Threshold Pharmaceuticals Announces Preclinical Data on Combination of Evofosfamide With Immune Checkpoint Inhibitors to Be Presented at the SITC 2015 Meeting

Threshold Pharmaceuticals, Inc.

today announced that preclinical data on the combination of evofosfamide with immune checkpoint inhibitors will be presented in a scientific poster at the Society for Immunotherapy of Cancer (SITC) annual meeting in Maryland, November 4-8, 2015. Evofosfamide is Threshold's investigational hypoxia-activated prodrug, which is currently the subject of two fully-enrolled Phase 3 clinical trials for which Threshold expects to announce top-line data around the end of 2015. "This is an exciting time for the field of cancer immunotherapy, and continued progress will depend on a better understanding of the tumor microenvironment and finding novel combination therapies that are more effective than immunotherapy alone," said Michael A. Curran, Ph.D., Assistant Professor at the University of Texas M.D. Anderson Cancer Center and senior author on the scientific poster. "Our research shows that hypoxia in the tumor microenvironment forms a barrier to T cell infiltration and fosters immunotherapy resistance in prostate cancer and other solid tumors," Curran said. "We found that evofosfamide-driven disruption of hypoxic zones sensitizes highly resistant prostate cancer models to treatment with immune checkpoint inhibitors anti-CTLA-4 and anti-PD-1." Research conducted in Curran's laboratory shows that hypoxic zones in prostate tumors resist infiltration by T cells, which are capable of attacking and killing tumor cells. In contrast, normoxic areas of the same tumor experience robust infiltration by T cells. In mouse models of prostate cancer, Curran and colleagues show that combination therapy with evofosfamide and anti-CTLA-4/anti-PD-1 treatment opens up the hypoxic zones to T cell infiltration. Furthermore, evofosfamide helps sensitize otherwise immunotherapy-resistant prostate tumors to anti-CTLA-4/anti-PD-1 therapy in models of prostate cancer as evidenced by the smallest tumor burdens on average being observed with combination therapy. "This combination of hypoxia disruption and T cell checkpoint blockade has potential to render some of the most therapeutically resistant cancers sensitive to immunotherapy," Curran said. "Combining with immunotherapy is an exciting possibility that fits well with our development strategy to maximize the potential therapeutic applications of evofosfamide," said Tillman Pearce, M.D., Chief Medical Officer at Threshold. "The data from Dr. Curran's research suggests that combining evofosfamide with immune checkpoint inhibitors warrants further investigation." The poster titled "Tumor hypoxia drives immune suppression and immunotherapy resistance" by Midan Ai et al. will be presented on Saturday, November 7, 2015, from 12:45 PM - 2:00 PM. The abstract is now available at http://www.sitcancer.org/2015 or by clicking here.