TroVax

# Overview
TroVax is a cancer immunotherapy product produced by Oxford BioMedica. It is a novel cancer vaccine in clinical development with potential application in most solid tumor types and delivers a novel proprietary tumor-associated antigen, 5T4, using a pox virus vector. 5T4 is broadly distributed throughout a wide range of solid cancers and the presence of the 5T4 antigen is correlated with poor prognosis.

# Indication
All solid tumors where the 5T4 tumor antigen is present. Clinical development is ongoing in renal cell carcinoma, colorectal cancer and prostate cancer, and is planned in breast cancer.

# Technical design
TroVax is a proprietary tumor-associated antigen, 5T4, delivered by the pox virus vector, modified vaccinia virus Ankara (MVA).

# Clinical status
Over 150 patients have now been treated with collectively over 500 doses of TroVax in multiple clinical trials. TroVax has been safe and well-tolerated. There have been no serious adverse events related to the product. TroVax has induced an anti-tumor immune response to the 5T4 tumor antigen in over 95% of evaluable patients. The strongest immune responders have also tended to show the greatest clinical benefit.
Oxford BioMedica began patient recruitment in a Phase III trial in renal cell carcinoma in November 2006. Phase II trials in renal cell carcinoma, colorectal cancer and prostate cancer are ongoing. Further Phase II and Phase III trials in colorectal cancer and other solid tumours are planned. The development strategy is designed to support initial product registration for TroVax in the United States in 2009.

# Completed Trials

## Phase I/II trial

### Colorectal cancer
TroVax was administered as a single agent post chemotherapy to combat Stage IV colorectal cancer. It induced an anti-tumor immune response in 94% of patients while 41% of patients showed periods of disease stabilization. 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

### Colorectal cancer (two trials)
TroVax was administered alongside first-line chemotherapy to combat Stage IV colorectal cancer. It induced an anti-tumor immune response in all patients while 95% of patients showed disease stabilization and 17% of patients showed complete tumor 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..

# Ongoing trials

## Phase II trials

### Colorectal cancer
Trovax is administered as an adjuvant to surgery to combat Stage IV colorectal cancer with operable liver metastases. It induced an anti-tumor immune response in 95% of patients while 56% of patients remained disease-free at a median follow-up of nine months.

### Renal cell carcinoma (four trials)
Trovax is administered alongside interleukin-2 or interferon-alpha to combat advanced or metastatic renal cell carcinoma. It has induced an anti-tumor immune response in 88% of patients while several patients have shown partial tumor responses.

### Prostate cancer
Trovax is administered either as a single agent or in combinations with GM-CSF to combat hormone-refractory prostate cancer. It has mounted an immune response in 85% of patients. Further data will be announced in November 2006.

## Phase III trials

### Renal cell carcinoma
Trovax is administered in combinations with interleukin-2, interferon-alpha, sunitinib to combat advanced or metastatic renal cell carcinoma to 700 patients, with the primary endpoint being the rate of overall survival. There is a Special Protocol Assessment agreement with the FDA that specifies the design, conduct, analysis and endpoints of the trial.

# In Design Trials

## Phase II trails

### Breast Cancer
TroVax will be administered after standard chemotherapy to combat Stage III/IV breast cancer to 120 patients, with the key endpoint being progression-free survival compared to historical controls. The United States clinical trial consortium, Southwest Oncology Group has received FDA clearance to start the trial with sponsorship from the United States National Cancer Institute and is expected to begin by end 2006.

## Phase III Trials

### Colorectal cancer
TroVax will be administered with adjuvant chemotherapy to combat Stage II/III colorectal cancer to approximately 3000 patients, with the primary endpoint of overall and disease-free survival at three years. Clinical trial network, QUASAR, is seeking funds for the proposed trial through appropriate agencies

# Commercialisation Strategy
Oxford BioMedica entered a global development and commercialisation agreement for TroVax in March 2007 with sanofi-aventis. There are many aspects to this agreement including co-funding the ongoing TRIST study and funding all other research, development, regulatory and commercialisation activities.
(Source: Oxford Biomedica, 11/09/2007)