In recent years, immuno-oncology has become one of the most promising and fastest growing areas of cancer research and drug development. Despite recent progress, many cancer patients do not respond adequately to approved immuno-oncology agents.
Cancers grow and spread because tumor cells have developed ways to evade elimination by the immune system. One of the most exciting recent discoveries in cancer therapy has been the identification of ways to release the “brakes” that tumor cells can place on immune cells, thereby allowing the immune system to once again mount a response to the tumor. This new approach, known as immune checkpoint inhibition, has the potential to not only reduce tumor growth like traditional therapies, but potentially eliminate the cancer entirely in some patients.
A key priority at Five Prime is building a comprehensive and complementary portfolio of immuno-oncology therapeutic candidates that will impact the tumor microenvironment by inhibiting immune check points, macrophages, and regulatory T cells, and by activating T cell agonist pathways. Our protein discovery platform is ideally suited to identify novel targets for next-generation immuno-oncology therapeutics, either as part of our own development programs or through our collaborations with leading pharmaceutical and biotech companies.
Internal Immuno-Oncology Drug Discovery Programs
Research & Discovery Activities
We believe Five Prime is well positioned to identify new targets and protein drugs in immuno-oncology because:
- Protein drugs, our focus, will be the best therapeutic strategy in immuno-oncology. Anti-tumor immunity often involves interactions between extracellular proteins that are not easily modulated with small molecule drugs.
- There are likely many new targets yet to be discovered. For example, the protein partners are not known for several proteins thought to have a role in modulating anti-tumor immunity, such as TIM-3, VISTA, B7-H3 and B7-H4. There are likely many additional proteins that regulate the immune response to tumors that have not yet been described or characterized.
- Our biologics discovery platform is designed to identify targets such as those involved in immuno-oncology.
Our proprietary library of more than 5,700 human extracellular proteins contains approximately 700 which are candidate immunomodulators. This is a portion of the library that we call the immunome. We are using our discovery platform to discover novel pathways and to identify protein partners for molecules known to be involved in the anti-tumor immune response. We are also applying our proprietary cell-based screening, in vivo screening, receptor-ligand matching and bioinformatics technologies in our immuno-oncology research program.
We have identified promising new antibody targets and ligand traps and are actively screening for and validating additional targets. In addition, we have several antibody campaigns underway. Our goal is to file one IND per year starting in 2017.
We have two potential preclinical therapeutic candidates in IND-enabling studies.
FPA150 (antibody to B7-H4)
Certain tumors, such as ovarian, breast and endometrial cancers, have a high level of B7-H4 expression on the surface of the cancer cells. Furthermore, B7-H4 has been shown to act as a checkpoint, suppressing CD8 T cells. We engineered this antibody to block the immunosuppressive function of B7-H4 acting on CD8 T cells as well as to drive ADCC to kill tumor cells that express B7-H4.
FPT155 (soluble version of CD80)
FPT155 is a soluble version of CD80, which is a natural immune regulatory molecule. This program came from our in vivo screens, which demonstrated that a soluble form of CD80 was striking in its potent in vivo anti-tumor activity when compared to 500 other immunome proteins.
FPT155 appears to enhance T cell responses through three possible mechanisms. First, it activates CD28, importantly without superagonism. Second, it also binds to CTLA4 and may block its immunosuppressive effects. Third, it can block the PD-1 checkpoint pathway because it binds directly to PD-L1.
Collaborations with Bristol-Myers Squibb
Five Prime and BMS initiated a discovery collaboration in March 2014 for the discovery, development and commercialization of immuno-oncology therapies directed toward targets identified in two undisclosed immune checkpoint pathways using Five Prime's proprietary target discovery platform. BMS is leveraging Five Prime's platform to advance its existing immuno-oncology programs by identifying the most viable drug targets for continued research and development. The terms of this agreement include approximately $50 million in an upfront payment, equity investment and research funding to Five Prime and we will be eligible to receive up to $300 million in future development, regulatory and sales-based milestone payments per collaboration target and tiered mid-single-digit rising to low-double-digit royalty payments on net sales.