On December 07, 2015 TG Therapeutics, Inc. (Nasdaq:TGTX), reported the presentation of pre-clinical data describing the synergy of the Company’s next generation PI3K-delta inhibitor, TGR-1202, with proteasome inhibitors in various hematologic cell lines and patient donor cells (Press release, TG Therapeutics, DEC 7, 2015, View Source [SID:1234508473]). The oral presentation was delivered by Changchun Deng, MD, PhD, Assistant Professor, Center of Lymphoid Malignancies, Columbia University Medical Center at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held at the Orange County Convention Center in Orlando, FL.

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Combination data was generated using TGR-1202, the PI3k-delta inhibitor idelalisib, and the proteasome inhibitors carfilzomib and bortezomib. Data revealed that the combination of TGR-1202 and carfilzomib was uniquely synergistic as compared to any other combination of a PI3K-delta inhibitor and proteasome inhibitor, including the combination of idelalisib and cafilzomib and idelalisib and bortezomib. These data were generated as part of a large pre-clinical research collaboration with the Center for Lymphoid Malignancies, whereby the activity and mechanism of action of TGR-1202 is being studied in a variety of in-vitro and in-vivo models.

Presently there are no agents approved that specifically target c-Myc, an oncogene often found constitutively active in a variety of cancers, including Diffuse Large B-Cell Lymphoma, and has recently been the target of a class of drugs knows as BET (bromodomain and extraterminal domain family) inhibitors. The combination of TGR-1202 and carfilzomib was found to potently inhibit cap dependent translation of c-Myc in all cell lines tested, including DLBCL, mantle cell lymphoma, multiple myeloma, T-cell lymphoma, and CLL cells. In these cell lines, inhibition of c-Myc expression resulted in increased caspase 3/7 activity and complete cleavage of PARP, both mechanisms of apoptosis. Importantly, the combination was not found to be cytotoxic when evaluated on healthy patient lymphocytes indicating the specificity towards malignant cells. As a result of these data, the combination of TGR-1202 and carfilzomib is intended to be studied in a Phase I/II clinical trial to be led by investigators at Columbia University Medical Center.

Commenting on the data, Owen A. O’Connor, MD, PhD, Professor of Medicine and Experimental Therapeutics, and Director of the Center for Lymphoid Malignancies at Columbia University Medical Center stated, "The development of agents that have the ability to inhibit the expression or activity of c-Myc, a key driver in a large variety of hematologic and solid-tumor malignancies, has long been an area of focused research which to date has yielded modest results. The potential for this unique combination is far reaching, and begins to explain the differentiated pharmacologic profile demonstrated by TGR-1202 in patients. We look forward to continuing to elucidate the mechanisms for TGR-1202’s unique tolerability and efficacy, as well as evaluating this combination in patients in our upcoming Phase I/II study."

Michael S. Weiss, the Company’s Executive Chairman and Interim CEO stated, "TGR-1202 has demonstrated strong activity with a differentiated safety and tolerability profile in patients across a variety of clinical trials, and we are eager to explore and understand the mechanisms that contribute to TGR-1202’s potential best-in-class attributes. We thank the investigators at Columbia University, especially Dr. Deng and Dr. O’Connor, for all their efforts on this important research program."

PRESENTATION DETAILS

A copy of the slides used for the oral presentation is available on the Company’s website at www.tgtherapeutics.com, located on the Publications Page, within the Pipeline section.