On September 19, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported the publication of new findings by research collaborators at University of California San Diego School of Medicine and Moores Cancer Center and Infinity scientists in the September 19 online issue of Nature (Press release, Infinity Pharmaceuticals, SEP 19, 2016, View Source [SID:SID1234515231]). The paper, entitled "PI3K-gamma is a molecular switch that controls immune suppression,"1 describes research showing that targeting macrophage signaling pathways by inhibiting phosphoinositide-3-kinase (PI3K)-gamma may open the possibility to further improving and refining emerging immunotherapies that boost the body’s own abilities to fight a range of diseases, including cancer. Infinity is conducting a Phase 1 clinical study of IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. IPI-549 is the only PI3K-gamma inhibitor in clinical development. Schedule your 30 min Free 1stOncology Demo! "Immunotherapies, such as T cell checkpoint inhibitors, are showing great promise in early treatments and trials, but they are not universally effective," said Judith A. Varner, PhD, professor in the departments of Pathology and Medicine at UC San Diego School of Medicine. "We have identified a new method to boost the effectiveness of current immune therapy. Our findings also improve our understanding of key mechanisms that control cancer immune suppression and could lead to the development of more effective immunotherapies."
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"The findings published today build upon other work by Infinity and our collaborators, reinforcing the therapeutic potential of Infinity’s selective PI3K-gamma inhibitor, IPI-549, to alter the immune-suppressive microenvironment, promoting an anti-tumor immune response that leads to tumor growth inhibition," stated Jeffery Kutok, M.D., Ph.D., vice president of biology and translational science at Infinity Pharmaceuticals and a co-author of the paper. "Infinity is excited to be at the forefront of advancing PI3K-gamma inhibition as a new immunotherapeutic approach that could potentially enhance existing treatment options, including checkpoint inhibitors."
When confronted by pathogens, injury or disease, the initial response of the body’s immune system comes in the form of macrophages, a type of white blood cell that express pro-inflammatory proteins called cytokines that, in turn, activate T cells, another immune cell, to attack the health threat. The macrophages then switch gears to express other cytokines that dampen T cell activation, stimulating tissue repair. In cancer, highly abundant macrophages express anti-inflammatory cytokines that induce immune suppression, leading to enhanced tumor growth.
In the Nature paper, researchers pinpoint a key, suspected player: an enzyme in macrophages called PI3K-gamma. In mouse studies, they found that macrophage PI3K-gamma signaling promotes immune suppression by inhibiting activation of anti-tumor T cells. Blocking PI3K-gamma activated the immune response and significantly suppressed growth of implanted tumors in animal models. It also boosted sensitivity of some tumors to existing anti-cancer drugs and synergized with existing immune therapy to eradicate tumors. Researchers also identified a molecular signature of immune suppression and response in mice and cancer patients that may be used to track the effectiveness of immune therapy.
Earlier this year, Infinity initiated its first clinical study of IPI-549 designed to explore safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with an anti-PD-1 antibody, a checkpoint inhibitor, in approximately 150 patients with advanced solid tumors, including non-small cell lung cancer and melanoma.2
"Infinity’s first clinical study of IPI-549 is progressing well, and we expect to initiate the first combination therapy cohort this Fall," said Julian Adams, Ph.D., president, research and development at Infinity. "We also look forward to the presentation of early clinical and new preclinical data at an immuno-therapy conference later this month."
Recently, Infinity announced that new preclinical data as well as early clinical data from the ongoing Phase 1 study will be presented for IPI-549 during the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival taking place September 25-28, 2016, in New York City. The IPI-549 presentations will take place during the poster session being held on Monday, September 26, from 5:15 p.m. – 7:45 p.m. ET (Poster Boards B070 and B032).
About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.
IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.