Corixa: Integrating immunotherapeutics
Authors: Robert M. Frederickson
Journal: Molecular Therapy (2003)

Our incomplete understanding of the elegant complexity of the immune system has complicated efforts to exploit it in the battle against cancer and infectious disease. Until recently, immunotherapeutics have been limited to prophylactic vaccines and global immunomodulators like interferon or cyclosporin. Seattle-based Corixa aims to add significantly to our immunological armamentarium by integrating a wide range of technology platforms, each of which alone possesses significant partnering potential. After twelve years at Immunex, Corixa cofounder Kenneth Grabstein was looking for a new challenge. Together with Steve Reed of the Seattle Biotechnology Research Institute (SBRI), he was interested in founding a company that would focus on the development of new tools to fight infectious disease—such as therapeutic vaccines. “We had learned that an effective immune response required activation of the cellular arm of the immune system,” adds Grabstein, “but to accomplish this with a vaccine, we needed to develop technologies that could trigger and boost the cytotoxic T-lymphocyte (CTL) response.” Steve Gillis, who founded Immunex, was a key player in Corixa's genesis. Says Grabstein, “Steve was well-known in the VC and industrial communities, and his experience was key to establishing and realizing Corixa's philosophy of partnering with big pharma.” Gillis elaborates, “Our philosophy has been to rely not only on organic, internal discovery but also opportunistic product in-licensing and company acquisition. This approach serves us well, particularly in times when institutional investor interest is low.” As it turns out, Gillis was also incubating a company developing therapeutic vaccines against cancer. Gillis realized that many of the challenges the two groups were facing were similar, and he got them working together. “At first I thought the idea of merging the groups was unwise as it created a broader focus for the company, but the reality is that many of the necessary technologies were similar,” says investor Joe Lacob of the Menlo Park, CA, venture firm Kleiner-Perkins. There are three important components to the antigenic response: antigens, adjuvants, and efficient ways of delivering the latter to APCs. The group recruited top-notch scientific partners and licensed their technology. These included Martin Cheever of the University of Washington and Olivera Finn from the University of Pittsburgh, both engaged in antigen discovery. They were joined by Harvard's Kenneth Rock, an expert in antigen presentation leading to a CTL response. “I was impressed by their integrated and comprehensive approach,” Rock says, “they saw the larger picture and understood that multiple components had to be in place for an effective T cell vaccine.” A venture capital round in 1994 raised $15 million based on the premise that the company would focus on transactions and partnerships with other biotech companies and with big pharma. An early priority of the new company was antigen discovery. These were the days of the so-called “genomic revolution,” as companies raced to identify disease-related genes with the hopes of patenting them. Their efforts have led to 800 “antigen” patent applications worldwide, with about 120 already issued. According to Reed, Corixa focuses on antigens that are recognized by the immune cells of those infected individuals who show no signs of disease, suggesting that the antigens may offer protection. Most but not all antigens are poorly immunogenic on their own. Adjuvants boost antigen potency mainly by enhancing the antibody response. However, the last decade has seen an explosion of knowledge in the molecular and cellular bases of T cell responses to both viruses and cancer. Corixa's powerful and popular MPL adjuvant came on board with the acquisition of Ribi ImmunoChem in 1999. MPL stands for monophosphoryl lipid A and is a derivative of a bacterial endotoxin. The formulation has either completed or is being tested in late-stage clinical studies of vaccine formulations for both infectious diseases and cancer, and licenses have been granted to Glaxo-Smith-Kline and Wyeth-Lederle, two leading developers of vaccines. Activation of the cellular arm of the immune system is dependent upon a diverse set of costimulatory signals that adjuvants must trigger—with the Toll-like receptor (TLRs) representing an important nexus of such signals. Knowledge that TLR4 is a target for MPL has allowed Corixa to develop small molecule agonists for the receptor, such as their RC-529 compound. RC-529 has shown good results in a phase III clinical trial when used in conjunction with a yeast-based recombinant hepatitis B antigen from Rhein-Biotech, who inked a license and supply agreement for RC-529 in April of 2002. The synthetic adjuvant is also in preclinical studies for use in treating cancer and autoimmune disease. Corixa continues to rely on revenue from investors and partnership deals, and they have their sights set on technologies and patents held by the vast number of small public biotech companies, many of which are left with less than a year of funding. Amazingly, given the current market conditions in the biotech community, the company did manage to pull off a private placement in August 2002 worth about $45 million—testimony to the influence of Corixa's management in the investor community. This influence will likely be key to Corixa's survival and the prospects for profitability within the coming years.