Press releases

Release issued 18th February 2002

Cambridge UK, 14 February 2002: Alizyme plc (LSE:AZM) has obtained positive preliminary results in a Phase II clinical trial with COLAL-PREDTM in ulcerative colitis patients with active disease.

COLAL-PREDTM, consists of pellets of an approved steroid (prednisolone sodium metasulphobenzoate) coated with Alizyme's proprietary colon drug delivery system (COLALÔ) presented in a capsule. The trial's objective was to demonstrate that the local release of the drug in the colon would provide efficacy without the usual undesirable side effects caused by steroid treatment.

A total of 37 patients with mild to moderate ulcerative colitis were enrolled into the randomised, double blind, parallel group study which was conducted in specialist gastroenterology clinics in the UK. The patients received either 60 or 40 mg of COLAL-PREDTM daily for four weeks, after which the dose was tapered off over the next three weeks. Patients' response was assessed by the Disease Activity Index ('DAI') and the Physicians Global Assessment ('PGA') which include patient symptoms, colonoscopic score and biopsy.

The preliminary results demonstrate an improvement in DAI and PGA in both the 60 and 40 mg patient groups of 63% and 35% respectively. This was associated with a clinical remission rate of 31% and 6% in these respective patient groups. These results are comparable with data from other clinical trials reported in the literature for conventional prednisolone formulations and dosing regimens.

COLAL-PREDTM was well tolerated, with no steroid-related adverse events. Morning cortisol levels, a marker of systemic side effects of steroids, were not changed from baseline at any time during the treatment period.

The data obtained has formed the basis of a new patent application that has been filed for COLAL-PREDTM.

"Obtaining a clinical response in ulcerative colitis patients without the usual debilitating steroid side-effects would be an important advance and these results with COLAL- PREDTM are very promising." said Prof. Christopher Hawkey, Consultant Gastroenterologist, Queens University Medical Centre, Nottingham, one of the investigators.

These results provide the basis for discussions with regulatory authorities in preparation for pivotal Phase III trials for treatment of active ulcerative colitis in Europe, which are planned to start by the end of 2002. This Phase III development is not expected to be as extensive as normally required for a new therapeutic agent, as it should be able to take advantage of the fact that the prednisolone derivative used is already approved in several European countries. The excellent safety profile demonstrated in this Phase II trial also underpins the rationale for a trial in the maintenance of remission. Approval by the UK Medicines Control Agency for a Phase III trial in this indication is separately announced today.

Approximately one million patients suffer from ulcerative colitis worldwide. The current market for ulcerative colitis drugs is estimated to be worth at least $500 million per annum and provides an attractive opportunity for a product with the profile of COLAL-PREDTM, which could contribute substantially to the continued growth in the value of this market.

Dr. Richard Palmer (Chief Executive Officer) commented:

"I am extremely pleased with these results as they provide proof of the product concept for COLAL-PREDTM and validate the specificity of the COLALTM colon delivery technology in patients. They provide the basis for moving this product into pivotal Phase III trials in preparation for product approval and commercialisation. In addition, the results enhance the opportunity for exploiting the COLALTM technology platform with other drugs."

For further information, please see Pharmalicensing profile for Alizyme PLC:

Dr Richard Palmer, Chief Executive Officer ALIZYME plc

Mr Tim McCarthy, Finance Director ALIZYME plc

Lisa Baderoon/Tim Anderson - Buchanan Communications

Editors Note

Alizyme plc

Alizyme is a biopharmaceutical company, based in Cambridge, UK, targeting the treatment and management of gastrointestinal disorders, obesity and diabetes. It has a portfolio of products which in addition to COLAL-PREDÔ includes ATL-1251 (Phase IIb for irritable bowel syndrome), ATL-962 (recently completed Phase I for obesity) and ATL-104 (recently completed Phase Ia for mucositis caused by cancer therapy). At the appropriate time Alizyme intends to license products to established pharmaceutical companies which will complete development, gain marketing approval and commercialise the products.

Inflammatory bowel disease and ulcerative colitis.

Inflammatory bowel disease describes two similar yet distinct inflammatory conditions, ulcerative colitis and Crohns' disease. These diseases affect the intestines and the digestive system. Symptoms include abdominal pain, cramping, bleeding, diarrhoea and fatigue. Ulcerative colitis is confined to the large intestine (colon) whereas Crohns' disease usually occurs in the small intestine.

Ulcerative colitis is a serious condition which cannot be completely cured by drugs and severe sufferers may eventually have to undergo surgery. Patients experience flare-ups of the disease for which the first line treatment usually involves steroids (e.g. prednisolone or prednisone). The dosage levels and the period of steroid treatment is restricted by the side effects which result from suppression of adrenal gland activity. When the inflammation subsides the patients are termed to be 'in remission', but usually need continued treatment with anti-inflammatory products (e.g. those based on 5-amino salicylic acid) to 'maintain' them in this state. The current drugs for 'maintenance of remission' are not completely effective and patients typically experience 1 to 2 flare-ups of active disease each year when a return to treatment with more potent anti- inflammatory drugs, such as steroids, is required. Not all patients respond to steroids and these may be treated with other anti-inflammatory preparations including new, and higher priced, drugs such as RemicadeÒ.

IBD affects over two million patients worldwide, over half of which have ulcerative colitis.

COLALÔ

COLALÔ is a drug delivery technology which enables drugs to be taken orally and then be specifically released when the preparation reaches the colon. Achieving colonic release with conventional oral dosage forms has proved difficult because of the variation between individuals in transit times and conditions within the gastrointestinal tract. COLALÔ overcomes this difficulty by covering small pellets containing the drug with a coating of ethylcellulose and a specific form of amylose (derived from starch). This coating prevents drug release in the stomach and small intestine. When the pellets reach the colon the amylose in the coating is broken down by bacterial enzymes and the drug is released.

Alizyme owns proprietary rights to use COLALÔ and is exploring the potential use of COLALÔ with other products.

COLALÔ and COLAL-PREDÔ are trademarks of Alizyme Therapeutics Limited.

The identification of compounds for successful research, their progress through development and the obtaining of regulatory approvals or authorisations before marketing, manufacture and/or distribution of products is not certain or a formality.

(18th February 2002) Alizyme obtains approval for Phase III clinical trial of COLAL-PREDTM in maintenance of Remission of Ulcerative Colitis

(17th January 2002) Successful clinical trial completion for Alizyme's Mucostis drug ATL-104

(18th December 2001) Stewart Siddall Resigns Due To Retirement

(17th December 2001) Obesity Drug Completes Phase I Clinincal Trial

(17th December 2001) Colal-Pred Completes Dosing in Phase II Trial