OXFORD BIOMEDICA ANNOUNCES ENCOURAGING RESULTS FROM THREE PHASE II TRIALS OF TROVAX IN PATIENTS WITH COLORECTAL CANCER

Oxford BioMedica (LSE: OXB), the leading gene therapy company, today announces encouraging results from three ongoing Phase II trials of TroVax, its lead cancer immunotherapy, in the treatment of metastatic colorectal cancer.

Highlights of the Phase II trial results:

• In two trials in the first line setting in combination with chemotherapy:
  • 25 patients are evaluable for immunological responses
  • 19 patients are evaluable for tumour responses (tumour stabilisation and tumour shrinkage)
  • The primary endpoints of safety and immunological responses have been achieved
  • The secondary endpoint of clinical benefit has exceeded expectation
  • The immune response rate was exceptionally high. All 25 patients mounted immune responses to the 5T4 tumour antigen
  • The tumour response rate was better than expected. Eighteen of 19 patients responded to treatment (three complete responses, ten partial responses and five disease stabilisations)
  • Chemotherapy did not affect the frequency of immune responses compared to the Phase I/II trials in second line treatment
• In Cancer Research UK's trial in the (neo) adjuvant to surgery setting, all eight evaluable patients mounted immune responses
• In all three trials, TroVax has an excellent safety profile to date. No serious adverse events were attributed to the product

New data from two trials in first line treatment of metastatic colorectal cancer with concomitant chemotherapy have confirmed previous indications that the primary endpoints of safety and immunological responses have been achieved. All patients that have reached the interim stage of the trial have shown an immune response to the 5T4 tumour antigen.

Today, the Company is also reporting that, in the two trials, the secondary endpoint of clinical benefit has exceeded expectation. Eighteen of 19 evaluable patients responded to treatment. Whilst five patients had disease stabilisation following treatment, 13 of the 19 patients were defined as clinical responders according to industry standard criteria. These comprised three complete (total tumour shrinkage) responders and ten partial (more than 30 per cent tumour shrinkage) responders.

In addition, analysis of the first evaluable patients in a third Phase II trial of TroVax in colorectal cancer patients undergoing surgery for liver metastases has shown that all patients have mounted an immune response against the target tumour antigen. This investigator initiated trial is sponsored by Cancer Research UK.

The results from the earlier Phase I/II studies showed a highly significant correlation between patients' immune response to TroVax and time to disease progression, which translated into a correlation with improved overall survival. Data emerging from the Phase II trials suggest that the magnitude and duration of immune responses may be even greater in first line treatment with concomitant chemotherapy and in the (neo) adjuvant setting with surgery. The new data reported today provide further evidence that TroVax may offer potential benefit to patients with colorectal cancer.

Commenting on the Phase II results with TroVax in colorectal cancer, Professor Alan Kingsman, Chief Executive of Oxford BioMedica, said: "We are very pleased with the progress of these three Phase II trials of TroVax in colorectal cancer. The high frequency of anti-5T4 responses in patients confirms the immunological effectiveness of TroVax and the preliminary clinical response data look promising. Based on current data, we are optimistic that TroVax will have a role to play in the treatment of cancer and we look forward to testing this in pivotal clinical studies."

Commenting on Cancer Research UK's initial Phase II results with TroVax in the adjuvant setting, Dr. Sally Burtles, Director of Drug Development of Cancer Research UK said: "We are delighted that the vaccine has stimulated an immune response to 5T4 in all of the evaluable patients to date. Further trials will be needed to find out if this translates into clinical benefit for patients."

Phase II trials of TroVax plus chemotherapy in first line treatment
Oxford BioMedica initiated two open label Phase II trials in first line treatment of metastatic colorectal cancer in 2003. The two trials were designed to investigate whether concomitant chemotherapy affected patients' immune responses to TroVax. Enrolment in both trials (TroVax plus IFL and TroVax plus FOLFOX) was completed in September 2004. The recruitment objective was to have ten evaluable patients in each trial. The primary endpoints were safety and demonstrable immune responses to the 5T4 tumour antigen.

On 1 September 2004, the Company reported that the primary endpoints were likely to be achieved based on preliminary data from 13 patients who had reached the interim analysis point, defined as four TroVax immunisations and more than eight cycles of chemotherapy. Of these patients, 11 (85 per cent) had mounted antibody and/or cellular anti-5T4 immune responses.

These encouraging results have been confirmed as the trials have progressed. To date, 25 patients have been assessed at the interim stage of the trial. There have been no serious adverse events attributed to TroVax treatment and the number of patients mounting an immune response has risen to 100 per cent with all 25 patients showing antibody and/or cellular responses to the tumour antigen.

Furthermore, 19 patients have been assessed for tumour responses (tumour stabilisation and tumour shrinkage), having received at least three TroVax immunisations and one or more computed tomography scans. Patients entered the trial with progressive disease, and 18 of 19 patients had a tumour response following treatment. Thirteen of 19 patients were classified as clinical responders, comprising three complete and ten partial responses.

Two independent studies of the chemotherapy regimens alone reported clinical response rates in evaluable patients of 41 and 50 per cent* respectively (Douillard et al., The Lancet 2000, vol 355, pp 1041-1047; de Gramont et al., Journal of Clinical Immunology 2000, vol 18, pp2938 –2947). However, a precise comparison with the TroVax trials is not possible owing to differences in the trial protocols and patient numbers.

Data from the two Phase II trials of TroVax will be presented at the American Society of Clinical Oncology (ASCO) meeting in Orlando, USA, in May 2005. The trials are on track to report full safety and immunological data as well as final tumour response statistics in the second half of 2005. Patient survival, which can be compared to historical controls, will be reported once the median survival has been reached in the two trials. This is anticipated towards the end of 2005.

A more detailed report of these two trials of TroVax with first line chemotherapy is set out below:

(i) TroVax plus IFL chemotherapy
In the trial of TroVax plus irinotecan, 5-flourouracil and leucovorin, a chemotherapy combination known as IFL, 19 patients have been recruited. The treatment regimen comprises six immunisations of TroVax and up to 12 cycles of chemotherapy. 13 patients have reached the preliminary analysis stage, and all 13 have mounted anti-5T4 immune responses.

Clinical and tumour responses have been assessed in 11 patients that have received four TroVax immunisations and completed chemotherapy treatment. Ten of 11 patients responded to treatment. Three patients had stable disease, while seven patients (64 per cent*) mounted clinical responses, comprising one complete response and six partial responses. For reference, the two-arm pivotal trial that supported approval of IFL chemotherapy alone in first line treatment of metastatic colorectal cancer, in a total of 338 patients, showed a clinical response rate of 41 per cent* for the evaluable IFL group (Douillard et al., 2000).

(ii) TroVax plus FOLFOX chemotherapy
The TroVax plus FOLFOX trial has recruited 17 patients, similarly receiving six immunisations of TroVax alongside chemotherapy. The current status is that 12 patients have reached the preliminary stage for immunological analysis and eight patients are evaluable for tumour responses. At the preliminary stage of four TroVax immunisations and eight cycles of chemotherapy, all 12 patients have mounted anti-5T4 immune responses.

Clinical responses were observed in six of the eight (75 per cent*) presently evaluable patients, comprising two complete responses and four partial responses. The two other evaluable patients experienced disease stabilisation following treatment, meaning that 100 per cent of evaluable patients responded to treatment. An independent two-arm trial with a comparable FOLFOX chemotherapy regimen and enrolment criteria, reported a confirmed clinical response rate of 50 per cent* and a tumour response rate, which includes disease stabilisation, of 82 per cent in a total of 420 patients (de Gramont et al., 2000).

Phase II trial of TroVax in patients undergoing surgery for resectable liver metastases
An investigator initiated, open label Phase II trial started in 2004, with sponsorship from Cancer Research UK, in colorectal cancer patients who have operable liver metastases. Patients receive TroVax immunisations before (neoadjuvant) and after (adjuvant) surgery. Recruitment into this 20-patient trial is over halfway completed.

Eleven patients have received the initial regimen of TroVax immunisations, two of which were subsequently withdrawn for being ineligible for surgery. The eight evaluable patients have achieved the primary endpoint of immune responses to the 5T4 tumour antigen, and are eligible for further TroVax doses. The most recent patient has not progressed far enough through the trial to assess immune responsiveness. TroVax has been safe and well tolerated in all patients treated to date in this trial.

The treatment schedule comprises two immunisations with TroVax before and after liver surgery and, potentially, a further two vaccinations. The endpoints of the study are safety, immunological responses to 5T4 and clinical benefit. Following surgery, these patients have a lower tumour burden and longer survival expectation than patients in Oxford BioMedica's other Phase II trials in colorectal cancer. This potentially makes them even more responsive to immunotherapy approaches such as TroVax. Patients are generally not given chemotherapy following liver surgery and there is a need for safe and effective treatments to help prevent disease relapse.

Full results from this Phase II trial of TroVax in the (neo) adjuvant setting of colorectal cancer treatment will be published in an appropriate clinical journal by Cancer Research UK once the study is completed.

Conclusion
More than 65 patients with colorectal cancer have been treated with TroVax to date in four clinical trials. Across all the trials, the safety profile of TroVax has been excellent and the majority (98 per cent) of assessable patients (50 patients) have mounted immune responses following treatment with TroVax. This is an exceptionally high response rate in the context of clinical studies with other cancer vaccines (Mocellin et al., Lancet Oncology 2004; vol 5: 681-9). TroVax has been investigated in different settings in these trials - first line treatment with chemotherapy, second line treatment and the (neo) adjuvant setting with surgery – and achieved its primary endpoints in each setting.

These data suggest that TroVax has therapeutic potential across all stages of colorectal cancer, supporting the notion that the product may reach large markets in this indication.

The Company and its clinical advisors are refining a strategy to achieve potential product registration of TroVax in 2008-09. This will provide Oxford BioMedica and its potential partners with a clear and rapid route to product commercialisation.

Other TroVax trials
In addition to the three ongoing Phase II trials in colorectal cancer, Oxford BioMedica is expanding the opportunity for TroVax to other tumour types. The Company believes that metastatic renal cell carcinoma (RCC) offers an attractive commercial opportunity for the development of TroVax. Studies show that the 5T4 antigen is present on over 90 per cent of RCC samples; current treatment options are ineffective or have serious side effects; and TroVax could benefit from orphan drug and fast track designations in this indication.

A Phase II trial in RCC with TroVax alongside high dose interleukin-2 is underway in the United States. Preliminary immunology data are expected around mid-2005. In breast cancer, the Southwest Oncology Group, which is a US clinical trials consortium, is expected to start a Phase II trial in late stage patients, in 2005.

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* Clinical response data from Oxford BioMedica's Phase II trials are unaudited. They are based on patients that are evaluable and use the industry standard Response Evaluation Criteria in Solid Tumours (RECIST). The data from the trials of the chemotherapy agents alone, cited in this press release, are derived from evaluable patients, using clinical response criteria set by the World Health Organisation (WHO). The criteria defined by RECIST and WHO are similar but not identical.

A telephone conference for analysts, to discuss the Phase II results with TroVax, was held at 11:30am (UK) on 2 March 2005. To access a recording of the call, which will be available for the following 10 days, please use the dial-in details below:

UK Dial in: 0845 245 5205
International Dial in: +44 1452 550 000
Access code: 2715834