NeuTec: MRSA, Cancer, Candidiasis, up for "grabs"

NeuTec Pharma plc is a biopharmaceutical company formed in 1997 specialising in the development of genetically recombinant antibodies, or "grabs", for the treatment of life-threatening infections.

The development of NeuTec's products differs from the traditional approach used by conventional pharmaceutical companies which screen numerous chemical compounds for activity against bacteria and fungi. Many of these compounds will be too toxic for human use. In contrast, NeuTec identifies naturally occurring potentially protective antibodies from patients who have recovered from infection and then uses its platform technology Fabtec(R) for the identification of new therapeutic antibody fragments. As a result, these "grabs" are likely to be intrinsically safer than antibiotics.

NeuTec's two leading drug candidates are Mycograb(R), which targets systemic candidiasis, and Aurograb(R), which targets Staphylococcus aureus including methicillin-resistant Staphylococcus aureus ("MRSA"). A confirmatory study completed in 2004 using Mycograb(R) demonstrated that use of this hsp90 inhibitor is highly effective in improving outcome and reducing mortality when given in combination with conventional antifungal drugs to patients with invasive fungal infections.

Hsp90 and cancer: there is increasing evidence that hsp90, as a molecular chaperone, plays an important role in the development, maintenance and progression of cancer, and as such hsp90 has been identified as a target for new cancer therapies (Workman 2004). Normally in humans, hsp90 is resident within the cell and functions intracellularly, acting as a cytosolic molecular chaperone (Picard 2004). But in certain types of cancers it appears on the cell surface. Hsp90 can function in the extra cellular space and has recently been found to be necessary for the extra cellular maturation of the matrix metalloproteinase MMP2, which is a secreted protein, known to be mediator of invasion by cancer cells. By assisting MMP2, hsp90 promotes the migration of cancer cells through the extra cellular protein meshwork (Picard 2004). Antibodies to hsp90 have been shown to cause a loss of invasiveness.

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Results / News
10 October 2005
Preliminary Results for the Year Ended 30 June 2005
NeuTec Pharma plc, the biopharmaceutical company exploiting the value of combination therapy in drug resistant infection and cancer, today announces its preliminary results for the year ended 30 June 2005.

NeuTec has taken genetically recombinant antibody ("grab") based therapeutic products directed towards life threatening infections to a late stage of clinical development. These grabs target hospital-acquired infections such as invasive candidiasis and MRSA, where there is a persistent failure to respond to conventional single drug therapy. Currently there is a validated application for market authorisation for the lead product Mycograb(R), an orphan drug, which has been submitted to the EMEA.

For the year ended 30 June 2005 the Company recorded a loss on ordinary activities before taxation of #3,922,000, compared with a loss in the corresponding period of #3,057,000. The increase in the loss is in line with expectations and is largely due to the increased expense in making an application to the European Regulator, in rolling out a commercialisation programme and in the initiation of new clinical trials (in advanced breast cancer and cryptococcal meningitis). Net cash inflow during the year was #20,652,000 (2004: outflow of #2,885,000) and cash balances at the year end were #28.6 million (2004: #7.9 million). The increase in cash balances reflects the receipt of #24,543,000 in August 2004, being the net proceeds from the successful Placing and Open Offer.

Key Points

* Mycograb(R), which binds to heat shock protein 90 ("hsp90"):

* application has been made to the EMEA for market authorisation in the treatment of invasive candidiasis. The Common Technical Document has been validated and a list of questions has been received from the Regulator. The Company is currently preparing its response to these questions and is intending to reply within the expected timetable;
* thirteen patients have been recruited in a multi-centre phase Ib open-label study to evaluate the safety and efficacy of Mycograb(R) administered in combination with Docetaxel in metastatic or recurrent breast cancer patients; and
* a successful application to the FDA for an Investigational New Drug ("IND") has been achieved for a phase III study to assess the efficacy and safety of Mycograb(R) as adjunctive therapy for cryptococcal meningitis in patients with AIDS.

* Commercialisation programme for the sale of Mycograb(R) in Europe:
* appointment of managerial level for European sales team;
* initiation of a compassionate use programme;
* manufacturing strategy in place to pursue regulatory approval and reduce cost of goods;
* leases entered into for European sales hub and new laboratory in the Manchester Science Park; and
* marketing strategy for conference and publication programmes to maximise product visibility.

* Aurograb(R), which targets methicillin resistant Staphylococcus aureus ("MRSA"), the hospital 'superbug':

* 121 patients have been enrolled in the phase III multi-centre, double-blind, placebo-controlled clinical trial. The study involves the recruitment of 150 evaluable patients with deep-seated staphylococcal infections.

Summary

Anthony Martin, Chairman, commented:

"NeuTec Pharma has continued to explore the potential clinical indications for its lead product, Mycograb(R): a validated application to the EMEA was made in March 2005 for the treatment of invasive candidiasis, a successful IND application has been made for the treatment of cryptococcal meningitis and recruitment is progressing well in a phase Ib breast cancer study. Additionally, our phase III clinical study using Aurograb(R) in MRSA patients is nearing completion of patient recruitment."

14 March 2005
Interim Results for the Six Months Ended 31 December 2004

NeuTec is developing a portfolio of antibody-based therapeutic products designed to treat life-threatening infections. The first of these, Mycograb(R), has successfully finished a Confirmatory Study in the treatment of disseminated candidiasis. The application process for Market Authorisation in Europe has commenced.

Financial Results
During the six month period to 31 December 2004, the Company recorded a loss before taxation of #1,643,000 (31 December 2003: #1,189,000). The increase in the loss reflects the commencement of commercial scale manufacturing of the lead product, Mycograb(R). The cash balance at the period end was #30,403,000 an increase of #20,982,000 since 31 December 2003, principally due to the receipt of #24,543,000 (net of issue costs) resulting from a successful Placing and Open Offer in July 2004.

Key Points
Mycograb(R), targeting invasive yeast infections, which can affect almost any part of the body:
* Reported the successful completion of a Confirmatory trial in July 2004
* Convincing statistical significance reported for both primary and secondary endpoints
* Significant reduction in Candida-attributable mortality
* Process of application for market authorisation in Europe commenced with delivery of the Common Technical Document to EMEA
* Progress to date consistent with market launch in 2006

Other Mycograb(R) developments:
* Commercial scale manufacturing contracts signed with, and technology transfer completed to, second larger scale CMO
* Contracts signed for future clinical studies in both Cryptococcus neoformans (in US, South America and South Africa) and in Carcinoma of the breast (Europe)
* Programme underway for presenting at International Conferences and Congresses
* Key European Countries identified for product launch pending market approval
* Appointment of Mr Alan Cooke as Head of Product Development
* Programme for a Named Patient Supply instigated

Aurograb(R), which targets methicillin-resistant Staphylococcus aureus ("MRSA"),
the hospital 'superbug':
* Phase III clinical trial progressing with completion of patient enrolment expected in 2005

Intellectual Property
* Continued strengthening of IP position via filing and granting of new patents

Anthony Martin, Chairman, commented:
"NeuTec continues to make excellent progress in transforming the Company into a successful bio-pharmaceutical business. Mycograb(R) has clearly demonstrated an impressive safety and efficacy profile and we remain confident of the drug's commercial prospects. The Company is now well funded and continues to make good progress with a low cash burn. Our phase III Aurograb trial for MRSA is progressing on schedule and we expect to complete recruitment in 2005."

Chairman's Statement
Substantial progress has been made in the first half of the financial year. The Company successfully raised #24.5 million in August 2004. We have moved our lead product further towards commercialisation and have secured an additional contract manufacturer as well as strengthened our management team. We have also made a number of advancements in other parts of the business through our
clinical trials programme.

Mycograb(R)
Mycograb(R), the Company's lead product, is based on a naturally-occurring human antibody response against hsp90, which helps the body defend itself against life threatening fungal infections. Invasive candidiasis, a fungal infection that occurs when Candida causes deep-seated infections and then spreads throughout the body, is the fourth most common blood stream infection among hospitalised patients. The mortality rate due to this infection has been reported as 10-19% on existing therapies.

- Clinical Trials
In July 2004 the Company reported the successful completion of a multi-national, double-blind, placebo-controlled trial to combat life-threatening fungal infection due to various species of the yeast Candida. The Confirmatory study involved 139 patients at 26 centres in 10 European countries and 2 sites in the US and demonstrated convincing statistical significance (P less than 0.001) both for the primary composite endpoint (clinical and culture-confirmed resolution of infection by day 10) and in separate evaluations of the two components of the combined endpoint.

A second clinically important endpoint used was Candida-attributable mortality at the four week follow-up visit (Day 33), and again there was a statistically significant difference between the treatment arms (P=0.025). As an additional culture-based endpoint, speed of culture-confirmed resolution of the infection was examined and this was over twice as fast in the Mycograb-treated group compared with placebo.

As a result of the above findings, NeuTec announced its intention to apply for market authorisation in Europe for Mycograb(R) in the treatment of invasive candidiasis in combination with amphotericin-B. NeuTec has begun the process of applying for market authorisation in Europe by delivering a Common Technical Document ("CTD") to the European Medicines Evaluation Agency ("EMEA"). Progress to date is consistent with a timetable for the market launch of Mycograb(R) in 2006.

- Programme for Compassionate Use
The Company has instigated a limited Named Patient Supply of Mycograb(R) using a UK based registered and licensed drug distributor who will provide initial distribution into the UK and Europe.

- Manufacturing
In November 2004 NeuTec signed a contract with CMC Biopharmaceuticals ("CMC"), a Contract Manufacturing Organisation based in Denmark specialising in E.coli fermentation. CMC are a full service provider who will provide process development, manufacturing, analytical and quality control services to NeuTec. The technology transfer process has completed successfully and scale up of production into a larger scale fermentation suite is currently taking place.

Additionally, a contract was signed last month with BioReliance Manufacturing GmbH, our existing manufacturer, for the production of additional stocks of Mycograb(R) for use in future clinical trials or for commercial sale.

- Commercial Programme
Mr Alan Cooke was appointed as Head of Product Development in October 2004. Previously, Alan spent 10 years involved in initiating the European sales of the first liposomal amphotericin-B in Europe.
NeuTec's market analysis has identified the key European centres for early product launch pending market approval. The Company believes its strategy of directly selling the product in Europe will maximise shareholder value from this product.

The Company is preparing to present at a series of Industry Meetings and Congresses in 2005. Members of the Mycograb(R) Study Group will be presenting on behalf of NeuTec at the International Society of Intensive Care and Emergency Medicine ("ISICEM") Conference in Brussels at the end of March and at the European Congress of Clinical Microbiology and Infectious Diseases ("ECCMID") in Copenhagen in April 2005.

- New indication: Cryptococcal Meningitis
A contract was signed in December 2004 with a division of Ingenix Pharmaceutical Services (UK) Limited for a phase III randomized, double-blind, and placebo controlled study to evaluate the safety and efficacy of Mycograb(R) to be employed as an add-on therapy to recommended induction treatment of cryptococcal meningitis. This study will take place in US and South America and a further study will commence in AIDS patients in South Africa. All of these trials are dependent upon obtaining regulatory and ethical approval.

The results from these studies will broaden the patient database, with respect to safety, to a non-intensive care unit-based patient population and at the same time explore an additional indication for the drug in combination with conventional rather than liposomal amphotericin B.

Cryptococcus neoformans has a high mortality rate: in the US, for example, mortality from this infection has recently been reported as varying from 11% to 21%. In vitro testing has demonstrated synergy between amphotericin-B and Mycograb(R) against this fungal infection. The Company recently published a paper in Diagnostic Microbiology and Infectious Disease 51 (2005) entitled "Evaluation of Mycograb(R), amphotericin-B, caspofungin, and fluconazole in combination against Cryptococcus neoformans by checkerboard and time-kill
methodologies."

- New indication: Cancer
A contract was signed in February 2005 with Pharm-Olam International Limited for a pharmacokinetic open-label study evaluating the safety and efficacy of Mycograb(R) administered intravenously in combination with a Taxotere (docetaxel). The study will involve approximately 20 patients with advanced carcinoma of the breast (phase Ib) and will take place in two European countries pending regulatory and ethical approval.

Aurograb(R)
Aurograb(R), which targets MRSA, is progressing through a double-blind placebo-controlled phase III clinical trial. The study commenced in May 2004 and involves the recruitment of 150 evaluable hospitalised patients with deep-seated staphylococcal infections. To date 74 patients have been recruited in 19 centres in 5 European countries. Following recent regulatory approval, a number of French centres are about to be initiated, increasing the number of active countries in the trial to six. There is a high incidence of MRSA in France and given current recruitment rates in the existing active centres we anticipate the completion of patient enrolment in 2005.

Methicillin Resistant Staphylococcus aureus, MRSA, is regarded as the hospital 'superbug' by virtue of its ability to spread and cause outbreaks with a high mortality rate of up to 60%.

Fatal and non-fatal cases have risen 15-fold in the last decade. Recently, the UK's Office for National Statistics figures revealed the number of deaths linked to MRSA doubled in the four years between 1999 and 2003, to 955. From April to September 2004, 3,519 NHS patients were infected with MRSA. It is estimated that the NHS spends around #1 billion per annum on hospital-acquired infections including MRSA.

Financial Results
The loss before taxation for the half year amounted to #1,643,000, compared with a loss in the corresponding period of #1,189,000. The increase in the loss is principally due to the commencement of commercial scale manufacturing of Mycograb(R), which accounted for #696,000 (2003: #nil).

Encouraged by the clinical data on Mycograb(R) and the near term opportunities available to create significant shareholder value, NeuTec successfully raised additional equity funds of #24.5 million (net of expenses) through a Placing and Open Offer in July 2004. As a result, the Company is well funded with cash balances at 31 December 2004 amounting to #30.4 million. Cash outflow continues to be managed very tightly and during the period under review the cash outflow (excluding the effect of the equity fund raising) amounted to #2,060,000,
compared with #1,392,000 in the corresponding period. This movement was in line
with our expectations.

Intellectual Property
During the period under review NeuTec has continued to strengthen its intellectual property rights portfolio. For example, the first patent has been granted in Europe on FABTEC(R), the Company's proprietary technology platform, and further patents have been granted against the hsp90 homologue in bacteria.

Outlook
We are making good progress in transforming NeuTec Pharma into a successful bio-pharmaceutical business in a specialist niche area using antibody based drugs. In the short to medium term we are seeking to increase the value of Mycograb(R) by demonstrating its clinical efficacy in other medical conditions whilst preparing for its market launch in 2006 in Europe for the treatment of invasive candidiasis. Additionally, we are working to complete the phase III study for Aurograb(R) in MRSA. With a pipeline of promising drugs and a healthy balance sheet, we look to the future with confidence.

Anthony Martin Ph.D
Chairman
14 March 2005