Oxford BioMedica (Oxford, U.K.) is a biopharmaceutical company focused on developing gene-based medicines in oncology and neurology. The company has two products in Phase II for colorectal, breast, and renal cell cancers, and a preclinical targeted antibody therapy collaboration with Wyeth (Madison, NJ).
The first product, TroVax, is a gene therapy based upon the ST4 cancer antigen that was licensed in from the U.K.'s Cancer Research Technology. An injection of the ST4 gene in a poxvirus vector stimulates immunity.
"TroVax breaks self-tolerance so the body mounts an immune response. We believe it can be used in many scenarios, commented Nick Woolf, senior vp, corporate strategy. The therapy is being developed for use in early- or late-stage disease, alone or in combination, and as an adjuvant to surgery.
The second product, MetXia, is a gene therapy which enhances the efficacy of cyclophosphamide (CPA) in cancer. CPA is a prodrug which needs to be activated to a cytotoxic drug by the P450 enzyme in the liver. CPA is linked to dose-limiting liver and systemic toxicity. But MetXia delivers the P450 gene direct to the tumor, allowing localized activation of CPA.
Proof-of-principle has been obtained in two Phase I/II trials in breast cancer and other accessible tumors, and the product is also in Phase I/II trials for advanced pancreatic cancer.
The company also has a program in Parkinson's disease and other neurological conditions using LentiVector, a technology for delivering genes to the nervous system. ProSavin, a product which delivers dopamine to the brain using this delivery system, is currently in preclinical for Parkinson's disease.
Meanwhile, Benitec (Mountain View, CA) is a drug discovery company that holds the only U.S. patent for RNAi use in vivo, according to the company. "From the IP point of view we are strong, as most other RNAi companies only hold licenses," said Sara Cunningham, Benitec's COO. The company uses a proprietary technology called DNA-directed RNA interference that triggers RNAi, which is a natural gene silencing process.
Benitec is working on programs in hepatitis C (HCV) and HIV/AIDS. The former was developed in-house at Avocell, an Australian company that was recently acquired by Benitec. RNAi is a natural mechanism for turning genes on and off, and RNAi-based therapies can be used in any disease that has a genetic basis, that is, viral infections, cancer, autoimmune, and inflammation.
RNA viruses such as HCV and HIV are "perfect targets for RNAi," says Cunningham. Mark Kay, co-founder of Avocell and an expert on liver disease, was the first to publish a proof-of-concept of RNAi (Nature, 2001).
"RNAi is a phenomenal tool for functional genomics and other applications," said Cunningham. "We know it works as a tool, but its therapeutic use is more speculative." That is why finding partners may be difficult until Phase II.
Benitec's HIV program should enter Phase I at the City of Hope Hospital, Los Angeles, for HIV/AIDS related lymphoma in Q4 2005, putting the company slightly behind Acuity Pharmaceuticals (Philadelphia), whose RNAi therapeutic has just entered the clinic.
Benitec is looking at a virally-delivered gene therapy using an ex vivo approach, but would like to try nongene therapy delivery methods too, because of the regulatory issues around gene therapy.
Finally, Atugen (Berlin) is involved in functional gene silencing using siRNA and has a strong IP position in this area. It started as a contract service business but has transformed itself into a drug discovery and development company with its own in-house oncology program. Having obtained in vivo proof-of-concept of the company's technology, Atugen is working on a number of proprietary targets, and also has a collaboration with Sanofi-Aventis (Paris).
On top of this, the company also has a profitable contract research business in target validation with customers in Europe, the U.S., and Japan.