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.
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 uses the binding interactions of soluble CD80 to (1) block CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T cell activation in the tumor microenvironment and (2) directly engage CD28 to further enhance its co-stimulatory T-cell activation activity (without super agonism).
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. The collaboration was subsequently expanded to include a third undisclosed immune checkpoint pathway. 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.
In January 2018, BMS submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration for a therapeutic candidate under the immune checkpoint pathway discovery collaboration between the companies. The first clinical candidate from the collaboration is a fully-human monoclonal antibody targeting TIM-3 (T-cell immunoglobulin and mucin domain-3), an immune checkpoint receptor that is known to limit the duration and magnitude of T-cell responses1.
In addition, BMS exercised its option to further extend the research term of the collaboration between the companies for the discovery, development and commercialization of immuno-oncology (I-O) therapies directed toward targets in two additional undisclosed immune checkpoint pathways. BMS has elected to extend the research term to March 2019 and will provide additional funding to Five Prime for the extended term. This is the second extension to the original collaboration term under the agreement that was established in March 2014.
Under the terms of the discovery collaboration agreement, BMS has exclusive, worldwide rights to develop and commercialize products directed toward certain protein targets in three checkpoint pathways. Five Prime is eligible to receive up to $300 million in future development, regulatory and sales-based milestone payments for each collaboration target, including TIM-3. Five Prime is also eligible to receive tiered royalties starting from mid-single-digit increasing to low-double-digit percentages of global net sales of each product commercialized by BMS.