PRODUCT DESCRIPTION
TroVax is a novel therapeutic cancer vaccine that has potential application in most solid tumour types. The product induces an immune response against the tumour-associated antigen 5T4, which is broadly distributed throughout a wide range of solid tumours. The product consists of a Modified Vaccinia Ankara (MVA) virus, which delivers the gene for 5T4.

INDICATION
All solid tumours where the 5T4 tumour antigen is present. Clinical development is ongoing in renal cell carcinoma, colorectal cancer and prostate cancer.

MARKET
Worldwide cancer vaccine revenues are estimated to reach approximately US$6 billion by 2010 (Arrowhead). With ongoing development in renal, colorectal and prostate cancer, TroVax is addressing markets that currently exceed US$8 billion based on annual sales of existing cancer treatments (Datamonitor).

TECHNICAL DESIGN
Proprietary tumour associated antigen, 5T4, delivered by the pox virus vector, modified vaccinia virus Ankara (MVA).

CLINICAL STATUS
Approximately 900 patients have been enrolled in clinical trials of TroVax in renal, colorectal and prostate cancer. TroVax has been safe and well tolerated. There have been no serious adverse events related to the product. TroVax has induced an anti-tumour immune response to the 5T4 tumour antigen in the majority of patients. The strongest immune responders have also tended to show the greatest clinical benefit.

A Phase III trial in patients with renal cell carcinoma (TRIST: Trovax Renal Immunotherapy Survival Trial) was initiated in November 2006. The TRIST study reached full recruitment of 700 patients in March 2008 and is designed to support product registration for TroVax in the United States in 2009. Two Phase III trials in colorectal cancer are expected to start in 2008 and a Phase II trial in prostate cancer is recruiting patients. in 2008 and a Phase II trial in prostate cancer is recruiting patients.

Completed Trials
Phase I/II Trial
Colorectal cancer – TroVax as a single agent post chemotherapy

• 22 patients with Stage IV metastatic colorectal cancer
• TroVax induced an anti-tumour immune response in 94 % of patients.
• 41 % of patients showed periods of disease stabilisation
• The immune response induced by TroVax correlated with time to disease progression (p < 0.01) and a relationship was determined with survival

Phase II Trials (two trials)
Colorectal cancer – TroVax alongside first line chemotherapy with FOLFOX or IFL

• 36 patients with Stage IV metastatic colorectal cancer
• TroVax induced an anti-tumour immune response in all patients
• 95 % of patients showed disease stabilisation
• 17 % of patients showed complete tumour responses
• In the TroVax plus FOLFOX trial, the immune response induced by TroVax correlated with tumour responses (p < 0.02)
• 25 % of patients were alive at an average follow-up time of almost two and a half years

Phase II Trial
Colorectal cancer – TroVax as an adjuvant to surgery

• 20 patients with Stage IV colorectal cancer with operable liver metastases
• Sponsored by Cancer Research UK
• TroVax induced an anti-tumour immune response in 95 % of patients
• 56 % of patients remained disease-free at a median follow-up of nine months
• Patients that mounted a strong anti-tumour immune response showed a significant survival benefit over non-responders (p = 0.009)

Phase II Trials (four trials)
Renal cell carcinoma – TroVax in combination with interleukin-2 or interferon-alpha

• 89 patients with advanced or metastatic renal cell carcinoma
• TroVax induced an anti-tumour immune response in over 95 % of patients
• 68 % of patients showed desease control
• Tumour responses were durable (over 17 months in some patients)
• The immune response induced by ToVax correlated with a decrease in tumour burden (p = 0.028)

Phase II Trial
Prostate cancer – TroVax as a single agent or in combination with GM-CSF

• 27 patients with hormone-refractory prostate cancer
• TroVax induced an anti-tumour immune response in all patients
• Patients that mounted a strong anti-tumour immune response showed a significant benefit to disease progression over non-responders (p = 0.024)

Ongoing Trials
Phase II Trial
Prostate cancer – TroVax in combination in docetaxel versus docetaxel alone

• 60 patients with hormone-refractory prostate cancer
• Patients recruitment is ongoing

Phase III Trial
Renal cell carcinoma – TroVax or placebo in combination with standard therapy

• TRIST: Trovax Renal Immunotherapy Survival Trial
• 700 patients with advanced or metastatic renal cell carcinoma
• Randomised and placebo-controlled
• Standard therapy is interleukin-2, interferon-alpha or sunitinib
• Patient recruitment completed
• The DSMB has conducted three interim analyses and recommended that the trial continues
• Primary endpoint is overall survival
• Special Protocol Assessment agreement with the FDA that specifies the design, conduct, analysis and endpoints of the trial
• See www.trovax.co.uk for more details on the trial

In Design Trials
Phase III Trial
Colorectal cancer – TroVax or placebo alongside adjuvant chemotherapy

• Approximately 3,000 patients with Stage II/III colorectal cancer
• Patients who have had surgical resection of their primary tumours and been treated with adjuvant chemotherapy
• Randomised and placebo-controlled
• Primary endpoint of disease-free survival at three years
• The clinical trial network, QUASAR, is conducting the trial with the support of Oxford BioMedica, sanofi-aventis and a variety of other sources
• Patient recruitment is expected to start in 2008

• FLAMENCO: First Line treAtment of patients with MEtastatic (N) COlorectal cancer
• Approximately 1,300 patients with Stage IV metastatic colorectal cancer
• Randomised and placebo-controlled
• Standard therapy is chemotherapy with or without bevacizumab
• Primary endpoint is overall survival
• Trial to be conducted by sanofi-aventis
• Patient recruitment is expected to start in 2008

DEVELOPMENT AND COMMERCIALISATION STRATEGY
Oxford BioMedica signed a global licensing agreement with sanofi-aventis in March 2007 to develop and commercialise TroVax for the treatment of cancer. Under the terms of the agreement, the companies are co-funding the ongoing Phase III TRIST study in renal cell carcinoma. Sanofi-aventis will fund all future research, development, regulatory and commercialisation activities. Sanofi-aventis plans to start Phase III development of TroVax in colorectal cancer in 2008. TroVax may also be developed for a range of other solid tumours including lung, breast and prostate cancer. In addition, Oxford BioMedica has an option to participate in the development of TroVax in exchange for enhanced commercial terms.

Sanofi-aventis will be responsible for the global commercialisation of TroVax and will book the sales worldwide. Oxford BioMedica retains an option to participate in the promotion of TroVax in the United States and the European Union.

PARTNERS / FUNDING
Cancer Research UK, UK
QUASAR, UK
sanofi-aventis, France

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