Oxford Biomedica reports new encouraging phase II results with TroVax® and progress in the development plan

Oxford BioMedica (LSE: OXB), a leading gene therapy company, reported today that encouraging data from five Phase II studies of TroVax, its lead cancer immunotherapy product, were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO). In addition, the Company provided an update on the clinical development plan for TroVax, which is progressing towards the start of Phase III trials in renal and colorectal cancer.

New Phase II results reported at ASCO:

• Updated analysis of unaudited tumour response data from two trials of TroVax plus chemotherapy in metastatic colorectal cancer showed that 95% of per protocol patients had disease control.
• Updated survival data from the two metastatic colorectal cancer trials showed that a third of the patients were still alive with an average follow-up time of more than two years.
• Data from Cancer Research UK’s trial of TroVax adjuvant therapy in colorectal cancer patients undergoing surgery for liver metastases showed that 96% of patients produced an anti-tumour immune response and 56% of operable patients remained disease-free after nine months of follow-up.
• First presentation of data from two studies of TroVax plus interleukin-2 in renal cell carcinoma showed that two of the first six evaluable patients (33%) had partial responses. If reproduced in a larger study this would compare favourably with a response rate of 10% for interleukin-2 alone.

Development plan update:

• QUASAR, a UK-based clinical trial network, has agreed to develop a Phase III trial of TroVax in approximately 3,000 patients with early stage colorectal cancer and the study will be submitted to the appropriate funding agencies.
• Phase III TRIST study in renal cell carcinoma is on course to start in the second half of 2006. Clinical Trial Applications are being filed in European countries as part of the implementation of the protocol, for which a Special Protocol Assessment was recently agreed with the FDA.
• Three further, small Phase II studies are starting in renal cell carcinoma, evaluating TroVax in combination with interferon-α and sunitinib.
• Recruitment is proceeding rapidly in the recently announced Phase II study of TroVax with GM-CSF in 24 patients with hormone refractory prostate cancer. Eleven patients have already been recruited.

Commenting on the Phase II results and progress on the development plan, Oxford BioMedica’s Chief Medical Officer, Dr Mike McDonald, said: “We are very pleased that the positive results from the Phase II colorectal cancer trials continue to be mirrored in renal cancer. There is growing interest in TroVax amongst the clinical community in both Europe and the USA. This external support has enabled us to broaden the clinical development of TroVax.”

On the approval by the QUASAR group of the proposed Phase III trial of TroVax, the Chairman of QUASAR and Head of Clinical Pharmacology at the University of Oxford, Professor David Kerr, said: “The QUASAR group is committed to the Phase III trial of TroVax in early stage colorectal cancer. We must now secure the necessary grant funding to start this important trial and potentially provide a novel therapy for this large patient group where treatment options have evolved little in recent years.”

Oxford BioMedica’s Chief Executive Officer, Professor Alan Kingsman added: “These new clinical results further illustrate the potential for TroVax to treat different cancers at different stages of disease and support our strategy of advancing to larger and pivotal registration trials. We look forward to starting our Phase III TRIST trial of TroVax in renal cancer later this year and working with both QUASAR and commercial partners on the design and initiation of additional trials in colorectal cancer.”

Phase II results of TroVax plus chemotherapy in colorectal cancer

Oxford BioMedica has completed two Phase II trials of TroVax in first-line treatment of metastatic colorectal cancer alongside two standard of care chemotherapy regimens: irinotecan, 5-fluorouracil and leucovorin (IFL) and oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX). The two single-arm, open-label trials enrolled a total of 36 patients. On 6 June 2006 at the ASCO meeting, the Company presented final safety and immunology data including new details of the cytotoxic T-cell response, efficacy results including an update on both tumour responses and survival, and also analysis of the relationship between the magnitude of immune responses and clinical benefit.

As reported previously, the primary endpoints of safety and anti-tumour immunological responses were achieved and the results confirmed the excellent safety profile of TroVax with no serious adverse events being attributed to the product. All 23 per protocol patients (≥3 TroVax immunisations and ≥6 chemotherapy cycles) across the two trials mounted an anti-tumour immune response. Immune responses were higher than in the Phase I/II study and cytotoxic T-lymphocyte (CD8+) levels were exceptionally high, reaching frequencies of 1 per 1000 peripheral blood mononuclear cells. Such high levels are normally only seen in infectious diseases where the CD8+ response frequently clears the infection.

Clinical benefit exceeded the Company’s expectation based on previously reported data for chemotherapy alone. Based on updated, unaudited computerised tomography (CT) scans, 95% of per protocol patients showed disease control, which is higher than the previously reported figure of 91%: 17% had complete responses; 43% had partial responses; and 35% had stable disease. In the TroVax plus FOLFOX trial, there was a statistically significant (p <0.02) correlation between patients’ 5T4-specific immune response and their tumour response.

The Company also presented updated survival information for the two studies. However, it should be noted that patient numbers are too small to provide a rigorous conclusion and comparisons with historical data can be unreliable. In the modified intent to treat group (≥2 TroVax immunisations) of 30 patients, TroVax extended median survival from 72 weeks to 80 weeks and improved survival at twelve months from 70% to 90%. Importantly, as at 10 May 2006, ten of the 30 patients remained alive with an average follow-up time of more than two years. The Company regards these data as encouraging and believe that, if these observations were reproduced in a pivotal study, they would be sufficient to support product registration.

Phase II results of TroVax adjuvant therapy in colorectal cancer:

Clinicians from the Christie Hospital and Paterson Institute for Cancer Research, both of Manchester, UK, have completed enrolment of a Phase II trial of TroVax in colorectal cancer patients who have operable liver metastases. The single-arm, open-label trial, which enrolled 20 patients, is sponsored by Cancer Research UK. Patients received TroVax immunisations before surgery (neoadjuvant) and after surgery (adjuvant). On 4 June 2006 at the ASCO meeting, the Principal Investigators for the trial presented safety and immunological data, and clinical outcomes from patient follow-up.

The primary objective of the trial was to investigate the immunological responses to TroVax during potentially curative surgery for colorectal cancer liver metastases. The group of patients selected for the trial had good performance status, but patients often have micro-metastatic disease that persists post-operatively. TroVax could provide a safe and effective treatment option for these patients that have a low but metastatic tumour burden.

TroVax was well tolerated in all patients with no serious adverse events associated with the product. Of the 20 patients recruited, 16 had successful surgical resection of their colorectal cancer liver metastases. All evaluable resected tumours were positive for the 5T4 antigen, the target for TroVax.

The primary endpoint of immunological response was achieved. In the intent to treat population, 19 of the 20 patients (95%) mounted anti-tumour immune responses against 5T4. Four patients were withdrawn for incorrect diagnosis or inoperable cancer. Clinical analysis was conducted on the remaining 16 evaluable patients. At a median follow-up of 9.1 months, nine of these 16 patients (56%) remained disease-free. Oxford BioMedica is encouraged by the data to date from Cancer Research UK’s trial of TroVax in this setting of adjuvant therapy to surgery for liver metastases.

Preliminary Phase II results of TroVax plus interleukin-2 (IL-2) in renal cell carcinoma

Two Phase II trials of TroVax with either high dose or low dose IL-2 are ongoing in the USA. The trials are designed to gather information on the safety of the combination treatments as well as on immune responses to the 5T4 tumour antigen. Results from the two trials were published in the ASCO Proceedings for the Annual Meeting.

To date, 27 of 50 patients have been recruited into the two trials. There have been no serious adverse events related to TroVax, which is consistent with the excellent safety profile of the product across all trials, and TroVax treatment was well tolerated. Across both trials, 15 of 17 evaluable (≥3 TroVax immunisations) patients (88%) have shown anti-tumour antibody responses to 5T4. The antibody levels were at the top end of the range reported from the Phase II trials with TroVax in patients with colorectal cancer undergoing chemotherapy. Analysis of cytotoxic T-lymphocyte responses is in progress.

To date, unaudited CT scans are available for the first six patients. Of these, two (33%) have shown partial responses based on industry-standard criteria known as Response Evaluation Criteria in Solid Tumours (RECIST). According to the literature, IL-2 is usually associated with a clinical response rate of only 10% in this patient group.

The Company and the Principal Investigators for these trials are encouraged by the frequency of clinical responses with TroVax, albeit in a small number of patients at this stage. These data endorse the Company’s strategy to initiate the Phase III TRIST trial, which includes TroVax alongside low dose IL-2.

Development plan update:

(i) Renal cell carcinoma (RCC)

The Company is expanding its Phase II programme in RCC with three additional single-arm, open-label Phase II studies to assess TroVax in combination with either interferon-alpha (IFNα) or sunitinib (Sutent®). These small trials are designed to broaden the clinical experience with TroVax and provide further support for the planned Phase III TRIST trial that will use IFN-α and Sutent®, in addition to IL-2, as standard of care treatments. Enrolment has commenced in the first of these studies, which are being conducted in centres in the UK and the USA.

The Company’s multi-centre, randomised, double-blind, placebo-controlled 700-patient Phase III trial, TRIST (TroVax Renal Immunotherapy Survival Trial), is on-track to commence recruitment in the second half of 2006. The manufacture of the trial material is largely complete. Oxford BioMedica secured an agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment in May 2006 and Clinical Trial Applications are in the process of being filed with the relevant European agencies. The trial is designed for rapid patient recruitment and has a primary endpoint of overall survival. The duration of the trial will be determined by the number of deaths in the study group. Median survival for this patient group is approximately 11 months. The trial protocol includes the appointment of a Safety and Efficacy Monitoring Board that will periodically review the data and make recommendations based on the safety and efficacy of the different treatment arms. TRIST is expected to reach a conclusion in 2008-09 and could support product registration in 2009.

(ii) Colorectal cancer

Oxford BioMedica has advanced its discussions with the QUASAR group, which is a UK-based clinical trial network, which has been funded from a variety of sources including the UK Medical Research Council and Department of Health. In November 2005, the Company reported that QUASAR had expressed interest in conducting a Phase III trial of TroVax in early stage (Stage II/III) colorectal cancer patients but that further evaluation was required. QUASAR has completed its evaluation, confirmed its commitment and will seek funding for the proposed trial through the appropriate agencies.

The proposed design is a randomised trial in about 3,000 patients. TroVax would be used during or after adjuvant chemotherapy with a primary endpoint of disease-free survival at three years. The study is likely to be configured to enable product registration in Europe and the USA. The QUASAR group has successfully conducted other large studies of adjuvant therapy in this disease setting. These previous QUASAR trials have enrolled about 7,000 patients over the last seven years.

Separately, the Company is planning a randomised trial in first-line treatment of metastatic (Stage IV) colorectal cancer. The preliminary trial design is to evaluate TroVax alongside standard of care treatment. It could be configured as a Phase IIb or Phase III trial. The final design of this trial depends on the outcome of licensing discussions, since the Company expects this trial to be funded and conducted by a commercial partner.

(iii) Prostate cancer

Oxford BioMedica reported on 23 May 2006 that a Phase II trial of TroVax in patients with prostate cancer had started. The trial, which is supported by the Methodist Hospital in Houston, is designed to enrol 24 men with hormone-refractory prostate cancer who have previously received chemotherapy or have refused chemotherapy and have progressive disease. The open-label trial has two arms (12 patients each) to assess the activity of TroVax alone versus TroVax alongside an approved treatment for prostate cancer, granulocyte macrophage-colony stimulating factor (GM-CSF). The primary objectives of the trial are to evaluate the safety and synergies of the combination treatment. Eleven patients have been enrolled into the trial to date.