On November 5, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that three posters featuring the company’s research activities are being presented during the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place November 4-8, 2015, in National Harbor, Maryland (Press release, Five Prime Therapeutics, NOV 5, 2015, View Source [SID:1234508048]). The posters will be made available at View Source following the presentations.

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cmFPA008, an Anti-Mouse CSF-1R Antibody, Combines with Multiple Immunotherapies to Reduce Tumor Growth in Nonclinical Models
Bellovin D, Wondyfraw N, Levin A, et al
Thursday, November 5, 2015

The authors sought to determine whether inhibition of CSF1R when combined with other immuno-oncology therapeutics enhanced the anti-tumor impact. The results show that treatment with cmFPA008, a surrogate antibody targeting mouse CSF1R, resulted in a marked reduction in tumor-associated macrophages (TAMs) and an increase in the relative abundance and activation of cytotoxic CD8+ T cells in preclinical models. In multiple murine tumor models, treatment with cmFPA008 also induced an increase in PD-L1 and significantly enhanced anti-tumor efficacy when combined with an anti-PD1 antibody. In addition, co-administration of cmFPA008 with an agonistic anti-CD40 antibody significantly enhanced tumor suppression compared to either therapy alone. The results provide support for ongoing clinical efforts to evaluate FPA008 as an anti-cancer immunotherapy, particularly in combination with other immuno-oncology therapeutics, including agonists of CD40. Five Prime has initiated a Phase 1a/1b clinical trial with Bristol-Myers Squibb to investigate the efficacy of FPA008 in combination with the anti-PD1 therapeutic OPDIVO (nivolumab) in six tumor types. Five Prime is also developing an agonist antibody to glucocorticoid-induced tumor necrosis factor receptor (GITR) that is expected to enter the clinic in 2017.

Identification of Novel Immune Regulators of Tumor Growth Using RIPPSSM Screening in vivo
Brennan T, Bellovin D, De La Torre J, et al
Friday, November 6, 2015

Five Prime is using its proprietary Rapid In Vivo Protein Production System (RIPPS) screening platform to discover novel protein therapeutics, targets, and drug combinations that can be used in alone or in combinations with other immuno-oncology agents. The authors screened 350 immune cell targets by RIPPS in the CT-26 tumor model and identified proteins that either enhance (potential drug target) or inhibit (potential therapeutic) tumor growth and display favorable changes in TIL (tumor-infiltrating lymphocyte) profiles. Five Prime identified several proteins with novel tumor-inhibiting or tumor-promoting activities. One of these proteins has been evaluated further and displays both strong CD3 infiltrate activity into the tumor and synergistic activity with PD1 blockade. Five Prime is conducting additional studies on each protein in other tumor models and in combination with known immune-modulating drugs.

Identification of a Novel T Cell Co-Inhibitory Receptor and Potential Therapeutic Antibody Target in Oncology
Sallee N, Karasyov A, Bellovin D, et al
Friday, November 6, 2015

In order to identify novel immune regulatory proteins and evaluate their potential as immuno-oncology therapeutic targets, Five Prime screened a subset of its library of human extracellular proteins in vitro for the ability to modulate immune responses. The authors discovered a number of novel T cell co-inhibitors, including one referred to as Novel Co-Inhibitor 1 (or NCI1), which was identified through its inhibitory activity on anti-CD3-stimulated human T cells in an in vitro assay. To confirm its activity, the authors demonstrated that the native protein expressed on an antigen-presenting cell line could inhibit antigen-stimulated CD8+ T cell activation and that blocking antibodies against this protein relieved the inhibition in vitro. This inhibitory activity translated to a murine system and overexpression of the protein in tumor-bearing mice resulted in increased tumor growth. However, blocking NCI1 with an antibody did not have a significant effect on tumor growth as a single agent in in vivo models, and the company is prioritizing other potential targets. The authors will report the further characterization of NCI1.