- Enhanced ADCC activity of FPA144 may play an important mechanistic role in anti-tumor efficacy in cancers with modest expression of FGFR2b.
- FPA144 may reprogram the tumor micro-environment to create synergistic anti-tumor activity when combined with PD-1 blockade
SOUTH SAN FRANCISCO, Calif., March 16, 2016 (GLOBE NEWSWIRE) -- Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, announced that it will feature new preclinical data on FPA144 in a poster presentation during the 2016 American Association for Cancer Research (AACR) Annual Meeting, being held April 16-20 in New Orleans.
Abstract #1407 titled, "FPA144, a Therapeutic Monoclonal Antibody Targeting the FGFR2b Receptor, Promotes Antibody Dependent Cell-Mediated Cytotoxicity and Stimulates Sensitivity to PD-1 the 4T1 Breast Tumor Model in Mice," is now accessible on the meeting website. The poster presentation will take place from Monday, April 18, 2016, from 8:00 AM - 12:00 PM in Section 22. The poster will be made available on the publications page of the Five Prime website following the presentation.
FPA144 is an FGFR2b-specific humanized monoclonal antibody designed to treat patients with cancers that overexpress the FGFR2b receptor. FPA144 is a targeted immunotherapy that has been engineered to recruit NK cells into the tumor microenvironment and kill cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC). At the 2014 AACR Annual Meeting, Five Prime presented data showing that FPA144 can produce complete and durable tumor growth inhibition in FGFR2b-overexpressing and FGFR2 gene-amplified gastric cancer xenografts in immune-compromised mice. The ongoing Phase 1 monotherapy trial is enrolling patients with gastric cancer, a disease in which FGFR2b protein overexpression and FGFR2 gene amplification have been associated with poor prognosis.
In recent months, Five Prime evaluated the anti-tumor effects and immune cell recruitment of FPA144 in the 4T1 model of breast cancer in immune-competent mice. Although the tumor cells in this model express FGFR2b, the FGFR2 gene is not amplified. Therapeutic treatment with FPA144 alone in the orthotopic 4T1 model resulted in a reduction in tumor burden (33%, P<0.001) and within 24 hours, the recruitment of NK cells to the site of tumor implantation, while a modified antibody lacking Fc effector function neither inhibited tumor growth nor led to the recruitment of NK cells. Together these data indicate that enhanced ADCC activity of FPA144 may have the potential to play an important mechanistic role in anti-tumor efficacy in cancers that have modest expression of FGFR2b.
In addition, four days after treatment with FPA144, there was an influx of T cells into the tumor as well as increased expression of PD-L1, providing a strong rationale that FPA144 may combine effectively with PD-1 blockade. Although PD-1 blockade by the RPM1-14 antibody did not inhibit tumor growth as a single agent in the 4T1 model, treatment with RPM1-14 in combination with FPA144, inhibited tumor growth by 49% (P<0.001), demonstrating an additive benefit of combination therapy. These results suggest that FPA144 alters the immune cell composition of the tumor microenvironment in a way that primes the tumor for additional anti-tumor activity when combined with PD-1 blockade.
About FPA144
FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Second, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.
About Five Prime
Five Prime Therapeutics, Inc. discovers and develops innovative therapeutics to improve the lives of patients with serious diseases. Five Prime's comprehensive discovery platform, which encompasses virtually every medically relevant extracellular protein, positions it to explore pathways in cancer, inflammation and their intersection in immuno-oncology, an area with significant therapeutic potential and a growing focus of the company's R&D activities. Five Prime has entered into strategic collaborations with leading global pharmaceutical companies and has promising product candidates in clinical and preclinical development. For more information, please visit www.fiveprime.com.
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