment of irritable bowel syndrome in both men and women.

The Company has developed a solid oral dosage form of AGI-001 and a Phase II clinical trial evaluating the efficacy of AGI-001 in the treatment of irritable bowel syndrome is currently ongoing. This is a randomised, double-blind, placebo-controlled, parallel group, dose escalation trial conducted over multiple sites in Ireland in a total of 67 patients. This study is fully enrolled and the treatment phase is now complete. It is expected that preliminary results of this trial will be available in Q2/Q3, 2006.

AGI-004 (mecamylamine) - diarrhoea-predominant Irritable Bowel Syndrome
("d-IBS")

AGI-004 is a controlled release transdermal patch containing mecamylamine which is being developed by AGI for the treatment of diarrhoea-predominant irritable bowel syndrome ("d-IBS") in both men and women.

AGI-004 is a controlled release form of mecamylamine with a lower peak-to-trough drug exposure profile which, coupled with a reduction in daily dosage, has demonstrated marked GI effects and a reduction of the traditional non-GI ganglion blocking effects. AGI has developed a controlled-release transdermal dosage form of AGI-004 and a Phase II clinical trial evaluating the efficacy of AGI-004 in the treatment of functional diarrhoea is currently ongoing. This trial is a randomised, double-blind, placebo-controlled, parallel group, dose escalation trial conducted at multiple sites in the US and Israel in a total of 82 functional diarrhoea patients. This study is fully enrolled and the treatment phase is ongoing. It is expected that preliminary results of this trial will be available in Q3/Q4, 2006.

AGI-006 (arbaclofen) - Functional Dyspepsia

AGI-006 is an oral dosage form of the R-isomer of baclofen (arbaclofen) which is being developed by AGI for the treatment of functional dyspepsia in both men and women.

A solid oral dosage form of AGI-006 has been developed and a Phase II clinical trial evaluating the efficacy of AGI-006 in the treatment of functional dyspepsia in both men and women is currently ongoing. This is a randomised, double-blind, placebo-controlled, parallel group, dose escalation trial conducted at multiple sites in Europe. Completion of enrollment is targeted for Q2/Q3 2006 and it is expected that preliminary results will be available in Q4 2006/Q1 2007.

AGI-022 (4-aminosalicylate sodium) - Ulcerative Colitis

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 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. 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 profiles 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 (omeprazole) - Gastro-Esophageal Reflux Disease (Nocturnal Acid Breakthrough)

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 compared to marketed omeprazole (PrLosec®). 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 6am). The Company plans to complete the optimisation of a lead formulation and a confirmatory human pharmacokinetics and pharmacodynamics study by the end of 2006.

Outlook

During 2006, AGI expects to complete and report on five Phase II clinical trials and the Company looks forward to a significant stream of clinical news through the remainder of the year. AGI is seeking in these trials to identify lead product candidates which can progress to further development for each of the important gastrointestinal clinical indications of functional dyspepsia and irritable bowel syndrome. The Company has two products in Phase II development for functional dyspepsia, AGI-001 (espindolol) which we expect to report in Q2, 2006 and AGI-006 (arbaclofen) which we expect to report in Q4, 2006/Q1, 2007, while there are three Phase II trials underway in irritable bowel syndrome, with AGI-003 (arverapamil) expected to report in Q2, 2006, AGI-001 (espindolol) expected to report during Q2/Q3, 2006 and AGI-004 (mecamylamine) results expected in Q3/Q4, 2006.

About AGI Therapeutics

AGI is a speciality pharmaceutical company which is focused on the development and commercialisation of differentiated drug products for gastrointestinal (''GI'') diseases and disorders.

The Company has a portfolio of product candidates derived from the Known Molecular Entity (''KME'') approach to drug re-profiling and development. KME is a re-profiling methodology used by the Company to identify existing therapeutic drugs which typically have been marketed for a number of years, have established safety profiles and can be developed for new clinical indications or with improved profiles in their existing clinical indications. In this way, the Company seeks to reduce the risk, time and cost of new product development as compared to the development of new chemical entities.

AGI has developed a range of product candidates to treat a variety of prevalent GI diseases and disorders, including irritable bowel syndrome, functional dyspepsia, ulcerative colitis and gastro-esophageal reflux disease. The Company is targeting areas of the GI therapeutic drug products market for its product candidates where there are currently unmet medical needs or where the effectiveness of existing drug therapies can be further improved.

The Company has six clinical stage product candidates which are either isomers or new drug delivery formulations of existing approved drugs, and which have established safety and tolerability profiles in their currently approved clinical indications. These product candidates are all in clinical development, including five Phase II trials.

AGI intends to complete its ongoing clinical trials and, dependent on the results of these trials, the Company will initiate Phase III development of a lead product candidate and will also seek to enter into licensing and development agreements with pharmaceutical companies so as to enhance the global market reach for its products and achieve optimal revenue and value opportunities for the Company.

Statements contained within this press release may contain forward-looking comments which involve risks and uncertainties that may cause actual results to vary from those contained in the forward-looking statements. In some cases, you can identify such forward-looking statements by terminology such as 'may', 'will', 'could', 'forecasts', 'expects', 'plans', 'anticipates', 'believes', 'estimates', 'predicts', 'potential', or 'continue'. Predictions and forward-looking references in this press release are subject to the satisfactory progress of research which is, by nature, unpredictable. Forward projections reflect management's best estimates based on information available at the time of issue.

< back to press releases