Immuno-Oncology 2

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, such as Bristol-Myers Squibb (BMS) and bluebird bio.

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. Our collaborations with Adimab and Vaccinex enable the development of therapeutic monoclonal antibodies for our targets and we have several antibody campaigns underway. Our goal is to file one IND per year starting in 2017.

GITR Agonist Antibody Program

In July 2015, Five Prime licensed Inhibrx’s novel agonist antibodies to glucocorticoid-induced tumor necrosis factor receptor (GITR), a pathway we identified in our protein library and proprietary in vivo screens as one of the most potent inhibitors of tumor growth. The GITR antibodies add an important mechanism that complements our existing immuno-oncology portfolio. Agonist antibodies have demonstrated the ability to induce tumor regressions in preclinical models, particularly when administered with other immuno-oncology therapies.

Additionally, the Inhibrx technology represents a potentially best-in-class approach for engineering a multivalent GITR agonistic antibody with properties aimed at enhancing efficacy and combinability with other therapies. These GITR antibodies could have broad therapeutic application as a monotherapy or in combination with approved checkpoint inhibitors or other therapies, including those in our own pipeline. The program has the potential to reach IND in 2017.

Collaborations with Bristol-Myers Squibb

In October 2015, Five Prime announced an exclusive worldwide license and collaboration agreement with BMS, a recognized leader in the field of immuno-oncology, for the development and commercialization of Five Prime's CSF1R antibody program, including FPA008. This agreement replaces the companies' existing clinical collaboration initiated in November 2014 to evaluate the combination of Opdivo (nivolumab), BMS’s PD-1 immune checkpoint inhibitor, with FPA008 in a Phase 1a/1b trial across six tumor types. Five Prime will continue running the trial through to completion and BMS is responsible for all study costs except Five Prime internal costs. BMS will drive future development in immuno-oncology as well as manufacturing and commercialization of FPA008, and Five Prime is continuing development of FPA008 in pigmented villonodular synovitis (PVNS) and may potentially explore combinations with its own oncology pipeline candidates. Five Prime also retains the right to co-promote FPA008 in the U.S.
Five Prime and BMS also 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.